Molecular analysis of the caecal and tracheal microbiome from heat-stressed broilers supplemented with prebiotic and probiotic

USDA-ARS?s Scientific Manuscript database

Gastrointestinal tract (GIT) commensal microbiota is important for host nutrition, health, and immunity, however, little information is available regarding the role of these commensals at other mucosal surfaces of the body. The present study is aimed at elucidating effects of feed supplementations ...

Host Genome Influence on Gut Microbial Composition and Microbial Prediction of Complex Traits in Pigs.

PubMed

Camarinha-Silva, Amelia; Maushammer, Maria; Wellmann, Robin; Vital, Marius; Preuss, Siegfried; Bennewitz, Jörn

2017-07-01

The aim of the present study was to analyze the interplay between gastrointestinal tract (GIT) microbiota, host genetics, and complex traits in pigs using extended quantitative-genetic methods. The study design consisted of 207 pigs that were housed and slaughtered under standardized conditions, and phenotyped for daily gain, feed intake, and feed conversion rate. The pigs were genotyped with a standard 60 K SNP chip. The GIT microbiota composition was analyzed by 16S rRNA gene amplicon sequencing technology. Eight from 49 investigated bacteria genera showed a significant narrow sense host heritability, ranging from 0.32 to 0.57. Microbial mixed linear models were applied to estimate the microbiota variance for each complex trait. The fraction of phenotypic variance explained by the microbial variance was 0.28, 0.21, and 0.16 for daily gain, feed conversion, and feed intake, respectively. The SNP data and the microbiota composition were used to predict the complex traits using genomic best linear unbiased prediction (G-BLUP) and microbial best linear unbiased prediction (M-BLUP) methods, respectively. The prediction accuracies of G-BLUP were 0.35, 0.23, and 0.20 for daily gain, feed conversion, and feed intake, respectively. The corresponding prediction accuracies of M-BLUP were 0.41, 0.33, and 0.33. Thus, in addition to SNP data, microbiota abundances are an informative source of complex trait predictions. Since the pig is a well-suited animal for modeling the human digestive tract, M-BLUP, in addition to G-BLUP, might be beneficial for predicting human predispositions to some diseases, and, consequently, for preventative and personalized medicine. Copyright © 2017 by the Genetics Society of America.

Modulation of Gut Microbiota in the Management of Metabolic Disorders: The Prospects and Challenges

PubMed Central

Erejuwa, Omotayo O.; Sulaiman, Siti A.; Ab Wahab, Mohd S.

2014-01-01

The gut microbiota plays a number of important roles including digestion, metabolism, extraction of nutrients, synthesis of vitamins, prevention against pathogen colonization, and modulation of the immune system. Alterations or changes in composition and biodiversity of the gut microbiota have been associated with many gastrointestinal tract (GIT) disorders such as inflammatory bowel disease and colon cancer. Recent evidence suggests that altered composition and diversity of gut microbiota may play a role in the increased prevalence of metabolic diseases. This review article has two main objectives. First, it underscores approaches (such as probiotics, prebiotics, antimicrobial agents, bariatric surgery, and weight loss strategies) and their prospects in modulating the gut microbiota in the management of metabolic diseases. Second, it highlights some of the current challenges and discusses areas of future research as it relates to the gut microbiota and metabolic diseases. The prospect of modulating the gut microbiota seems promising. However, considering that research investigating the role of gut microbiota in metabolic diseases is still in its infancy, more rigorous and well-designed in vitro, animal and clinical studies are needed. PMID:24608927

Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota.

PubMed

Robertson, Ruairi C; Kaliannan, Kanakaraju; Strain, Conall R; Ross, R Paul; Stanton, Catherine; Kang, Jing X

2018-05-24

The early-life gut microbiota plays a critical role in host metabolism in later life. However, little is known about how the fatty acid profile of the maternal diet during gestation and lactation influences the development of the offspring gut microbiota and subsequent metabolic health outcomes. Here, using a unique transgenic model, we report that maternal endogenous n-3 polyunsaturated fatty acid (PUFA) production during gestation or lactation significantly reduces weight gain and markers of metabolic disruption in male murine offspring fed a high-fat diet. However, maternal fatty acid status appeared to have no significant effect on weight gain in female offspring. The metabolic phenotypes in male offspring appeared to be mediated by comprehensive restructuring of gut microbiota composition. Reduced maternal n-3 PUFA exposure led to significantly depleted Epsilonproteobacteria, Bacteroides, and Akkermansia and higher relative abundance of Clostridia. Interestingly, offspring metabolism and microbiota composition were more profoundly influenced by the maternal fatty acid profile during lactation than in utero. Furthermore, the maternal fatty acid profile appeared to have a long-lasting effect on offspring microbiota composition and function that persisted into adulthood after life-long high-fat diet feeding. Our data provide novel evidence that weight gain and metabolic dysfunction in adulthood is mediated by maternal fatty acid status through long-lasting restructuring of the gut microbiota. These results have important implications for understanding the interaction between modern Western diets, metabolic health, and the intestinal microbiome.

Gastrointestinal Tract Colonization Dynamics by Different Enterococcus faecium Clades

PubMed Central

Montealegre, Maria Camila; Singh, Kavindra V.; Murray, Barbara E.

2016-01-01

Colonization of the gastrointestinal tract (GIT) generally precedes infection with antibiotic-resistant Enterococcus faecium. We used a mouse GIT colonization model to test differences in the colonization levels by strains from different E. faecium lineages: clade B, part of the healthy human microbiota; subclade A1, associated with infections; and subclade A2, primarily associated with animals. After mono-inoculation, there was no significant difference in colonization (measured as the geometric mean number of colony-forming units per gram) by the E. faecium clades at any time point (P > .05). However, in competition assays, with 6 of the 7 pairs, clade B strains outcompeted clade A strains in their ability to persist in the GIT; this difference was significant in some pairs by day 2 and in all pairs by day 14 (P < .0008–.0283). This observation may explain the predominance of clade B in the community and why antibiotic-resistant hospital-associated E. faecium are often replaced by clade B strains once patients leave the hospital. PMID:26671890

Association between oxidative status and the composition of intestinal microbiota along the gastrointestinal tract.

PubMed

Gyuraszova, Marianna; Kovalcikova, Alexandra; Gardlik, Roman

2017-06-01

Studies have shown that the microbiota along the gastrointestinal tract (GIT) plays an important role when it comes to the maintenance of its proper functions. Many studies exist that have analyzed the composition of the bacterial community in the different regions of the GIT of humans and model animals. Microbial imbalance leads to several systemic disorders, including cardiovascular and renal disease. The imbalance between the production of reactive oxygen species (ROS) and their elimination by antioxidants leads to oxidative stress. Oxidative stress plays an important role in a variety of physiological processes, as well as disease. The continuous formation of ROS in the GIT is the result of the interaction between intestinal mucosa, symbiotic bacteria and dietary factors. It has also been proven that ROS play a role in the pathogenesis of several GI disorders, including IBD. We hypothesized that the levels of advanced glycation end products (AGEs) would be the highest in the ileum, caecum or colon, where the microbiota mostly consist of butyrate producing bacteria, Bacterioides, Clostridium, Ruminococcus or Bifidobacterium, which derive energy through carbohydrate fermentation. We also assumed that advanced oxidation protein products (AOPP) mostly act in the segments, where bacteria reside and which are responsible for the amino acid fermentation, such as caecum or colon. Lipid hydroxyperoxides are generated during digestion in the stomach, which contains absorbed oxygen and has a low pH. According to this we hypothesized that the highest concentration of thiobarbituric acid reacting substances (TBARS) could be in the stomach, which, however, has not been confirmed. Because Lactobacilli are able to produce catalase, an endogenous antioxidant, and are abundant in the small intestine, we hypothesized that antioxidant capacity (measured by ferric reducing ability) would be the highest here. The highest levels of AGEs were found in the caecum. The highest level of TBARS was found in the jejunum of the rats. The assessment of our hypothesis also revealed high levels of AOPP in the caecum. It has been shown that AOPP contributes to the progression of IBD. The ferric reducing ability of tissue was the lowest in the colon of the experimental animals, which is in accordance with previous studies that show that rat colon has a lower total antioxidant capacity than the small bowel. In summary, we offer some insight into the differences between the oxidative status along the GIT of rats and some advice concerning supportive antioxidant therapy of gastrointestinal diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain.

PubMed

Jašarević, Eldin; Howerton, Christopher L; Howard, Christopher D; Bale, Tracy L

2015-09-01

The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neurodevelopmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring. Therefore, to examine the hypothesis that changes in the vaginal microbiome are associated with effects on the offspring gut microbiota and on the developing brain, we used genomic, proteomic and metabolomic technologies to examine outcomes in our mouse model of early prenatal stress. Multivariate modeling identified broad proteomic changes to the maternal vaginal environment that influence offspring microbiota composition and metabolic processes essential for normal neurodevelopment. Maternal stress altered proteins related to vaginal immunity and abundance of Lactobacillus, the prominent taxa in the maternal vagina. Loss of maternal vaginal Lactobacillus resulted in decreased transmission of this bacterium to offspring. Further, altered microbiota composition in the neonate gut corresponded with changes in metabolite profiles involved in energy balance, and with region- and sex-specific disruptions of amino acid profiles in the developing brain. Taken together, these results identify the vaginal microbiota as a novel factor by which maternal stress may contribute to reprogramming of the developing brain that may predispose individuals to neurodevelopmental disorders.

Birth mode-dependent association between pre-pregnancy maternal weight status and the neonatal intestinal microbiome.

PubMed

Mueller, Noel T; Shin, Hakdong; Pizoni, Aline; Werlang, Isabel C; Matte, Ursula; Goldani, Marcelo Z; Goldani, Helena A S; Dominguez-Bello, Maria Gloria

2016-04-01

The intestinal microbiome is a unique ecosystem that influences metabolism in humans. Experimental evidence indicates that intestinal microbiota can transfer an obese phenotype from humans to mice. Since mothers transmit intestinal microbiota to their offspring during labor, we hypothesized that among vaginal deliveries, maternal body mass index is associated with neonatal gut microbiota composition. We report the association of maternal pre-pregnancy body mass index on stool microbiota from 74 neonates, 18 born vaginally (5 to overweight or obese mothers) and 56 by elective C-section (26 to overweight or obese mothers). Compared to neonates delivered vaginally to normal weight mothers, neonates born to overweight or obese mothers had a distinct gut microbiota community structure (weighted UniFrac distance PERMANOVA, p < 0.001), enriched in Bacteroides and depleted in Enterococcus, Acinetobacter, Pseudomonas, and Hydrogenophilus. We show that these microbial signatures are predicted to result in functional differences in metabolic signaling and energy regulation. In contrast, among elective Cesarean deliveries, maternal body mass index was not associated with neonatal gut microbiota community structure (weighted UniFrac distance PERMANOVA, p = 0.628). Our findings indicate that excess maternal pre-pregnancy weight is associated with differences in neonatal acquisition of microbiota during vaginal delivery, but not Cesarean delivery. These differences may translate to altered maintenance of metabolic health in the offspring.

Birth mode-dependent association between pre-pregnancy maternal weight status and the neonatal intestinal microbiome

PubMed Central

Mueller, Noel T.; Shin, Hakdong; Pizoni, Aline; Werlang, Isabel C.; Matte, Ursula; Goldani, Marcelo Z.; Goldani, Helena A. S.; Dominguez-Bello, Maria Gloria

2016-01-01

The intestinal microbiome is a unique ecosystem that influences metabolism in humans. Experimental evidence indicates that intestinal microbiota can transfer an obese phenotype from humans to mice. Since mothers transmit intestinal microbiota to their offspring during labor, we hypothesized that among vaginal deliveries, maternal body mass index is associated with neonatal gut microbiota composition. We report the association of maternal pre-pregnancy body mass index on stool microbiota from 74 neonates, 18 born vaginally (5 to overweight or obese mothers) and 56 by elective C-section (26 to overweight or obese mothers). Compared to neonates delivered vaginally to normal weight mothers, neonates born to overweight or obese mothers had a distinct gut microbiota community structure (weighted UniFrac distance PERMANOVA, p < 0.001), enriched in Bacteroides and depleted in Enterococcus, Acinetobacter, Pseudomonas, and Hydrogenophilus. We show that these microbial signatures are predicted to result in functional differences in metabolic signaling and energy regulation. In contrast, among elective Cesarean deliveries, maternal body mass index was not associated with neonatal gut microbiota community structure (weighted UniFrac distance PERMANOVA, p = 0.628). Our findings indicate that excess maternal pre-pregnancy weight is associated with differences in neonatal acquisition of microbiota during vaginal delivery, but not Cesarean delivery. These differences may translate to altered maintenance of metabolic health in the offspring. PMID:27033998

Clinical Relevance of Gastrointestinal Microbiota During Pregnancy: A Primer for Nurses.

PubMed

Chung, Seon-Yoon; Ravel, Jacques; Regan, Mary

2018-01-01

Emerging evidence about the human microbiome, a collective term for all the microorganisms living in and on the human body, consistently demonstrates the critical influence it has on host physiology and disease risk. The microbiota in the gastrointestinal (GI) tract has the most significant and far-reaching effect on human physiology. The maternal GI microbiota can decrease the risk of adverse pregnancy outcomes by modulating energy extraction, glucose metabolism, vitamin production, and host immunity essential for optimal maternal and neonatal health. Moreover, the maternal GI microbiota is thought to influence colonization of the fetus and neonate that may predispose them to different health trajectories. This article provides a basic understanding about the influence of the structure of the maternal GI microbiota, the fundamental role it plays during pregnancy, and the factors that influence the structure, and subsequently function, of the GI microbiota in the general and pregnant population. While only a small number of studies have examined this topic during pregnancy, the preponderance of the evidence supports the need to clarify baseline structure and function of GI microbiota and its associations with pregnancy outcomes. In addition, the results from the studies conducted in the general population can be extrapolated to pregnancy in many cases. This knowledge is essential for clinicians who need to understand the implications of the microbiota for disease and wellness in order to address the care factors that may adversely influence the GI microbiota during pregnancy.

Dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus.

PubMed

Wang, Jinfeng; Zheng, Jiayong; Shi, Wenyu; Du, Nan; Xu, Xiaomin; Zhang, Yanming; Ji, Peifeng; Zhang, Fengyi; Jia, Zhen; Wang, Yeping; Zheng, Zhi; Zhang, Hongping; Zhao, Fangqing

2018-05-14

The initial colonisation of the human microbiota and the impact of maternal health on neonatal microbiota at birth remain largely unknown. The aim of our study is to investigate the possible dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus (GDM) and to estimate the potential risks of the microbial shift to neonates. Pregnant women and neonates suffering from GDM were enrolled and 581 maternal (oral, intestinal and vaginal) and 248 neonatal (oral, pharyngeal, meconium and amniotic fluid) samples were collected. To avoid vaginal bacteria contaminations, the included neonates were predominantly delivered by C-section, with their samples collected within seconds of delivery. Numerous and diverse bacterial taxa were identified from the neonatal samples, and the samples from different neonatal body sites were grouped into distinct clusters. The microbiota of pregnant women and neonates was remarkably altered in GDM, with a strong correlation between certain discriminatory bacteria and the oral glucose tolerance test. Microbes varying by the same trend across the maternal and neonatal microbiota were observed, revealing the intergenerational concordance of microbial variation associated with GDM. Furthermore, lower evenness but more depletion of KEGG orthologues and higher abundance of some viruses (eg, herpesvirus and mastadenovirus) were observed in the meconium microbiota of neonates associated with GDM. GDM can alter the microbiota of both pregnant women and neonates at birth, which sheds light on another form of inheritance and highlights the importance of understanding the formation of early-life microbiome. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study.

PubMed

Azad, M B; Konya, T; Persaud, R R; Guttman, D S; Chari, R S; Field, C J; Sears, M R; Mandhane, P J; Turvey, S E; Subbarao, P; Becker, A B; Scott, J A; Kozyrskyj, A L

2016-05-01

Dysbiosis of the infant gut microbiota may have long-term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut microbiota, and to explore whether breastfeeding modifies these effects. Prospective pregnancy cohort of Canadian infants born in 2010-2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Study. General community. Representative sub-sample of 198 healthy term infants from the CHILD Study. Maternal IAP exposures and birth method were documented from hospital records and breastfeeding was reported by mothers. Infant gut microbiota was characterised by Illumina 16S rRNA sequencing of faecal samples at 3 and 12 months. Infant gut microbiota profiles. In this cohort, 21% of mothers received IAP for Group B Streptococcus prophylaxis or pre-labour rupture of membranes; another 23% received IAP for elective or emergency caesarean section (CS). Infant gut microbiota community structures at 3 months differed significantly with all IAP exposures, and differences persisted to 12 months for infants delivered by emergency CS. Taxon-specific composition also differed, with the genera Bacteroides and Parabacteroides under-represented, and Enterococcus and Clostridium over-represented at 3 months following maternal IAP. Microbiota differences were especially evident following IAP with emergency CS, with some changes (increased Clostridiales and decreased Bacteroidaceae) persisting to 12 months, particularly among non-breastfed infants. Intrapartum antibiotics in caesarean and vaginal delivery are associated with infant gut microbiota dysbiosis, and breastfeeding modifies some of these effects. Further research is warranted to explore the health consequences of these associations. Maternal #antibiotics during childbirth alter the infant gut #microbiome. © 2015 Royal College of Obstetricians and Gynaecologists.

The gastrointestinal microbiome and its association with the control of pathogens in broiler chicken production: A review

PubMed Central

Clavijo, Viviana

2018-01-01

Abstract The microbiome of the broiler chicken gastrointestinal tract (GIT) has been extensively studied, and it has been amply demonstrated that it plays an important role in the health of the host, as it has a positive impact on the immune system, the physiology of the GIT, and productivity. Also, the microbiota is involved in reducing and preventing colonization by enteric pathogens through the process of competitive exclusion and the production of bacteriostatic and bactericidal substances. The taxonomic composition of the microbiota is affected by different factors, such as the organ, the age of the animal, diet and the use of antimicrobials. Different kinds of additives that regulate the microbial community in feed include probiotics (live microorganisms that when administered in adequate amounts confer a health benefit on the host), prebiotics (ingredients that stimulate increased beneficial microbial activity in the digestive system in order to improve the health of the host) and phytobiotics (primary or secondary components of plants that contain bioactive compounds that exert a positive effect on the growth and health of animals). Phages may potentially provide an integrated solution to modulate the intestinal microbiome of chicken intestines, as they reduce specific pathogenic microbial populations, permitting the proliferation of beneficial microbiota. Studies have shown that the use of cocktails of phages, especially in high concentrations and with short lapses of time between exposure to the bacteria and treatment with phages, optimize the reduction of Salmonella in chickens. Each of these technologies has demonstrable positive effects on the health of the host and the reduction of the pathogen load in controlled assays. This paper presents a comprehensive summary of the role of the microbiota in the broiler chicken gastrointestinal tract, and discusses the usefulness of different strategies for its modulation to control pathogens, with a particular emphasis on bacteriophages. PMID:29253263

Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats.

PubMed

Paul, Heather A; Bomhof, Marc R; Vogel, Hans J; Reimer, Raylene A

2016-02-12

Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy.

Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats

PubMed Central

Paul, Heather A.; Bomhof, Marc R.; Vogel, Hans J.; Reimer, Raylene A.

2016-01-01

Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy. PMID:26868870

Gastrointestinal Tract Colonization Dynamics by Different Enterococcus faecium Clades.

PubMed

Montealegre, Maria Camila; Singh, Kavindra V; Murray, Barbara E

2016-06-15

Colonization of the gastrointestinal tract (GIT) generally precedes infection with antibiotic-resistant Enterococcus faecium We used a mouse GIT colonization model to test differences in the colonization levels by strains from different E. faecium lineages: clade B, part of the healthy human microbiota; subclade A1, associated with infections; and subclade A2, primarily associated with animals. After mono-inoculation, there was no significant difference in colonization (measured as the geometric mean number of colony-forming units per gram) by the E. faecium clades at any time point (P > .05). However, in competition assays, with 6 of the 7 pairs, clade B strains outcompeted clade A strains in their ability to persist in the GIT; this difference was significant in some pairs by day 2 and in all pairs by day 14 (P < .0008-.0283). This observation may explain the predominance of clade B in the community and why antibiotic-resistant hospital-associated E. faecium are often replaced by clade B strains once patients leave the hospital. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Infant Gut Microbiota Development Is Driven by Transition to Family Foods Independent of Maternal Obesity.

PubMed

Laursen, Martin Frederik; Andersen, Louise B B; Michaelsen, Kim F; Mølgaard, Christian; Trolle, Ellen; Bahl, Martin Iain; Licht, Tine Rask

2016-01-01

The first years of life are paramount in establishing our endogenous gut microbiota, which is strongly affected by diet and has repeatedly been linked with obesity. However, very few studies have addressed the influence of maternal obesity on infant gut microbiota, which may occur either through vertically transmitted microbes or through the dietary habits of the family. Additionally, very little is known about the effect of diet during the complementary feeding period, which is potentially important for gut microbiota development. Here, the gut microbiotas of two different cohorts of infants, born either of a random sample of healthy mothers (n = 114), or of obese mothers (n = 113), were profiled by 16S rRNA amplicon sequencing. Gut microbiota data were compared to breastfeeding patterns and detailed individual dietary recordings to assess effects of the complementary diet. We found that maternal obesity did not influence microbial diversity or specific taxon abundances during the complementary feeding period. Across cohorts, breastfeeding duration and composition of the complementary diet were found to be the major determinants of gut microbiota development. In both cohorts, gut microbial composition and alpha diversity were thus strongly affected by introduction of family foods with high protein and fiber contents. Specifically, intake of meats, cheeses, and Danish rye bread, rich in protein and fiber, were associated with increased alpha diversity. Our results reveal that the transition from early infant feeding to family foods is a major determinant for gut microbiota development. IMPORTANCE The potential influence of maternal obesity on infant gut microbiota may occur either through vertically transmitted microbes or through the dietary habits of the family. Recent studies have suggested that the heritability of obesity may partly be caused by the transmission of "obesogenic" gut microbes. However, the findings presented here suggest that maternal obesity per se does not affect the overall composition of the gut microbiota and its development after introduction of complementary foods. Rather, progression in complementary feeding is found to be the major determinant for gut microbiota establishment. Expanding our understanding of the influence of complementary diet on the development and establishment of the gut microbiota will provide us with the knowledge to tailor a beneficial progression of our intestinal microbial community.

Infant Gut Microbiota Development Is Driven by Transition to Family Foods Independent of Maternal Obesity

PubMed Central

Laursen, Martin Frederik; Andersen, Louise B. B.; Michaelsen, Kim F.; Mølgaard, Christian; Trolle, Ellen; Bahl, Martin Iain

2016-01-01

ABSTRACT The first years of life are paramount in establishing our endogenous gut microbiota, which is strongly affected by diet and has repeatedly been linked with obesity. However, very few studies have addressed the influence of maternal obesity on infant gut microbiota, which may occur either through vertically transmitted microbes or through the dietary habits of the family. Additionally, very little is known about the effect of diet during the complementary feeding period, which is potentially important for gut microbiota development. Here, the gut microbiotas of two different cohorts of infants, born either of a random sample of healthy mothers (n = 114), or of obese mothers (n = 113), were profiled by 16S rRNA amplicon sequencing. Gut microbiota data were compared to breastfeeding patterns and detailed individual dietary recordings to assess effects of the complementary diet. We found that maternal obesity did not influence microbial diversity or specific taxon abundances during the complementary feeding period. Across cohorts, breastfeeding duration and composition of the complementary diet were found to be the major determinants of gut microbiota development. In both cohorts, gut microbial composition and alpha diversity were thus strongly affected by introduction of family foods with high protein and fiber contents. Specifically, intake of meats, cheeses, and Danish rye bread, rich in protein and fiber, were associated with increased alpha diversity. Our results reveal that the transition from early infant feeding to family foods is a major determinant for gut microbiota development. IMPORTANCE The potential influence of maternal obesity on infant gut microbiota may occur either through vertically transmitted microbes or through the dietary habits of the family. Recent studies have suggested that the heritability of obesity may partly be caused by the transmission of “obesogenic” gut microbes. However, the findings presented here suggest that maternal obesity per se does not affect the overall composition of the gut microbiota and its development after introduction of complementary foods. Rather, progression in complementary feeding is found to be the major determinant for gut microbiota establishment. Expanding our understanding of the influence of complementary diet on the development and establishment of the gut microbiota will provide us with the knowledge to tailor a beneficial progression of our intestinal microbial community. PMID:27303699

The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism.

PubMed

Zhou, Liyuan; Xiao, Xinhua

2018-04-27

Obesity is considered a global epidemic. Specifically, obesity during pregnancy programs an increased risk of the offspring developing metabolic disorders in addition to the adverse effects on the mother per se Large numbers of human and animal studies have demonstrated that the gut microbiota plays a pivotal role in obesity and metabolic diseases. Similarly, maternal obesity during pregnancy is associated with alterations in the composition and diversity of the intestine microbial community. Recently, the microbiota in the placenta, amniotic fluid, and meconium in healthy gestations has been investigated, and the results supported the "in utero colonization hypothesis" and challenged the traditional "sterile womb" that has been acknowledged worldwide for more than a century. Thus, the offspring microbiota, which is crucial for the immune and metabolic function and further health in the offspring, might be established prior to birth. As a detrimental intrauterine environment, maternal obesity influences the microbial colonization and increases the risk of metabolic diseases in offspring. This review discusses the role of the microbiota in the impact of maternal obesity during pregnancy on offspring metabolism and further analyzes related probiotic or prebiotic interventions to prevent and treat obesity and metabolic diseases. © 2018 The Author(s).

The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism

PubMed Central

Zhou, Liyuan; Xiao, Xinhua

2017-01-01

Obesity is considered a global epidemic. Specifically, obesity during pregnancy programs an increased risk of the offspring developing metabolic disorders in addition to the adverse effects on the mother per se. Large numbers of human and animal studies have demonstrated that the gut microbiota plays a pivotal role in obesity and metabolic diseases. Similarly, maternal obesity during pregnancy is associated with alterations in the composition and diversity of the intestine microbial community. Recently, the microbiota in the placenta, amniotic fluid, and meconium in healthy gestations has been investigated, and the results supported the “in utero colonization hypothesis” and challenged the traditional “sterile womb” that has been acknowledged worldwide for more than a century. Thus, the offspring microbiota, which is crucial for the immune and metabolic function and further health in the offspring, might be established prior to birth. As a detrimental intrauterine environment, maternal obesity influences the microbial colonization and increases the risk of metabolic diseases in offspring. This review discusses the role of the microbiota in the impact of maternal obesity during pregnancy on offspring metabolism and further analyzes related probiotic or prebiotic interventions to prevent and treat obesity and metabolic diseases. PMID:29208770

Microbial ecology and host-microbiota interactions during early life stages

PubMed Central

Collado, Maria Carmen; Cernada, Maria; Baüerl, Christine; Vento, Máximo; Pérez-Martínez, Gaspar

2012-01-01

The role of human microbiota has been redefined during recent years and its physiological role is now much more important than earlier understood. Intestinal microbial colonization is essential for the maturation of immune system and for the developmental regulation of the intestinal physiology. Alterations in this process of colonization have been shown to predispose and increase the risk to disease later in life. The first contact of neonates with microbes is provided by the maternal microbiota. Moreover, mode of delivery, type of infant feeding and other perinatal factors can influence the establishment of the infant microbiota. Taken into consideration all the available information it could be concluded that the exposure to the adequate microbes early in gestation and neonatal period seems to have a relevant role in health. Maternal microbial environment affects maternal and fetal immune physiology and, of relevance, this interaction with microbes at the fetal-maternal interface could be modulated by specific microbes administered to the pregnant mother. Indeed, probiotic interventions aiming to reduce the risk of immune-mediated diseases may appear effective during early life. PMID:22743759

Pregnancy-related changes in the maternal gut microbiota are dependent upon the mother's periconceptional diet

PubMed Central

Gohir, Wajiha; Whelan, Fiona J; Surette, Michael G; Moore, Caroline; Schertzer, Jonathan D; Sloboda, Deborah M

2015-01-01

Shifts in the maternal gut microbiome have been implicated in metabolic adaptations to pregnancy. We investigated how pregnancy and diet interact to influence the composition of the maternal gut microbiota. Female C57BL/6 mice were fed either a control or a high fat diet for 8 weeks prior to mating. After confirmation of pregnancy, maternal weight gain and food intake were recorded. Fecal pellets were collected at 2 timepoints prior to mating (at the beginning of the experiment, and after 6 weeks of the specified diet) and at 4 timepoints during pregnancy (gestation day 0.5, 5.5, 10.5, and 15.5). The microbial composition and predicted metabolic functionality of the non-pregnant and pregnant gut was determined via sequencing of the variable 3 region of the 16S rRNA gene. Upon conception, differences in gut microbial communities were observed in both control and high fat-fed mice, including an increase in mucin-degrading bacteria. Control versus high fat-fed pregnant mice possessed the most profound changes to their maternal gut microbiota as indicated by statistically significant taxonomic differences. High fat-fed pregnant mice, when compared to control-fed animals, were found to be significantly enriched in microbes involved in metabolic pathways favoring fatty acid, ketone, vitamin, and bile synthesis. We show that pregnancy-induced changes in the female gut microbiota occur immediately at the onset of pregnancy, are vulnerable to modulation by diet, but are not dependent upon increases in maternal weight gain during pregnancy. High fat diet intake before and during pregnancy results in distinctive shifts in the pregnant gut microbiota in a gestational-age dependent manner and these shifts predict significant differences in the abundance of genes that favor lipid metabolism, glycolysis and gluconeogenic metabolic pathways over the course of pregnancy. PMID:26322500

Salivary microbiomes of indigenous Tsimane mothers and infants are distinct despite frequent premastication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Cliff S.; Martin, Melanie Ann; Dichosa, Armand E. K.

Background Premastication, the transfer of pre-chewed food, is a common infant and young child feeding practice among the Tsimane, forager-horticulturalists living in the Bolivian Amazon. Research conducted primarily with Western populations has shown that infants harbor distinct oral microbiota from their mothers. Premastication, which is less common in these populations, may influence the colonization and maturation of infant oral microbiota, including via transmission of oral pathogens. We collected premasticated food and saliva samples from Tsimane mothers and infants (9–24 months of age) to test for evidence of bacterial transmission in premasticated foods and overlap in maternal and infant salivary microbiota.more » We extracted bacterial DNA from two premasticated food samples and 12 matched salivary samples from maternal-infant pairs. DNA sequencing was performed with MiSeq (Illumina). We evaluated maternal and infant microbial composition in terms of relative abundance of specific taxa, alpha and beta diversity, and dissimilarity distances. Results The bacteria in saliva and premasticated food were mapped to 19 phyla and 400 genera and were dominated by Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. The oral microbial communities of Tsimane mothers and infants who frequently share premasticated food were well-separated in a non-metric multi-dimensional scaling ordination (NMDS) plot. Infant microbiotas clustered together, with weighted Unifrac distances significantly differing between mothers and infants. Infant saliva contained more Firmicutes ( p  < 0.01) and fewer Proteobacteria ( p  < 0.05) than did maternal saliva. Many genera previously associated with dental and periodontal infections, e.g.  Neisseria , Gemella , Rothia , Actinomyces , Fusobacterium , and Leptotrichia , were more abundant in mothers than in infants. Conclusions Salivary microbiota of Tsimane infants and young children up to two years of age do not appear closely related to those of their mothers, despite frequent premastication and preliminary evidence that maternal bacteria is transmitted to premasticated foods. Infant physiology and diet may constrain colonization by maternal bacteria, including several oral pathogens.« less

Salivary microbiomes of indigenous Tsimane mothers and infants are distinct despite frequent premastication

DOE PAGES

Han, Cliff S.; Martin, Melanie Ann; Dichosa, Armand E. K.; ...

2016-11-03

Background Premastication, the transfer of pre-chewed food, is a common infant and young child feeding practice among the Tsimane, forager-horticulturalists living in the Bolivian Amazon. Research conducted primarily with Western populations has shown that infants harbor distinct oral microbiota from their mothers. Premastication, which is less common in these populations, may influence the colonization and maturation of infant oral microbiota, including via transmission of oral pathogens. We collected premasticated food and saliva samples from Tsimane mothers and infants (9–24 months of age) to test for evidence of bacterial transmission in premasticated foods and overlap in maternal and infant salivary microbiota.more » We extracted bacterial DNA from two premasticated food samples and 12 matched salivary samples from maternal-infant pairs. DNA sequencing was performed with MiSeq (Illumina). We evaluated maternal and infant microbial composition in terms of relative abundance of specific taxa, alpha and beta diversity, and dissimilarity distances. Results The bacteria in saliva and premasticated food were mapped to 19 phyla and 400 genera and were dominated by Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. The oral microbial communities of Tsimane mothers and infants who frequently share premasticated food were well-separated in a non-metric multi-dimensional scaling ordination (NMDS) plot. Infant microbiotas clustered together, with weighted Unifrac distances significantly differing between mothers and infants. Infant saliva contained more Firmicutes ( p  < 0.01) and fewer Proteobacteria ( p  < 0.05) than did maternal saliva. Many genera previously associated with dental and periodontal infections, e.g.  Neisseria , Gemella , Rothia , Actinomyces , Fusobacterium , and Leptotrichia , were more abundant in mothers than in infants. Conclusions Salivary microbiota of Tsimane infants and young children up to two years of age do not appear closely related to those of their mothers, despite frequent premastication and preliminary evidence that maternal bacteria is transmitted to premasticated foods. Infant physiology and diet may constrain colonization by maternal bacteria, including several oral pathogens.« less

Spatial Variation of the Gut Microbiota in Broiler Chickens as Affected by Dietary Available Phosphorus and Assessed by T-RFLP Analysis and 454 Pyrosequencing

PubMed Central

Green-Engert, Rebecca; Hoelzle, Katharina; Zeller, Ellen; Seifert, Jana; Hoelzle, Ludwig E.; Rodehutscord, Markus

2015-01-01

Molecular fingerprinting and sequencing based techniques have been widely used to characterize microbial communities. Terminal restriction fragment length polymorphism (T-RFLP) and 454-pyrosequencing were used to determine the microorganisms present in the different sections of the chicken gastrointestinal tract (GIT) (crop, jejunum, ileum and caeca). Broilers fed with diets differing in phosphorous (P) and calcium (Ca) as well as in phytase levels were used to study the microbiota of the upper and lower part of the GIT. A database with terminal restriction fragments (T-RF) of the most important organism present in the different gastrointestinal sections was constructed. The analysis revealed a distinct microbial assemblage on each section. Regardless of the diet, crop, jejunum and ileum were mainly colonized by Lactobacillaceae, and caeca were the most diverse site. The correlation between Lactobacillus crispatus and L. reuteri was positive in the crop, but negative in the jejunum. In crop samples, higher P and Ca levels led to a shift in the abundance of L. reuteri and L. crispatus to L. salivarius and L. taiwanensis whereas in the ileum supplementation of phytase favored L. salivarius and L. taiwanensis but resulted in decreased abundance of L. crispatus. Both methods were correlating significantly, being T-RFLP a reliable fingerprinting method to rapidly analyze large numbers of samples in a cost-effective and rapid manner. Results are easy to interpret with no need of deep bioinformatics knowledge and can be integrated with taxonomic information. PMID:26588075

Spatial Variation of the Gut Microbiota in Broiler Chickens as Affected by Dietary Available Phosphorus and Assessed by T-RFLP Analysis and 454 Pyrosequencing.

PubMed

Witzig, Maren; Carminha-Silva, Amelia; Camarinha da Silva, Amelia; Green-Engert, Rebecca; Hoelzle, Katharina; Zeller, Ellen; Seifert, Jana; Hoelzle, Ludwig E; Rodehutscord, Markus

2015-01-01

Molecular fingerprinting and sequencing based techniques have been widely used to characterize microbial communities. Terminal restriction fragment length polymorphism (T-RFLP) and 454-pyrosequencing were used to determine the microorganisms present in the different sections of the chicken gastrointestinal tract (GIT) (crop, jejunum, ileum and caeca). Broilers fed with diets differing in phosphorous (P) and calcium (Ca) as well as in phytase levels were used to study the microbiota of the upper and lower part of the GIT. A database with terminal restriction fragments (T-RF) of the most important organism present in the different gastrointestinal sections was constructed. The analysis revealed a distinct microbial assemblage on each section. Regardless of the diet, crop, jejunum and ileum were mainly colonized by Lactobacillaceae, and caeca were the most diverse site. The correlation between Lactobacillus crispatus and L. reuteri was positive in the crop, but negative in the jejunum. In crop samples, higher P and Ca levels led to a shift in the abundance of L. reuteri and L. crispatus to L. salivarius and L. taiwanensis whereas in the ileum supplementation of phytase favored L. salivarius and L. taiwanensis but resulted in decreased abundance of L. crispatus. Both methods were correlating significantly, being T-RFLP a reliable fingerprinting method to rapidly analyze large numbers of samples in a cost-effective and rapid manner. Results are easy to interpret with no need of deep bioinformatics knowledge and can be integrated with taxonomic information.

Maternal consumption of fructo-oligosaccharide diminishes the severity of skin inflammation in offspring of NC/Nga mice.

PubMed

Fujiwara, Reiko; Takemura, Naoki; Watanabe, Jun; Sonoyama, Kei

2010-02-01

Strategies to manipulate the gut microbiota in infancy have been considered to prevent the development of allergic diseases later in life. We aimed to elucidate the effects of maternal dietary supplementation with a prebiotic oligosaccharide on gut microbiota and spontaneously developing atopic dermatitis-like skin lesions in the offspring of NC/Nga mice. Female NC/Nga mice were fed diets either with or without fructo-oligosaccharide supplementation during pregnancy and lactation. After weaning, offspring were fed the diets supplemented with or without fructo-oligosaccharide for 11 weeks in an air-uncontrolled conventional room. Changes in gut microbiota were assessed by denaturing gradient gel electrophoresis of the PCR-amplified 16S rRNA gene. Skin lesions were evaluated by a clinical score and scratching behaviour. Serum antibody levels were measured by ELISA, and expression levels of cytokines and chemokines in lesional tissue were evaluated by quantitative RT-PCR. Maternal supplementation with fructo-oligosaccharide modulated the gut microbiota in sucklings. Although maternal supplementation with fructo-oligosaccharide suppressed the increase in clinical skin severity score and scratching behaviour in offspring, dietary fructo-oligosaccharide after weaning was less effective. The diminution of skin lesions was accompanied by lower serum concentrations of total IgG1 and lower expression levels of TNF-alpha in the lesional tissue. These data suggest that maternal consumption of fructo-oligosaccharide diminishes the severity of atopic dermatitis-like skin lesions in the offspring of NC/Nga mice.

Resveratrol Prevents the Development of Hypertension Programmed by Maternal Plus Post-Weaning High-Fructose Consumption Through Modulation of Oxidative Stress, Nutrient-Sensing Signals, and Gut Microbiota.

PubMed

Tain, You-Lin; Lee, Wei-Chia; Wu, Kay L H; Leu, Steve; Chan, Julie Y H

2018-04-30

High-fructose (HF) intake, oxidative stress, nutrient-sensing signals, and gut microbiota dysbiosis are closely related to the development of hypertension. We investigated whether resveratrol can prevent hypertension induced by maternal plus post-weaning HF diets in adult offspring via the above-mentioned mechanisms. Female Sprague-Dawley rats received either a normal (ND) or 60% high-fructose (HF) diet during gestation and lactation. Male offspring were assigned to five groups (maternal diet/post-weaning diet; n = 8/group): ND/ND, ND/HF, HF/ND, HF/HF, and HF/HF+ Resveratrol. Resveratrol (50 mg/L) was administered in drinking water from weaning to three months of age. We found that HF/HF induced hypertension in adult offspring. Maternal HF diet altered gut microbiota composition in adult offspring, including decreasing the abundance of genera Bacteroides, Dysgonomonas, and Turicibacter, while increasing phylum Verrucomicrobia and Akkermansia muciniphila. Additionally, HF/HF diets increased oxidative stress and decreased renal mRNA expression of Prkaa2, Prkag2, Ppara, Pparb, Ppargc1a, and Sirt4. Resveratrol reduced renal oxidative stress, activated nutrient-sensing signals, modulated gut microbiota, and prevented associated HF/HF-induced programmed hypertension. Targeting oxidative stress, nutrient-sensing signals, and gut microbiota by resveratrol might be a useful therapeutic strategy for treatment of hypertension induced by excessive consumption of fructose in the adult rat offspring. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Diversified Microbiota of Meconium Is Affected by Maternal Diabetes Status

PubMed Central

Hu, Jianzhong; Nomura, Yoko; Bashir, Ali; Fernandez-Hernandez, Heriberto; Itzkowitz, Steven; Pei, Zhiheng; Stone, Joanne; Loudon, Holly; Peter, Inga

2013-01-01

Objectives This study was aimed to assess the diversity of the meconium microbiome and determine if the bacterial community is affected by maternal diabetes status. Methods The first intestinal discharge (meconium) was collected from 23 newborns stratified by maternal diabetes status: 4 mothers had pre-gestational type 2 diabetes mellitus (DM) including one mother with dizygotic twins, 5 developed gestational diabetes mellitus (GDM) and 13 had no diabetes. The meconium microbiome was profiled using multi-barcode 16S rRNA sequencing followed by taxonomic assignment and diversity analysis. Results All meconium samples were not sterile and contained diversified microbiota. Compared with adult feces, the meconium showed a lower species diversity, higher sample-to-sample variation, and enrichment of Proteobacteria and reduction of Bacteroidetes. Among the meconium samples, the taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the DM group showing higher alpha-diversity than that of no-diabetes or GDM groups. No global difference was found between babies delivered vaginally versus via Cesarean-section. Regression analysis showed that the most robust predictor for the meconium microbiota composition was the maternal diabetes status that preceded pregnancy. Specifically, Bacteroidetes (phyla) and Parabacteriodes (genus) were enriched in the meconium in the DM group compared to the no-diabetes group. Conclusions Our study provides evidence that meconium contains diversified microbiota and is not affected by the mode of delivery. It also suggests that the meconium microbiome of infants born to mothers with DM is enriched for the same bacterial taxa as those reported in the fecal microbiome of adult DM patients. PMID:24223144

Fetal programming of overweight through the microbiome: boys are disproportionately affected.

PubMed

Kozyrskyj, A L; Kalu, R; Koleva, P T; Bridgman, S L

2016-02-01

Maternal and childhood obesity in pregnancy are worrisome public health issues facing our world today. New gene sequencing methods have advanced our knowledge of the disruptive effect of birth interventions and postnatal exposures on the maturation of gut microbiota and immunity during infancy. Yet, little is known about the impact of maternal pregnancy overweight on gut microbes and related processes, and how this may affect overweight risk in offspring. To address this gap in knowledge, we surveyed human studies for evidence in children, infants and pregnant women to piece together the limited literature and generate hypotheses for future investigation. From this literature, we learned that higher Lactobacillus yet lower Bacteroides spp. colonization of gut microbiota within 3 months of birth predicted risk for infant and child overweight. The abundance of bifidobacteria and staphylococci also appeared to play a role in the association with overweight, as did infant fecal immunoglobulin A levels, glycoproteins of the gut immune system that are acquired from breast milk and produced by the infant. We proposed that pregnancy overweight influences the compositional structure of gut microbiota in infants through vertical transfer of microbiota and/or their metabolites during pregnancy, delivery and breastfeeding. Finally, we brought forward emerging evidence on sex dimorphism, as well as ethnic and geographic variation, in reported associations between maternal overweight-induced gut microbiota dysbiosis and overweight risk.

Inheritance and Establishment of Gut Microbiota in Chickens

PubMed Central

Ding, Jinmei; Dai, Ronghua; Yang, Lingyu; He, Chuan; Xu, Ke; Liu, Shuyun; Zhao, Wenjing; Xiao, Lu; Luo, Lingxiao; Zhang, Yan; Meng, He

2017-01-01

In mammals, the microbiota can be transmitted from the placenta, uterus, and vagina of the mother to the infant. Unlike mammals, development of the avian embryo is a process isolated from the mother and thus in the avian embryo the gut microbial developmental process remains elusive. To explore the establishment and inheritance of the gut microbiome in the avian embryo, we used the chicken as the model organism to investigate the gut microbial composition in embryos, chicks, and maternal hens. We observed: (1) 28 phyla and 162 genera of microbes in embryos where the dominated genus was Halomonas (79%). (2) 65 genera were core microbiota in all stages with 42% and 62% gut microbial genera of embryo were found in maternal hen and chick, respectively. There was a moderate correlation (0.40) between the embryo and maternal, and 0.52 between the embryo and chick at the family level. (3) Gut microbes that are involved in substance metabolism, infectious disease, and environmental adaptation are enriched in embryos, chicks, and maternal hens, respectively. (4) 94% genera of gut microbial composition were similar among three different chicken breeds which were maintained under similar conditions. Our findings provide evidence to support the hypothesis that part of the microbial colonizers harbored in early embryos were inherited from maternal hens, and the gut microbial abundance and diversity were influenced by environmental factors and host genetic variation during development. PMID:29067020

Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer.

PubMed

Dominguez-Bello, Maria G; De Jesus-Laboy, Kassandra M; Shen, Nan; Cox, Laura M; Amir, Amnon; Gonzalez, Antonio; Bokulich, Nicholas A; Song, Se Jin; Hoashi, Marina; Rivera-Vinas, Juana I; Mendez, Keimari; Knight, Rob; Clemente, Jose C

2016-03-01

Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C-section were exposed to maternal vaginal fluids at birth. Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns during the first 30 d of life was enriched in vaginal bacteria--which were underrepresented in unexposed C-section-delivered infants--and the microbiome similarity to those of vaginally delivered infants was greater in oral and skin samples than in anal samples. Although the long-term health consequences of restoring the microbiota of C-section-delivered infants remain unclear, our results demonstrate that vaginal microbes can be partially restored at birth in C-section-delivered babies.

Probiotics in digestive diseases: focus on Lactobacillus GG.

PubMed

Pace, F; Pace, M; Quartarone, G

2015-12-01

Probiotics are becoming increasingly important in basic and clinical research, but they are also a subject of considerable economic interest due to their expanding popularity. They are live micro-organisms which, when administered in adequate amounts, confer a health benefit to the host. From this very well-known definition, it is clear that, unlike drugs, probiotics might be useful in healthy subjects to reduce the risk of developing certain diseases or to optimise some physiological functions. They also may offer some advantages in already ill persons in relieving symptoms and signs, e.g. people with acute diarrhea. According to current definitions, probiotics should survive both gastric acid and bile to reach the small intestine and colon, where they exert their effects. Many of these are available in a lyophilized (freeze-dried) pill form, though some are available in yogurt or as packets (sachets), which can be mixed into non-carbonated drinks. The present review focuses on three main issues: 1) understanding why, at present, probiotics are so interesting for doctors and consumers; 2) reviewing the available data on probiotic use in digestive diseases, in particular irritable bowel syndrome (IBS), (prevention of) infectious diarrhea, inflammatory bowel disease (IBD), non-alcoholic fatty liver disease (NAFLD), and colorectal cancer (CRC); 3) highlighting the individual profile of Lactobacillus GG (LGG) in the above contexts, providing an assessment as well as recommendations on its use in gastro-intestinal tract (GIT) disorders. Research studies conducted in animals and humans with the main probiotics strains for GIT diseases, and published from the early 1990s to 2014 have been considered. PubMed, Medline and Ovid were the main sources adopted for data retrieving. The increasing attention on probiotics is a direct consequence of the improvement in the techniques for studying microbiota. Until recently, its composition has been analysed by culture-based methods that use differential media to select for specific populations of bacteria according to their metabolic requirements. Lactobacillus and Bifidobacterium species are by and large the most commonly used probiotics. Strictly speaking, however, the term "probiotic" should be reserved for live microbes that have been shown in controlled human studies to provide a health benefit. Taking into account patients suffering from the most common gastrointestinal diseases, in whose establishment the GI microbiota plays a key role, probiotics have to be considered as very promising agents, capable of beneficially modulating the intestinal ecosystem, which is perturbed in cases of dysbiosis. Although more clinical data are still needed to better assess the clinical relevance of probiotics, to date, procariota such as Bifidobacteria and Lactobacilli strains, and eucariota such as some Saccharomyces strains are among the most widely used agents in GIT disorders. LGG is a well-known probiotic strain that was isolated more than 20 years ago by Goldin and Gorbach from a faecal sample of a healthy adult, based on several selection criteria: high adhesion in vitro, high resistance against gastric acidity and high antimicrobial activity against pathogens such as Salmonella. In vivo studies have also shown a good persistence of LGG in the human GIT. Since its isolation, LGG has become one of the best clinically documented probiotic strains. A growing body of evidence suggests benefits such as prevention and relief of various types of diarrhoea, and treatment of relapsing Clostridium difficile colitis. Thus, with respect to both adaptation to the GIT and probiotic effects, LGG can be regarded as a prototypical probiotic strain.

Exploring the contribution of maternal antibiotics and breastfeeding to development of the infant microbiome and pediatric obesity.

PubMed

Lemas, Dominick J; Yee, Shanique; Cacho, Nicole; Miller, Darci; Cardel, Michelle; Gurka, Matthew; Janicke, David; Shenkman, Elizabeth

2016-12-01

Pediatric obesity, a significant public health concern, has been associated with adult premature mortality and the development of type 2 diabetes and cardiovascular disease. Evidence has suggested that the gut microbiota is associated with pediatric obesity. Establishment of the infant gut microbiome is dependent on a dynamic maternal-infant microbiota exchange during early life. The objective of this review is to describe maternal factors such as feeding practices and antibiotic use that may influence the infant gut microbiome and risk for obesity. The complex components in human milk have many nutritional benefits to the infant; however, the microbiome in human milk may be an important factor to help regulate the infant's weight. We discuss maternal antibiotics and the effects on breast milk as critical exposures that alter the infant's gut microbiome and influence the risk of pediatric obesity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Obesity and overweight: Impact on maternal and milk microbiome and their role for infant health and nutrition.

PubMed

Garcia-Mantrana, Izaskun; Collado, Maria Carmen

2016-08-01

Obesity, particularly in infants, is becoming a significant public health problem that has reached "epidemic" status worldwide. Obese children have an increased risk of developing obesity-related diseases, such as metabolic syndromes and diabetes, as well as increased risk of mortality and adverse health outcomes later in life. Experimental data show that maternal obesity has negative effects on the offspring's health in the short and long term. Increasing evidence suggests a key role for microbiota in host metabolism and energy harvest, providing novel tools for obesity prevention and management. The maternal environment, including nutrition and microbes, influences the likelihood of developing childhood diseases, which may persist and be exacerbated in adulthood. Maternal obesity and weight gain also influence microbiota composition and activity during pregnancy and lactation. They affect microbial diversity in the gut and breast milk. Such microbial changes may be transferred to the offspring during delivery and also during lactation, affecting infant microbial colonisation and immune system maturation. Thus, an adequate nutritional and microbial environment during the peri-natal period may provide a window of opportunity to reduce the risk of obesity and overweight in our infants using targeted strategies aimed at modulating the microbiota during early life. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microbiome assembly of avian eggshells and their potential as transgenerational carriers of maternal microbiota.

PubMed

van Veelen, H Pieter J; Salles, Joana Falcão; Tieleman, B Irene

2018-05-01

The microbiome is essential for development, health and homeostasis throughout an animal's life. Yet, the origins and transmission processes governing animal microbiomes remain elusive for non-human vertebrates, oviparous vertebrates in particular. Eggs may function as transgenerational carriers of the maternal microbiome, warranting characterisation of egg microbiome assembly. Here, we investigated maternal and environmental contributions to avian eggshell microbiota in wild passerine birds: woodlark Lullula arborea and skylark Alauda arvensis. Using 16S rRNA gene sequencing, we demonstrated in both lark species, at the population and within-nest levels, that bacterial communities of freshly laid eggs were distinct from the female cloacal microbiome. Instead, soil-borne bacteria appeared to thrive on freshly laid eggs, and eggshell microbiota composition strongly resembled maternal skin, body feather and nest material communities, sources in direct contact with laid eggs. Finally, phylogenetic structure analysis and microbial source tracking underscored species sorting from directly contacting sources rather than in vivo-transferred symbionts. The female-egg-nest system allowed an integrative assessment of avian egg microbiome assembly, revealing mixed modes of symbiont acquisition not previously documented for vertebrate eggs. Our findings illuminated egg microbiome origins, which suggested a limited potential of eggshells for transgenerational transmission, encouraging further investigation of eggshell microbiome functions in vertebrates.

Fat and vitamin intakes during pregnancy have stronger relations with a pro-inflammatory maternal microbiota than does carbohydrate intake.

PubMed

Mandal, Siddhartha; Godfrey, Keith M; McDonald, Daniel; Treuren, Will V; Bjørnholt, Jørgen V; Midtvedt, Tore; Moen, Birgitte; Rudi, Knut; Knight, Rob; Brantsæter, Anne Lise; Peddada, Shyamal D; Eggesbø, Merete

2016-10-19

Although diet is known to have a major modulatory influence on gut microbiota, knowledge of the specific roles of particular vitamins, minerals, and other nutrients is limited. Modulation of the composition of the microbiota in pregnant women is especially important as maternal microbes are transferred during delivery and initiate the colonization process in the infant. We studied the associations between intake of specific dietary nutrients during pregnancy and gut microbiota composition. Utilizing the Norwegian NoMIC cohort, we examined the relations between intakes of 28 dietary macro- and micronutrients during pregnancy, derived from food frequency questionnaires administered to 60 women in the second trimester, and observed taxonomic differences in their gut microbiota four days after delivery (assessed through Illumina 16S rRNA amplicon analysis). Higher dietary intakes of fat-soluble vitamins, especially vitamin D, were associated with reduced microbial alpha diversity (p value <0.001). Furthermore, using recently developed statistical methodology, we discovered that the variations in fat-soluble vitamins, saturated and mono-unsaturated fat, and cholesterol intake, were associated with changes in phyla composition. Specifically, vitamin D, mono-unsaturated fat, cholesterol, and retinol were associated with relative increases in Proteobacteria, which is a phylum known to encompass multiple pathogens and to have pro-inflammatory properties. In contrast, saturated fat, vitamin E, and protein were associated with relative decreases in Proteobacteria. The results in this article indicate that fats and fat-soluble vitamins are among the most potent dietary modulators of gut microbiota in mothers. The shifts in microbiota due to diet need to be further studied alongside gut microbiota changes during pregnancy to better understand the impact on infant gut microbiota.

Seasonal, spatial, and maternal effects on gut microbiome in wild red squirrels.

PubMed

Ren, Tiantian; Boutin, Stan; Humphries, Murray M; Dantzer, Ben; Gorrell, Jamieson C; Coltman, David W; McAdam, Andrew G; Wu, Martin

2017-12-21

Our understanding of gut microbiota has been limited primarily to findings from human and laboratory animals, but what shapes the gut microbiota in nature remains largely unknown. To fill this gap, we conducted a comprehensive study of gut microbiota of a well-studied North American red squirrel (Tamiasciurus hudsonicus) population. Red squirrels are territorial, solitary, and live in a highly seasonal environment and therefore represent a very attractive system to study factors that drive the temporal and spatial dynamics of gut microbiota. For the first time, this study revealed significant spatial patterns of gut microbiota within a host population, suggesting limited dispersal could play a role in shaping and maintaining the structure of gut microbial communities. We also found a remarkable seasonal rhythm in red squirrel's gut microbial composition manifested by a tradeoff between relative abundance of two genera Oscillospira and Corpococcus and clearly associated with seasonal variation in diet availability. Our results show that in nature, environmental factors exert a much stronger influence on gut microbiota than host-associated factors including age and sex. Despite strong environmental effects, we found clear evidence of individuality and maternal effects, but host genetics did not seem to be a significant driver of the gut microbial communities in red squirrels. Taken together, the results of this study emphasize the importance of external ecological factors rather than host attributes in driving temporal and spatial patterns of gut microbiota in natural environment.

Low Maternal Microbiota Sharing across Gut, Breast Milk and Vagina, as Revealed by 16S rRNA Gene and Reduced Metagenomic Sequencing.

PubMed

Avershina, Ekaterina; Angell, Inga Leena; Simpson, Melanie; Storrø, Ola; Øien, Torbjørn; Johnsen, Roar; Rudi, Knut

2018-05-01

The maternal microbiota plays an important role in infant gut colonization. In this work we have investigated which bacterial species are shared across the breast milk, vaginal and stool microbiotas of 109 women shortly before and after giving birth using 16S rRNA gene sequencing and a novel reduced metagenomic sequencing (RMS) approach in a subgroup of 16 women. All the species predicted by the 16S rRNA gene sequencing were also detected by RMS analysis and there was good correspondence between their relative abundances estimated by both approaches. Both approaches also demonstrate a low level of maternal microbiota sharing across the population and RMS analysis identified only two species common to most women and in all sample types ( Bifidobacterium longum and Enterococcus faecalis ). Breast milk was the only sample type that had significantly higher intra- than inter- individual similarity towards both vaginal and stool samples. We also searched our RMS dataset against an in silico generated reference database derived from bacterial isolates in the Human Microbiome Project. The use of this reference-based search enabled further separation of Bifidobacterium longum into Bifidobacterium longum ssp. longum and Bifidobacterium longum ssp. infantis . We also detected the Lactobacillus rhamnosus GG strain, which was used as a probiotic supplement by some women, demonstrating the potential of RMS approach for deeper taxonomic delineation and estimation.

Low Maternal Microbiota Sharing across Gut, Breast Milk and Vagina, as Revealed by 16S rRNA Gene and Reduced Metagenomic Sequencing

PubMed Central

Angell, Inga Leena; Storrø, Ola; Øien, Torbjørn; Johnsen, Roar; Rudi, Knut

2018-01-01

The maternal microbiota plays an important role in infant gut colonization. In this work we have investigated which bacterial species are shared across the breast milk, vaginal and stool microbiotas of 109 women shortly before and after giving birth using 16S rRNA gene sequencing and a novel reduced metagenomic sequencing (RMS) approach in a subgroup of 16 women. All the species predicted by the 16S rRNA gene sequencing were also detected by RMS analysis and there was good correspondence between their relative abundances estimated by both approaches. Both approaches also demonstrate a low level of maternal microbiota sharing across the population and RMS analysis identified only two species common to most women and in all sample types (Bifidobacterium longum and Enterococcus faecalis). Breast milk was the only sample type that had significantly higher intra- than inter- individual similarity towards both vaginal and stool samples. We also searched our RMS dataset against an in silico generated reference database derived from bacterial isolates in the Human Microbiome Project. The use of this reference-based search enabled further separation of Bifidobacterium longum into Bifidobacterium longum ssp. longum and Bifidobacterium longum ssp. infantis. We also detected the Lactobacillus rhamnosus GG strain, which was used as a probiotic supplement by some women, demonstrating the potential of RMS approach for deeper taxonomic delineation and estimation. PMID:29724017

Impact of human milk bacteria and oligosaccharides on neonatal gut microbiota establishment and gut health.

PubMed

Jost, Ted; Lacroix, Christophe; Braegger, Christian; Chassard, Christophe

2015-07-01

Neonatal gut microbiota establishment represents a crucial stage for gut maturation, metabolic and immunologic programming, and consequently short- and long-term health status. Human milk beneficially influences this process due to its dynamic profile of age-adapted nutrients and bioactive components and by providing commensal maternal bacteria to the neonatal gut. These include Lactobacillus spp., as well as obligate anaerobes such as Bifidobacterium spp., which may originate from the maternal gut via an enteromammary pathway as a novel form of mother-neonate communication. Additionally, human milk harbors a broad range of oligosaccharides that promote the growth and activity of specific bacterial populations, in particular, Bifidobacterium and Bacteroides spp. This review focuses on the diversity and origin of human milk bacteria, as well as on milk oligosaccharides that influence neonatal gut microbiota establishment. This knowledge can be used to develop infant formulae that more closely mimic nature's model and sustain a healthy gut microbiota. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Review: Dietary fiber utilization and its effects on physiological functions and gut health of swine.

PubMed

Jha, R; Berrocoso, J D

2015-09-01

Although dietary fiber (DF) negatively affects energy and nutrient digestibility, there is growing interest for the inclusion of its fermentable fraction in pig diets due to their functional properties and potential health benefits beyond supplying energy to the animals. This paper reviews some of the relevant information available on the role of different types of DF on digestion of nutrients in different sections of the gut, the fermentation process and its influence on gut environment, especially production and utilization of metabolites, microbial community and gut health of swine. Focus has been given on DF from feed ingredients (grains and coproducts) commonly used in pig diets. Some information on the role DF in purified form in comparison with DF in whole matrix of feed ingredients is also presented. First, composition and fractions of DF in different feed ingredients are briefly reviewed. Then, roles of different fractions of DF on digestion characteristics and physiological functions in the gastrointestinal tract (GIT) are presented. Specific roles of different fractions of DF on fermentation characteristics and their effects on production and utilization of metabolites in the GIT have been discussed. In addition, roles of DF fermentation on metabolic activity and microbial community in the intestine and their effects on intestinal health are reviewed and discussed. Evidence presented in this review indicates that there is wide variation in the composition and content of DF among feed ingredients, thereby their physico-chemical properties in the GIT of swine. These variations, in turn, affect the digestion and fermentation characteristics in the GIT of swine. Digestibility of DF from different feed ingredients is more variable and lower than that of other nutrients like starch, sugars, fat and CP. Soluble fractions of DF are fermented faster, produce higher amounts of volatile fatty acid than insoluble fractions, and favors growth of beneficial microbiota. Thus, selective inclusion of DF in diets can be used as a nutritional strategy to optimize the intestinal health of pigs, despite its lower digestibility and consequential negative effect on digestibility of other nutrients.

Maternal group B Streptococcus and the infant gut microbiota.

PubMed

Cassidy-Bushrow, A E; Sitarik, A; Levin, A M; Lynch, S V; Havstad, S; Ownby, D R; Johnson, C C; Wegienka, G

2016-02-01

Early patterns of gut colonization may predispose children to adult disease. Exposures in utero and during delivery are associated with the infant gut microbiome. Although ~35% of women carry group B strep (GBS; Streptococcus agalactiae) during pregnancy, it is unknown if GBS presence influences the infant gut microbiome. As part of a population-based, general risk birth cohort, stool specimens were collected from infant's diapers at research visits conducted at ~1 and 6 months of age. Using the Illumina MiSeq (San Diego, CA) platform, the V4 region of the bacterial 16S rRNA gene was sequenced. Infant gut bacterial community compositional differences by maternal GBS status were evaluated using permutational multivariate analysis of variance. Individual operational taxonomic units (OTUs) were tested using a zero-inflated negative binomial model. Data on maternal GBS and infant gut microbiota from either 1 (n=112) or 6-month-old stool (n=150) specimens was available on 262 maternal-child pairs. Eighty women (30.5%) were GBS+, of who 58 (72.5%) were given intrapartum antibiotics. After adjusting for maternal race, prenatal antifungal use and intrapartum antibiotics, maternal GBS status was statistically significantly associated with gut bacterial composition in the 6 month visit specimen (Canberra R 2=0.008, P=0.008; Unweighted UniFrac R 2=0.010, P=0.011). Individual OTU tests revealed that infants of GBS+ mothers were significantly enriched for specific members of the Clostridiaceae, Ruminococcoceae, and Enterococcaceae in the 6 month specimens compared with infants of GBS- mothers. Whether these taxonomic differences in infant gut microbiota at 6 months lead to differential predisposition for adult disease requires additional study.

Different concentrations of grape seed extract affect in vitro starch fermentation by porcine small and large intestinal inocula.

PubMed

Wang, Dongjie; Williams, Barbara A; Ferruzzi, Mario G; D'Arcy, Bruce R

2013-01-01

Grape seed extract (GSE) phenolics have potential health-promoting properties, either from compounds present within the extract, or metabolites resulting from gastrointestinal tract (GIT) fermentation of these compounds. This study describes how GSE affected the kinetics and end-products of starch fermentation in vitro using pig intestinal and fecal inocula. Six GSE concentrations (0, 60, 125, 250, 500, and 750 µg ml⁻¹ were fermented in vitro by porcine ileal and fecal microbiota using starch as the energy source. Cumulative gas production, and end-point short chain fatty acids and ammonia were measured. GSE phenolics altered the pattern (gas kinetics, and end-products such as SCFA and NH₄⁺) of starch fermentation by both inocula, at concentrations above 250 µg ml⁻¹ . Below this level, neither inoculum showed any significant (P > 0.05) effect of the GSE. The results show that GSE phenolics at a concentration over 250 µg ml⁻¹ can have measurable effects on microbial activity in an in vitro fermentation system, as evidenced by the changes in kinetics and end-products from starch fermentation. This suggests that fermentation patterns could be conceivably shifted in the actual GIT, though further evidence will be required from in vivo studies. Copyright © 2012 Society of Chemical Industry.

Functional role of oppA encoding an oligopeptide-binding protein from Lactobacillus salivarius Ren in bile tolerance.

PubMed

Wang, Guohong; Li, Dan; Ma, Xiayin; An, Haoran; Zhai, Zhengyuan; Ren, Fazheng; Hao, Yanling

2015-08-01

Lactobacillus salivarius is a member of the indigenous microbiota of the human gastrointestinal tract (GIT), and some L. salivarius strains are considered as probiotics. Bile tolerance is a crucial property for probiotic bacteria to survive the transit through the GIT and exert their beneficial effects. In this work, the functional role of oppA encoding an oligopeptide transporter substrate-binding protein from L. salivarius Ren in bile salt tolerance was investigated. In silico analysis revealed that the oppA gene encodes a 61.7-kDa cell surface-anchored hydrophilic protein with a canonical lipoprotein signal peptide. Homologous overexpression of OppA was shown to confer 20-fold higher tolerance to 0.5 % oxgall in L. salivarius Ren. Furthermore, the recombinant strain exhibited 1.8-fold and 3.6-fold higher survival when exposed to the sublethal concentration of sodium taurocholate and sodium taurodeoxycholate, respectively, while no significant change was observed when exposed to sodium glycocholate and sodium glycodeoxycholate (GDCA). Our results indicate that OppA confers specific resistance to taurine-conjugated bile salts in L. salivarius Ren. In addition, the OppA overexpression strain also showed significant increased resistance to heat and salt stresses, suggesting the protective role of OppA against multiple stresses in L. salivarius Ren.

A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.

PubMed

Val-Laillet, David; Besson, Marie; Guérin, Sylvie; Coquery, Nicolas; Randuineau, Gwénaëlle; Kanzari, Ameni; Quesnel, Hélène; Bonhomme, Nathalie; Bolhuis, J Elizabeth; Kemp, Bas; Blat, Sophie; Le Huërou-Luron, Isabelle; Clouard, Caroline

2017-05-01

A suboptimal early nutritional environment ( i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs ( Sus scrofa ) the impact of maternal diet [standard diet (SD) vs. Western diet (WD)] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows ( n = 17) and their piglets ( n = 65), and on spatial cognition ( n = 51), hippocampal plasticity ( n = 17), and food preferences/motivation ( n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations ( P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100-d-old piglets ( P < 0.05 or P < 0.10, depending on short-chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels ( P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high-fat and -sucrose (HFS) diet ( P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards ( P < 0.01). WD piglets had higher working memory ( P = 0.015) and reference memory ( P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer ( P = 0.03) and decreased neurogenesis ( P < 0.005), but increased cell proliferation ( P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets' blood lipid levels, microbiota activity, gut-brain axis, and neurocognitive abilities after weaning.-Val-Laillet, D., Besson, M., Guérin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huërou-Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs. © FASEB.

Fetal exposures and perinatal influences on the stool microbiota of premature infants

PubMed Central

Chernikova, Diana A.; Koestler, Devin C.; Hoen, Anne Gatewood; Housman, Molly L.; Hibberd, Patricia L.; Moore, Jason H.; Morrison, Hilary G.; Sogin, Mitchell L.; Ul-Abideen, Muhammad Zain; Madan, Juliette C.

2015-01-01

Objective To test the hypothesis that maternal complications significantly affect gut colonization patterns in very low birth weight infants. Methods 49 serial stool samples were obtained weekly from 9 extremely premature infants enrolled in a prospective longitudinal study. Sequencing of the bacterial 16S rRNA gene from stool samples was performed to approximate the intestinal microbiome. Linear mixed effects models were used to evaluate relationships between perinatal complications and intestinal microbiome development. Results Subjects with prenatal exposure to a non-sterile intrauterine environment, i.e. PPPROM and chorioamnionitis exposure, were found to have a relatively higher abundance of potentially pathogenic bacteria in the stool across all time points compared to subjects without those exposures, irrespective of exposure to postnatal antibiotics. Compared with those delivered by Caesarean section, vaginally delivered subjects were found to have significantly lower diversity of stool microbiota across all time points, with lower abundance of many genera, most in the family Enterobacteriaceae. Conclusions We identified persistently increased potential pathogen abundance in the developing stool microbiota of subjects exposed to a non-sterile uterine environment. Maternal complications appear to significantly influence the diversity and bacterial composition of the stool microbiota of premature infants, with findings persisting over time. PMID:25394613

A review of the source and function of microbiota in breast milk.

PubMed

Latuga, M Susan; Stuebe, Alison; Seed, Patrick C

2014-01-01

Breast milk contains a rich microbiota composed of viable skin and non-skin bacteria. The extent of the breast milk microbiota diversity has been revealed through new culture-independent studies using microbial DNA signatures. However, the extent to which the breast milk microbiota are transferred from mother to infant and the function of these breast milk microbiota for the infant are only partially understood. Here, we appraise hypotheses regarding the formation of breast milk microbiota, including retrograde infant-to-mother transfer and enteromammary trafficking, and we review current knowledge of mechanisms determining the extent of breast milk microbiota transfer from mother to infant. We highlight known functions of constituents in the breast milk microbiota-to enhance immunity, liberate nutrients, synergize with breast milk oligosaccharides to enhance intestinal barrier function, and strengthen a functional gut-brain axis. We also consider the pathophysiology of maternal mastitis with respect to a dysbiosis or abnormal shift in the breast milk microbiota. In conclusion, through a complex, highly evolved process in the early stages of discovery, mothers transfer the breast milk microbiota to their infants to impact infant growth and development. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Searching for the gut microbial contributing factors to social behavior in rodent models of autism spectrum disorder.

PubMed

Needham, Brittany D; Tang, Weiyi; Wu, Wei-Li

2018-05-01

Social impairment is one of the major symptoms in multiple psychiatric disorders, including autism spectrum disorder (ASD). Accumulated studies indicate a crucial role for the gut microbiota in social development, but these mechanisms remain unclear. This review focuses on two strategies adopted to elucidate the complicated relationship between gut bacteria and host social behavior. In a top-down approach, researchers have attempted to correlate behavioral abnormalities with altered gut microbial profiles in rodent models of ASD, including BTBR mice, maternal immune activation (MIA), maternal valproic acid (VPA) and maternal high-fat diet (MHFD) offspring. In a bottom-up approach, researchers use germ-free (GF) animals, antibiotics, probiotics or pathogens to manipulate the intestinal environment and ascertain effects on social behavior. The combination of both approaches will hopefully pinpoint specific bacterial communities that control host social behavior. Further discussion of how brain development and circuitry is impacted by depletion of gut microbiota is also included. The converging evidence strongly suggests that gut microbes affect host social behavior through the alteration of brain neural circuits. Investigation of intestinal microbiota and host social behavior will unveil any bidirectional communication between the gut and brain and provide alternative therapeutic targets for ASD. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 474-499, 2018. © 2018 Wiley Periodicals, Inc.

Prevalence of Antibiotic Resistance Genes among Human Gut-Derived Bifidobacteria.

PubMed

Duranti, Sabrina; Lugli, Gabriele Andrea; Mancabelli, Leonardo; Turroni, Francesca; Milani, Christian; Mangifesta, Marta; Ferrario, Chiara; Anzalone, Rosaria; Viappiani, Alice; van Sinderen, Douwe; Ventura, Marco

2017-02-01

The microbiota of the human gastrointestinal tract (GIT) may regularly be exposed to antibiotics, which are used to prevent and treat infectious diseases caused by bacteria and fungi. Bacterial communities of the gut retain a reservoir of antibiotic resistance (AR) genes, and antibiotic therapy thus positively selects for those microorganisms that harbor such genetic features, causing microbiota modulation. During the first months following birth, bifidobacteria represent some of the most dominant components of the human gut microbiota, although little is known about their AR gene complement (or resistome). In the current study, we assessed the resistome of the Bifidobacterium genus based on phenotypic and genotypic data of members that represent all currently recognized bifidobacterial (sub)species. Moreover, a comparison between the bifidobacterial resistome and gut metagenome data sets from adults and infants shows that the bifidobacterial community present at the first week following birth possesses a reduced AR arsenal compared to that present in the infant bifidobacterial population in subsequent weeks of the first year of life. Our findings reinforce the concept that the early infant gut microbiota is more susceptible to disturbances by antibiotic treatment than the gut microbiota developed at a later life stage. The spread of resistance to antibiotics among bacterial communities has represented a major concern since their discovery in the last century. The risk of genetic transfer of resistance genes between microorganisms has been extensively investigated due to its relevance to human health. In contrast, there is only limited information available on antibiotic resistance among human gut commensal microorganisms such as bifidobacteria, which are widely exploited by the food industry as health-promoting microorganisms or probiotic ingredients. In the current study, we explored the occurrence of antibiotic resistance genes in the genomes of bifidobacteria and evaluated their genetic mobility to other human gut commensal microorganisms. Copyright © 2017 American Society for Microbiology.

The effects of maternal and post-weaning diet interaction on glucose metabolism and gut microbiota in male mice offspring

PubMed Central

Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Qi, Cuijuan; Wang, Tong

2016-01-01

Substantial studies demonstrated that maternal nutrition can significantly determine the susceptibility to developing some metabolic diseases in offspring. However, investigations into the later-life effects of these diets on gut microbiota in the offspring are limited. Our objective was to explore the effects of maternal and post-weaning diet interaction on offspring's gut microbiota and glucose metabolism in later life. The male offspring of dams fed on either a high-fat (HF) diet or control (C) diet and then weaned to either a HF or C diet, generating four groups: C–C, HF–C, C–HF and HF–HF (n=8 in each group). The C–C offspring had lower body weight than C–HF group at 16 weeks of age (P<0.01) and both C–HF and HF–HF offspring had higher body weight than C–C group at 24 and 32 weeks of age (P<0.001 respectively). The blood glucose (BG) levels of the male offspring from the C and HF dams weaned HF diet were significantly higher at 30 min, 60 min and 120 min (P<0.001) after intraperitoneal glucose administration compared with those of the C–C group. The C–HF group had higher BG at 30 min than HF–HF group (P<0.01). Furthermore, area under the curve (AUC) in C–HF and HF–HF groups was also significantly larger than C–C group (P<0.001). Fasting BG and homoeostasis model assessment of insulin resistance (HOMA-IR) of the offspring were significantly higher in C–HF and HF–HF groups than C–C group at 32 weeks of age (P<0.05). Operational taxonomic unit (OTU), Chao and Shannon indexes showed a significantly lower diversity in C–HF offspring compared with HF–C and C–C groups (P<0.05). The dominant phyla of all the groups were Bacteroidetes, Firmicutes and Proteobacteria, which also showed significantly different percentages in the group (P<0.05). Furthermore, it is indicated that Lactobacillus and Bacteroides were significantly associated with glucose response to a glucose load (P<0.05). In conclusion, maternal and post-weaning diet interaction predisposes the offspring to aberrant glucose metabolism and alterations of gut microbiota in later life. Our study is novel in focusing on the effects of maternal and post-weaning diet interaction on offspring gut microbiota and glucose metabolism in later life. PMID:27129301

Tracing of the fecal microbiota of commercial pigs at five growth stages from birth to shipment.

PubMed

Han, Geon Goo; Lee, Jun-Yeong; Jin, Gwi-Deuk; Park, Jongbin; Choi, Yo Han; Kang, Sang-Kee; Chae, Byung Jo; Kim, Eun Bae; Choi, Yun-Jaie

2018-04-16

The intestinal microbiota affect various physiological traits of host animals such as brain development, obesity, age, and the immune system. In the swine industry, understanding the relationship between intestinal microbiota and growth stage is essential because growth stage is directly related to the feeding system of pigs, thus we studied the intestinal microbiota of 32 healthy pigs across five sows at 10, 21, 63, 93, and 147 d of ages. The intestinal microbiota were altered with growth of pigs and were separated into three distinct clusters. The relative abundance of several phyla and genera were significantly different between growth stages. We observed co-occurrence pattern of the intestinal microbiota at each growth stage. In addition, we predicted the functions of the intestinal microbiota and confirmed that several KEGG pathways were significantly different between growth stages. We also explored the relationship between the intestinal microbiota and innate factors such as the maternal effect and gender. When pigs were young, innate factors affected on construction of intestinal microbiota, however this tendency was disappeared with growth. Our findings broaden the understanding of microbial ecology, and the results will be used as a reference for investigating host-microbe interactions in the swine industry.

Impaired spine formation and learning in GPCR kinase 2 interacting protein-1 (GIT1) knockout mice.

PubMed

Menon, Prashanthi; Deane, Rashid; Sagare, Abhay; Lane, Steven M; Zarcone, Troy J; O'Dell, Michael R; Yan, Chen; Zlokovic, Berislav V; Berk, Bradford C

2010-03-04

The G-protein coupled receptor (GPCR)-kinase interacting proteins 1 and 2 (GIT1 and GIT2) are scaffold proteins with ADP-ribosylating factor GTPase activity. GIT1 and GIT2 control numerous cellular functions and are highly expressed in neurons, endothelial cells and vascular smooth muscle cells. GIT1 promotes dendritic spine formation, growth and motility in cultured neurons, but its role in brain in vivo is unknown. By using global GIT1 knockout mice (GIT1 KO), we show that compared to WT controls, deletion of GIT1 results in markedly reduced dendritic length and spine density in the hippocampus by 36.7% (p<0.0106) and 35.1% (p<0.0028), respectively. This correlated with their poor adaptation to new environments as shown by impaired performance on tasks dependent on learning. We also studied the effect of GIT1 gene deletion on brain microcirculation. In contrast to findings in systemic circulation, GIT1 KO mice had an intact blood-brain barrier and normal regional cerebral blood flow as determined with radiotracers. Thus, our data suggest that GIT1 plays an important role in brain in vivo by regulating spine density involved in synaptic plasticity that is required for processes involved in learning. 2009 Elsevier B.V. All rights reserved.

The origin of human milk bacteria: is there a bacterial entero-mammary pathway during late pregnancy and lactation?

PubMed

Rodríguez, Juan M

2014-11-01

Human milk is a source of bacteria to the infant gut; however, the origin of milk bacteria, as well as their impact on neonatal gut microbiota establishment, remains largely unknown. In the past years, results provided by different research groups suggest that certain bacteria from the maternal gastrointestinal tract could translocate through a mechanism involving mononuclear immune cells, migrate to the mammary glands via an endogenous cellular route (the bacterial entero-mammary pathway), and subsequently colonize the gastrointestinal tract of the breast-fed neonate. If such findings are confirmed in the future, we could exert a positive influence on infant health by modulating the maternal gut microbiota. © 2014 American Society for Nutrition.

Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota

PubMed Central

Madore, Charlotte; Leyrolle, Quentin; Lacabanne, Chloé; Benmamar-Badel, Anouk; Joffre, Corinne; Nadjar, Agnes

2016-01-01

Several genetic causes of autism spectrum disorder (ASD) have been identified. However, more recent work has highlighted that certain environmental exposures early in life may also account for some cases of autism. Environmental insults during pregnancy, such as infection or malnutrition, seem to dramatically impact brain development. Maternal viral or bacterial infections have been characterized as disruptors of brain shaping, even if their underlying mechanisms are not yet fully understood. Poor nutritional diversity, as well as nutrient deficiency, is strongly associated with neurodevelopmental disorders in children. For instance, imbalanced levels of essential fatty acids, and especially polyunsaturated fatty acids (PUFAs), are observed in patients with ASD and other neurodevelopmental disorders (e.g., attention deficit hyperactivity disorder (ADHD) and schizophrenia). Interestingly, PUFAs, and specifically n-3 PUFAs, are powerful immunomodulators that exert anti-inflammatory properties. These prenatal dietary and immunologic factors not only impact the fetal brain, but also affect the microbiota. Recent work suggests that the microbiota could be the missing link between environmental insults in prenatal life and future neurodevelopmental disorders. As both nutrition and inflammation can massively affect the microbiota, we discuss here how understanding the crosstalk between these three actors could provide a promising framework to better elucidate ASD etiology. PMID:27840741

Fetal exposures and perinatal influences on the stool microbiota of premature infants.

PubMed

Chernikova, Diana A; Koestler, Devin C; Hoen, Anne Gatewood; Housman, Molly L; Hibberd, Patricia L; Moore, Jason H; Morrison, Hilary G; Sogin, Mitchell L; Zain-Ul-Abideen, Muhammad; Madan, Juliette C

2016-01-01

To test the hypothesis that maternal complications significantly affect gut colonization patterns in very low birth weight infants. Forty-nine serial stool samples were obtained weekly from nine extremely premature infants enrolled in a prospective longitudinal study. Sequencing of the bacterial 16S rRNA gene from stool samples was performed to approximate the intestinal microbiome. Linear mixed effects models were used to evaluate relationships between perinatal complications and intestinal microbiome development. Subjects with prenatal exposure to a non-sterile intrauterine environment, i.e. prolonged preterm premature rupture of membranes (PPPROM) and chorioamnionitis exposure, were found to have a relatively higher abundance of potentially pathogenic bacteria in the stool across all time points compared to subjects without those exposures, irrespective of exposure to postnatal antibiotics. Compared with those delivered by Caesarean section, vaginally delivered subjects were found to have significantly lower diversity of stool microbiota across all time points, with lower abundance of many genera, most in the family Enterobacteriaceae. We identified persistently increased potential pathogen abundance in the developing stool microbiota of subjects exposed to a non-sterile uterine environment. Maternal complications appear to significantly influence the diversity and bacterial composition of the stool microbiota of premature infants, with findings persisting over time.

Installing and Setting Up the Git Software Tool on OS X | High-Performance

Science.gov Websites

Computing | NREL the Git Software Tool on OS X Installing and Setting Up the Git Software Tool on OS X Learn how to install the Git software tool on OS X for use with the Peregrine system. You can . Binary Installer for OS X - Easiest! You can download the latest version of git from http://git-scm.com

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions.

PubMed

Mamantopoulos, Michail; Ronchi, Francesca; McCoy, Kathy D; Wullaert, Andy

2018-04-19

Several human diseases are thought to evolve due to a combination of host genetic mutations and environmental factors that include alterations in intestinal microbiota composition termed dysbiosis. Although in some cases, host genetics may shape the gut microbiota and enable it to provoke disease, experimentally disentangling cause and consequence in such host-microbe interactions requires strict control over non-genetic confounding factors. Mouse genetic studies previously proposed Nlrp6/ASC inflammasomes as innate immunity regulators of the intestinal ecosystem. In contrast, using littermate-controlled experimental setups, we recently showed that Nlrp6/ASC inflammasomes do not alter the gut microbiota composition. Our analyses indicated that maternal inheritance and long-term separate housing are non-genetic confounders that preclude the use of non-littermate mice when analyzing host genetic effects on intestinal ecology. Here, we summarize and discuss our gut microbiota analyses in inflammasome-deficient mice for illustrating the importance of littermate experimental design in studying host-microbiota interactions.

Administration of Non-Absorbable Antibiotics to Pregnant Mice to Perturb the Maternal Gut Microbiota Is Associated with Alterations in Offspring Behavior.

PubMed

Tochitani, Shiro; Ikeno, Takahiro; Ito, Tatsuhito; Sakurai, Asuka; Yamauchi, Tomoki; Matsuzaki, Hideo

2016-01-01

There is increasing evidence that the gut microbiota plays a major role in host health and disease. In this study, we examined whether perturbation of the maternal gut microbiota during pregnancy, induced by administration of non-absorbable antibiotics to pregnant dams, influences the behavior of offspring. Terminal restriction fragment length polymorphism analyses of fecal bacterial composition showed that the relative abundance of the bacterial order Lactobacillales was lower in offspring born from antibiotic-treated dams (20.7 ± 3.4%) than in control offspring (42.1 ± 6.2%) at P24, while the relative abundance of the bacterial family Clostridium subcluster XIVa was higher in offspring born from antibiotic-treated dams (34.2 ± 5.0%) than in control offspring (16.4 ± 3.3%). Offspring born from antibiotic-treated dams exhibited low locomotor activity in both familiar and novel environments, and preferred to explore in the peripheral area of an unfamiliar field at postnatal week 4. At postnatal weeks 7-8, no difference was observed in the level of locomotor activity between control offspring and offspring from antibiotic-treated dams, while the tendency for the offspring from antibiotic-treated dams to be less engaged in exploring the inside area was still observed. The behavioral phenotypes of the offspring from antibiotic-treated dams at postnatal week 4 could be rescued to a considerable extent through fostering of these offspring by normal dams from postnatal day 1. Although the detailed underlying mechanisms are not fully elucidated, the present results suggest that administration of non-absorbable antibiotics to pregnant dams to perturb the maternal gut microbiota during pregnancy leads to alterations in the behavior of their offspring.

Using the Git Software Tool on the Peregrine System | High-Performance

Science.gov Websites

branch workflow. Create a local branch called "experimental" based on the current master... git branch experimental Use your branch (start working on that experimental branch....) git checkout experimental git pull origin experimental # work, work, work, commit.... Send local branch to the repo git push

An ADP-Ribosylation Factor GTPase-activating Protein Git2-short/KIAA0148 Is Involved in Subcellular Localization of Paxillin and Actin Cytoskeletal Organization

PubMed Central

Mazaki, Yuichi; Hashimoto, Shigeru; Okawa, Katsuya; Tsubouchi, Asako; Nakamura, Kuniaki; Yagi, Ryohei; Yano, Hajime; Kondo, Akiko; Iwamatsu, Akihiro; Mizoguchi, Akira; Sabe, Hisataka

2001-01-01

Paxillin acts as an adaptor protein in integrin signaling. We have shown that paxillin exists in a relatively large cytoplasmic pool, including perinuclear areas, in addition to focal complexes formed at the cell periphery and focal adhesions formed underneath the cell. Several ADP-ribosylation factor (ARF) GTPase-activating proteins (GAPs; ARFGAPs) have been shown to associate with paxillin. We report here that Git2-short/KIAA0148 exhibits properties of a paxillin-associated ARFGAP and appears to be colocalized with paxillin, primarily at perinuclear areas. A fraction of Git2-short was also localized to actin-rich structures at the cell periphery. Unlike paxillin, however, Git2-short did not accumulate at focal adhesions underneath the cell. Git2-short is a short isoform of Git2, which is highly homologous to p95PKL, another paxillin-binding protein, and showed a weaker binding affinity toward paxillin than that of Git2. The ARFGAP activities of Git2 and Git2-short have been previously demonstrated in vitro, and we provided evidence that at least one ARF isoform, ARF1, is an intracellular substrate for the GAP activity of Git2-short. We also showed that Git2-short could antagonize several known ARF1-mediated phenotypes: overexpression of Git2-short, but not its GAP-inactive mutant, caused the redistribution of Golgi protein β-COP and reduced the amounts of paxillin-containing focal adhesions and actin stress fibers. Perinuclear localization of paxillin, which was sensitive to ARF inactivation, was also affected by Git2-short overexpression. On the other hand, paxillin localization to focal complexes at the cell periphery was unaffected or even augmented by Git2-short overexpression. Therefore, an ARFGAP protein weakly interacting with paxillin, Git2-short, exhibits pleiotropic functions involving the regulation of Golgi organization, actin cytoskeletal organization, and subcellular localization of paxillin, all of which need to be coordinately regulated during integrin-mediated cell adhesion and intracellular signaling. PMID:11251077

The GIT–PIX complexes regulate the chemotactic response of rat basophilic leukaemia cells

PubMed Central

Gavina, Manuela; Za, Lorena; Molteni, Raffaella; Pardi, Ruggero; Curtis, Ivan de

2009-01-01

Background information. Cell motility entails the reorganization of the cytoskeleton and membrane trafficking for effective protrusion. The GIT–PIX protein complexes are involved in the regulation of cell motility and adhesion and in the endocytic traffic of members of the family of G-protein-coupled receptors. We have investigated the function of the endogenous GIT complexes in the regulation of cell motility stimulated by fMLP (formyl-Met-Leu-Phe) peptide, in a rat basophilic leukaemia RBL-2H3 cell line stably expressing an HA (haemagglutinin)-tagged receptor for the fMLP peptide. Results. Our analysis shows that RBL cells stably transfected with the chemoattractant receptor expressed both GIT1–PIX and GIT2–PIX endogenous complexes. We have used silencing of the different members of the complex by small interfering RNAs to study the effects on a number of events linked to agonist-induced cell migration. We found that cell adhesion was not affected by depletion of any of the proteins of the GIT complex, whereas agonist-enhanced cell spreading was inhibited. Analysis of agonist-stimulated haptotactic cell migration indicated a specific positive effect of GIT1 depletion on trans-well migration. The internalization of the formyl-peptide receptor was also inhibited by depletion of GIT1 and GIT2. The effects of the GIT complexes on trafficking of the receptors was confirmed by an antibody-enhanced agonist-induced internalization assay, showing that depletion of PIX, GIT1 or GIT2 protein caused decreased perinuclear accumulation of internalized receptors. Conclusions. Our results show that endogenous GIT complexes are involved in the regulation of chemoattractant-induced cell motility and receptor trafficking, and support previous findings indicating an important function of the GIT complexes in the regulation of different G-protein-coupled receptors. Our results also indicate that endogenous GIT1 and GIT2 regulate distinct subsets of agonist-induced responses and suggest a possible functional link between the control of receptor trafficking and the regulation of cell motility by GIT proteins. PMID:19912111

Assessment of the QuantiFERON-TB Gold In-Tube test for the detection of Mycobacterium tuberculosis infection in United States Navy recruits.

PubMed

Lempp, Jason M; Zajdowicz, Margan J; Hankinson, Arlene L; Toney, Sean R; Keep, Lisa W; Mancuso, James D; Mazurek, Gerald H

2017-01-01

Immunologic tests such as the tuberculin skin test (TST) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infection, both latent M. tuberculosis infection (LTBI) and infection manifesting as active tuberculosis disease (TB). These tests need high specificity to minimize unnecessary treatment and high sensitivity to allow maximum detection and prevention of TB. Estimate QFT-GIT specificity, compare QFT-GIT and TST results, and assess factor associations with test discordance among U.S. Navy recruits. Among 792 subjects with completed TST and QFT-GIT, 42(5.3%) had TST indurations ≥10mm, 23(2.9%) had indurations ≥15mm, 14(1.8%) had positive QFT-GIT results, and 5(0.6%) had indeterminate QFT-GITs. Of 787 subjects with completed TST and determinate QFT-GIT, 510(64.8%) were at low-risk for infection, 277(35.2%) were at increased risk, and none had TB. Among 510 subjects at low-risk (presumed not infected), estimated TST specificity using a 15mm cutoff, 99.0% (95%CI: 98.2-99.9%), and QFT-GIT specificity, 98.8% (95%CI: 97.9-99.8%), were not significantly different (p>0.99). Most discordance was among recruits at increased risk of infection, and most was TST-positive but QFT-GIT-negative discordance. Of 18 recruits with TST ≥15mm but QFT-GIT negative discordance, 14(78%) were at increased risk. TB prevalence in country of birth was the strongest predictor of positive TST results, positive QFT-GIT results, and TST-positive but QFT-GIT-negative discordance. Reactivity to M. avium purified protein derivative (PPD) was associated with positive TST results and with TST-positive but QFT-GIT-negative discordance using a 10 mm cutoff, but not using a 15 mm cutoff or with QFT-GIT results. M. tuberculosis infection prevalence was low, with the vast majority of infection occurring in recruits with recognizable risks. QFT-GIT and TST specificities were high and not significantly different. Negative QFT-GIT results among subjects with TST induration ≥15 mm who were born in countries with high TB prevalence, raise concerns.

Setting Up Git Software Tool on Linux | High-Performance Computing | NREL

Science.gov Websites

system. Before you can get started using the github.nrel.gov git repos, you'll have to do some basic shell (SSH) keys created on those systems. If this is the case, for more information, see using the git Steps - Using a Remote Git Repository Now you have all the basic configuration for using git with a

The composition of the gut microbiota throughout life, with an emphasis on early life

PubMed Central

Rodríguez, Juan Miguel; Murphy, Kiera; Stanton, Catherine; Ross, R. Paul; Kober, Olivia I.; Juge, Nathalie; Avershina, Ekaterina; Rudi, Knut; Narbad, Arjan; Jenmalm, Maria C.; Marchesi, Julian R.; Collado, Maria Carmen

2015-01-01

The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3–5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health. PMID:25651996

Inulin supplementation during gestation mitigates acrylamide-induced maternal and fetal brain oxidative dysfunctions and neurotoxicity in rats.

PubMed

Krishna, Gokul; Muralidhara

2015-01-01

Accumulating evidence suggests that the developing brain is more susceptible to a variety of chemicals. Recent studies have shown a link between the enteric microbiota and brain function. While supplementation of non-digestible oligosaccharides during pregnancy has been demonstrated to positively influence human health mediated through stimulation of beneficial microbiota, our understanding on their neuromodulatory propensity is limited. In the present study, our primary focus was to examine whether supplementation of inulin (a well known fructan) during gestation can abrogate acrylamide (ACR)-induced oxidative impairments and neurotoxicity in maternal and fetal brain of rats. Initially, in a dose-determinative study, we recapitulated the impact of ACR exposure during gestation days (GD 6-19) on gestational parameters, extent of oxidative impairments in brain (maternal/fetal), cholinergic function and neurotoxicity. Subsequently, pregnant rats orally (gavage) administered with inulin (IN, 2 g/kg/day in two equal installments) supplements during gestation days (GD 0-19) were exposed to ACR (200 ppm) in drinking water. IN supplements significantly attenuated ACR-induced changes in exploratory activity (reduced open field exploration) measured on GD 14. Further, IN restored the placental weights among ACR exposed dams. Analysis of biochemical markers revealed that IN supplements effectively offset ACR associated oxidative stress not only in the maternal brain, but in the fetal brain as well. Elevated levels of protein carbonyls in maternal brain regions were completely normalized with IN supplements. More importantly, IN supplements significantly augmented the number of Bifidobacteria in the cecum of ACR rats which correlated well with the neurorestorative effect as evidenced by restored dopamine levels in the maternal cortex and fetal brain acetylcholinesterase activity among ACR-exposed dams. Further, IN supplements also conferred significant protection against mitochondrial dysfunction induced by ACR in both milieus. Although the precise mechanism/s by which IN supplements during pregnancy attenuate ACR induced neurotoxic impact merits further investigations, we hypothesize that it may mediate through enhanced enteric microbiota and abrogation of oxidative stress. Further, our study provides an experimental approach to explore the neuroprotective role of prebiotic oligosaccharides during pregnancy in reducing the adverse impact of developmental neurotoxicants. Copyright © 2015 Elsevier Inc. All rights reserved.

Gestational diabetes is associated with changes in placental microbiota and microbiome.

PubMed

Bassols, Judit; Serino, Matteo; Carreras-Badosa, Gemma; Burcelin, Rémy; Blasco-Baque, Vincent; Lopez-Bermejo, Abel; Fernandez-Real, José-Manuel

2016-12-01

The human microbiota is a modulator of the immune system. Variations in the placental microbiota could be related with pregnancy disorders. We profiled the placental microbiota and microbiome in women with gestational diabetes (GDM) and studied its relation to maternal metabolism and placental expression of anti-inflammatory cytokines. Placental microbiota and microbiome and expression of anti-inflammatory cytokines (IL10, TIMP3, ITGAX, and MRC1MR) were analyzed in placentas from women with GDM and from control women. Fasting insulin, glucose, O'Sullivan glucose, lipids, and blood cell counts were assessed at second and third trimester of pregnancy. Bacteria belonging to the Pseudomonadales order and Acinetobacter genus showed lower relative abundance in women with GDM compared to control (P < 0.05). In GDM, lower abundance of placental Acinetobacter associated with a more adverse metabolic (higher O'Sullivan glucose) and inflammatory phenotype (lower blood eosinophil count and lower placental expression of IL10 and TIMP3) (P < 0.05 to P = 0.001). Calcium signaling pathway was increased in GDM placental microbiome. A distinct microbiota profile and microbiome is present in GDM. Acinetobacter has been recently shown to induce IL-10 in mice. GDM could constitute a state of placental microbiota-driven altered immunologic tolerance, making placental microbiota a new target for therapy in GDM.

Glipizide. A review of the pharmacoeconomic implications of the extended-release formulation in type 2 diabetes mellitus.

PubMed

Foster, R H; Plosker, G L

2000-09-01

Glipizide is a second generation sulphonylurea agent that is available in a Gastrointestinal Therapeutic System (GITS) extended-release formulation. Glipizide GITS provides more stable plasma drug concentrations than the immediate-release formulation and the once-daily regimen may optimise patient compliance. In patients with type 2 diabetes mellitus, glipizide GITS is at least as effective as the immediate-release formulation of glipizide in providing glycaemic control, and may have a greater effect on fasting plasma glucose levels. Any therapeutic advantage over other antidiabetic agents remains to be established, but in a preliminary report (n = 40) glipizide GITS provided better glycaemic control and produced less fasting insulinaemia than glibenclamide (glyburide). The incidence of hypoglycaemic symptoms with glipizide GITS is low (< or = 3%). Quality of life was improved compared with baseline after 12 weeks' treatment with glipizide GITS 5 to 20 mg/day plus diet in a US double-blind, placebo-controlled trial in 569 patients with type 2 diabetes mellitus. Hyperglycaemic symptom-related distress decreased with glipizide GITS treatment, while hypoglycaemic symptom-related distress was not significantly increased compared with placebo plus diet. Quality of life during glipizide GITS treatment has not been compared with that during treatment with other antidiabetic agents. Monthly productivity losses related to absenteeism were $US91 (1995 values) per patient lower in the glipizide GITS group compared with the placebo group in the latter prospective study. Productivity parameters improved slightly or did not change significantly in the glipizide GITS group, but deteriorated in the placebo group. Differences in direct healthcare costs between groups were small and not comprehensively reported. Glipizide GITS was the least costly strategy for first-line therapy in a US cost-of-treatment model of the first 3 years after diagnosis of type 2 diabetes mellitus. The total per-patient cost was $US4867 with glipizide GITS, $US5196 with metformin and $US5249 with acarbose (1996/1997 values). Monthly drug acquisition costs were lower, and glycosylated haemoglobin levels and patient compliance were improved, after formulary conversion from the immediate-release to the GITS formulation of glipizide in a US single-hospital retrospective analysis. Glipizide GITS produced better cost outcomes than metformin and acarbose in a model of 3 years' treatment of type 2 diabetes mellitus. Glipizide GITS had pharmacoeconomic and quality of life advantages over diet alone in the short term, but more clinically relevant comparisons with other antidiabetic agents are needed. There are limitations to the present data, but the available pharmacoeconomic data have been favourable for glipizide GITS.

Review: Maternal health and the placental microbiome.

PubMed

Pelzer, Elise; Gomez-Arango, Luisa F; Barrett, Helen L; Nitert, Marloes Dekker

2017-06-01

Over the past decade, the role of the microbiome in regulating metabolism, immune function and behavior in humans has become apparent. It has become clear that the placenta is not a sterile organ, but rather has its own endogenous microbiome. The composition of the placental microbiome is distinct from that of the vagina and has been reported to resemble the oral microbiome. Compared to the gut microbiome, the placental microbiome exhibits limited microbial diversity. This review will focus on the current understanding of the placental microbiota in normal healthy pregnancy and also in disease states including preterm birth, chorioamnionitis and maternal conditions such as obesity, gestational diabetes mellitus and preeclampsia. Factors known to alter the composition of the placental microbiota will be discussed in the final part of this review. Copyright © 2016. Published by Elsevier Ltd.

Amniotic fluid: Source of trophic factors for the developing intestine

PubMed Central

Dasgupta, Soham; Arya, Shreyas; Choudhary, Sanjeev; Jain, Sunil K

2016-01-01

The gastrointestinal tract (GIT) is a complex system, which changes in response to requirements of the body. GIT represents a barrier to the external environment. To achieve this, epithelial cells must renew rapidly. This renewal of epithelial cells starts in the fetal life under the influence of many GIT peptides by swallowing amniotic fluid (AF). Development and maturation of GIT is a very complex cascade that begins long before birth and continues during infancy and childhood by breast-feeding. Many factors like genetic preprogramming, local and systemic endocrine secretions and many trophic factors (TF) from swallowed AF contribute and modulate the development and growth of the GIT. GIT morphogenesis, differentiation and functional development depend on the activity of various TF in the AF. This manuscript will review the role of AF borne TF in the development of GIT. PMID:26909227

G-protein-coupled receptor-2-interacting protein-1 is required for endothelial cell directional migration and tumor angiogenesis via cortactin-dependent lamellipodia formation.

PubMed

Majumder, Syamantak; Sowden, Mark P; Gerber, Scott A; Thomas, Tamlyn; Christie, Christine K; Mohan, Amy; Yin, Guoyong; Lord, Edith M; Berk, Bradford C; Pang, Jinjiang

2014-02-01

Recent evidence suggests G-protein-coupled receptor-2-interacting protein-1 (GIT1) overexpression in several human metastatic tumors, including breast, lung, and prostate. Tumor metastasis is associated with an increase in angiogenesis. We have showed previously that GIT1 is required for postnatal angiogenesis during lung development. However, the functional role of GIT1 in pathological angiogenesis during tumor growth is unknown. In the present study, we show inhibition of angiogenesis in matrigel implants as well as reduced tumor angiogenesis and melanoma tumor growth in GIT1-knockout mice. We demonstrate that this is a result of impaired directional migration of GIT1-depleted endothelial cells toward a vascular endothelial growth factor gradient. Cortactin-mediated lamellipodia formation in the leading edge is critical for directional migration. We observed a significant reduction in cortactin localization and lamellipodia formation in the leading edge of GIT1-depleted endothelial cells. We specifically identified that the Spa homology domain (aa 250-420) of GIT1 is required for GIT1-cortactin complex localization to the leading edge. The mechanisms involved extracellular signal-regulated kinases 1 and 2-mediated Cortactin-S405 phosphorylation and activation of Rac1/Cdc42. Finally, using gain of function studies, we show that a constitutively active mutant of cortactin restored directional migration of GIT1-depleted cells. Our data demonstrated that a GIT1-cortactin association through GIT1-Spa homology domain is required for cortactin localization to the leading edge and is essential for endothelial cell directional migration and tumor angiogenesis.

Maternal western diet causes inflammatory milk and TLR2/4-dependent neonatal toxicity.

PubMed

Du, Yang; Yang, Marie; Lee, Syann; Behrendt, Cassie L; Hooper, Lora V; Saghatelian, Alan; Wan, Yihong

2012-06-15

For all newborn mammals, mother's milk is the perfect nourishment, crucial for their postnatal development. Here we report that, unexpectedly, maternal western diet consumption in mice causes the production of toxic milk that contains excessive long chain and saturated fatty acids, which triggers ceramide accumulation and inflammation in the nursing neonates, manifested as alopecia. This neonatal toxicity requires Toll-like-receptors (TLR), but not gut microbiota, because TLR2/4 deletion or TLR4 inhibition confers resistance, whereas germ-free mice remain sensitive. These findings unravel maternal western diet-induced inflammatory milk secretion as a novel aspect of the metabolic syndrome at the maternal offspring interface.

Gut microbiota in Drosophila melanogaster interacts with Wolbachia but does not contribute to Wolbachia-mediated antiviral protection.

PubMed

Ye, Yixin H; Seleznev, Andrei; Flores, Heather A; Woolfit, Megan; McGraw, Elizabeth A

2017-02-01

Animals experience near constant infection with microorganisms. A significant proportion of these microbiota reside in the alimentary tract. There is a growing appreciation for the roles gut microbiota play in host biology. The gut microbiota of insects, for example, have been shown to help the host overcome pathogen infection either through direct competition or indirectly by stimulating host immunity. These defenses may also be supplemented by coinfecting maternally inherited microbes such as Wolbachia. The presence of Wolbachia in a host can delay and/or reduce death caused by RNA viruses. Whether the gut microbiota of the host interacts with Wolbachia, or vice versa, the precise role of Wolbachia in antiviral protection is not known. In this study, we used 16S rDNA sequencing to characterise changes in gut microbiota composition in Drosophila melanogaster associated with Wolbachia infection and antibiotic treatment. We subsequently tested whether changes in gut composition via antibiotic treatment altered Wolbachia-mediated antiviral properties. We found that both antibiotics and Wolbachia significantly reduced the biodiversity of the gut microbiota without changing the total microbial load. We also showed that changing the gut microbiota composition with antibiotic treatment enhanced Wolbachia density but did not confer greater antiviral protection against Drosophila C virus to the host. We concluded there are significant interactions between Wolbachia and gut microbiota, but changing gut microbiota composition is not likely to be a means through which Wolbachia conveys antiviral protection to its host. Copyright © 2016. Published by Elsevier Inc.

Gut microbiota: a source of novel tools to reduce the risk of human disease?

PubMed

Collado, Maria Carmen; Rautava, Samuli; Isolauri, Erika; Salminen, Seppo

2015-01-01

Modern civilization is faced with a progressive increase in immune-mediated or inflammatory health problems such as allergic disease, autoimmune disorders, and obesity. An extended version of the hygiene hypothesis has been introduced to emphasize the intimate interrelationship among diet, the immune system, microbiome, and origins of human disease: the modern infant, particularly when delivered by cesarean section and without the recommended exclusive breastfeeding, may lack sufficient stimulation of the mucosal immune system to generate a tolerogenic immune milieu and instead be prone to develop chronic inflammatory conditions. These deviations may take the form of allergic or autoimmune disease, or predispose the child to higher weight gain and obesity. Moreover, evidence supports the role of first microbial contacts in promoting and maintaining a balanced immune response in early life and recent findings suggest that microbial contact begins prior to birth and is shaped by the maternal microbiota. Maternal microbiota may prove to be a safe and effective target for interventions decreasing the risk of allergic and noncommunicable diseases in future generations. These results support the hypothesis that targeting early interaction with microbes might offer an applicable strategy to prevent disease.

Serial testing of refugees for latent tuberculosis using the QuantiFERON-gold in-tube: effects of an antecedent tuberculin skin test.

PubMed

Baker, Cristina A; Thomas, William; Stauffer, William M; Peterson, Phillip K; Tsukayama, Dean T

2009-04-01

Screening for latent tuberculosis infection (LTBI) in refugee populations immigrating to low-incidence countries remains a challenge. We assessed the characteristics of the QuantiFERON-Gold In-Tube (QFT-GIT) compared with the tuberculin skin test (TST) in 198 refugees of all ages from tuberculosis-endemic countries. Diagnostic agreement between the first QFT-GIT and simultaneous TST was 78% (kappa = 0.56) and between serial QFT-GITs was 89% (kappa = 0.76). In serial QFT-GIT testing, 70% of subjects had an increased QFT-GIT value, perhaps the result of an antecedent TST in the setting of previous TB exposure. This boosting seemed to become less prevalent with time from TST and occurred less frequently in those with negative first QFT-GIT readings. Despite small changes in the quantitative results caused by nonspecific variation and boosting, the diagnostic result of the QFT-GIT was reliable. The QFT-GIT shows the potential to replace the TST for LTBI screening in refugees from tuberculosis-endemic areas.

IFN-γ release assay conversions and reversions. Challenges with serial testing in U.S. health care workers.

PubMed

Joshi, Manish; Monson, Thomas P; Joshi, Anita; Woods, Gail L

2014-03-01

IFN-γ release assays (IGRAs) including the QuantiFERON-TB gold in-tube test (QFT-GIT) are increasingly used in place of the tuberculin skin test (TST) in surveillance programs for Mycobacterium tuberculosis infection in the United States. However, data on conversions, reversions, and predictive value of QFT in such programs for health care workers (HCWs) are limited. The purpose of this study is to assess long-term reproducibility and conversion and reversion rates of QFT-GIT among HCWs who underwent serial testing at a tertiary care center in the United States. Retrospective chart review of HCWs at the Central Arkansas Veterans Healthcare System (CAVHS) who underwent serial testing with QFT-GIT as a part of their employee screening between November 1, 2008 and January 31, 2011. A total of 2,303 HCWs had at least 2 QFT-GITs 1 year apart. The initial QFT-GIT was positive for 69 and 2 were indeterminate. Of these 69 HCWs, 31 (45%) reverted on repeat testing, and 25 of 31 (80.6%) HCWs who reverted had a negative look-back TST. Of the 2,232 HCWs with an initial negative QFT-GIT, 71 (3.2%) converted on repeat testing. A third QFT-GIT assay was performed in 41 of the 71 converters and 90% (37 of 41) reverted back to negative. Only two HCWs had TST and QFT-GIT conversion. Poor IGRA reproducibility and a low predictive value of QFT-GIT conversions indicate that QFT-GIT with current interpretation criteria should not be used for serial screening of U.S. HCWs. Negative TSTs have higher reproducibility than QFT-GIT for serial testing of HCWs in low tuberculosis incidence settings.

Early Microbes Modify Immune System Development and Metabolic Homeostasis—The “Restaurant” Hypothesis Revisited

PubMed Central

Nash, Michael J.; Frank, Daniel N.; Friedman, Jacob E.

2017-01-01

The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research. PMID:29326657

Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance.

PubMed

Gibson, D L; Gill, S K; Brown, K; Tasnim, N; Ghosh, S; Innis, S; Jacobson, K

2015-01-01

Our previous studies revealed that offspring from rat dams fed fish oil (at 8% and 18% energy), developed impaired intestinal barriers sensitizing the colon to exacerbated injury later in life. To discern the mechanism, we hypothesized that in utero exposure to fish oil, rich in n-3 polyunsaturated fatty acid (PUFA), caused abnormal intestinal reparative responses to mucosal injury through differences in intestinal microbiota and the presence of naïve immune cells. To identify such mechanisms, gut microbes and naïve immune cells were compared between rat pups born to dams fed either n-6 PUFA, n-3 PUFA or breeder chow. Maternal exposure to either of the PUFA rich diets altered the development of the intestinal microbiota with an overall reduction in microbial density. Using qPCR, we found that each type of PUFA differentially altered the major gut phyla; fish oil increased Bacteroidetes and safflower oil increased Firmicutes. Both PUFA diets reduced microbes known to dominate the infant gut like Enterobacteriaceae and Bifidobacteria spp. when compared to the chow group. Uniquely, maternal fish oil diets resulted in offspring showing blooms of opportunistic pathogens like Bilophila wadsworthia, Enterococcus faecium and Bacteroides fragilis in their gut microbiota. As well, fish oil groups showed a reduction in colonic CD8+ T cells, CD4+ Foxp3+ T cells and arginase+ M2 macrophages. In conclusion, fish oil supplementation in pharmacological excess, at 18% by energy as shown in this study, provides an example where excess dosing in utero can prime offspring to harbor intestinal pathobionts and alter immune cell homeostasis.

Maternal western diet causes inflammatory milk and TLR2/4-dependent neonatal toxicity

PubMed Central

Du, Yang; Yang, Marie; Lee, Syann; Behrendt, Cassie L.; Hooper, Lora V.; Saghatelian, Alan; Wan, Yihong

2012-01-01

For all newborn mammals, mother's milk is the perfect nourishment, crucial for their postnatal development. Here we report that, unexpectedly, maternal western diet consumption in mice causes the production of toxic milk that contains excessive long chain and saturated fatty acids, which triggers ceramide accumulation and inflammation in the nursing neonates, manifested as alopecia. This neonatal toxicity requires Toll-like-receptors (TLR), but not gut microbiota, because TLR2/4 deletion or TLR4 inhibition confers resistance, whereas germ-free mice remain sensitive. These findings unravel maternal western diet-induced inflammatory milk secretion as a novel aspect of the metabolic syndrome at the maternal offspring interface. PMID:22713870

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption

PubMed Central

Siddiqui, Sana; Lustig, Ana; Carter, Arnell; Sankar, Mathavi; Daimon, Caitlin M.; Premont, Richard T.; Etienne, Harmonie; van Gastel, Jaana; Azmi, Abdelkrim; Janssens, Jonathan; Becker, Kevin G.; Zhang, Yongqing; Wood, William; Lehrmann, Elin; Martin, James G.; Martin, Bronwen; Taub, Dennis D.; Maudsley, Stuart

2017-01-01

Recent research has proposed that GIT2 (G protein-coupled receptor kinase interacting protein 2) acts as an integrator of the aging process through regulation of ‘neurometabolic’ integrity. One of the commonly accepted hallmarks of the aging process is thymic involution. At a relatively young age, 12 months old, GIT2−/− mice present a prematurely distorted thymic structure and dysfunction compared to age-matched 12 month-old wild-type control (C57BL/6) mice. Disruption of thymic structure in GIT2−/− (GIT2KO) mice was associated with a significant reduction in the expression of the cortical thymic marker, Troma-I (cytokeratin 8). Double positive (CD4+CD8+) and single positive CD4+ T cells were also markedly reduced in 12 month-old GIT2KO mice compared to age-matched control wild-type mice. Coincident with this premature thymic disruption in GIT2KO mice was the unique generation of a novel cervical ‘organ’, i.e. ‘parathymic lobes’. These novel organs did not exhibit classical peripheral lymph node-like characteristics but expressed high levels of T cell progenitors that were reflexively reduced in GIT2KO thymi. Using signaling pathway analysis of GIT2KO thymus and parathymic lobe transcriptomic data we found that the molecular signaling functions lost in the dysfunctional GIT2KO thymus were selectively reinstated in the novel parathymic lobe – suggestive of a compensatory effect for the premature thymic disruption. Broader inspection of high-dimensionality transcriptomic data from GIT2KO lymph nodes, spleen, thymus and parathymic lobes revealed a systemic alteration of multiple proteins (Dbp, Tef, Per1, Per2, Fbxl3, Ddit4, Sin3a) involved in the multidimensional control of cell cycle clock regulation, cell senescence, cellular metabolism and DNA damage. Altered cell clock regulation across both immune and non-immune tissues therefore may be responsible for the premature ‘aging’ phenotype of GIT2KO mice. PMID:28260693

Endothelial nitric-oxide synthase (eNOS) is activated through G-protein-coupled receptor kinase-interacting protein 1 (GIT1) tyrosine phosphorylation and Src protein.

PubMed

Liu, Songling; Premont, Richard T; Rockey, Don C

2014-06-27

Nitric oxide (NO) is a critical regulator of vascular tone and plays an especially prominent role in liver by controlling portal blood flow and pressure within liver sinusoids. Synthesis of NO in sinusoidal endothelial cells by endothelial nitric-oxide synthase (eNOS) is regulated in response to activation of endothelial cells by vasoactive signals such as endothelins. The endothelin B (ETB) receptor is a G-protein-coupled receptor, but the mechanisms by which it regulates eNOS activity in sinusoidal endothelial cells are not well understood. In this study, we built on two previous strands of work, the first showing that G-protein βγ subunits mediated activation of phosphatidylinositol 3-kinase and Akt to regulate eNOS and the second showing that eNOS directly bound to the G-protein-coupled receptor kinase-interacting protein 1 (GIT1) scaffold protein, and this association stimulated NO production. Here we investigated the mechanisms by which the GIT1-eNOS complex is formed and regulated. GIT1 was phosphorylated on tyrosine by Src, and Y293F and Y554F mutations reduced GIT1 phosphorylation as well as the ability of GIT1 to bind to and activate eNOS. Akt phosphorylation activated eNOS (at Ser(1177)), and Akt also regulated the ability of Src to phosphorylate GIT1 as well as GIT1-eNOS association. These pathways were activated by endothelin-1 through the ETB receptor; inhibiting receptor-activated G-protein βγ subunits blocked activation of Akt, GIT1 tyrosine phosphorylation, and ET-1-stimulated GIT1-eNOS association but did not affect Src activation. These data suggest a model in which Src and Akt cooperate to regulate association of eNOS with the GIT1 scaffold to facilitate NO production. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Use of interferon-gamma release assays in a health care worker screening program: experience from a tertiary care centre in the United States.

PubMed

Joshi, Manish; Monson, Thomas P; Woods, Gail L

2012-01-01

Interferon-gamma release assays including the QuantiFERON-TB Gold In-Tube test (QFT-GIT [Cellestis Ltd, Australia]) may be used in place of the tuberculin skin test (TST) in surveillance programs for Mycobacterium tuberculosis infection control. However, data on performance and practicality of the QFT-GIT in such programs for health care workers (HCWs) are limited. To assess the performance, practicality and reversion rate of the QFT-GIT among HCWs at a tertiary health care institution in the United States. Retrospective chart review of HCWs at Central Arkansas Veterans Healthcare System (Arkansas, USA) who underwent QFT-GIT testing as a part of their employee screening between November 1, 2008 and October 31, 2009. QFT-GIT was used to screen 3290 HCWs. The initial QFT-GIT was interpreted as positive for 129 (3.9%) HCWs, negative for 3155 (95.9%) and indeterminate for six (0.2%). Testing with QFT-GIT was repeated in 45 HCWs who had positive results on the initial test. The QFT-GIT reverted to negative in 18 (40.0%) HCWs, all of whom had negative TST status and initial interferon-gamma values of 0.35 IU⁄mL to 2.0 IU⁄mL. The QFT-GIT test is feasible in large health care setting as an alternative to TST for M tuberculosis infection screening in HCWs but is not free from challenges. The major concerns are the high number of positive test results and high reversion rates on repeat testing, illustrating poor short-term reproducibility of positive QFT-GIT test results. These results suggest adopting a borderline zone between interferon-gamma values of 0.35 IU⁄mL to 2.0 IU⁄mL, and cautious clinical interpretation of values in this range.

Automation of an interferon-γ release assay and comparison to the tuberculin skin test for screening basic military trainees for Mycobacterium tuberculosis infection.

PubMed

Goodwin, Donald J; Mazurek, Gerald H; Campbell, Brandon H; Bohanon, Jamaria; West, Kevin B; Bell, James J; Powell, Richard; Toney, Sean; Morris, John A; Yamane, Grover K; Sjoberg, Paul A

2014-03-01

We automated portions of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) and assessed its quality when performed concurrently with the tuberculin skin test (TST) among U.S. Air Force basic military trainees (BMTs). The volume of blood collected for QFT-GIT was monitored. At least one of the three tubes required for QFT-GIT had blood volume outside the recommended 0.8- to 1.2-mL range for 688 (29.0%) of 2,373 subjects who had their blood collected. Of the 2,124 subjects who had TST and QFT-GIT completed, TST was positive for 0.6%; QFT-GIT was positive for 0.3% and indeterminate for 2.0%. Among 2,081 subjects with completed TST and determinate QFT-GIT results, overall agreement was 99.5% but positive agreement was 5.6%. Specificity among the 1,546 low-risk BMTs was identical (99.7%). Indeterminate QFT-GIT results were 2.7 times more likely when mitogen tubes contained >1.2 mL blood than when containing 0.8- to 1.2-mL blood. Automation can facilitate QFT-GIT completion, especially if the recommended volume of blood is collected. Mycobacterium tuberculosis infection prevalence among BMTs based on TST and QFT-GIT is similar and low. Selectively testing those with significant risk may be more appropriate than universal testing of all recruits. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development

PubMed Central

Indrio, Flavia; Martini, Silvia; Francavilla, Ruggiero; Corvaglia, Luigi; Cristofori, Fernanda; Mastrolia, Salvatore Andrea; Neu, Josef; Rautava, Samuli; Russo Spena, Giovanna; Raimondi, Francesco; Loverro, Giuseppe

2017-01-01

Epigenetic modifications are among the most important mechanisms by which environmental factors can influence early cellular differentiation and create new phenotypic traits during pregnancy and within the neonatal period without altering the deoxyribonucleic acid sequence. A number of antenatal and postnatal factors, such as maternal and neonatal nutrition, pollutant exposure, and the composition of microbiota, contribute to the establishment of epigenetic changes that can not only modulate the individual adaptation to the environment but also have an influence on lifelong health and disease by modifying inflammatory molecular pathways and the immune response. Postnatal intestinal colonization, in turn determined by maternal flora, mode of delivery, early skin-to-skin contact and neonatal diet, leads to specific epigenetic signatures that can affect the barrier properties of gut mucosa and their protective role against later insults, thus potentially predisposing to the development of late-onset inflammatory diseases. The aim of this review is to outline the epigenetic mechanisms of programming and development acting within early-life stages and to examine in detail the role of maternal and neonatal nutrition, microbiota composition, and other environmental factors in determining epigenetic changes and their short- and long-term effects. PMID:28879172

Drain current enhancement induced by hole injection from gate of 600-V-class normally off gate injection transistor under high temperature conditions up to 200 °C

NASA Astrophysics Data System (ADS)

Ishii, Hajime; Ueno, Hiroaki; Ueda, Tetsuzo; Endoh, Tetsuo

2018-06-01

In this paper, the current–voltage (I–V) characteristics of a 600-V-class normally off GaN gate injection transistor (GIT) from 25 to 200 °C are analyzed, and it is revealed that the drain current of the GIT increases during high-temperature operation. It is found that the maximum drain current (I dmax) of the GIT is 86% higher than that of a conventional 600-V-class normally off GaN metal insulator semiconductor hetero-FET (MIS-HFET) at 150 °C, whereas the GIT obtains 56% I dmax even at 200 °C. Moreover, the mechanism of the drain current increase of the GIT is clarified by examining the relationship between the temperature dependence of the I–V characteristics of the GIT and the gate hole injection effect determined from the shift of the second transconductance (g m) peak of the g m–V g characteristic. From the above, the GIT is a promising device with enough drivability for future power switching applications even under high-temperature conditions.

The Escherichia coli O157:H7 bovine rumen fluid proteome reflects adaptive bacterial responses.

PubMed

Kudva, Indira T; Stanton, Thaddeus B; Lippolis, John D

2014-02-21

To obtain insights into Escherichia coli O157:H7 (O157) survival mechanisms in the bovine rumen, we defined the growth characteristics and proteome of O157 cultured in rumen fluid (RF; pH 6.0-7.2 and low volatile fatty acid content) obtained from rumen-fistulated cattle fed low protein content "maintenance diet" under diverse in vitro conditions. Bottom-up proteomics (LC-MS/MS) of whole cell-lysates of O157 cultured under anaerobic conditions in filter-sterilized RF (fRF; devoid of normal ruminal microbiota) and nutrient-depleted and filtered RF (dRF) resulted in an anaerobic O157 fRF-and dRF-proteome comprising 35 proteins functionally associated with cell structure, motility, transport, metabolism and regulation, but interestingly, not with O157 virulence. Shotgun proteomics-based analysis using isobaric tags for relative and absolute quantitation used to further study differential protein expression in unfiltered RF (uRF; RF containing normal rumen microbial flora) complemented these results. Our results indicate that in the rumen, the first anatomical compartment encountered by this human pathogen within the cattle gastrointestinal tract (GIT), O157 initiates a program of specific gene expression that enables it to adapt to the in vivo environment, and successfully transit to its colonization sites in the bovine GIT. Further experiments in vitro using uRF from animals fed different diets and with additional O157 strains, and in vivo using rumen-fistulated cattle will provide a comprehensive understanding of the adaptive mechanisms involved, and help direct evolution of novel modalities for blocking O157 infection of cattle.

Impact of gut microbiota on the fly's germ line.

PubMed

Elgart, Michael; Stern, Shay; Salton, Orit; Gnainsky, Yulia; Heifetz, Yael; Soen, Yoav

2016-04-15

Unlike vertically transmitted endosymbionts, which have broad effects on their host's germ line, the extracellular gut microbiota is transmitted horizontally and is not known to influence the germ line. Here we provide evidence supporting the influence of these gut bacteria on the germ line of Drosophila melanogaster. Removal of the gut bacteria represses oogenesis, expedites maternal-to-zygotic-transition in the offspring and unmasks hidden phenotypic variation in mutants. We further show that the main impact on oogenesis is linked to the lack of gut Acetobacter species, and we identify the Drosophila Aldehyde dehydrogenase (Aldh) gene as an apparent mediator of repressed oogenesis in Acetobacter-depleted flies. The finding of interactions between the gut microbiota and the germ line has implications for reproduction, developmental robustness and adaptation.

Gut microbiota and malnutrition.

PubMed

Million, Matthieu; Diallo, Aldiouma; Raoult, Didier

2017-05-01

Malnutrition is the leading cause of death worldwide in children under the age of five, and is the focus of the first World Health Organization (WHO) Millennium Development Goal. Breastfeeding, food and water security are major protective factors against malnutrition and critical factors in the maturation of healthy gut microbiota, characterized by a transient bifidobacterial bloom before a global rise in anaerobes. Early depletion in gut Bifidobacterium longum, a typical maternal probiotic, known to inhibit pathogens, represents the first step in gut microbiota alteration associated with severe acute malnutrition (SAM). Later, the absence of the Healthy Mature Anaerobic Gut Microbiota (HMAGM) leads to deficient energy harvest, vitamin biosynthesis and immune protection, and is associated with diarrhea, malabsorption and systemic invasion by microbial pathogens. A therapeutic diet and infection treatment may be unable to restore bifidobacteria and HMAGM. Besides refeeding and antibiotics, future trials including non-toxic missing microbes and nutrients necessary to restore bifidobacteria and HMAGM, including prebiotics and antioxidants, are warranted in children with severe or refractory disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Git as an Encrypted Distributed Version Control System

DTIC Science & Technology

2015-03-01

options. The algorithm uses AES- 256 counter mode with an IV derived from SHA -1-HMAC hash (this is nearly identical to the GCM mode discussed earlier...built into the internal structure of Git. Every file in a Git repository is check summed with a SHA -1 hash, a one-way function with arbitrarily long...implementation. Git-encrypt calls OpenSSL cryptography library command line functions. The default cipher used is AES- 256 - Electronic Code Book (ECB), which is

Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery.

PubMed

Chu, Derrick M; Ma, Jun; Prince, Amanda L; Antony, Kathleen M; Seferovic, Maxim D; Aagaard, Kjersti M

2017-03-01

Human microbial communities are characterized by their taxonomic, metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early third trimester (n = 81) were prospectively enrolled for longitudinal sampling through 6 weeks after delivery, and a second matched cross-sectional cohort (n = 81) was additionally recruited for sampling once at the time of delivery. Samples across multiple body sites, including stool, oral gingiva, nares, skin and vagina were collected for each maternal-infant dyad. Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery, with the notable exception of the neonatal meconium. However, by 6 weeks after delivery, the infant microbiota structure and function had substantially expanded and diversified, with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with the cesarean mode of delivery in some body sites (oral gingiva, nares and skin; R 2 = 0.038), this was not true for neonatal stool (meconium; Mann-Whitney P > 0.05), and there was no observable difference in community function regardless of delivery mode. For infants at 6 weeks of age, the microbiota structure and function had expanded and diversified with demonstrable body site specificity (P < 0.001, R 2 = 0.189) but without discernable differences in community structure or function between infants delivered vaginally or by cesarean surgery (P = 0.057, R 2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes substantial reorganization, which is primarily driven by body site and not by mode of delivery.

Maturation of the Infant Microbiome Community Structure and Function Across Multiple Body Sites and in Relation to Mode of Delivery

PubMed Central

Chu, Derrick M.; Ma, Jun; Prince, Amanda L.; Antony, Kathleen M.; Seferovic, Maxim D.; Aagaard, Kjersti M.

2017-01-01

Human microbial communities are characterized by their taxonomic, metagenomic, and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to assess the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites, and assess the impact of mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early 3rd trimester (n=81) were prospectively enrolled for longitudinal sampling through 6 weeks post-delivery, and a second matched cross-sectional cohort (n=81) was additionally recruited for sampling once at delivery. Samples were collected for each maternal-infant dyad across multiple body sites, including stool, oral gingiva, nares, skin and vagina. 16S rRNA gene sequencing analysis and whole genome shotgun sequencing was performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogenous across all body sites at delivery, with the notable exception of neonatal meconium. However, by 6 weeks, the infant microbiota structure and function had significantly expanded and diversified, with body site serving as the primary determinant of the bacterial community composition and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with Cesarean delivery in some body sites (oral, nares, and skin; R2 = 0.038), this was not true in neonatal stool (meconium, Mann-Whitney p>0.05) and there was no observable difference in community function regardless of delivery mode. By 6 weeks of age, the infant microbiota structure and function had expanded and diversified with demonstrable body site specificity (p<0.001, R2 = 0.189), and no discernable differences in neither community structure nor function by Cesarean delivery were identifiable (p=0.057, R2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes significant reorganization that is primarily driven by body site and not by mode of delivery. PMID:28112736

GIT1/βPIX signaling proteins and PAK1 kinase regulate microtubule nucleation.

PubMed

Černohorská, Markéta; Sulimenko, Vadym; Hájková, Zuzana; Sulimenko, Tetyana; Sládková, Vladimíra; Vinopal, Stanislav; Dráberová, Eduarda; Dráber, Pavel

2016-06-01

Microtubule nucleation from γ-tubulin complexes, located at the centrosome, is an essential step in the formation of the microtubule cytoskeleton. However, the signaling mechanisms that regulate microtubule nucleation in interphase cells are largely unknown. In this study, we report that γ-tubulin is in complexes containing G protein-coupled receptor kinase-interacting protein 1 (GIT1), p21-activated kinase interacting exchange factor (βPIX), and p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1) in various cell lines. Immunofluorescence microscopy revealed association of GIT1, βPIX and activated PAK1 with centrosomes. Microtubule regrowth experiments showed that depletion of βPIX stimulated microtubule nucleation, while depletion of GIT1 or PAK1 resulted in decreased nucleation in the interphase cells. These data were confirmed for GIT1 and βPIX by phenotypic rescue experiments, and counting of new microtubules emanating from centrosomes during the microtubule regrowth. The importance of PAK1 for microtubule nucleation was corroborated by the inhibition of its kinase activity with IPA-3 inhibitor. GIT1 with PAK1 thus represent positive regulators, and βPIX is a negative regulator of microtubule nucleation from the interphase centrosomes. The regulatory roles of GIT1, βPIX and PAK1 in microtubule nucleation correlated with recruitment of γ-tubulin to the centrosome. Furthermore, in vitro kinase assays showed that GIT1 and βPIX, but not γ-tubulin, serve as substrates for PAK1. Finally, direct interaction of γ-tubulin with the C-terminal domain of βPIX and the N-terminal domain of GIT1, which targets this protein to the centrosome, was determined by pull-down experiments. We propose that GIT1/βPIX signaling proteins with PAK1 kinase represent a novel regulatory mechanism of microtubule nucleation in interphase cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics.

PubMed

Ajslev, T A; Andersen, C S; Gamborg, M; Sørensen, T I A; Jess, T

2011-04-01

To investigate whether delivery mode (vaginal versus by caesarean section), maternal pre-pregnancy body mass index (BMI) and early exposure to antibiotics (<6 months of age) influence child's risk of overweight at age 7 years, hence supporting the hypotheses that environmental factors influencing the establishment and diversity of the gut microbiota are associated with later risk of overweight. Longitudinal, prospective study with measure of exposures in infancy and follow-up at age 7 years. A total of 28 354 mother-child dyads from the Danish National Birth Cohort, with information on maternal pre-pregnancy BMI, delivery mode and antibiotic administration in infancy, were assessed. Logistic regression analyses were performed with childhood height and weight at the 7-year follow-up as outcome measures. Delivery mode was not significantly associated with childhood overweight (odds ratio (OR):1.18, 95% confidence interval (CI): 0.95-1.47). Antibiotics during the first 6 months of life led to increased risk of overweight among children of normal weight mothers (OR: 1.54, 95% CI: 1.09-2.17) and a decreased risk of overweight among children of overweight mothers (OR: 0.54, 95% CI: 0.30-0.98). The same tendency was observed among children of obese mothers (OR: 0.85, 95% CI: 0.41-1.76). The present cohort study revealed that a combination of early exposures, including delivery mode, maternal pre-pregnancy BMI and antibiotics in infancy, influences the risk of overweight in later childhood. This effect may potentially be explained by an impact on establishment and diversity of the microbiota.

Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance

PubMed Central

Gibson, DL; Gill, SK; Brown, K; Tasnim, N; Ghosh, S; Innis, S; Jacobson, K

2015-01-01

Our previous studies revealed that offspring from rat dams fed fish oil (at 8% and 18% energy), developed impaired intestinal barriers sensitizing the colon to exacerbated injury later in life. To discern the mechanism, we hypothesized that in utero exposure to fish oil, rich in n-3 polyunsaturated fatty acid (PUFA), caused abnormal intestinal reparative responses to mucosal injury through differences in intestinal microbiota and the presence of naïve immune cells. To identify such mechanisms, gut microbes and naïve immune cells were compared between rat pups born to dams fed either n-6 PUFA, n-3 PUFA or breeder chow. Maternal exposure to either of the PUFA rich diets altered the development of the intestinal microbiota with an overall reduction in microbial density. Using qPCR, we found that each type of PUFA differentially altered the major gut phyla; fish oil increased Bacteroidetes and safflower oil increased Firmicutes. Both PUFA diets reduced microbes known to dominate the infant gut like Enterobacteriaceae and Bifidobacteria spp. when compared to the chow group. Uniquely, maternal fish oil diets resulted in offspring showing blooms of opportunistic pathogens like Bilophila wadsworthia, Enterococcus faecium and Bacteroides fragilis in their gut microbiota. As well, fish oil groups showed a reduction in colonic CD8+ T cells, CD4+ Foxp3+ T cells and arginase+ M2 macrophages. In conclusion, fish oil supplementation in pharmacological excess, at 18% by energy as shown in this study, provides an example where excess dosing in utero can prime offspring to harbor intestinal pathobionts and alter immune cell homeostasis. PMID:25559197

Maternal use of probiotics during pregnancy and effects on their offspring's health in an unselected population.

PubMed

Rutten, Nicole; Van der Gugten, Anne; Uiterwaal, Cuno; Vlieger, Arine; Rijkers, Ger; Van der Ent, Kors

2016-02-01

Probiotics are used by women in the perinatal period and may improve balance of microbiota, with possible health benefits for both mother and baby. Characteristics and (health) behaviour patterns of mothers using probiotics during pregnancy, and health effects on their offspring, were investigated. Differences between mothers using probiotics during pregnancy and those who did not, were assessed. In total, 341 out of 2491 (13.7%) mothers reported use of probiotics during pregnancy. There were no significant differences in maternal features (gestation, age, ethnicity, education) between users and non-users. Logistic regression analyses showed that consumption of probiotics was significantly associated with use of homeopathic products [odds ratio (OR) 1.65, 95% confidence interval (CI) 1.17-2.33, p = 0.005], maternal history of smoking (OR 1.72, 95% CI 1.25-2.37, p = 0.001) and paternal history of smoking (OR 1.39, 95% CI 1.01-1.89, p = 0.05). Common disease symptoms during the first year of life in the offspring did not differ between both groups. The use of probiotics or other health-related products without doctor's prescription during pregnancy might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not seem to induce positive health effects in the offspring in an unselected population. Aberrant microbiota compositions have been detected during critical periods when early programming occurs including pregnancy and early neonatal life. Probiotics modulate intestinal microbiota composition and are associated with positive health effects. The use of probiotics or other health-related products without doctor's prescription during pregnancy is associated with and might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not induce positive health effects in the offspring in this unselected population.

Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age.

PubMed

Bae, Won; Park, Kyoung Un; Song, Eun Young; Kim, Se Joong; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Yim, Jae-Joon; Lee, Choon-Taek; Lee, Jae Ho

2016-01-01

Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T-SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30-49 years, 86.5% and 94.7%; 50-69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age.

Predictors of discordant tuberculin skin test and QuantiFERON®-TB Gold In-Tube results in various high-risk groups.

PubMed

Weinfurter, P; Blumberg, H M; Goldbaum, G; Royce, R; Pang, J; Tapia, J; Bethel, J; Mazurek, G H; Toney, S; Albalak, R

2011-08-01

Persons in whom targeted testing for latent tuberculosis infection (LTBI) is recommended in Seattle, Washington; Atlanta, Georgia; and central North Carolina, United States. To compare the performance of an interferon-gamma release assay (QuantiFERON®-TB Gold In-Tube [QFT-GIT]) with the tuberculin skin test (TST) among foreign-born, homeless, human immunodeficiency virus (HIV) infected and substance abuse persons tested for LTBI. A cross-sectional study requiring participants to have a blood test, a TST and data collected. Of 1653 persons, 19.5% were TST-positive and 14.0% were QFT-GIT-positive. Overall concordance was moderate (kappa 0.53; 95%CI 0.47-0.58). Compared to concordant positive results, TST+/QFT-GIT- discordance was associated with HIV infection and sex, while TST-/QFT-GIT+ discordance was associated with HIV and inversely associated with foreign birth. Compared to concordant negative results, TST-/QFT-GIT+ discordance was associated with foreign birth and age ≥50 years, while TST+/QFT-GIT-discordance was associated with foreign birth, age 30-49 years, being Black and inversely associated with HIV. HIV infection was significantly associated with indeterminate QFT-GIT results. QFT-GIT may be an improvement over the TST for diagnosing LTBI in foreign-born and older persons, and may be as useful as the TST in HIV-infected persons. The sensitivity of both tests may be low in HIV-infected persons.

Evaluation of Fecal Microbiota Transfer as Treatment for Postweaning Diarrhea in Research-Colony Puppies.

PubMed

Burton, Erin N; O'Connor, Erin; Ericsson, Aaron C; Franklin, Craig L

2016-01-01

Frequently just prior to or at weaning (approximate age, 6 to 8 wk), puppies in research settings often develop diarrheal disease, which may be due, in part, to an immature and unstable intestinal microbiota that is permissive to opportunistic pathogens. The overall objective of this study was to assess whether fecal microbiota transfer (FMT) increased the transmission of a stable maternal microbiota to pups and decreased the incidence of postweaning diarrhea. Puppies were designated by litter as treated (FMT) or sham-treated. The FMT group received fecal inoculum orally for 5 consecutive days during weaning (at 6 to 8 wk of age). Diarrhea was evaluated according to a published scoring system for 11 d during the weaning period. Fresh feces were collected from dams and puppies at 3 d before weaning and 3, 10, and 24 d after weaning for analysis of the fecal microbiota by using 16S rRNA amplicon sequencing. The composition of fecal inoculum refrigerated at 3 to 5 °C was stable for at least 5 d. No diarrhea was reported in either group during the study period, making comparison of treated and control groups problematic. However, 16S rRNA gene analysis revealed microbial variability across time in both groups. Therefore, although the fecal microbiota of neither group of puppies mirrored the dam at any of the designated time points, the data provided fundamental and novel information regarding the dynamic maturation process of the fecal microbiota of puppies after weaning.

Gastrointestinal microbiota and mucosal immune gene expression in neonatal pigs reared in a cross-fostering model.

PubMed

Maradiaga, Nidia; Aldridge, Brian; Zeineldin, Mohamed; Lowe, James

2018-05-06

Cross fostering is employed to equalize the number of piglet between litters ensuring colostrum intake for their survival and growth. However, little is known about the impact of cross fostering on the intestinal microbiota and mucosal immune gene expression of the neonatal pig. The objective of this study was to determine the influence of maternal microbial communities on the gastrointestinal (GI) microbiota and mucosal immune gene expression in young pigs reared in a cross-fostering model. Piglets were given high quality colostrum from birth dam or foster dam upon birth. Twenty-four piglets were randomly assigned at birth to 1 of 3 treatments according to colostrum source and postcolostral milk feeding during, as follow: treatment 1 (n = 8), received colostrum and post-colostral milk feeding from their own dam; treatment 2 (n = 8), received colostrum from foster dam and returned to their own dam for post-colostral milk feeding; and treatment 3 (n = 8), received colostrum and post-colostral milk feeding from foster dam. Genomic DNA was extracted, and the V1-V3 hypervariable region of the bacterial 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Quantitative real-time PCR analysis was also performed to quantify the expression of toll-like receptors (TLR) 2, TLR 4, TLR 10, tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin (IL) 4 and IL 10. Data analysis revealed that microbial communities were varied according to the GI biogeographical location, with colon being the most diverse section. Bacterial communities in both maternal colostrum and vaginal samples were significantly associated with those present in the fecal samples of piglets. Cross-fostering did not affect bacterial communities present in the piglet GI tract. However, the mRNA expression of TLR and inflammatory cytokines changed (P < 0.05) with biogeographical location in the GI tract. Higher mRNA expression of TLR and inflammatory cytokines was observed in ileum and ileum associated lymph tissues. This study suggests an impact of colostrum and maternal microbial communities on the microbiota development and mucosal immune gene expression in the newly born piglet. This study revealed novel information about the distribution and expression patterns of TLR and inflammatory cytokines in the GI tract of the young pig. Future studies are needed to determine the role and clinical importance of the mucosal microbiota and mucosal gene expression in health, productivity, and susceptibility to the development of GI disease, in piglets. Published by Elsevier Ltd.

Reducing Friction: An Update on the NCIP Open Development Initiative - NCI BioMedical Informatics Blog

Cancer.gov

NCIP has migrated 132 repositories from the NCI subversion repository to our public NCIP GitHub channel with the goal of facilitating third party contributions to the existing code base. Within the GitHub environment, we are advocating use of the GitHub “fork and pull” model.

[Random Variable Read Me File

NASA Technical Reports Server (NTRS)

Teubert, Christopher; Sankararaman, Shankar; Cullo, Aiden

2017-01-01

Readme for the Random Variable Toolbox usable manner. is a Web-based Git version control repository hosting service. It is mostly used for computer code. It offers all of the distributed version control and source code management (SCM) functionality of Git as well as adding its own features. It provides access control and several collaboration features such as bug tracking, feature requests, task management, and wikis for every project.[3] GitHub offers both plans for private and free repositories on the same account[4] which are commonly used to host open-source software projects.[5] As of April 2017, GitHub reports having almost 20 million users and 57 million repositories,[6] making it the largest host of source code in the world.[7] GitHub has a mascot called Octocat, a cat with five tentacles and a human-like face

Impact of maternal antibodies and infant gut microbiota on the immunogenicity of rotavirus vaccines in African, Indian and European infants: protocol for a prospective cohort study.

PubMed

Sindhu, Kuladaipalayam Natarajan C; Cunliffe, Nigel; Peak, Matthew; Turner, Mark; Darby, Alistair; Grassly, Nicholas; Gordon, Melita; Dube, Queen; Babji, Sudhir; Praharaj, Ira; Verghese, Valsan; Iturriza-Gómara, Miren; Kang, Gagandeep

2017-03-29

Gastroenteritis is the leading cause of morbidity and mortality among young children living in resource-poor settings, majority of which is attributed to rotavirus. Rotavirus vaccination can therefore have a significant impact on infant mortality. However, rotavirus vaccine efficacy in Sub-Saharan Africa and Southeast Asia is significantly lower than in high-income countries. Maternally derived antibodies, infant gut microbiota and concomitant oral polio vaccination have been proposed as potential reasons for poor vaccine performance in low-income settings. The overall aim of this study is to compare the role of maternally derived antibodies and infant gut microbiota in determining immune response to rotavirus vaccine in high-income and low-income settings, using the same vaccine and a similar study protocol. The study is an observational cohort in three countries-Malawi, India and UK. Mothers will be enrolled in third trimester of pregnancy and followed up, along with infants after delivery, until the infant completes two doses of oral rotavirus vaccine (along with routine immunisation). The levels of prevaccination maternally derived rotavirus-specific antibodies (IgG) will be correlated with infant seroconversion and antibody titres, 4 weeks after the second dose of rotavirus vaccine. Both within-country and between-country comparisons of gut microbiome will be carried out between children who seroconvert and those who do not. The impact of oral polio vaccine coadministration on rotavirus vaccine response will be studied in Indian infants. Ethical approvals have been obtained from Integrated Research Application System (IRAS, NHS ethics) in UK, College of Medicine Research and Ethics Committee (COMREC) in Malawi and Institutional Review Board (IRB), Christian Medical College, Vellore in India. Participant recruitment and follow-up is ongoing at all three sites. Analysis of data, followed by publication of the results, is expected in 2018. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effectiveness of skin-to-skin contact versus care-as-usual in mothers and their full-term infants: study protocol for a parallel-group randomized controlled trial.

PubMed

Cooijmans, Kelly H M; Beijers, Roseriet; Rovers, Anne C; de Weerth, Carolina

2017-07-06

Twenty-to-forty percent of women experience postpartum depressive symptoms, which can affect both the mother and infant. In preterm infants, daily skin-to-skin contact (SSC) between the mother and her infant has been shown to decrease maternal postpartum depressive symptoms. In full-term infants, only two studies investigated SSC effects on maternal depressive symptoms and found similar results. Research in preterm infants also showed that SSC improves other mental and physical health outcomes of the mother and the infant, and improves the quality of mother-infant relationship. This randomized controlled trial will investigate the effects of a SSC intervention on maternal postpartum depressive symptoms and additional outcomes in mothers and their full-term infants. Moreover, two potential underlying mechanisms for the relation between SSC and the maternal and infant outcomes will be examined, namely maternal oxytocin concentrations and infant intestinal microbiota. Design: A parallel-group randomized controlled trial. 116 mothers and their full-term infants. Mothers in the SSC condition will be requested to provide daily at least one continuous hour of SSC to their infant. The intervention starts immediately after birth and lasts for 5 weeks. Mothers in the control condition will not be requested to provide SSC. Maternal and infant outcomes will be measured at 2 weeks, 5 weeks, 12 weeks and 1 year after birth. maternal postpartum depressive symptoms. Secondary maternal outcomes: mental health (anxiety, stress, traumatic stress following child birth, sleep quality), physical health (physical recovery from the delivery, health, breastfeeding, physiological stress), mother-infant relationship (mother-infant bond, quality of maternal caregiving behavior). Secondary infant outcomes: behavior (fussing and crying, sleep quality), physical health (growth and health, physiological stress), general development (regulation capacities, social-emotional capacities, language, cognitive and motor capacities). Secondary underlying mechanisms: maternal oxytocin concentrations, infant intestinal microbiota. As a simple and cost-effective intervention, SSC may benefit both the mother and her full-term infant in the short-and long-term. Additionally, if SSC is shown to be effective in low-risk mother-infant dyads, then thought could be given to developing programs in high-risk samples and using SSC in a preventive manner. NTR5697 ; Registered on March 13, 2016.

Lactobacillus salivarius: bacteriocin and probiotic activity.

PubMed

Messaoudi, S; Manai, M; Kergourlay, G; Prévost, H; Connil, N; Chobert, J-M; Dousset, X

2013-12-01

Lactic acid bacteria (LAB) antimicrobial peptides typically exhibit antibacterial activity against food-borne pathogens, as well as spoilage bacteria. Therefore, they have attracted the greatest attention as tools for food biopreservation. In some countries LAB are already extensively used as probiotics in food processing and preservation. LAB derived bacteriocins have been utilized as oral, topical antibiotics or disinfectants. Lactobacillus salivarius is a promising probiotic candidate commonly isolated from human, porcine, and avian gastrointestinal tracts (GIT), many of which are producers of unmodified bacteriocins of sub-classes IIa, IIb and IId. It is a well-characterized bacteriocin producer and probiotic organism. Bacteriocins may facilitate the introduction of a producer into an established niche, directly inhibit the invasion of competing strains or pathogens, or modulate the composition of the microbiota and influence the host immune system. This review gives an up-to-date overview of all L. salivarius strains, isolated from different origins, known as bacteriocin producing and/or potential probiotic. Copyright © 2013 Elsevier Ltd. All rights reserved.

Immunohistochemical study on gastrointestinal endocrine cells of four reptiles

PubMed Central

Huang, Xu-Gen; Wu, Xiao-Bing

2005-01-01

AIM: To clarify the types, regional distributions and distribution densities as well as morphological features of gastrointestinal (GI) endocrine cells in various parts of the gastrointestinal track (GIT) of four reptiles, Gekko japonicus, Eumeces chinensis, Sphenomorphus indicus and Eumeces elegans. METHODS: Paraffin-embedded sections (5 μm) of seven parts (cardia, fundus, pylorus, duodenum, jejunum, ileum, rectum) of GIT dissected from the four reptiles were prepared. GI endocrine cells were revealed by using immunohistochemical techniques of streptavidin-peroxidase (S-P) method. Seven types of antisera against 5-hydroxy-tryptamine (5-HT), somatostatin (SS), gastrin (GAS), glucagon (GLU), substance P (SP), insulin and pancreatic polypeptide were identified and then GI endocrine cells were photomicrographed and counted. RESULTS: The GI endocrine system of four reptiles was a complex structure containing many endocrine cell types similar in morphology to those found in higher vertebrates. Five types of GI endocrine cells, namely 5-HT, SS, GAS, SP and GLU immunoreactive (IR) cells were identified in the GIT of G. japonicus, E. chinensis and S. indicus; while in the GIT of E. elegans only the former three types of endocrine cells were observed. No PP- and INS- IR cells were found in all four reptiles. 5-HT-IR cells, which were most commonly found in the pylorus or duodenum, distributed throughout the whole GIT of four reptiles. However, their distribution patterns varied from each other. SS-IR cells, which were mainly found in the stomach especially in the pylorus and/or fundus, were demonstrated in the whole GIT of E. chinensis, only showed restricted distribution in the other three species. GAS-IR cells, with a much restricted distribution, were mainly demonstrated in the pylorus and/or the proximal small intestine of four reptiles. GLU-IR cells exhibited a limited and species-dependent variant distribution in the GIT of four reptiles. SP-IR cells were found throughout the GIT except for jejunum in E. elegans and showed a restricted distribution in the GIT of G. japonicus and S. indicus. In the GIT of four reptiles the region with the highest degree of cell type heterogeneity was pylorus and most types of GI endocrine cells along the GIT showed the peak density in pylorus as well. CONCLUSION: Some common and unique features of the distribution and morphology of different types of GI endocrine cells are found in four reptiles. This common trait may reflect the similarity in digestive physiology of various vertebrates. PMID:16222743

Empirical analysis on the human dynamics of blogging behavior on GitHub

NASA Astrophysics Data System (ADS)

Yan, Deng-Cheng; Wei, Zong-Wen; Han, Xiao-Pu; Wang, Bing-Hong

2017-01-01

GitHub is a social collaborative coding platform on which software developers not only collaborate on codes but also share knowledge through blogs using GitHub Pages. In this article, we analyze the blogging behavior of software developers on GitHub Pages. The results show that both the commit number and the inter-event time of two consecutive blogging actions follow heavy-tailed distribution. We further observe a significant variety of activity among individual developers, and a strongly positive correlation between the activity and the power-law exponent of the inter-event time distribution. We also find a difference between the user behaviors of GitHub Pages and other online systems which is driven by the diversity of users and length of contents. In addition, our result shows an obvious difference between the majority of developers and elite developers in their burstiness property.

Growth and Morbidity of Gambian Infants are Influenced by Maternal Milk Oligosaccharides and Infant Gut Microbiota

PubMed Central

Davis, Jasmine C. C.; Lewis, Zachery T.; Krishnan, Sridevi; Bernstein, Robin M.; Moore, Sophie E.; Prentice, Andrew M.; Mills, David A.; Lebrilla, Carlito B.; Zivkovic, Angela M.

2017-01-01

Human milk oligosaccharides (HMOs) play an important role in the health of an infant as substrate for beneficial gut bacteria. Little is known about the effects of HMO composition and its changes on the morbidity and growth outcomes of infants living in areas with high infection rates. Mother’s HMO composition and infant gut microbiota from 33 Gambian mother/infant pairs at 4, 16, and 20 weeks postpartum were analyzed for relationships between HMOs, microbiota, and infant morbidity and growth. The data indicate that lacto-N-fucopentaose I was associated with decreased infant morbidity, and 3′-sialyllactose was found to be a good indicator of infant weight-for-age. Because HMOs, gut microbiota, and infant health are interrelated, the relationship between infant health and their microbiome were analyzed. While bifidobacteria were the dominant genus in the infant gut overall, Dialister and Prevotella were negatively correlated with morbidity, and Bacteroides was increased in infants with abnormal calprotectin. Mothers nursing in the wet season (July to October) produced significantly less oligosaccharides compared to those nursing in the dry season (November to June). These results suggest that specific types and structures of HMOs are sensitive to environmental conditions, protective of morbidity, predictive of growth, and correlated with specific microbiota. PMID:28079170

Growth and Morbidity of Gambian Infants are Influenced by Maternal Milk Oligosaccharides and Infant Gut Microbiota

NASA Astrophysics Data System (ADS)

Davis, Jasmine C. C.; Lewis, Zachery T.; Krishnan, Sridevi; Bernstein, Robin M.; Moore, Sophie E.; Prentice, Andrew M.; Mills, David A.; Lebrilla, Carlito B.; Zivkovic, Angela M.

2017-01-01

Human milk oligosaccharides (HMOs) play an important role in the health of an infant as substrate for beneficial gut bacteria. Little is known about the effects of HMO composition and its changes on the morbidity and growth outcomes of infants living in areas with high infection rates. Mother’s HMO composition and infant gut microbiota from 33 Gambian mother/infant pairs at 4, 16, and 20 weeks postpartum were analyzed for relationships between HMOs, microbiota, and infant morbidity and growth. The data indicate that lacto-N-fucopentaose I was associated with decreased infant morbidity, and 3‧-sialyllactose was found to be a good indicator of infant weight-for-age. Because HMOs, gut microbiota, and infant health are interrelated, the relationship between infant health and their microbiome were analyzed. While bifidobacteria were the dominant genus in the infant gut overall, Dialister and Prevotella were negatively correlated with morbidity, and Bacteroides was increased in infants with abnormal calprotectin. Mothers nursing in the wet season (July to October) produced significantly less oligosaccharides compared to those nursing in the dry season (November to June). These results suggest that specific types and structures of HMOs are sensitive to environmental conditions, protective of morbidity, predictive of growth, and correlated with specific microbiota.

Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt

PubMed Central

Bisanz, Jordan E.; Enos, Megan K.; PrayGod, George; Seney, Shannon; Macklaim, Jean M.; Chilton, Stephanie; Willner, Dana; Knight, Rob; Fusch, Christoph; Fusch, Gerhard; Gloor, Gregory B.; Burton, Jeremy P.

2015-01-01

The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study. PMID:25979893

Interferon Gamma-Based Detection of Latent Tuberculosis Infection in the Border States of Nuevo Leon and Tamaulipas, Mexico

PubMed Central

Oren, Eyal; Alatorre-Izaguirre, Gabriela; Vargas-Villarreal, Javier; Moreno-Treviño, Maria Guadalupe; Garcialuna-Martinez, Javier; Gonzalez-Salazar, Francisco

2015-01-01

Nearly one-third of the world’s population is infected with latent tuberculosis (LTBI). Tuberculosis (TB) rates in the border states are higher than national rates in both the US and Mexico, with the border accounting for 30% of total registered TB cases in both countries. However, LTBI rates in the general population in Mexican border states are unknown. In this region, LTBI is diagnosed using the tuberculin skin test (TST). New methods of detection more specific than TST have been developed, although there is currently no gold standard for LTBI detection. Our objective is to demonstrate utility of the Quantiferon TB gold In-Tube (QFT-GIT) test compared with the TST to detect LTBI among border populations. This is an observational, cross-sectional study carried out in border areas of the states of Nuevo Leon and Tamaulipas, Mexico. Participants (n = 210) provided a TST and blood sample for the QFT-GIT. Kappa coefficients assessed the agreement between TST and QFT-GIT. Participant characteristics were compared using Fisher exact tests. Thirty-eight percent of participants were diagnosed with LTBI by QFT-GIT. The proportion of LTBI detected using QFT-GIT was almost double [38% (79/210)] that found by TST [19% (39/210)] (P < 0.001). Concordance between TST and QFT-GIT was low (kappa = 0.37). We recommend further studies utilizing the QFT-GIT test to detect LTBI among border populations. PMID:26484340

Interferon Gamma-Based Detection of Latent Tuberculosis Infection in the Border States of Nuevo Leon and Tamaulipas, Mexico.

PubMed

Oren, Eyal; Alatorre-Izaguirre, Gabriela; Vargas-Villarreal, Javier; Moreno-Treviño, Maria Guadalupe; Garcialuna-Martinez, Javier; Gonzalez-Salazar, Francisco

2015-01-01

Nearly one-third of the world's population is infected with latent tuberculosis (LTBI). Tuberculosis (TB) rates in the border states are higher than national rates in both the US and Mexico, with the border accounting for 30% of total registered TB cases in both countries. However, LTBI rates in the general population in Mexican border states are unknown. In this region, LTBI is diagnosed using the tuberculin skin test (TST). New methods of detection more specific than TST have been developed, although there is currently no gold standard for LTBI detection. Our objective is to demonstrate utility of the Quantiferon TB gold In-Tube (QFT-GIT) test compared with the TST to detect LTBI among border populations. This is an observational, cross-sectional study carried out in border areas of the states of Nuevo Leon and Tamaulipas, Mexico. Participants (n = 210) provided a TST and blood sample for the QFT-GIT. Kappa coefficients assessed the agreement between TST and QFT-GIT. Participant characteristics were compared using Fisher exact tests. Thirty-eight percent of participants were diagnosed with LTBI by QFT-GIT. The proportion of LTBI detected using QFT-GIT was almost double [38% (79/210)] that found by TST [19% (39/210)] (P < 0.001). Concordance between TST and QFT-GIT was low (kappa = 0.37). We recommend further studies utilizing the QFT-GIT test to detect LTBI among border populations.

betaPIX controls cell motility and neurite extension by regulating the distribution of GIT1.

PubMed

Za, Lorena; Albertinazzi, Chiara; Paris, Simona; Gagliani, Mariacristina; Tacchetti, Carlo; de Curtis, Ivan

2006-07-01

Cell motility entails the reorganization of the cytoskeleton and membrane trafficking for effective protrusion. GIT1/p95-APP1 is a member of a family of GTPase-activating proteins for ARF GTPases that affect endocytosis, adhesion and migration. GIT1 associates with paxillin and a complex including the Rac/Cdc42 exchanging factors PIX/Cool and the kinase PAK. In this study, we show that overexpression of betaPIX induces the accumulation of endogenous and overexpressed GIT1 at large structures similar to those induced by an ArfGAP-defective mutant of GIT1 (p95-C2). Immunohistochemical analysis and immunoelectron microscopy reveal that these structures include the endogenous transferrin receptor. Time-lapse analysis during motogenic stimuli shows that the formation and perinuclear accumulation of the p95-C2-positive structures is paralleled by inhibition of lamellipodium formation and cell retraction. Both dimerization and a functional SH3 domain of betaPIX are required for the accumulation of GIT1 in fibroblasts, which is prevented by the monomeric PIX-PG-DeltaLZ. This mutant also prevents the formation of endocytic aggregates and inhibition of neurite outgrowth in retinal neurons expressing p95-C2. Our results indicate that betaPIX is an important regulator of the subcellular distribution of GIT1, and suggest that alteration in the level of expression of the complex affects the endocytic compartment and cell motility.

Developmental origins of NAFLD: a womb with a clue

PubMed Central

Wesolowski, Stephanie R.; El Kasmi, Karim C.; Jonscher, Karen R.; Friedman, Jacob E.

2017-01-01

Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally. Deleterious exposures in utero include fetal hypoxia, increased nutrient supply, inflammation and altered gut microbiota that might produce metabolic clues, including fatty acids, metabolites, endotoxins, bile acids and cytokines, which prime the infant liver for NAFLD in a persistent manner and increase susceptibility to NASH. Mechanistic links to early disease pathways might involve shifts in lipid metabolism, mitochondrial dysfunction, pioneering gut microorganisms, macrophage programming and epigenetic changes that alter the liver microenvironment, favouring liver injury. In this Review, we discuss how maternal, fetal, neonatal and infant exposures provide developmental clues and mechanisms to help explain NAFLD acceleration and increased disease prevalence. Mechanisms identified in clinical and preclinical models suggest important opportunities for prevention and intervention that could slow down the growing epidemic of NAFLD in the next generation. PMID:27780972

Sharing environmental models: An Approach using GitHub repositories and Web Processing Services

NASA Astrophysics Data System (ADS)

Stasch, Christoph; Nuest, Daniel; Pross, Benjamin

2016-04-01

The GLUES (Global Assessment of Land Use Dynamics, Greenhouse Gas Emissions and Ecosystem Services) project established a spatial data infrastructure for scientific geospatial data and metadata (http://geoportal-glues.ufz.de), where different regional collaborative projects researching the impacts of climate and socio-economic changes on sustainable land management can share their underlying base scenarios and datasets. One goal of the project is to ease the sharing of computational models between institutions and to make them easily executable in Web-based infrastructures. In this work, we present such an approach for sharing computational models relying on GitHub repositories (http://github.com) and Web Processing Services. At first, model providers upload their model implementations to GitHub repositories in order to share them with others. The GitHub platform allows users to submit changes to the model code. The changes can be discussed and reviewed before merging them. However, while GitHub allows sharing and collaborating of model source code, it does not actually allow running these models, which requires efforts to transfer the implementation to a model execution framework. We thus have extended an existing implementation of the OGC Web Processing Service standard (http://www.opengeospatial.org/standards/wps), the 52°North Web Processing Service (http://52north.org/wps) platform to retrieve all model implementations from a git (http://git-scm.com) repository and add them to the collection of published geoprocesses. The current implementation is restricted to models implemented as R scripts using WPS4R annotations (Hinz et al.) and to Java algorithms using the 52°North WPS Java API. The models hence become executable through a standardized Web API by multiple clients such as desktop or browser GIS and modelling frameworks. If the model code is changed on the GitHub platform, the changes are retrieved by the service and the processes will be updated accordingly. The admin tool of the 52°North WPS was extended to support automated retrieval and deployment of computational models from GitHub repositories. Once the R code is available in the GitHub repo, the contained process can be easily deployed and executed by simply defining the GitHub repository URL in the WPS admin tool. We illustrate the usage of the approach by sharing and running a model for land use system archetypes developed by the Helmholtz Centre for Environmental Research (UFZ, see Vaclavik et al.). The original R code was extended and published in the 52°North WPS using both, public and non-public datasets (Nüst et al., see also https://github.com/52North/glues-wps). Hosting the analysis in a Git repository now allows WPS administrators, client developers, and modelers to easily work together on new versions or completely new web processes using the powerful GitHub collaboration platform. References: Hinz, M. et. al. (2013): Spatial Statistics on the Geospatial Web. In: The 16th AGILE International Conference on Geographic Information Science, Short Papers. http://www.agile-online.org/Conference_Paper/CDs/agile_2013/Short_Papers/SP_S3.1_Hinz.pdf Nüst, D. et. al.: (2015): Open and reproducible global land use classification. In: EGU General Assembly Conference Abstracts . Vol. 17. European Geophysical Union, 2015, p. 9125, http://meetingorganizer.copernicus. org/EGU2015/EGU2015- 9125.pdf Vaclavik, T., et. al. (2013): Mapping global land system archetypes. Global Environmental Change 23(6): 1637-1647. Online available: October 9, 2013, DOI: 10.1016/j.gloenvcha.2013.09.004

BetaPIX and GIT1 regulate HGF-induced lamellipodia formation and WAVE2 transport.

PubMed

Morimura, Shigeru; Suzuki, Katsuo; Takahashi, Kazuhide

2009-05-08

Formation of lamellipodia is the first step during cell migration, and involves actin reassembly at the leading edge of migrating cells through the membrane transport of WAVE2. However, the factors that regulate WAVE2 transport to the cell periphery for initiating lamellipodia formation have not been elucidated. We report here that in human breast cancer MDA-MB-231 cells, the hepatocyte growth factor (HGF) induced the association between the constitutive complex of betaPIX and GIT1 with WAVE2, which was concomitant with the induction of lamellipodia formation and WAVE2 transport. Although depletion of betaPIX by RNA interference abrogated the HGF-induced WAVE2 transport and lamellipodia formation, GIT1 depletion caused HGF-independent WAVE2 transport and lamellipodia formation. Collectively, we suggest that betaPIX releases cells from the GIT1-mediated suppression of HGF-independent responses and recruits GIT1 to WAVE2, thereby facilitating HGF-induced WAVE2 transport and lamellipodia formation.

Towards an improved understanding of processes controlling absorption efficiency and biomagnification of organic chemicals by fish.

PubMed

Xiao, Ruiyang; Arnot, Jon A; MacLeod, Matthew

2015-11-01

Dietary exposure is considered the dominant pathway for fish exposed to persistent, hydrophobic chemicals in the environment. Here we present a dynamic, fugacity-based three-compartment bioaccumulation model that describes the fish body as one compartment and the gastrointestinal tract (GIT) as two compartments. The model simulates uptake from the GIT by passive diffusion and micelle-mediated diffusion, and chemical degradation in the fish and the GIT compartments. We applied the model to a consistent measured dietary uptake and depuration dataset for rainbow trout (n=215) that is comprised of chlorinated benzenes, biphenyls, dioxins, diphenyl ethers, and polycyclic aromatic hydrocarbons (PAHs). Model performance relative to the measured data is statistically similar regardless of whether micelle-mediated diffusion is included; however, there are considerable uncertainties in modeling this process. When degradation in the GIT is assumed to be negligible, modeled chemical elimination rates are similar to measured rates; however, predicted concentrations of the PAHs are consistently higher than measurements by up to a factor of 20. Introducing a kinetic limit on chemical transport from the fish compartment to the GIT and increasing the rate constant for degradation of PAHs in tissues of the liver and/or GIT are required to achieve good agreement between the modelled and measured concentrations for PAHs. Our results indicate that the apparent low absorption efficiency of PAHs relative to the chemicals with similar hydrophobicity is attributable to biotransformation in the liver and/or the GIT. Our results provide process-level insights about controls on the extent of bioaccumulation of chemicals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nutritional programming of gastrointestinal tract development. Is the pig a good model for man?

PubMed

Guilloteau, Paul; Zabielski, Romuald; Hammon, Harald M; Metges, Cornelia C

2010-06-01

The consequences of early-life nutritional programming in man and other mammalian species have been studied chiefly at the metabolic level. Very few studies, if any, have been performed in the gastrointestinal tract (GIT) as the target organ, but extensive GIT studies are needed since the GIT plays a key role in nutrient supply and has an impact on functions of the entire organism. The possible deleterious effects of nutritional programming at the metabolic level were discovered following epidemiological studies in human subjects, and confirmed in animal models. Investigating the impact of programming on GIT structure and function would need appropriate animal models due to ethical restrictions in the use of human subjects. The aim of the present review is to discuss the use of pigs as an animal model as a compromise between ethically acceptable animal studies and the requirement of data which can be interpolated to the human situation. In nutritional programming studies, rodents are the most frequently used model for man, but GIT development and digestive function in rodents are considerably different from those in man. In that aspect, the pig GIT is much closer to the human than that of rodents. The swine species is closely comparable with man in many nutritional and digestive aspects, and thus provides ample opportunity to be used in investigations on the consequences of nutritional programming for the GIT. In particular, the 'sow-piglets' dyad could be a useful tool to simulate the 'human mother-infant' dyad in studies which examine short-, middle- and long-term effects and is suggested as the reference model.

Allocation of endogenous and dietary protein in the reconstitution of the gastrointestinal tract in migratory blackcaps at stopover sites.

PubMed

Muñoz-Garcia, Agustí; Aamidor, Sarah E; McCue, Marshall D; McWilliams, Scott R; Pinshow, Berry

2012-04-01

During migratory flight, the mass of the gastrointestinal tract (GIT) and its associated organs in small birds decreases in size by as much as 40%, compared with the preflight condition because of the catabolism of protein. At stopover sites, birds need 2-3 days to rebuild their GIT so that they can restore body mass and fat reserves to continue migration. The source of protein used to rebuild the GIT may be exogenous (from food ingested) or endogenous (reallocated from other organs) or both. Because the relative contribution of these sources to rebuild the GIT of migratory birds is not yet known, we mimicked in-flight fasting and then re-feeding in two groups of blackcaps (Sylvia atricapilla), a Palearctic migratory passerine. The birds were fed a diet containing either 3% or 20% protein to simulate different refueling scenarios. During re-feeding, birds received known doses of (15)N-(l)-leucine before we measured the isotope concentrations in GIT and associated digestive organs and in locomotory muscles. We then quantified the extent to which blackcaps rebuilt their GIT with endogenous and/or dietary protein while refeeding after a fast. Our results indicate that blackcaps fed the low-protein diet incorporated less exogenous nitrogen into their tissues than birds fed the 20% protein diet. They also allocated relatively more exogenous protein to the GIT than to pectoral muscle than those birds re-fed with the high-protein diet. However, this compensation was not sufficient for birds eating the low-protein diet to rebuild their intestine at the same rate as the birds re-fed the high-protein diet. We concluded that blackcaps must choose stopover sites at which they can maximize protein intake to minimize the time it takes to rebuild their GIT and, thus, resume migration as soon as possible.

Role of phospholipase Cgamma1 in cell spreading requires association with a beta-Pix/GIT1-containing complex, leading to activation of Cdc42 and Rac1.

PubMed

Jones, Neil P; Katan, Matilda

2007-08-01

The significance of multiprotein signaling complexes in cell motility is becoming increasingly important. We have previously shown that phospholipase Cgamma1 (PLCgamma1) is critical for integrin-mediated cell spreading and motility (N. Jones et al., J. Cell Sci. 118:2695-2706, 2005). In the current study we show that, on a basement membrane-type matrix, PLCgamma1 associates with the adaptor protein GIT1 and the Rac1/Cdc42 guanine exchange factor beta-Pix; GIT1 and beta-Pix form tight complexes independently of PLCgamma1. The association of PLCgamma1 with the complex requires both GIT1 and beta-Pix and the specific array region (gammaSA) of PLCgamma1. Mutations of PLCgamma1 within the gammaSA region reveal that association with this complex is essential for the phosphorylation of PLCgamma1 and the progression to an elongated morphology after integrin engagement. Short interfering RNA (siRNA) depletion of either beta-Pix or GIT1 inhibited cell spreading in a fashion similar to that seen with siRNA against PLCgamma1. Furthermore, siRNA depletion of PLCgamma1, beta-Pix, or GIT1 inhibited Cdc42 and Rac1 activation, while constitutively active forms of Cdc42 or Rac1, but not RhoA, were able to rescue the elongation of these cells. Signaling of the PLCgamma1/GIT1/beta-Pix complex to Cdc42/Rac1 was found to involve the activation of calpains, calcium-dependent proteases. Therefore, we propose that the association of PLCgamma1 with complexes containing GIT1 and beta-Pix is essential for its role in integrin-mediated cell spreading and motility. As a component of this complex, PLCgamma1 is also involved in the activation of Cdc42 and Rac1.

Kinetics of a Tuberculosis-Specific Gamma Interferon Release Assay in Military Personnel with a Positive Tuberculin Skin Test▿ †

PubMed Central

van Brummelen, Sigrid E.; Bauwens, Anja M.; Schlösser, Noël J.; Arend, Sandra M.

2010-01-01

Treatment of latent Mycobacterium tuberculosis infection on the basis of the tuberculin skin test (TST) result is inaccurate due to the false-positive TST results that occur after Mycobacterium bovis BCG vaccination or exposure to nontuberculous mycobacteria (NTM). Gamma interferon release assays (IGRAs) are based on M. tuberculosis-specific antigens. In a previous study among BCG-naïve military employees, a positive TST result after deployment was mostly associated with a negative IGRA result, suggesting exposure to NTM. Data regarding the kinetics of IGRAs are limited and controversial. The present study aimed to reassess the rate of false-positive TST results and to evaluate the kinetics of the Quantiferon TB Gold In-Tube assay (QFT-Git) in military personnel with a positive TST result. QFT-Git was performed at the time of inclusion in the study and was repeated after 2, 6, 12, and 18 or 24 months. Of 192 participants, 17 were recruits and 175 were screened after deployment (n = 169) or because of travel or health care work. Baseline positive QFT-Git results were observed in 7/17 (41.2%) and 12/174 (6.9%) participants, respectively. During follow-up, a negative QFT-Git result remained negative in 163/165 (98.8%) participants. Of 18 subjects with an initial positive QFT-Git result, reversion to a negative result occurred in 1/6 (16%) recruits, whereas it occurred in 8/12 (66%) subjects after deployment or with other risk factors (P = 0.046). The quantitative result was significantly lower in subjects with reversion than in those with consistent positive results (P = 0.017). This study confirmed a low rate of positive QFT-Git results among military personnel with a positive TST result after deployment, supporting the hypothesis of exposure to NTM. Reversion of the majority of initially low-positive QFT-Git results indicates that QFT-Git may be useful for the diagnosis of later reinfections. PMID:20375241

Temporal Stability and the Effect of Transgenerational Transfer on Fecal Microbiota Structure in a Long Distance Migratory Bird

PubMed Central

Kreisinger, Jakub; Kropáčková, Lucie; Petrželková, Adéla; Adámková, Marie; Tomášek, Oldřich; Martin, Jean-François; Michálková, Romana; Albrecht, Tomáš

2017-01-01

Animal bodies are inhabited by a taxonomically and functionally diverse community of symbiotic and commensal microorganisms. From an ecological and evolutionary perspective, inter-individual variation in host-associated microbiota contributes to physiological and immune system variation. As such, host-associated microbiota may be considered an integral part of the host’s phenotype, serving as a substrate for natural selection. This assumes that host-associated microbiota exhibits high temporal stability, however, and that its composition is shaped by trans-generational transfer or heritable host-associated microbiota modulators encoded by the host genome. Although this concept is widely accepted, its crucial assumptions have rarely been tested in wild vertebrate populations. We performed 16S rRNA metabarcoding on an extensive set of fecal microbiota (FM) samples from an insectivorous, long-distance migratory bird, the barn swallow (Hirundo rustica). Our data revealed clear differences in FM among juveniles and adults as regards taxonomic and functional composition, diversity and co-occurrence network complexity. Multiple FM samples from the same juvenile or adult collected within single breeding seasons exhibited higher similarity than expected by chance, as did adult FM samples over two consecutive years. Despite low effect sizes for FM stability over time at the community level, we identified an adult FM subset with relative abundances exhibiting significant temporal consistency, possibly inducing long-term effects on the host phenotype. Our data also indicate a slight maternal (but not paternal) effect on FM composition in social offspring, though this is unlikely to persist into adulthood. We discuss our findings in the context of both evolution and ecology of microbiota vs. host interactions and barn swallow biology. PMID:28220109

Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt.

PubMed

Bisanz, Jordan E; Enos, Megan K; PrayGod, George; Seney, Shannon; Macklaim, Jean M; Chilton, Stephanie; Willner, Dana; Knight, Rob; Fusch, Christoph; Fusch, Gerhard; Gloor, Gregory B; Burton, Jeremy P; Reid, Gregor

2015-08-01

The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice

PubMed Central

Wu, Jianfeng; Wen, Xiaoquan William; Faulk, Christopher; Boehnke, Kevin; Zhang, Huapeng; Dolinoy, Dana C.; Xi, Chuanwu

2016-01-01

Heavy metal pollution is a principle source of environmental contamination. Epidemiological and animal data suggest that early life lead (Pb) exposure results in critical effects on epigenetic gene regulation and child and adult weight trajectories. Using a mouse model of human-relevant exposure, we investigated the effects of perinatal Pb exposure on gut microbiota in adult mice, and the link between gut microbiota and bodyweight changes. Following Pb exposure during gestation and lactation via maternal drinking water, bodyweight in Avy strain wild-type non-agouti (a/a) offspring was tracked through adulthood. Gut microbiota of adult mice were characterized by deep DNA sequencing of bacterial 16S ribosomal RNA genes. Data analyses were stratified by sex and adjusted for litter effects. A Bayesian variable selection algorithm was used to analyze associations between bacterial operational taxonomic units and offspring adult bodyweight. Perinatal Pb exposure was associated with increased adult bodyweight in male (P < .05) but not in female offspring (P = .24). Cultivable aerobes decreased and anaerobes increased in Pb-exposed offspring (P < .005 and P < .05, respectively). Proportions of the 2 predominant phyla (Bacteroidetes and Firmicutes) shifted inversely with Pb exposure, and whole bacterial compositions were significantly different (analysis of molecular variance, P < .05) by Pb exposure without sex bias. In males, changes in gut microbiota were highly associated with adult bodyweight (P = .028; effect size = 2.59). Thus, perinatal Pb exposure results in altered adult gut microbiota regardless of sex, and these changes are highly correlated with increased bodyweight in males. Adult gut microbiota can be shaped by early exposures and may contribute to disease risks in a sex-specific manner. PMID:26962054

CIVET: Continuous Integration, Verification, Enhancement, and Testing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alger, Brian; Gaston, Derek R.; Permann, Cody J

A Git server (GitHub, GitLab, BitBucket) sends event notifications to the Civet server. These are either a " Pull Request" or a "Push" notification. Civet then checks the database to determine what tests need to be run and marks them as ready to run. Civet clients, running on dedicated machines, query the server for available jobs that are ready to run. When a client gets a job it executes the scripts attached to the job and report back to the server the output and exit status. When the client updates the server, the server will also update the Git servermore » with the result of the job, as well as updating the main web page.« less

Group B Streptococcus and the Vaginal Microbiota.

PubMed

Rosen, Geoffrey H; Randis, Tara M; Desai, Purnahamsi V; Sapra, Katherine J; Ma, Bing; Gajer, Pawel; Humphrys, Michael S; Ravel, Jacques; Gelber, Shari E; Ratner, Adam J

2017-09-15

Streptococcus agalactiae (group B Streptococcus [GBS]) is an important neonatal pathogen and emerging cause of disease in adults. The major risk factor for neonatal disease is maternal vaginal colonization. However, little is known about the relationship between GBS and vaginal microbiota. Vaginal lavage samples from nonpregnant women were tested for GBS, and amplicon-based sequencing targeting the 16S ribosomal RNA V3-V4 region was performed. Four hundred twenty-eight of 432 samples met the high-quality read threshold. There was no relationship between GBS carriage and demographic characteristics, α-diversity, or overall vaginal microbiota community state type (CST). Within the non-Lactobacillus-dominant CST IV, GBS positive status was significantly more prevalent in CST IV-A than CST IV-B. Significant clustering by GBS status was noted on principal coordinates analysis, and 18 individual taxa were found to be significantly associated with GBS carriage by linear discriminant analysis. After adjusting for race/ethnicity, 4 taxa were positively associated with GBS, and 6 were negatively associated. Vaginal microbiota CST and α-diversity are not related to GBS status. However, specific microbial taxa are associated with colonization of this important human pathogen, highlighting a potential role for the microbiota in promotion or inhibition of GBS colonization. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

[Bacterial Translocation from Intestine: Microbiological, Immunological and Pathophysiological Aspects].

PubMed

Podoprigora, G I; Kafarskaya, L I; Bainov, N A; Shkoporov, A N

2015-01-01

Bacterial translocation (BT) is both pathology and physiology phenomenon. In healthy newborns it accompanies the process of establishing the autochthonous intestinal microbiota and the host microbiome. In immunodeficiency it can be an aethio-pathogenetic link and a manifestation of infection or septic complications. The host colonization resistance to exogenous microbic colonizers is provided by gastrointestinal microbiota in concert with complex constitutional and adaptive defense mechanisms. BT may be result of barrier dysfunction and self-purification mechanisms involving the host myeloid cell phagocytic system and opsonins. Dynamic cell humoral response to microbial molecular patterns that occurs on the mucous membranes initiates receptorsignalingpathways and cascade ofreactions. Their vector and results are largely determined by cross-reactivity between microbiome and the host genome. Enterocyte barriers interacting with microbiota play leading role in providing adaptive, homeostatic and stress host reactivity. Microcirculatory ischemic tissue alterations and inflammatory reactions increase the intestinal barrier permeability and BT These processes a well as mechanisms for apoptotic cells and bacteria clearance are justified to be of prospective research interest. The inflammatory and related diseases caused by alteration and dysfunction of the intestinal barrier are reasonably considered as diseases of single origin. Maternal microbiota affects theformation of the innate immune system and the microbiota of the newborn, including intestinal commensal translocation during lactation. Deeper understanding of intestinal barrier mechanisms needs complex microbiological, immunological, pathophysiological, etc. investigations using adequate biomodels, including gnotobiotic animals.

Efficacy and safety of nifedipine GITS in Asians with hypertension: results of a post-marketing surveillance study in China.

PubMed

Runlin, Gao; Junren, Zhu; Guozhang, Liu; Weizhong, Zhang; Tingjie, Zhang; Ningling, Sun; Landen, Harald

2007-01-01

This post-marketing surveillance study assessed the efficacy, safety and tolerability of treatment with nifedipine GITS (gastrointestinal therapeutic system) in hypertensive patients with different risk profiles under normal daily practice conditions in China. A total of 7395 patients were included in 564 outpatient clinics. Patients received 30mg or 60mg of nifedipine GITS, which could be up- and down-titrated if necessary. Efficacy, safety and tolerability data were collected at up to three follow-up visits. Patient documentation was completed using standardised and barcoded case report forms. Descriptive and explorative analyses of the data were performed. At endpoint, 93% of patients were receiving 30mg of nifedipine GITS and 7% were taking 60mg of nifedipine GITS. The mean observation period was 9 +/- 7 weeks. At endpoint, the mean BP reduction was 27.7/14.8mm Hg; 43% of patients had a systolic BP <140mm Hg, and 58% had a diastolic BP <90mm Hg. BP control as recommended by international guidelines was achieved in 43.5% of all patients. A total of 3163 patients (42.8%) received additional antihypertensive medication, of which ACE inhibitors were most commonly used (40.7%), followed by beta-adrenoceptor antagonists (25.8%).Twenty-nine patients (0.4%) experienced a total of 39 adverse events. Subjective physicians' assessments of efficacy, tolerability and patient acceptance of nifedipine GITS treatment returned ratings of 'very good' and 'good' in 91-95% of each category. Nifedipine GITS proved to be effective and well tolerated for the treatment of hypertension in 7395 Chinese patients under normal daily practice conditions. The results confirm the findings and experience of previously performed clinical studies.

Advances in gastroenterology--opportunities and challenges for the dental practitioner.

PubMed

Nolan, Anita

2012-04-01

As the oral cavity marks the beginning of the gastrointestinal tract (GIT), it is not surprising that it frequently mirrors disease that occurs lower in the GIT. Increasingly, clinical signs in the oral cavity are recognized as future predictors and prognostic indicators of GIT and, indeed, other systemic disease. This paper discusses recent advances in the overlap area of Oral Medicine and Gastroenterology and the significant role of the dental practitioner in the management of these patients.

A Revised Model for Dosimetry in the Human Small Intestine

DOE Office of Scientific and Technical Information (OSTI.GOV)

John Poston; Nasir U. Bhuiyan; R. Alex Redd

2005-02-28

A new model for an adult human gastrointestinal tract (GIT) has been developed for use in internal dose estimations to the wall of the GIT and to the other organs and tissues of the body from radionuclides deposited in the lumenal contents of the five sections of the GIT. These sections were the esophasgus, stomach, small intestine, upper large intestine, and the lower large intestine. The wall of each section was separated from its lumenal contents.

Comparative genomics of the Bifidobacterium breve taxon.

PubMed

Bottacini, Francesca; O'Connell Motherway, Mary; Kuczynski, Justin; O'Connell, Kerry Joan; Serafini, Fausta; Duranti, Sabrina; Milani, Christian; Turroni, Francesca; Lugli, Gabriele Andrea; Zomer, Aldert; Zhurina, Daria; Riedel, Christian; Ventura, Marco; van Sinderen, Douwe

2014-03-01

Bifidobacteria are commonly found as part of the microbiota of the gastrointestinal tract (GIT) of a broad range of hosts, where their presence is positively correlated with the host's health status. In this study, we assessed the genomes of thirteen representatives of Bifidobacterium breve, which is not only a frequently encountered component of the (adult and infant) human gut microbiota, but can also be isolated from human milk and vagina. In silico analysis of genome sequences from thirteen B. breve strains isolated from different environments (infant and adult faeces, human milk, human vagina) shows that the genetic variability of this species principally consists of hypothetical genes and mobile elements, but, interestingly, also genes correlated with the adaptation to host environment and gut colonization. These latter genes specify the biosynthetic machinery for sortase-dependent pili and exopolysaccharide production, as well as genes that provide protection against invasion of foreign DNA (i.e. CRISPR loci and restriction/modification systems), and genes that encode enzymes responsible for carbohydrate fermentation. Gene-trait matching analysis showed clear correlations between known metabolic capabilities and characterized genes, and it also allowed the identification of a gene cluster involved in the utilization of the alcohol-sugar sorbitol. Genome analysis of thirteen representatives of the B. breve species revealed that the deduced pan-genome exhibits an essentially close trend. For this reason our analyses suggest that this number of B. breve representatives is sufficient to fully describe the pan-genome of this species. Comparative genomics also facilitated the genetic explanation for differential carbon source utilization phenotypes previously observed in different strains of B. breve.

Clostridium perfringens epsilon toxin inhibits the gastrointestinal transit in mice.

PubMed

Losada-Eaton, D M; Fernandez-Miyakawa, M E

2010-12-01

Epsilon toxin produced by Clostridium perfringens type B and D is a potent toxin that is responsible for a highly fatal enterotoxemia in sheep and goats. In vitro, epsilon toxin produces contraction of the rat ileum as the result of an indirect action, presumably mediated through the autonomic nervous system. To examine the impact of epsilon toxin in the intestinal transit, gastric emptying (GE) and gastrointestinal transit (GIT) were evaluated after intravenous and oral administration of epsilon toxin in mice. Orally administered epsilon toxin produced a delay on the GIT. Inhibition of the small intestinal transit was observed as early as 1 h after the toxin was administered orally but the effects were not observed after 1 week. Epsilon toxin also produced an inhibition in GE and a delay on the GIT when relatively high toxin concentrations were given intravenously. These results indicate that epsilon toxin administered orally or intravenously to mice transitorily inhibits the GIT. The delay in the GIT induced by epsilon toxin could be relevant in the pathogenesis of C. perfringens type B and D enterotoxemia. Copyright © 2010 Elsevier Ltd. All rights reserved.

Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients.

PubMed

Zhou, Xiao-Yan; Li, Ming; Li, Xia; Long, Xin; Zuo, Xiu-Li; Hou, Xiao-Hua; Cong, Ying-Zi; Li, Yan-Qing

2016-06-14

To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research.

2,4-Dinitrofluorobenzene-induced contact hypersensitivity response in NC/Nga mice fed fructo-oligosaccharide.

PubMed

Fujiwara, Reiko; Sasajima, Naho; Takemura, Naoki; Ozawa, Keisuke; Nagasaka, Yuki; Okubo, Takuma; Sahasakul, Yuraporn; Watanabe, Jun; Sonoyama, Kei

2010-01-01

Strategies to manipulate gut microbiota in infancy have been considered to prevent the development of allergic diseases later in life. We previously demonstrated that maternal dietary supplementation with fructo-oligosaccharide (FOS) during pregnancy and lactation modulated the composition of gut microbiota and diminished the severity of spontaneously developing atopic dermatitis-like skin lesions in the offspring of NC/Nga mice. The present study tested whether dietary FOS affects contact hypersensitivity (CHS), another model for allergic skin disease, in NC/Nga mice. In experiment 1, 5-wk-old female NC/Nga mice were fed diets either with or without FOS supplementation for 3 wk and then received 2,4-dinitrofluorobenzene (DNFB) on the ear auricle 5 times at 7-d intervals. FOS supplementation reduced CHS response as demonstrated by ear swelling. Quantitative RT-PCR analysis showed that mRNA levels for interleukin (IL)-10, IL-12p40, and IL-17 in the lesional ear skin were significantly lower in mice fed FOS. In experiment 2, female NC/Nga mice were fed diets either with or without FOS during pregnancy and lactation. After weaning, offspring were fed the diets supplemented with or without FOS. Three weeks after weaning, offspring received DNFB on the ear auricle 4 times at 7-d intervals. Although FOS supplementation after weaning reduced ear swelling, maternal FOS consumption was ineffective in offspring. The present data suggest that dietary FOS reduces CHS while maternal FOS consumption is ineffective in offspring of DNFB-treated NC/Nga mice.

Stress during pregnancy alters temporal and spatial dynamics of the maternal and offspring microbiome in a sex-specific manner

PubMed Central

Jašarević, Eldin; Howard, Christopher D.; Misic, Ana M.; Beiting, Daniel P.; Bale, Tracy L.

2017-01-01

The microbiome is a regulator of host immunity, metabolism, neurodevelopment, and behavior. During early life, bacterial communities within maternal gut and vaginal compartments can have an impact on directing these processes. Maternal stress experience during pregnancy may impact offspring development by altering the temporal and spatial dynamics of the maternal microbiome during pregnancy. To examine the hypothesis that maternal stress disrupts gut and vaginal microbial dynamics during critical prenatal and postnatal windows, we used high-resolution 16S rRNA marker gene sequencing to examine outcomes in our mouse model of early prenatal stress. Consistent with predictions, maternal fecal communities shift across pregnancy, a process that is disrupted by stress. Vaginal bacterial community structure and composition exhibit lasting disruption following stress exposure. Comparison of maternal and offspring microbiota revealed that similarities in bacterial community composition was predicted by a complex interaction between maternal body niche and offspring age and sex. Importantly, early prenatal stress influenced offspring bacterial community assembly in a temporal and sex-specific manner. Taken together, our results demonstrate that early prenatal stress may influence offspring development through converging modifications to gut microbial composition during pregnancy and transmission of dysbiotic vaginal microbiome at birth. PMID:28266645

The human milk microbiota: origin and potential roles in health and disease.

PubMed

Fernández, Leónides; Langa, Susana; Martín, Virginia; Maldonado, Antonio; Jiménez, Esther; Martín, Rocío; Rodríguez, Juan M

2013-03-01

Human milk has been traditionally considered sterile; however, recent studies have shown that it represents a continuous supply of commensal, mutualistic and/or potentially probiotic bacteria to the infant gut. Culture-dependent and -independent techniques have revealed the dominance of staphylococci, streptococci, lactic acid bacteria and bifidobacteria in this biological fluid, and their role on the colonization of the infant gut. These bacteria could protect the infant against infections and contribute to the maturation of the immune system, among other functions. Different studies suggest that some bacteria present in the maternal gut could reach the mammary gland during late pregnancy and lactation through a mechanism involving gut monocytes. Thus, modulation of maternal gut microbiota during pregnancy and lactation could have a direct effect on infant health. On the other hand, mammary dysbiosis may lead to mastitis, a condition that represents the first medical cause for undesired weaning. Selected strains isolated from breast milk can be good candidates for use as probiotics. In this review, their potential uses for the treatment of mastitis and to inhibit mother-to-infant transfer of HIV are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis

PubMed Central

Garrett, Wendy S.; Gallini, Carey A.; Yatsunenko, Tanya; Michaud, Monia; DuBois, Andrea; Delaney, Mary L.; Punit, Shivesh; Karlsson, Maria; Bry, Lynn; Glickman, Jonathan N.; Gordon, Jeffrey I.; Onderdonk, Andrew B.; Glimcher, Laurie H.

2010-01-01

SUMMARY In inflammatory bowel disease, the relationship between a host and gut microbial community goes awry. We have characterized the fecal microbial communities in a mouse IBD model driven by T-bet deficiency in the innate immune system. 16S rRNA-based analysis of T-bet−/− × Rag2−/− and Rag2−/− mice revealed distinctive communities that correlate with host genotype. Culture-based surveys, invasion assays, antibiotic treatment, and TNF-α blockade disclosed that the presence of Klebsiella pneumoniae and Proteus mirabilis correlates with colitis in T-bet−/− × Rag2−/− animals, and that T-bet−/− × Rag2−/− derived strains can elicit colitis in Rag2−/− and wild-type adults. Cross-fostering experiments provided evidence for the role of these organisms in maternal transmission of disease. This model provides a foundation for defining how gut microbial communities work in concert with specific culturable colitogenic agents to cause IBD, and a foundation for conducting proof-of-concept tests of new preventative or therapeutic measures directed at components of the gut microbiota and/or host. PMID:20833380

A distinct and divergent lineage of genomic island-associated Type IV Secretion Systems in Legionella.

PubMed

Wee, Bryan A; Woolfit, Megan; Beatson, Scott A; Petty, Nicola K

2013-01-01

Legionella encodes multiple classes of Type IV Secretion Systems (T4SSs), including the Dot/Icm protein secretion system that is essential for intracellular multiplication in amoebal and human hosts. Other T4SSs not essential for virulence are thought to facilitate the acquisition of niche-specific adaptation genes including the numerous effector genes that are a hallmark of this genus. Previously, we identified two novel gene clusters in the draft genome of Legionella pneumophila strain 130b that encode homologues of a subtype of T4SS, the genomic island-associated T4SS (GI-T4SS), usually associated with integrative and conjugative elements (ICE). In this study, we performed genomic analyses of 14 homologous GI-T4SS clusters found in eight publicly available Legionella genomes and show that this cluster is unusually well conserved in a region of high plasticity. Phylogenetic analyses show that Legionella GI-T4SSs are substantially divergent from other members of this subtype of T4SS and represent a novel clade of GI-T4SSs only found in this genus. The GI-T4SS was found to be under purifying selection, suggesting it is functional and may play an important role in the evolution and adaptation of Legionella. Like other GI-T4SSs, the Legionella clusters are also associated with ICEs, but lack the typical integration and replication modules of related ICEs. The absence of complete replication and DNA pre-processing modules, together with the presence of Legionella-specific regulatory elements, suggest the Legionella GI-T4SS-associated ICE is unique and may employ novel mechanisms of regulation, maintenance and excision. The Legionella GI-T4SS cluster was found to be associated with several cargo genes, including numerous antibiotic resistance and virulence factors, which may confer a fitness benefit to the organism. The in-silico characterisation of this new T4SS furthers our understanding of the diversity of secretion systems involved in the frequent horizontal gene transfers that allow Legionella to adapt to and exploit diverse environmental niches.

A Distinct and Divergent Lineage of Genomic Island-Associated Type IV Secretion Systems in Legionella

PubMed Central

Wee, Bryan A.; Woolfit, Megan; Beatson, Scott A.; Petty, Nicola K.

2013-01-01

Legionella encodes multiple classes of Type IV Secretion Systems (T4SSs), including the Dot/Icm protein secretion system that is essential for intracellular multiplication in amoebal and human hosts. Other T4SSs not essential for virulence are thought to facilitate the acquisition of niche-specific adaptation genes including the numerous effector genes that are a hallmark of this genus. Previously, we identified two novel gene clusters in the draft genome of Legionella pneumophila strain 130b that encode homologues of a subtype of T4SS, the genomic island-associated T4SS (GI-T4SS), usually associated with integrative and conjugative elements (ICE). In this study, we performed genomic analyses of 14 homologous GI-T4SS clusters found in eight publicly available Legionella genomes and show that this cluster is unusually well conserved in a region of high plasticity. Phylogenetic analyses show that Legionella GI-T4SSs are substantially divergent from other members of this subtype of T4SS and represent a novel clade of GI-T4SSs only found in this genus. The GI-T4SS was found to be under purifying selection, suggesting it is functional and may play an important role in the evolution and adaptation of Legionella. Like other GI-T4SSs, the Legionella clusters are also associated with ICEs, but lack the typical integration and replication modules of related ICEs. The absence of complete replication and DNA pre-processing modules, together with the presence of Legionella-specific regulatory elements, suggest the Legionella GI-T4SS-associated ICE is unique and may employ novel mechanisms of regulation, maintenance and excision. The Legionella GI-T4SS cluster was found to be associated with several cargo genes, including numerous antibiotic resistance and virulence factors, which may confer a fitness benefit to the organism. The in-silico characterisation of this new T4SS furthers our understanding of the diversity of secretion systems involved in the frequent horizontal gene transfers that allow Legionella to adapt to and exploit diverse environmental niches. PMID:24358157

Water system is a controlling variable modulating bacterial diversity of gastrointestinal tract and performance in rainbow trout.

PubMed

Betiku, Omolola C; Yeoman, Carl J; Gaylord, T Gibson; Americus, Benjamin; Olivo, Sarah; Duff, Glenn C; Sealey, Wendy M

2018-01-01

A two-phase feeding study evaluating performance of rainbow trout and comparing luminal and mucosal gastrointestinal tract (GIT) bacterial community compositions when fed two alternative protein diets in two rearing systems was conducted. Alternative protein diets (animal protein and plant protein diets) balanced with crystalline amino acids: lysine, methionine and threonine or unbalanced, were fed to rainbow trout in two separate water systems (recirculating (RR) and flow-through (FF)) for a period of 16 weeks. The four diets, each contained 38% digestible protein and 20% fats, were fed to rainbow trout with an average weight of 12.02 ± 0.61 g, and sorted at 30 fish/tank and 12 tanks per dietary treatment. Phase 1 lasted for 8 weeks after which fish from each tank were randomly divided, with one-half moved to new tanks of the opposing system (i.e. from RR to FF and vice versa). The remaining halves were retained in their initial tank and system, and fed their original diets for another 8 weeks (phase 2). After the 16th week, 3 fish/tank were sampled for each of proximate analysis, body indexes and 16S rRNA analysis of GIT microbiota. Fish weight (P = 0.0008, P = 0.0030, P<0.0010) and body fat (P = 0.0008, P = 0.0041, P = 0.0177) were significantly affected by diet, diet quality (balanced or unbalanced) and system, respectively. Feed intake (P = 0.0008) and body energy (P<0.0010) were altered by system. Body indexes were not affected by dietary treatment and water systems. Compositional dissimilarities existed between samples from the rearing water and GIT locations (ANOSIM: (R = 0.29, P = 0.0010), PERMANOVA: R = 0.39, P = 0.0010), but not in dietary samples (ANOSIM: R = 0.004, P = 0.3140, PERMANOVA: R = 0.008, P = 0.4540). Bacteria were predominantly from the phyla Proteobacteria, Firmicutes and Bacteroidetes. Their abundance differed with more dissimilarity in the luminal samples (ANOSIM: R = 0.40, P = 0.0010, PERMANOVA: R = 0.56, P = 0.0010) than those from the mucosal intestine (ANOSIM: R = 0.37, P = 0.0010, PERMANOVA: R = 0.41, P = 0.0010). Bacteria generally associated with carbohydrate and certain amino acids metabolism were observed in the mucosal intestine while rearing water appeared to serve as the main route of colonization of Aeromonas and Acinetobacter in the rainbow trout.

Water system is a controlling variable modulating bacterial diversity of gastrointestinal tract and performance in rainbow trout

PubMed Central

Yeoman, Carl J.; Gaylord, T. Gibson; Americus, Benjamin; Olivo, Sarah; Duff, Glenn C.; Sealey, Wendy M.

2018-01-01

A two-phase feeding study evaluating performance of rainbow trout and comparing luminal and mucosal gastrointestinal tract (GIT) bacterial community compositions when fed two alternative protein diets in two rearing systems was conducted. Alternative protein diets (animal protein and plant protein diets) balanced with crystalline amino acids: lysine, methionine and threonine or unbalanced, were fed to rainbow trout in two separate water systems (recirculating (RR) and flow-through (FF)) for a period of 16 weeks. The four diets, each contained 38% digestible protein and 20% fats, were fed to rainbow trout with an average weight of 12.02 ± 0.61 g, and sorted at 30 fish/tank and 12 tanks per dietary treatment. Phase 1 lasted for 8 weeks after which fish from each tank were randomly divided, with one-half moved to new tanks of the opposing system (i.e. from RR to FF and vice versa). The remaining halves were retained in their initial tank and system, and fed their original diets for another 8 weeks (phase 2). After the 16th week, 3 fish/tank were sampled for each of proximate analysis, body indexes and 16S rRNA analysis of GIT microbiota. Fish weight (P = 0.0008, P = 0.0030, P<0.0010) and body fat (P = 0.0008, P = 0.0041, P = 0.0177) were significantly affected by diet, diet quality (balanced or unbalanced) and system, respectively. Feed intake (P = 0.0008) and body energy (P<0.0010) were altered by system. Body indexes were not affected by dietary treatment and water systems. Compositional dissimilarities existed between samples from the rearing water and GIT locations (ANOSIM: (R = 0.29, P = 0.0010), PERMANOVA: R = 0.39, P = 0.0010), but not in dietary samples (ANOSIM: R = 0.004, P = 0.3140, PERMANOVA: R = 0.008, P = 0.4540). Bacteria were predominantly from the phyla Proteobacteria, Firmicutes and Bacteroidetes. Their abundance differed with more dissimilarity in the luminal samples (ANOSIM: R = 0.40, P = 0.0010, PERMANOVA: R = 0.56, P = 0.0010) than those from the mucosal intestine (ANOSIM: R = 0.37, P = 0.0010, PERMANOVA: R = 0.41, P = 0.0010). Bacteria generally associated with carbohydrate and certain amino acids metabolism were observed in the mucosal intestine while rearing water appeared to serve as the main route of colonization of Aeromonas and Acinetobacter in the rainbow trout. PMID:29664968

210Polonium bioaccessibility assessment in algae for human consumption: An in vitro gastrointestinal digestion method.

PubMed

Desideri, Donatella; Meli, Maria Assunta; Roselli, Carla; Feduzi, Laura; Ugolini, Lucia

2017-01-01

The occurrence and mobility of natural radioactive element as 210 Polonium ( 210 Po) in 13 commercial algae consumed in Italy by humans were determined because the effects on human health need to take into account the bioavailability of these elements. The simulation of gastrointestinal (GIT) digestion was divided into three stages and was accomplished using three different artificial solutions: saliva, gastric, and synthetic bile-pancreas solution. The same sample was treated in two different ways: a) only gastric digestion and b) complete GIT digestion (gastric digestion followed by bile-pancreas solution). The difference between Po gastric mobility with respect to that found for GIT digestion was not significant; in fact, Po mobility exhibited a mean value 17.2 ± 15.1% and 19.5 ± 11.5% for gastric and GIT digestion, respectively.

LHCb migration from Subversion to Git

NASA Astrophysics Data System (ADS)

Clemencic, M.; Couturier, B.; Closier, J.; Cattaneo, M.

2017-10-01

Due to user demand and to support new development workflows based on code review and multiple development streams, LHCb decided to port the source code management from Subversion to Git, using the CERN GitLab hosting service. Although tools exist for this kind of migration, LHCb specificities and development models required careful planning of the migration, development of migration tools, changes to the development model, and redefinition of the release procedures. Moreover we had to support a hybrid situation with some software projects hosted in Git and others still in Subversion, or even branches of one projects hosted in different systems. We present the way we addressed the special LHCb requirements, the technical details of migrating large non standard Subversion repositories, and how we managed to smoothly migrate the software projects following the schedule of each project manager.

From the "little brain" gastrointestinal infection to the "big brain" neuroinflammation: a proposed fast axonal transport pathway involved in multiple sclerosis.

PubMed

Deretzi, Georgia; Kountouras, Jannis; Grigoriadis, Nikolaos; Zavos, Christos; Chatzigeorgiou, Stavros; Koutlas, Evangelos; Tsiptsios, Iakovos

2009-11-01

The human central nervous system (CNS) is targeted by different pathogens which, apart from pathogens' intranasal inoculation or trafficking into the brain through infected blood cells, may use a distinct pathway to bypass the blood-brain barrier by using the gastrointestinal tract (GIT) retrograde axonal transport through sensory or motor fibres. The recent findings regarding the enteric nervous system (often called the "little brain") similarities with CNS and GIT axonal transport of infections resulting in CNS neuroinflammation are mainly reviewed in this article. We herein propose that the GIT is the vulnerable area through which pathogens (such as Helicobacter pylori) may influence the brain and induce multiple sclerosis pathologies, mainly via the fast axonal transport by the afferent neurones connecting the GIT to brain.

The Gastrointestinal Microbiome and Musculoskeletal Diseases: A Beneficial Role for Probiotics and Prebiotics

PubMed Central

Vitetta, Luis; Coulson, Samantha; Linnane, Anthony W.; Butt, Henry

2013-01-01

Natural medicines are an attractive option for patients diagnosed with common and debilitating musculoskeletal diseases such as Osteoarthritis (OA) or Rheumatoid Arthritis (RA). The high rate of self-medication with natural products is due to (1) lack of an available cure and (2) serious adverse events associated with chronic use of pharmaceutical medications in particular non-steroidal anti-inflammatory drugs (NSAIDs) and high dose paracetamol. Pharmaceuticals to treat pain may disrupt gastrointestinal (GIT) barrier integrity inducing GIT inflammation and a state of and hyper-permeability. Probiotics and prebiotics may comprise plausible therapeutic options that can restore GIT barrier functionality and down regulate pro-inflammatory mediators by modulating the activity of, for example, Clostridia species known to induce pro-inflammatory mediators. The effect may comprise the rescue of gut barrier physiological function. A postulated requirement has been the abrogation of free radical formation by numerous natural antioxidant molecules in order to improve musculoskeletal health outcomes, this notion in our view, is in error. The production of reactive oxygen species (ROS) in different anatomical environments including the GIT by the epithelial lining and the commensal microbe cohort is a regulated process, leading to the formation of hydrogen peroxide which is now well recognized as an essential second messenger required for normal cellular homeostasis and physiological function. The GIT commensal profile that tolerates the host does so by regulating pro-inflammatory and anti-inflammatory GIT mucosal actions through the activity of ROS signaling thereby controlling the activity of pathogenic bacterial species. PMID:25437335

The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases.

PubMed

Chen, Chen; Song, Xiaolei; Wei, Weixia; Zhong, Huanzi; Dai, Juanjuan; Lan, Zhou; Li, Fei; Yu, Xinlei; Feng, Qiang; Wang, Zirong; Xie, Hailiang; Chen, Xiaomin; Zeng, Chunwei; Wen, Bo; Zeng, Liping; Du, Hui; Tang, Huiru; Xu, Changlu; Xia, Yan; Xia, Huihua; Yang, Huanming; Wang, Jian; Wang, Jun; Madsen, Lise; Brix, Susanne; Kristiansen, Karsten; Xu, Xun; Li, Junhua; Wu, Ruifang; Jia, Huijue

2017-10-17

Reports on bacteria detected in maternal fluids during pregnancy are typically associated with adverse consequences, and whether the female reproductive tract harbours distinct microbial communities beyond the vagina has been a matter of debate. Here we systematically sample the microbiota within the female reproductive tract in 110 women of reproductive age, and examine the nature of colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find distinct microbial communities in cervical canal, uterus, fallopian tubes and peritoneal fluid, differing from that of the vagina. The results reflect a microbiota continuum along the female reproductive tract, indicative of a non-sterile environment. We also identify microbial taxa and potential functions that correlate with the menstrual cycle or are over-represented in subjects with adenomyosis or infertility due to endometriosis. The study provides insight into the nature of the vagino-uterine microbiome, and suggests that surveying the vaginal or cervical microbiota might be useful for detection of common diseases in the upper reproductive tract.Whether the female reproductive tract harbours distinct microbiomes beyond the vagina has been a matter of debate. Here, the authors show a subject-specific continuity in microbial communities at six sites along the female reproductive tract, indicative of a non-sterile environment.

Establishment of Normal Gut Microbiota Is Compromised under Excessive Hygiene Conditions

PubMed Central

Schmidt, Bettina; Mulder, Imke E.; Musk, Corran C.; Aminov, Rustam I.; Lewis, Marie; Stokes, Christopher R.; Bailey, Mick; Prosser, James I.; Gill, Bhupinder P.; Pluske, John R.; Kelly, Denise

2011-01-01

Background Early gut colonization events are purported to have a major impact on the incidence of infectious, inflammatory and autoimmune diseases in later life. Hence, factors which influence this process may have important implications for both human and animal health. Previously, we demonstrated strong influences of early-life environment on gut microbiota composition in adult pigs. Here, we sought to further investigate the impact of limiting microbial exposure during early life on the development of the pig gut microbiota. Methodology/Principal Findings Outdoor- and indoor-reared animals, exposed to the microbiota in their natural rearing environment for the first two days of life, were transferred to an isolator facility and adult gut microbial diversity was analyzed by 16S rRNA gene sequencing. From a total of 2,196 high-quality 16S rRNA gene sequences, 440 phylotypes were identified in the outdoor group and 431 phylotypes in the indoor group. The majority of clones were assigned to the four phyla Firmicutes (67.5% of all sequences), Proteobacteria (17.7%), Bacteroidetes (13.5%) and to a lesser extent, Actinobacteria (0.1%). Although the initial maternal and environmental microbial inoculum of isolator-reared animals was identical to that of their naturally-reared littermates, the microbial succession and stabilization events reported previously in naturally-reared outdoor animals did not occur. In contrast, the gut microbiota of isolator-reared animals remained highly diverse containing a large number of distinct phylotypes. Conclusions/Significance The results documented here indicate that establishment and development of the normal gut microbiota requires continuous microbial exposure during the early stages of life and this process is compromised under conditions of excessive hygiene. PMID:22164261

Effect of prolonged incubation time on results of the QuantiFERON TB gold in-tube assay for diagnosis of latent tuberculosis infection.

PubMed

Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo; Yim, Jae-Joon

2013-09-01

Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results.

Effect of Prolonged Incubation Time on Results of the QuantiFERON TB Gold In-Tube Assay for Diagnosis of Latent Tuberculosis Infection

PubMed Central

Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo

2013-01-01

Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results. PMID:23825190

Lactobacillus reuteri suppresses E. coli O157:H7 in bovine ruminal fluid: Toward a pre-slaughter strategy to improve food safety?

PubMed Central

Bertin, Yolande; Laurier, Marie; Durand, Alexandra; Duchez, David; Segura, Audrey; Thévenot-Sergentet, Delphine; Baruzzi, Federico; Chaucheyras-Durand, Frédérique; Forano, Evelyne

2017-01-01

The bovine gastrointestinal tract (GIT) is the main reservoir for enterohaemorrhagic Escherichia coli (EHEC) responsible for food-borne infections. Therefore, it is crucial to develop strategies, such as EHEC suppression by antagonistic microorganisms, to reduce EHEC survival in the GIT of cattle and to limit shedding and food contamination. Most human-derived Lactobacillus reuteri strains produce hydroxypropionaldehyde (HPA), an antimicrobial compound, during anaerobic reduction of glycerol. The capacity of L. reuteri LB1-7, a strain isolated from raw bovine milk, to produce HPA and its antimicrobial activity against an O157:H7 EHEC strain (FCH6) were evaluated in bovine rumen fluid (RF) under strict anaerobiosis. EHEC was totally suppressed when incubated in RF inoculated with L. reuteri LB1-7 and supplemented with 80 mM glycerol (RF-Glyc80). The addition of LB1-7 or glycerol alone did not modify EHEC survival in RF. Glycerol was converted to HPA (up to 14 mM) by LB1-7 during incubation in RF-Glyc80, and HPA production appeared to be responsible for EHEC suppression. The bactericidal activity of L. reuteri LB1-7, the concentration of glycerol required and the level of HPA produced depended on physiological and ecological environments. In vitro experiments also showed that EHEC inoculated in rumen fluid and exposed to L. reuteri and glycerol had a very limited growth in rectal contents. However, L. reuteri exerted an antimicrobial activity against the rumen endogenous microbiota and perturbed feedstuff degradation in the presence of glycerol. The potential administration of L. reuteri and glycerol in view of application to finishing beef cattle at the time of slaughter is discussed. Further in vivo studies will be important to confirm the efficiency of L. reuteri and glycerol supplementation against EHEC shedding in ruminants. PMID:29091926

Lactobacillus reuteri suppresses E. coli O157:H7 in bovine ruminal fluid: Toward a pre-slaughter strategy to improve food safety?

PubMed

Bertin, Yolande; Habouzit, Chloé; Dunière, Lysiane; Laurier, Marie; Durand, Alexandra; Duchez, David; Segura, Audrey; Thévenot-Sergentet, Delphine; Baruzzi, Federico; Chaucheyras-Durand, Frédérique; Forano, Evelyne

2017-01-01

The bovine gastrointestinal tract (GIT) is the main reservoir for enterohaemorrhagic Escherichia coli (EHEC) responsible for food-borne infections. Therefore, it is crucial to develop strategies, such as EHEC suppression by antagonistic microorganisms, to reduce EHEC survival in the GIT of cattle and to limit shedding and food contamination. Most human-derived Lactobacillus reuteri strains produce hydroxypropionaldehyde (HPA), an antimicrobial compound, during anaerobic reduction of glycerol. The capacity of L. reuteri LB1-7, a strain isolated from raw bovine milk, to produce HPA and its antimicrobial activity against an O157:H7 EHEC strain (FCH6) were evaluated in bovine rumen fluid (RF) under strict anaerobiosis. EHEC was totally suppressed when incubated in RF inoculated with L. reuteri LB1-7 and supplemented with 80 mM glycerol (RF-Glyc80). The addition of LB1-7 or glycerol alone did not modify EHEC survival in RF. Glycerol was converted to HPA (up to 14 mM) by LB1-7 during incubation in RF-Glyc80, and HPA production appeared to be responsible for EHEC suppression. The bactericidal activity of L. reuteri LB1-7, the concentration of glycerol required and the level of HPA produced depended on physiological and ecological environments. In vitro experiments also showed that EHEC inoculated in rumen fluid and exposed to L. reuteri and glycerol had a very limited growth in rectal contents. However, L. reuteri exerted an antimicrobial activity against the rumen endogenous microbiota and perturbed feedstuff degradation in the presence of glycerol. The potential administration of L. reuteri and glycerol in view of application to finishing beef cattle at the time of slaughter is discussed. Further in vivo studies will be important to confirm the efficiency of L. reuteri and glycerol supplementation against EHEC shedding in ruminants.

Analysis of bacterial community shifts in the gastrointestinal tract of pigs fed diets supplemented with β-glucan from Laminaria digitata, Laminaria hyperborea and Saccharomyces cerevisiae.

PubMed

Murphy, P; Dal Bello, F; O'Doherty, J; Arendt, E K; Sweeney, T; Coffey, A

2013-07-01

This study was designed to evaluate the effects of algal and yeast β-glucans on the porcine gastrointestinal microbiota, specifically the community of Lactobacillus, Bifidobacterium and coliforms. A total of 48 pigs were fed four diets over a 28-day period to determine the effect that each had on these communities. The control diet consisted of wheat and soya bean meal. The remaining three diets contained wheat and soya bean meal supplemented with β-glucan at 250 g/tonne from Laminaria digitata, Laminaria hyperborea or Saccharomyces cerevisiae. Faecal samples were collected from animals before feeding each diet and after the feeding period. The animals were slaughtered the following day and samples were collected from the stomach, ileum, caecum, proximal colon and distal colon. Alterations in Lactobacillus in the gastrointestinal tract (GIT) were analysed using denaturing gradient gel electrophoresis (DGGE) profiles generated by group-specific 16S rRNA gene PCR amplicons. Plate count analysis was also performed to quantify total coliforms. DGGE profiles indicated that all β-glucan diets provoked the emergence of a richer community of Lactobacillus. The richest community of lactobacilli emerged after feeding L. digitata (LD β-glucan). Plate count analysis revealed that the L. hyperborea (LH β-glucan) diet had a statistically significant effect on the coliform counts in the proximal colon in comparison with the control diet. β-glucan from L. digitata and S. cerevisiae also generally reduced coliforms but to a lesser extent. Nevertheless, the β-glucan diets did not significantly reduce levels of Lactobacillus or Bifidobacterium. DGGE analysis of GIT samples indicated that the three β-glucan diets generally promoted the establishment of a more varied range of Lactobacillus species in the caecum, proximal and distal colon. The LH β-glucan had the most profound reducing effect on coliform counts when compared with the control diet and diets supplemented with L. digitata and S. cerevisiae β-glucans.

Network-assisted target identification for haploinsufficiency and homozygous profiling screens

PubMed Central

Wang, Sheng

2017-01-01

Chemical genomic screens have recently emerged as a systematic approach to drug discovery on a genome-wide scale. Drug target identification and elucidation of the mechanism of action (MoA) of hits from these noisy high-throughput screens remain difficult. Here, we present GIT (Genetic Interaction Network-Assisted Target Identification), a network analysis method for drug target identification in haploinsufficiency profiling (HIP) and homozygous profiling (HOP) screens. With the drug-induced phenotypic fitness defect of the deletion of a gene, GIT also incorporates the fitness defects of the gene’s neighbors in the genetic interaction network. On three genome-scale yeast chemical genomic screens, GIT substantially outperforms previous scoring methods on target identification on HIP and HOP assays, respectively. Finally, we showed that by combining HIP and HOP assays, GIT further boosts target identification and reveals potential drug’s mechanism of action. PMID:28574983

Improving the efficiency of feed utilization in poultry by selection. 1. Genetic parameters of anatomy of the gastro-intestinal tract and digestive efficiency.

PubMed

de Verdal, Hugues; Narcy, Agnès; Bastianelli, Denis; Chapuis, Hervé; Même, Nathalie; Urvoix, Séverine; Le Bihan-Duval, Elisabeth; Mignon-Grasteau, Sandrine

2011-07-06

Feed costs represent about 70% of the costs of raising broilers. The main way to decrease these costs is to improve feed efficiency by modification of diet formulation, but one other possibility would be to use genetic selection. Understanding the genetic architecture of the gastro-intestinal tract (GIT) and the impact of the selection criterion on the GIT would be of particular interest. We therefore studied the genetic parameters of AMEn (Apparent metabolisable energy corrected for zero nitrogen balance), feed efficiency, and GIT traits in chickens.Genetic parameters were estimated for 630 broiler chickens of the eighth generation of a divergent selection experiment on AMEn. Birds were reared until 23 d of age and fed a wheat-based diet. The traits measured were body weight (BW), feed conversion ratio (FCR), AMEn, weights of crop, liver, gizzard and proventriculus, and weight, length and density of the duodenum, jejunum and ileum. The heritability estimates of BW, FCR and AMEn were moderate. The heritability estimates were higher for the GIT characteristics except for the weights of the proventriculus and liver. Gizzard weight was negatively correlated with density (weight to length ratio) of duodenum, jejunum and ileum. Proventriculus and gizzard weights were more strongly correlated with AMEn than with FCR, which was not the case for intestine weight and density. GIT traits were largely dependent on genetics and that selecting on AMEn or FCR would modify them. Phenotypic observations carried out in the divergent lines selected on AMEn were consistent with estimated genetic correlations between AMEn and GIT traits.

Free-living protozoa in the gastrointestinal tract and feces of pigs: Exploration of an unknown world and towards a protocol for the recovery of free-living protozoa.

PubMed

Chavatte, N; Lambrecht, E; Van Damme, I; Sabbe, K; Houf, K

2016-07-30

Associations with free-living protozoa (FLP) have been implicated in the persistence of foodborne pathogenic bacteria in food-related environments. To date however no information is available on the presence of FLP in the gastrointestinal tract (GIT) of pigs, which represents an important reservoir for zoonotic foodborne bacteria and hence a potential location for associations with FLP. This is at least partly due to the lack of adequate protocols to recover FLP from intestinal content and feces. In the present study different protocols to recover FLP from the porcine GIT and feces were tested. The most effective protocols were then applied to explore the presence of live FLP in the pig GIT and feces. A filtration based protocol was identified as the most suitable method to recover viable FLP from the porcine GIT and feces. Cultivable FLP were recovered from different parts of the GIT, suggesting at least a transient presence of FLP in this habitat. Free-living amoebae species (Acanthamoeba spp., Hyperamoeba sp., Vannella sp., Vermamoeba vermiformis, hartmannellids and vahlkampfiids) but also ciliates (Colpoda sp. and Tetrahymena/Glaucoma lookalike) and flagellates (cercomonads, bodonids and glissomonads) were recovered and cultured from pig intestinal content. Acanthamoeba hatchetti and Filamoeba sinensis were isolated for the first time from pig intestinal content. Despite high gastric acidity, non-cyst forming amoeba species were also detected which suggests survival of their trophozoites in the animal GIT. Copyright © 2016 Elsevier B.V. All rights reserved.

Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice.

PubMed

Wu, Jianfeng; Wen, Xiaoquan William; Faulk, Christopher; Boehnke, Kevin; Zhang, Huapeng; Dolinoy, Dana C; Xi, Chuanwu

2016-06-01

Heavy metal pollution is a principle source of environmental contamination. Epidemiological and animal data suggest that early life lead (Pb) exposure results in critical effects on epigenetic gene regulation and child and adult weight trajectories. Using a mouse model of human-relevant exposure, we investigated the effects of perinatal Pb exposure on gut microbiota in adult mice, and the link between gut microbiota and bodyweight changes. Following Pb exposure during gestation and lactation via maternal drinking water, bodyweight in A(vy) strain wild-type non-agouti (a/a) offspring was tracked through adulthood. Gut microbiota of adult mice were characterized by deep DNA sequencing of bacterial 16S ribosomal RNA genes. Data analyses were stratified by sex and adjusted for litter effects. A Bayesian variable selection algorithm was used to analyze associations between bacterial operational taxonomic units and offspring adult bodyweight. Perinatal Pb exposure was associated with increased adult bodyweight in male (P < .05) but not in female offspring (P = .24). Cultivable aerobes decreased and anaerobes increased in Pb-exposed offspring (P < .005 and P < .05, respectively). Proportions of the 2 predominant phyla (Bacteroidetes and Firmicutes) shifted inversely with Pb exposure, and whole bacterial compositions were significantly different (analysis of molecular variance, P < .05) by Pb exposure without sex bias. In males, changes in gut microbiota were highly associated with adult bodyweight (P = .028; effect size = 2.59). Thus, perinatal Pb exposure results in altered adult gut microbiota regardless of sex, and these changes are highly correlated with increased bodyweight in males. Adult gut microbiota can be shaped by early exposures and may contribute to disease risks in a sex-specific manner. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Git Replacement for the

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, P.

2014-09-23

GRAPE is a tool for managing software project workflows for the Git version control system. It provides a suite of tools to simplify and configure branch based development, integration with a project's testing suite, and integration with the Atlassian Stash repository hosting tool.

Similarity of the oral microbiota of pre-school children with that of their caregivers in a population-based study.

PubMed

Tanner, A C R; Milgrom, P M; Kent, R; Mokeem, S A; Page, R C; Liao, S I A; Riedy, C A; Bruss, J B

2002-12-01

This study evaluated the similarity between the oral microbiota of young children and that of their adult caregivers. Oral samples from children (174 dentate and 18 pre-dentate) aged 6-36 months and their caregivers in Saipan were assayed using a DNA probe assay. Many species including Streptococcus mutans, Streptococcus sobrinus, Actinomyces species, Campylobacter rectus, Fusobacterium nucleatum, Prevotella intermedia, and Porphyromonas gingivalis were detected in dentate and pre-dentate children, whereas Bacteroides forsythus was detected only in dentate children. A higher percentage of children were positive for the detection of an individual species if the caregiver was also positive. There were significant relative risks of species detection between dentate children and their caregivers. By logistic regression, there were significant positive associations between species detection in caregiver and in child, but not between species detection and child age or maternal education level. In conclusion, dental pathogens were detected in young, including pre-dentate, children. The microbial profiles of children were strongly associated with the microbiota of their caregivers.

Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients

PubMed Central

Zhou, Xiao-Yan; Li, Ming; Li, Xia; Long, Xin; Zuo, Xiu-Li; Hou, Xiao-Hua; Cong, Ying-Zi; Li, Yan-Qing

2016-01-01

AIM: To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. METHODS: Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. RESULTS: Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. CONCLUSION: The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research. PMID:27298564

Pharmacokinetic profile of nifedipine GITS in hypertensive patients with chronic renal impairment.

PubMed

Schneider, R; Stolero, D; Griffel, L; Kobelt, R; Brendel, E; Iaina, A

1994-01-01

25 hypertensive patients with normal or impaired renal function underwent pharmacokinetic and safety studies after single and multiple dose administration of nifedipine GITS (Gastro-Intestinal Therapeutic System) 60mg tablets. Complete pharmacokinetic data were obtained from 23 of these patients. Blood pressure and heart rate changes were compatible with the known properties of the drug. Impaired renal function did not affect the maximum plasma concentrations or bioavailability of nifedipine after single or multiple dose administration of nifedipine GITS, nor was there any evidence of excessive drug accumulation in the presence of renal impairment.

Dose-response association between salivary cotinine levels and Mycobacterium tuberculosis infection.

PubMed

Shin, S S; Laniado-Laborin, R; Moreno, P G; Novotny, T E; Strathdee, S A; Garfein, R S

2013-11-01

Tijuana, Mexico. To describe the association between salivary cotinine levels and interferon-gamma (IFN-γ) release assay results. We conducted a cross-sectional study among injection drug users. Salivary cotinine levels were measured using NicAlert, a semi-quantitative dipstick assay. QuantiFERON©-TB Gold In-Tube (QFT-GIT) was used to determine Mycobacterium tuberculosis infection. Among 234 participants, the prevalence of QFT-GIT positivity for NicAlert cotinine categories 0 (non-smoking), 1 (second-hand smoke exposure or low-level smoking) and 26 (regular smoking) were respectively 42.1%, 46.4% and 65.2% (Ptrend 0.012). We found increasing trends in QFT-GIT positivity (Ptrend 0.003) and IFN-γ concentrations (Spearman's r 0.200, P 0.002) across cotinine levels 0 to 6. In multivariable log-binomial regression models adjusted for education, cotinine levels were not associated with QFT-GIT positivity when included as smoking categories (1 and 26 vs. 0), but were independently associated with QFT-GIT positivity when included as an ordinal variable (prevalence ratio 1.09 per 1 cotinine level, 95%CI 1.021.16). Our findings suggest that a dose-response relationship exists between tobacco smoke exposure and M. tuberculosis infection. Longitudinal studies that use biochemical measures for smoking status are needed to confirm our findings.

Zipf rank approach and cross-country convergence of incomes

NASA Astrophysics Data System (ADS)

Shao, Jia; Ivanov, Plamen Ch.; Urošević, Branko; Stanley, H. Eugene; Podobnik, Boris

2011-05-01

We employ a concept popular in physics —the Zipf rank approach— in order to estimate the number of years that EU members would need in order to achieve "convergence" of their per capita incomes. Assuming that trends in the past twenty years continue to hold in the future, we find that after t≈30 years both developing and developed EU countries indexed by i will have comparable values of their per capita gross domestic product {\\cal G}_{i,t} . Besides the traditional Zipf rank approach we also propose a weighted Zipf rank method. In contrast to the EU block, on the world level the Zipf rank approach shows that, between 1960 and 2009, cross-country income differences increased over time. For a brief period during the 2007-2008 global economic crisis, at world level the {\\cal G}_{i,t} of richer countries declined more rapidly than the {\\cal G}_{i,t} of poorer countries, in contrast to EU where the {\\cal G}_{i,t} of developing EU countries declined faster than the {\\cal G}_{i,t} of developed EU countries, indicating that the recession interrupted the convergence between EU members. We propose a simple model of GDP evolution that accounts for the scaling we observe in the data.

Latent tuberculosis infection among close contacts of multidrug-resistant tuberculosis patients in central Taiwan.

PubMed

Huang, Y-W; Shen, G-H; Lee, J-J; Yang, W-T

2010-11-01

Both the tuberculin skin test (TST) and the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) may be used to detect Mycobacterium tuberculosis infection. A positive reaction to either test can indicate latent tuberculosis infection (LTBI). These tests can be used to study the rate of infection in contacts of multidrug-resistant tuberculosis (MDR-TB) patients. To evaluate the transmission status of MDR-TB patients in Taiwan by examining their close contacts and to compare the efficiency of TST and QFT-GIT. Chest radiographs, TST and QFT-GIT were performed in household contacts of confirmed MDR-TB patients to determine their infection status. A total of 78 close contacts of confirmed MDR-TB patients were included in the study. The majority of the MDR-TB patients were parents of the close contacts and lived in the same building; 46% of the subjects were TST-positive and 19% were QFT-GIT-positive, indicating LTBI that was likely to develop into active MDR-TB. There was a lack of consistency between TST and QFT-GIT results in subjects with previous bacille Calmette-Guérin vaccination. Household contacts of MDR-TB patients are likely to develop LTBI; thus, follow-up and monitoring are mandatory to provide treatment and reduce the occurrence of active infection.

Epithelial, metabolic and innate immunity transcriptomic signatures differentiating the rumen from other sheep and mammalian gastrointestinal tract tissues.

PubMed

Xiang, Ruidong; Oddy, Victor Hutton; Archibald, Alan L; Vercoe, Phillip E; Dalrymple, Brian P

2016-01-01

Background. Ruminants are successful herbivorous mammals, in part due to their specialized forestomachs, the rumen complex, which facilitates the conversion of feed to soluble nutrients by micro-organisms. Is the rumen complex a modified stomach expressing new epithelial (cornification) and metabolic programs, or a specialised stratified epithelium that has acquired new metabolic activities, potentially similar to those of the colon? How has the presence of the rumen affected other sections of the gastrointestinal tract (GIT) of ruminants compared to non-ruminants? Methods. Transcriptome data from 11 tissues covering the sheep GIT, two stratified epithelial and two control tissues, was analysed using principal components to cluster tissues based on gene expression profile similarity. Expression profiles of genes along the sheep GIT were used to generate a network to identify genes enriched for expression in different compartments of the GIT. The data from sheep was compared to similar data sets from two non-ruminants, pigs (closely related) and humans (more distantly related). Results. The rumen transcriptome clustered with the skin and tonsil, but not the GIT transcriptomes, driven by genes from the epidermal differentiation complex, and genes encoding stratified epithelium keratins and innate immunity proteins. By analysing all of the gene expression profiles across tissues together 16 major clusters were identified. The strongest of these, and consistent with the high turnover rate of the GIT, showed a marked enrichment of cell cycle process genes (P = 1.4 E-46), across the whole GIT, relative to liver and muscle, with highest expression in the caecum followed by colon and rumen. The expression patterns of several membrane transporters (chloride, zinc, nucleosides, amino acids, fatty acids, cholesterol and bile acids) along the GIT was very similar in sheep, pig and humans. In contrast, short chain fatty acid uptake and metabolism appeared to be different between the species and different between the rumen and colon in sheep. The importance of nitrogen and iodine recycling in sheep was highlighted by the highly preferential expression of SLC14A1-urea (rumen), RHBG-ammonia (intestines) and SLC5A5-iodine (abomasum). The gene encoding a poorly characterized member of the maltase-glucoamylase family (MGAM2), predicted to play a role in the degradation of starch or glycogen, was highly expressed in the small and large intestines. Discussion. The rumen appears to be a specialised stratified cornified epithelium, probably derived from the oesophagus, which has gained some liver-like and other specialized metabolic functions, but probably not by expression of pre-existing colon metabolic programs. Changes in gene transcription downstream of the rumen also appear have occurred as a consequence of the evolution of the rumen and its effect on nutrient composition flowing down the GIT.

Epithelial, metabolic and innate immunity transcriptomic signatures differentiating the rumen from other sheep and mammalian gastrointestinal tract tissues

PubMed Central

Xiang, Ruidong; Oddy, Victor Hutton; Archibald, Alan L.; Vercoe, Phillip E.

2016-01-01

Background. Ruminants are successful herbivorous mammals, in part due to their specialized forestomachs, the rumen complex, which facilitates the conversion of feed to soluble nutrients by micro-organisms. Is the rumen complex a modified stomach expressing new epithelial (cornification) and metabolic programs, or a specialised stratified epithelium that has acquired new metabolic activities, potentially similar to those of the colon? How has the presence of the rumen affected other sections of the gastrointestinal tract (GIT) of ruminants compared to non-ruminants? Methods. Transcriptome data from 11 tissues covering the sheep GIT, two stratified epithelial and two control tissues, was analysed using principal components to cluster tissues based on gene expression profile similarity. Expression profiles of genes along the sheep GIT were used to generate a network to identify genes enriched for expression in different compartments of the GIT. The data from sheep was compared to similar data sets from two non-ruminants, pigs (closely related) and humans (more distantly related). Results. The rumen transcriptome clustered with the skin and tonsil, but not the GIT transcriptomes, driven by genes from the epidermal differentiation complex, and genes encoding stratified epithelium keratins and innate immunity proteins. By analysing all of the gene expression profiles across tissues together 16 major clusters were identified. The strongest of these, and consistent with the high turnover rate of the GIT, showed a marked enrichment of cell cycle process genes (P = 1.4 E−46), across the whole GIT, relative to liver and muscle, with highest expression in the caecum followed by colon and rumen. The expression patterns of several membrane transporters (chloride, zinc, nucleosides, amino acids, fatty acids, cholesterol and bile acids) along the GIT was very similar in sheep, pig and humans. In contrast, short chain fatty acid uptake and metabolism appeared to be different between the species and different between the rumen and colon in sheep. The importance of nitrogen and iodine recycling in sheep was highlighted by the highly preferential expression of SLC14A1-urea (rumen), RHBG-ammonia (intestines) and SLC5A5-iodine (abomasum). The gene encoding a poorly characterized member of the maltase-glucoamylase family (MGAM2), predicted to play a role in the degradation of starch or glycogen, was highly expressed in the small and large intestines. Discussion. The rumen appears to be a specialised stratified cornified epithelium, probably derived from the oesophagus, which has gained some liver-like and other specialized metabolic functions, but probably not by expression of pre-existing colon metabolic programs. Changes in gene transcription downstream of the rumen also appear have occurred as a consequence of the evolution of the rumen and its effect on nutrient composition flowing down the GIT. PMID:26989612

Metagenomic Study Suggests That the Gut Microbiota of the Giant Panda (Ailuropoda melanoleuca) May Not Be Specialized for Fiber Fermentation

PubMed Central

Guo, Wei; Mishra, Sudhanshu; Zhao, Jiangchao; Tang, Jingsi; Zeng, Bo; Kong, Fanli; Ning, Ruihong; Li, Miao; Zhang, Hengzhi; Zeng, Yutian; Tian, Yuanliangzi; Zhong, Yihang; Luo, Hongdi; Liu, Yunhan; Yang, Jiandong; Yang, Mingyao; Zhang, Mingwang; Li, Yan; Ni, Qingyong; Li, Caiwu; Wang, Chengdong; Li, Desheng; Zhang, Hemin; Zuo, Zhili; Li, Ying

2018-01-01

Bamboo-eating giant panda (Ailuropoda melanoleuca) is an enigmatic species, which possesses a carnivore-like short and simple gastrointestinal tract (GIT). Despite the remarkable studies on giant panda, its diet adaptability status continues to be a matter of debate. To resolve this puzzle, we investigated the functional potential of the giant panda gut microbiome using shotgun metagenomic sequencing of fecal samples. We also compared our data with similar data from other animal species representing herbivores, carnivores, and omnivores from current and earlier studies. We found that the giant panda hosts a bear-like gut microbiota distinct from those of herbivores indicated by the metabolic potential of the microbiome in the gut of giant pandas and other mammals. Furthermore, the relative abundance of genes involved in cellulose- and hemicellulose-digestion, and enrichment of enzymes associated with pathways of amino acid degradation and biosynthetic reactions in giant pandas echoed a carnivore-like microbiome. Most significantly, the enzyme assay of the giant panda's feces indicated the lowest cellulase and xylanase activity among major herbivores, shown by an in-vitro experimental assay of enzyme activity for cellulose and hemicellulose-degradation. All of our results consistently indicate that the giant panda is not specialized to digest cellulose and hemicellulose from its bamboo diet, making the giant panda a good mammalian model to study the unusual link between the gut microbiome and diet. The increased food intake of the giant pandas might be a strategy to compensate for the gut microbiome functions, highlighting a strong need of conservation of the native bamboo forest both in high- and low-altitude ranges to meet the great demand of bamboo diet of giant pandas. PMID:29503636

Metagenomic Study Suggests That the Gut Microbiota of the Giant Panda (Ailuropoda melanoleuca) May Not Be Specialized for Fiber Fermentation.

PubMed

Guo, Wei; Mishra, Sudhanshu; Zhao, Jiangchao; Tang, Jingsi; Zeng, Bo; Kong, Fanli; Ning, Ruihong; Li, Miao; Zhang, Hengzhi; Zeng, Yutian; Tian, Yuanliangzi; Zhong, Yihang; Luo, Hongdi; Liu, Yunhan; Yang, Jiandong; Yang, Mingyao; Zhang, Mingwang; Li, Yan; Ni, Qingyong; Li, Caiwu; Wang, Chengdong; Li, Desheng; Zhang, Hemin; Zuo, Zhili; Li, Ying

2018-01-01

Bamboo-eating giant panda ( Ailuropoda melanoleuca ) is an enigmatic species, which possesses a carnivore-like short and simple gastrointestinal tract (GIT). Despite the remarkable studies on giant panda, its diet adaptability status continues to be a matter of debate. To resolve this puzzle, we investigated the functional potential of the giant panda gut microbiome using shotgun metagenomic sequencing of fecal samples. We also compared our data with similar data from other animal species representing herbivores, carnivores, and omnivores from current and earlier studies. We found that the giant panda hosts a bear-like gut microbiota distinct from those of herbivores indicated by the metabolic potential of the microbiome in the gut of giant pandas and other mammals. Furthermore, the relative abundance of genes involved in cellulose- and hemicellulose-digestion, and enrichment of enzymes associated with pathways of amino acid degradation and biosynthetic reactions in giant pandas echoed a carnivore-like microbiome. Most significantly, the enzyme assay of the giant panda's feces indicated the lowest cellulase and xylanase activity among major herbivores, shown by an in-vitro experimental assay of enzyme activity for cellulose and hemicellulose-degradation. All of our results consistently indicate that the giant panda is not specialized to digest cellulose and hemicellulose from its bamboo diet, making the giant panda a good mammalian model to study the unusual link between the gut microbiome and diet. The increased food intake of the giant pandas might be a strategy to compensate for the gut microbiome functions, highlighting a strong need of conservation of the native bamboo forest both in high- and low-altitude ranges to meet the great demand of bamboo diet of giant pandas.

The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology

PubMed Central

Mach, Núria; Foury, Aline; Kittelmann, Sandra; Reigner, Fabrice; Moroldo, Marco; Ballester, Maria; Esquerré, Diane; Rivière, Julie; Sallé, Guillaume; Gérard, Philippe; Moisan, Marie-Pierre; Lansade, Léa

2017-01-01

Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days −30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella, and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus, on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to confer better stress response adaptation following weaning. This study identified potential microbial biomarkers that could predict the likelihood for physiological adaptations to weaning in horses, although causality remains to be addressed. PMID:28790932

The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology.

PubMed

Mach, Núria; Foury, Aline; Kittelmann, Sandra; Reigner, Fabrice; Moroldo, Marco; Ballester, Maria; Esquerré, Diane; Rivière, Julie; Sallé, Guillaume; Gérard, Philippe; Moisan, Marie-Pierre; Lansade, Léa

2017-01-01

Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days -30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella , and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus , on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to confer better stress response adaptation following weaning. This study identified potential microbial biomarkers that could predict the likelihood for physiological adaptations to weaning in horses, although causality remains to be addressed.

Maternal Antibiotic-Induced Early Changes in Microbial Colonization Selectively Modulate Colonic Permeability and Inducible Heat Shock Proteins, and Digesta Concentrations of Alkaline Phosphatase and TLR-Stimulants in Swine Offspring

PubMed Central

Arnal, Marie-Edith; Zhang, Jing; Erridge, Clett; Smidt, Hauke; Lallès, Jean-Paul

2015-01-01

Elevated intake of high energy diets is a risk factor for the development of metabolic diseases and obesity. High fat diets cause alterations in colonic microbiota composition and increase gut permeability to bacterial lipopolysaccharide, and subsequent low-grade chronic inflammation in mice. Chronic inflammatory bowel diseases are increasing worldwide and may involve alterations in microbiota-host dialog. Metabolic disorders appearing in later life are also suspected to reflect changes in early programming. However, how the latter affects the colon remains poorly studied. Here, we hypothesized that various components of colonic physiology, including permeability, ion exchange and protective inducible heat shock proteins (HSP) are influenced in the short- and long-terms by early disturbances in microbial colonization. The hypothesis was tested in a swine model. Offspring were born to control mothers (n = 12) or mothers treated with the antibiotic (ATB) amoxicillin around parturition (n = 11). Offspring were slaughtered between 14 and 42 days of age to study short-term effects. For long-term effects, young adult offspring from the same litters consumed a normal or a palm oil-enriched diet for 4 weeks between 140 and 169 days of age. ATB treatment transiently modified maternal fecal microbiota although the minor differences observed for offspring colonic microbiota were nonsignificant. In the short-term, consistently higher HSP27 and HSP70 levels and transiently increased horseradish peroxidase permeability in ATB offspring colon were observed. Importantly, long-term consequences included reduced colonic horseradish peroxidase permeability, and increased colonic digesta alkaline phosphatase (AP) and TLR2- and TLR4-stimulant concentrations in rectal digesta in adult ATB offspring. Inducible HSP27 and HSP70 did not change. Interactions between early ATB treatment and later diet were noted for paracellular permeability and concentrations of colonic digesta AP. In conclusion, our data suggest that early ATB-induced changes in bacterial colonization modulate important aspects of colonic physiology in the short- and long-terms. PMID:25689154

Maternal antibiotic-induced early changes in microbial colonization selectively modulate colonic permeability and inducible heat shock proteins, and digesta concentrations of alkaline phosphatase and TLR-stimulants in swine offspring.

PubMed

Arnal, Marie-Edith; Zhang, Jing; Erridge, Clett; Smidt, Hauke; Lallès, Jean-Paul

2015-01-01

Elevated intake of high energy diets is a risk factor for the development of metabolic diseases and obesity. High fat diets cause alterations in colonic microbiota composition and increase gut permeability to bacterial lipopolysaccharide, and subsequent low-grade chronic inflammation in mice. Chronic inflammatory bowel diseases are increasing worldwide and may involve alterations in microbiota-host dialog. Metabolic disorders appearing in later life are also suspected to reflect changes in early programming. However, how the latter affects the colon remains poorly studied. Here, we hypothesized that various components of colonic physiology, including permeability, ion exchange and protective inducible heat shock proteins (HSP) are influenced in the short- and long-terms by early disturbances in microbial colonization. The hypothesis was tested in a swine model. Offspring were born to control mothers (n = 12) or mothers treated with the antibiotic (ATB) amoxicillin around parturition (n = 11). Offspring were slaughtered between 14 and 42 days of age to study short-term effects. For long-term effects, young adult offspring from the same litters consumed a normal or a palm oil-enriched diet for 4 weeks between 140 and 169 days of age. ATB treatment transiently modified maternal fecal microbiota although the minor differences observed for offspring colonic microbiota were nonsignificant. In the short-term, consistently higher HSP27 and HSP70 levels and transiently increased horseradish peroxidase permeability in ATB offspring colon were observed. Importantly, long-term consequences included reduced colonic horseradish peroxidase permeability, and increased colonic digesta alkaline phosphatase (AP) and TLR2- and TLR4-stimulant concentrations in rectal digesta in adult ATB offspring. Inducible HSP27 and HSP70 did not change. Interactions between early ATB treatment and later diet were noted for paracellular permeability and concentrations of colonic digesta AP. In conclusion, our data suggest that early ATB-induced changes in bacterial colonization modulate important aspects of colonic physiology in the short- and long-terms.

Temporal and spatial variation of the human microbiota during pregnancy

PubMed Central

DiGiulio, Daniel B.; Callahan, Benjamin J.; McMurdie, Paul J.; Costello, Elizabeth K.; Lyell, Deirdre J.; Robaczewska, Anna; Sun, Christine L.; Goltsman, Daniela S. A.; Wong, Ronald J.; Shaw, Gary; Stevenson, David K.; Holmes, Susan P.; Relman, David A.

2015-01-01

Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals. PMID:26283357

Temporal and spatial variation of the human microbiota during pregnancy.

PubMed

DiGiulio, Daniel B; Callahan, Benjamin J; McMurdie, Paul J; Costello, Elizabeth K; Lyell, Deirdre J; Robaczewska, Anna; Sun, Christine L; Goltsman, Daniela S A; Wong, Ronald J; Shaw, Gary; Stevenson, David K; Holmes, Susan P; Relman, David A

2015-09-01

Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.

Maternal high fat diet and its consequence on the gut microbiome: A rat model.

PubMed

Mann, Phyllis E; Huynh, Kevin; Widmer, Giovanni

2017-11-14

The biological changes that occur during pregnancy in the female mammal include shifts in hormonal regulation in preparation for parturition and lactation, and changes in energy metabolism. In women, studies have also shown that during pregnancy there is a reduction in bacterial species richness in the gut. In the current experiment rats were used to model the interaction of diet, reproductive status, and intestinal bacterial microbiota during pregnancy and lactation. In Experiment 1 rats were exposed to either standard chow or high-fat chow (60%) and were divided into two groups: unmated (NULL) or mated (RE). In Experiment 2, both NULL and RE rats were exposed to high-fat chow for a 30-day period. High-throughput sequencing of the 16S rRNA gene revealed that pregnancy impacted the gut microbiota in a similar manner to humans. The impact of reproductive status on microbiota composition, however, was stronger in rats fed a high-fat (HF) diet. Diet-induced changes replicated some of the changes observed in humans, such as increasing the Firmicutes/Bacteroidetes ratio. However, in contrast to humans, pregnancy in rats did not increase β-diversity between microbiota from different animals. These results indicate that during pregnancy in rats, the gut microbiota is altered in a similar manner to that which occurs in women, and that these changes are further exaggerated by exposure to a HF diet. Thus, the rat may allow modelling the effects of consumption of HF food during pregnancy and enable future studies to determine the risks of HF diets during pregnancy and its consequences on the offspring.

The role of breast-feeding in infant immune system: a systems perspective on the intestinal microbiome.

PubMed

Praveen, Paurush; Jordan, Ferenc; Priami, Corrado; Morine, Melissa J

2015-09-24

The human intestinal microbiota changes from being sparsely populated and variable to possessing a mature, adult-like stable microbiome during the first 2 years of life. This assembly process of the microbiota can lead to either negative or positive effects on health, depending on the colonization sequence and diet. An integrative study on the diet, the microbiota, and genomic activity at the transcriptomic level may give an insight into the role of diet in shaping the human/microbiome relationship. This study aims at better understanding the effects of microbial community and feeding mode (breast-fed and formula-fed) on the immune system, by comparing intestinal metagenomic and transcriptomic data from breast-fed and formula-fed babies. We re-analyzed a published metagenomics and host gene expression dataset from a systems biology perspective. Our results show that breast-fed samples co-express genes associated with immunological, metabolic, and biosynthetic activities. The diversity of the microbiota is higher in formula-fed than breast-fed infants, potentially reflecting the weaker dependence of infants on maternal microbiome. We mapped the microbial composition and the expression patterns for host systems and studied their relationship from a systems biology perspective, focusing on the differences. Our findings revealed that there is co-expression of more genes in breast-fed samples but lower microbial diversity compared to formula-fed. Applying network-based systems biology approach via enrichment of microbial species with host genes revealed the novel key relationships of the microbiota with immune and metabolic activity. This was supported statistically by data and literature.

Effects of parental care on resource allocation into immune defense and buccal microbiota in mouthbrooding cichlid fishes.

PubMed

Keller, Isabel S; Bayer, Till; Salzburger, Walter; Roth, Olivia

2018-05-01

Sexual dimorphism is founded upon a resource allocation trade-off between investments in reproduction versus other life-history traits including the immune system. In species with conventional parental care roles, theory predicts that males maximize their lifetime reproductive success by allocating resources toward sexual selection, while females achieve this through prolonging their lifespan. Here, we examine the interrelation between sexual dimorphism and parental care strategies in closely related maternal and biparental mouthbrooding cichlid fishes from East African Lake Tanganyika. We measured cellular immune parameters, examined the relative expression of 28 immune system and life history-related candidate genes and analyzed the microbiota composition in the buccal cavity. According to our predictions, maternal mouthbrooders are more sexually dimorphic in immune parameters than biparental mouthbrooders, which has possibly arisen through a differential resource allocation into parental care versus secondary sexual traits. Biparental mouthbrooders, on the other hand, which share the costs of parental care, feature an upregulated adaptive immune response and stronger antiviral properties, while their inflammation response is reduced. Overall, our results suggest a differential resource allocation trade-off between the two modes of parental investment. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Companion animals symposium: role of microbes in canine and feline health.

PubMed

Kil, D Y; Swanson, K S

2011-05-01

Whether in an ocean reef, a landfill, or a gastrointestinal tract (GIT), invisible communities of highly active and adaptable microbes prosper. Over time, mammals have developed a symbiosis with microbes that are important inhabitants not only in the GIT, but also in the mouth, skin, and urogenital tract. In the GIT, the number of commensal microbes exceeds the total number of host cells by at least 10 times. The GIT microbes play a critical role in nutritional, developmental, defensive, and physiologic processes in the host. Recent evidence also suggests a role of GIT microbes in metabolic phenotype and disease risk (e.g., obesity, metabolic syndrome) of the host. Proper balance is a key to maintaining GIT health. Balanced microbial colonization is also important for other body regions such as the oral cavity, the region with the greatest prevalence of disease in dogs and cats. A significant obstruction to studying microbial populations has been the lack of tools to identify and quantify microbial communities accurately and efficiently. Most of the current knowledge of microbial populations has been established by traditional cultivation methods that are not only laborious, time-consuming, and often inaccurate, but also greatly limited in scope. However, recent advances in molecular-based techniques have resulted in a dramatic improvement in studying microbial communities. These DNA-based high-throughput technologies have enabled us to more clearly characterize the identity and metabolic activity of microbes living in the host and their association with health and diseases. Despite this recent progress, however, published data pertaining to microbial communities of dogs and cats are still lacking in comparison with data in humans and other animals. More research is required to provide a more detailed description of the canine and feline microbiome and its role in health and disease.

Comparison of cost-effectiveness between the quantiFERON-TB Gold-In-Tube and T-Spot tests for screening health-care workers for latent tuberculosis infection.

PubMed

Mukai, Shigeto; Shigemura, Katsumi; Yamamichi, Fukashi; Kitagawa, Koichi; Takami, Nozomi; Nomi, Masashi; Arakawa, Soichi; Fujisawa, Masato

2017-01-01

There are several methods used to screen for latent tuberculosis (TB) infection (LTBI) including the QuantiFERON-TB Gold-in-Tube (QFT-GIT) and T-SPOT-TB (T-SPOT) tests. Many studies have reported the equivalence of these two methods, but it is unclear which of them is more cost effective. We investigated the age and cost issues of these tests in screening for LTBI among health-care workers. One hundred and forty new employees during 2008-2011 in our hospital were screened using the QFT-GIT test, and 140 new employees during 2011-2014 were screened with the T-SPOT test for LTBI. The results of both tests were classified as positive, undetermined (retesting required), or negative. There were six positive results (4.29%), eight undetermined results (5.71%), and 126 negative results (90.0%) with the QFT-GIT test. As for the T-SPOT test, there were eight positive results (5.71%), three undetermined results (2.14%), and 129 negative results (92.1%). Fourteen LTBI employees (6 in QFT-GIT and 8 in T-SPOT) were detected statistically equally using the two methods (P = 0.79). The total costs, including those incurred for retesting, were $7,711.86 (US dollar) and $6,525.42 for the QFT-GIT and T-SPOT tests (cost of one test is $55.08 for QFT-GIT and $46.61 for T-SPOT), respectively. T-SPOT is one of the options for screening for LTBI partly owing to the viewpoint of cost-effectiveness. Further prospective studies need to be considered for a definitive conclusion.

Diagnostic usefulness of the QuantiFERON-TB gold in-tube test (QFT-GIT) for tuberculous vertebral osteomyelitis.

PubMed

Choi, Sungim; Jung, Kyung Hwa; Son, Hyo-Ju; Lee, Seung Hyun; Hong, Jung Min; Kim, Min Chul; Kim, Min Jae; Chong, Yong Pil; Sung, Heungsup; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2018-05-01

Interferon (IFN)-γ-releasing assay for diagnosing tuberculosis (TB) has shown promise; however, there are only a few reports on usefulness of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral osteomyelitis. All patients presenting at a tertiary hospital between January 2010 and July 2016 with suspected TB vertebral osteomyelitis were retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We used QFT-GIT to measure the IFN-γ response to ESAT-6, CFP-10 and TB7.7. A total of 141 patients were enrolled; 32 (23%) were categorized as having confirmed TB, (1%) as probable TB, 14 (10%) as possible TB and 93 (66%) as not TB. Of these, 16 patients with probable and possible TB were excluded from the final analysis. Chronic granulomas with/without necrosis, acid-fast bacilli stain, M. tuberculosis polymerase chain reaction and cultures for M. tuberculosis were positive in 14 (44%), 12 (38%), 22 (69%) and 28 (88%) patients, respectively, among the 32 patients with confirmed TB. The overall sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive result, and likelihood ratio for a negative result of the QFT-GIT for TB vertebral osteomyelitis were 91% (95% confidence interval [CI], 75-98%), 65% (95% CI, 54-75%), 50% (95% CI, 42-58%), 95% (95% CI, 86-98%), 2.59 (95% CI, 1.89-3.55) and 0.14 (95% CI, 0.05-0.43), respectively. The QFT-GIT appears to be a useful adjunct test for diagnosing TB vertebral osteomyelitis because the negative test results may be useful for excluding a diagnosis of active TB vertebral osteomyelitis.

Can multidetector CT detect the site of gastrointestinal tract injury in trauma? – A retrospective study

PubMed Central

Panda, Ananya; Kumar, Atin; Gamanagatti, Shivanand; Das, Ranjita; Paliwal, Swati; Gupta, Amit; Kumar, Subodh

2017-01-01

PURPOSE We aimed to assess the performance of computed tomography (CT) in localizing site of traumatic gastrointestinal tract (GIT) injury and determine the diagnostic value of CT signs in site localization. METHODS CT scans of 97 patients with surgically proven GIT or mesenteric injuries were retrospectively reviewed by radiologists blinded to surgical findings. Diagnosis of either GIT or mesenteric injuries was made. In patients with GIT injuries, site of injury and presence of CT signs such as focal bowel wall hyperenhancement, hypoenhancement, wall discontinuity, wall thickening, extramural air, intramural air, perivisceral infiltration, and active vascular contrast leak were evaluated. RESULTS Out of 97 patients, 90 had GIT injuries (70 single site injuries and 20 multiple site injuries) and seven had isolated mesenteric injury. The overall concordance between CT and operative findings for exact site localization was 67.8% (61/90), partial concordance rate was 11.1% (10/90), and discordance rate was 21.1% (19/90). For single site localization, concordance rate was 77.1% (54/70), discordance rate was 21.4% (15/70), and partial concordance rate was 1.4% (1/70). In multiple site injury, concordance rate for all sites of injury was 35% (7/20), partial concordance rate was 45% (9/20), and discordance rate was 20% (4/20). For upper GIT injuries, wall discontinuity was the most accurate sign for localization. For small bowel injury, intramural air and hyperenhancement were the most specific signs for site localization, while for large bowel injury, wall discontinuity and hypoenhancement were the most specific signs. CONCLUSION CT performs better in diagnosing small bowel injury compared with large bowel injury. CT can well predict the presence of multiple site injury but has limited performance in exact localization of all injury sites. PMID:27924777

Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity.

PubMed

Mueller, N T; Whyatt, R; Hoepner, L; Oberfield, S; Dominguez-Bello, M G; Widen, E M; Hassoun, A; Perera, F; Rundle, A

2015-04-01

Cesarean section (CS) and antibiotic use during pregnancy may alter normal maternal-offspring microbiota exchange, thereby contributing to aberrant microbial colonization of the infant gut and increased susceptibility to obesity later in life. We hypothesized that (i) maternal use of antibiotics in the second or third trimester of pregnancy and (ii) CS are independently associated with higher risk of childhood obesity in the offspring. Of the 727 mothers enrolled in the Northern Manhattan Mothers and Children Study, we analyzed the 436 mother-child dyads followed until 7 years of age with complete data. We ascertained prenatal antibiotic use by a questionnaire administered late in the third trimester, and delivery mode by medical record. We derived age- and sex-specific body mass index (BMI) z-scores using the CDC SAS Macro, and defined obesity as BMI z⩾95th percentile. We used binary regression with robust variance and linear regression models adjusted for maternal age, ethnicity, pre-gravid BMI, maternal receipt of public assistance, birth weight, sex, breastfeeding in the first year and gestational antibiotics or delivery mode. Compared with children not exposed to antibiotics during the second or third trimester, those exposed had 84% (33-154%) higher risk of obesity, after multivariable adjustment. Second or third trimester antibiotic exposure was also positively associated with BMI z-scores, waist circumference and % body fat (all P<0.05). Independent of prenatal antibiotic usage, CS was associated with 46% (8-98%) higher offspring risk of childhood obesity. Associations were similar for elective and non-elective CS. In our cohort, CS and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity. Future studies that address the limitations of our study are warranted to determine if prenatal antibiotic use is associated with offspring obesity. Research is also needed to determine if alterations in neonatal gut microbiota underlie the observed associations.

Mother's Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity.

PubMed

Le Doare, Kirsty; Holder, Beth; Bassett, Aisha; Pannaraj, Pia S

2018-01-01

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant's developing mucosal immune system. It is believed that bacteria from the mother's intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell-cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development.

Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin.

PubMed

Brown, Richard G; Marchesi, Julian R; Lee, Yun S; Smith, Ann; Lehne, Benjamin; Kindinger, Lindsay M; Terzidou, Vasso; Holmes, Elaine; Nicholson, Jeremy K; Bennett, Phillip R; MacIntyre, David A

2018-01-24

Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.

Installing and Setting Up Git Software Tool on Windows | High-Performance

Science.gov Websites

projects somewhere. In this example, we'll put our work in a "projects" folder inside the " GIT bash options. We'll also assume you'll want to start-off using the GUI. In our example, we've

Exceptional preservation reveals gastrointestinal anatomy and evolution in early actinopterygian fishes

PubMed Central

Argyriou, Thodoris; Clauss, Marcus; Maxwell, Erin E.; Furrer, Heinz; Sánchez-Villagra, Marcelo R.

2016-01-01

Current knowledge about the evolutionary morphology of the vertebrate gastrointestinal tract (GIT) is hindered by the low preservation potential of soft tissues in fossils. Exceptionally preserved cololites of individual †Saurichthys from the Middle Triassic of Switzerland provide unique insights into the evolutionary morphology of the GIT. The GIT of †Saurichthys differed from that of other early actinopterygians, and was convergent to that of some living sharks and rays, in exhibiting up to 30 turns of the spiral valve. Dissections and literature review demonstrate the phylogenetic diversity of GIT features and signs of biological factors that influence its morphology. A phylogenetically informed analysis of a dataset containing 134 taxa suggests that body size and phylogeny are important factors affecting the spiral valve turn counts. The high number of turns in the spiral valve of †Saurichthys and some recent sharks and rays reflect both energetically demanding lifestyles and the evolutionary histories of the groups. PMID:26732746

Continuous integration for concurrent MOOSE framework and application development on GitHub

DOE PAGES

Slaughter, Andrew E.; Peterson, John W.; Gaston, Derek R.; ...

2015-11-20

For the past several years, Idaho National Laboratory’s MOOSE framework team has employed modern software engineering techniques (continuous integration, joint application/framework source code repos- itories, automated regression testing, etc.) in developing closed-source multiphysics simulation software (Gaston et al., Journal of Open Research Software vol. 2, article e10, 2014). In March 2014, the MOOSE framework was released under an open source license on GitHub, significantly expanding and diversifying the pool of current active and potential future contributors on the project. Despite this recent growth, the same philosophy of concurrent framework and application development continues to guide the project’s development roadmap. Severalmore » specific practices, including techniques for managing multiple repositories, conducting automated regression testing, and implementing a cascading build process are discussed in this short paper. Furthermore, special attention is given to describing the manner in which these practices naturally synergize with the GitHub API and GitHub-specific features such as issue tracking, Pull Requests, and project forks.« less

Continuous integration for concurrent MOOSE framework and application development on GitHub

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slaughter, Andrew E.; Peterson, John W.; Gaston, Derek R.

For the past several years, Idaho National Laboratory’s MOOSE framework team has employed modern software engineering techniques (continuous integration, joint application/framework source code repos- itories, automated regression testing, etc.) in developing closed-source multiphysics simulation software (Gaston et al., Journal of Open Research Software vol. 2, article e10, 2014). In March 2014, the MOOSE framework was released under an open source license on GitHub, significantly expanding and diversifying the pool of current active and potential future contributors on the project. Despite this recent growth, the same philosophy of concurrent framework and application development continues to guide the project’s development roadmap. Severalmore » specific practices, including techniques for managing multiple repositories, conducting automated regression testing, and implementing a cascading build process are discussed in this short paper. Furthermore, special attention is given to describing the manner in which these practices naturally synergize with the GitHub API and GitHub-specific features such as issue tracking, Pull Requests, and project forks.« less

[Wernicke-Korsakoff syndrome].

PubMed

Kotov, S V; Lobakov, A I; Isakova, E V; Stashuk, G A; Volchenkova, T V

To study the diagnosis and treatment of non-alcoholic Wernicke-Korsakoff syndrome (WKS). Eight patients (5 men and 3 women), mean age 38,9±1,4 years, with WKS developed due to acute gastrointestinal tract (GIT) disease (3 patients), the exacerbation of chronic GIT disease with malabsorption (2 patients) and after surgery on the upper GIT (3 patients) were included in the study. The disease manifested with consciousness disturbance, symptoms of ataxia, eye movement disorders and bulbar syndrome that developed after 24-48 h. Treatment resistant tonic-clonic seizures were developed in 1 patient. MRI revealed hyper intensive signals on T2-weighted images in the hypothalamus, mamillar bodies, brain stem, hippocampus as well as contrast accumulation in the mamillar bodies. Treatment with vitamin B complex (neurobion) and thiamine exerted a positive effect. Patients with GIT disease with malabsorption are at risk of WKS. Consciousness disturbance, symptoms of ataxia, eye movement disorders indicate the necessity of treatment with thiamine that allows to prevent the development of stable cognitive deficit.

Validation of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 in English- and Chinese-speaking patients in a multi-ethnic Singapore systemic sclerosis cohort.

PubMed

Low, Andrea Hsiu Ling; Xin, Xiaohui; Law, Weng Giap; Teng, Gim Gee; Santosa, Amelia; Lim, Anita; Chan, Grace; Ng, Swee Cheng; Thumboo, Julian

2017-07-01

The aim of this study was to (1) translate the Gastrointestinal Tract Instrument (GIT) 2.0 from English to Chinese and (2) validate both versions in a multi-ethnic systemic sclerosis cohort in Singapore (SCORE). The English GIT2.0 was translated to Chinese using a standard forward-backward translation approach. Psychometric evaluation of the GIT2.0 included internal consistency reliability (using Cronbach's alpha), test-retest reliability (using intra-class correlation coefficient (ICC)), scale level factor analysis, and construct validity (using Spearman correlation) against the modified Scleroderma Health Assessment Questionnaire (S-HAQ) and the SF-36 v2. Most of the patients were females (88.6%) and Chinese (78.2%), with mean (SD) age of 51.0 (13.0) years and median disease duration of 4.5 years. We administered English (n = 146) and Chinese (n = 74) GIT2.0. The mean (SD) total GIT score was 0.29 (0.37). There was good internal consistency (Cronbach's alpha >0.70 for all subscales) and good test-retest reliability for the scale and all subscales (ICC 0.71-0.92) except for "diarrhoea" (ICC = 0.54). Our hypothesised a priori construct validity was supported by moderate correlations between the total GIT score and S-HAQ GI subscale (r = 0.446), and the social functioning subscale and SF36v2 role-social domain (r = 0.337), and weak-to-moderate correlation between the emotional subscale and SF-36v2 role-emotional (r = 0.295) and mental health (r = 0.298) domains and mental component summary (r = 0.356). Exploratory factor analysis of the seven subscales yielded a two-factor solution explaining 69.63% of the total variance. This study provides evidence for the reliability and validity of the English and Chinese GIT2.0 to be used in Singapore for research and routine practice.

Characterization of glucagon-like peptide 2 pathway member expression in bovine gastrointestinal tract.

PubMed

Connor, E E; Baldwin, R L; Capuco, A V; Evock-Clover, C M; Ellis, S E; Sciabica, K S

2010-11-01

Glucagon-like peptide 2 (GLP-2), secreted by enteroendocrine cells, has several physiological effects on the intestine of monogastric species, including promotion of growth of intestinal epithelium, reduction of epithelial cell apoptosis, and enhancement of intestinal blood flow, nutrient absorption, and epithelial barrier function. The regulatory functions of GLP-2 in the ruminant gastrointestinal tract (GIT) have not been well studied. The objectives of this investigation were to characterize the mRNA expression of 4 members of the GLP-2 pathway throughout the bovine GIT, including (1) proglucagon (GCG), the parent peptide from which GLP-2 is derived through cleavage by prohormone convertase; (2) prohormone convertase (PCSK1); (3) GLP-2 receptor (GLP2R); and (4) dipeptidyl peptidase IV (DPP4), the enzyme that inactivates GLP-2. Gene expression was evaluated in rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, and rectum collected at slaughter from prepubertal heifers, mature cows in early, mid, and late lactation, and nonlactating cows (n=3 per stage) by a gene expression profiling assay. In addition, mRNA expression of 14 genes involved in nutrient transport, enzyme activity, blood flow, apoptosis, and proliferation were evaluated in the 9 GIT tissues for their association with GCG and GLP2R mRNA expression. Immunohistochemistry was used to localize GLP2R protein in tissues of the lower GIT. Results indicated that mRNA expression of GCG, PCSK1, GLP2R, and DPP4 varies across the 9 GIT tissues, with greatest expression in small and large intestines, and generally nondetectable levels in forestomachs. Expression of DPP4 and GLP2R mRNA varied by developmental stage or lactational state in intestinal tissues. Expression of GCG or GLP2R mRNA was correlated with molecular markers of proliferation, apoptosis, blood flow, enzyme activity, and urea transport, depending on the tissue examined, which suggests a potential for involvement of GLP-2 in these physiological processes in the ruminant GIT. The GLP2R protein was expressed in intestinal crypts of the bovine GIT, which is consistent with the distribution in monogastric species. Our findings support a functional role of the GLP-2 pathway in bovine GIT and the potential for use of GLP-2 as a therapy to improve intestinal function and nutrient absorption in ruminants. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Factors That Contribute to Indeterminate Results From the QuantiFERON-TB Gold In-Tube Test in Patients With Inflammatory Bowel Disease.

PubMed

Kaur, Manreet; Singapura, Prianka; Kalakota, Neeharika; Cruz, Guillermina; Shukla, Richa; Ahsan, Sidra; Tansel, Aylin; Thrift, Aaron P; El-Serag, Hashem B

2017-11-23

The QuantiFERON-Tuberculosis Gold In-Tube (QFT-GIT) (QIAGEN Group, Hilden, Germany) test is widely used to screen for latent Mycobacterium tuberculosis infection in patients with inflammatory bowel diseases (IBD) before treatment with a tumor necrosis factor antagonist. The test frequently produces indeterminate results, prompting additional testing. We evaluated factors associated with indeterminate results from the QFT-GIT test among patients with IBD. We conducted a case-control study among eligible adults with QFT-GIT test results and a concomitant diagnosis of IBD receiving care at a tertiary referral center from 2011 through 2013. We compared patients with IBD with indeterminate and determinate (positive or negative) results from the QFT-GIT test. We collected data on patient demographics, clinical features, laboratory parameters, and medication use from medical charts. We calculated odds ratios (OR) and 95% CIs using multivariate logistic regression models. A total of 400 patients with IBD (265 Crohn's disease and 135 ulcerative colitis) were included in the final analyses. Indeterminate results were noted in 11.5% of patients. At the time of testing, a higher proportion of patients with indeterminate results from the QFT-GIT test were on systemic corticosteroid therapy (60.9% vs 30.5% of patients with conclusive test results; P < .001), had levels of C-reactive protein above 0.8 mg (62.2% vs 39.9% of patients with clear test results; P = .005), had an erythrocyte sedimentation rate above 15 mm/h (55.6% vs 35.8% of patients with clear test results; P = .01), had serum levels of albumin below 3.5 g/dL (33.3% vs 6.3% of patients with clear test results; P < .001), and had low levels of hemoglobin (52.2% vs 28.3% of patients with clear test results; P = .001). In multivariable analysis, corticosteroid use (adjusted OR, 2.92; 95% CI, 1.44-5.88; P = .003) and serum levels of albumin below 3.5 g/dL (adjusted OR, 3.62; 95% CI, 1.36-9.60; P = .009) were independently associated with increased risk of indeterminate QFT-GIT test results. We did not identify a dose-related effect with corticosteroid therapy and the odds of indeterminate QFT-GIT test results. In a case-control study of patients with IBD, we associated systemic corticosteroid therapy and low levels of albumin with an increased likelihood of having indeterminate QFT-GIT test result. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Mangiferin, a natural xanthone, accelerates gastrointestinal transit in mice involving cholinergic mechanism

PubMed Central

Morais, Talita Cavalcante; Lopes, Synara Cavalcante; Carvalho, Karine Maria Martins Bezerra; Arruda, Bruno Rodrigues; de Souza, Francisco Thiago Correia; Trevisan, Maria Teresa Salles; Rao, Vietla Satyanarayana; Santos, Flávia Almeida

2012-01-01

AIM: To investigate the effects of mangiferin on gastrointestinal transit (GIT) in normal and constipated mice, together with the possible mechanism. METHODS: Intragastrically-administered charcoal meal was used to measure GIT in overnight starved Swiss mice. In the first experiments, mangiferin (3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg, po) or tegaserod (1 mg/kg, ip) were administered 30 min before the charcoal meal to study their effects on normal transit. In the second series, mangiferin (30 mg/kg) was tested on delayed GIT induced by several different pharmacological agonists (morphine, clonidine, capsaicin) or antagonists (ondansetron, verapamil, and atropine) whereas in the third series, mangiferin (30 mg/kg, 100 mg/kg and 300 mg/kg) or tegaserod (1 mg/kg) were tested on 6 h fecal pellets outputted by freely fed mice. The ratio of wet to dry weight was calculated and used as a marker of fecal water content. RESULTS: Mangiferin administered orally significantly (P < 0.05) accelerated GIT at 30 mg/kg and 100 mg/kg (89% and 93%, respectively), similarly to 5-hydroxytryptamine4 (5-HT4) agonist tegaserod (81%) when compared to vehicle-treated control (63%). Co-administered mangiferin (30 mg/kg) totally reversed the inhibitory effect of opioid agonist morphine, 5-HT3-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT, but only to a partial extent with the GIT-delay induced by α2-adrenoceptor agonist clonidine, and calcium antagonist verapamil. However, co-administered atropine completely blocked the stimulant effect of mangiferin on GIT, suggesting the involvement of muscarinic acetylcholine receptor activation. Although mangiferin significantly enhanced the 6 h fecal output at higher doses (245.5 ± 10.43 mg vs 161.9 ± 10.82 mg and 227.1 ± 20.11 mg vs 161.9 ± 10.82 mg of vehicle-treated control, at 30 and 100 mg/kg, P < 0.05, respectively), the effect of tegaserod was more potent (297.4 ± 7.42 mg vs 161.9 ± 10.82 mg of vehicle-treated control, P < 0.05). Unlike tegaserod, which showed an enhanced water content in fecal pellets (59.20% ± 1.09% vs 51.44% ± 1.19% of control, P < 0.05), mangiferin evidenced no such effect, indicating that it has only a motor and not a secretomotor effect. CONCLUSION: Our data indicate the prokinetic action of mangiferin. It can stimulate the normal GIT and also overcome the drug-induced transit delay, via a cholinergic physiological mechanism. PMID:22783044

Growth advantage of Streptococcus thermophilus over Lactobacillus bulgaricus in vitro and in the gastrointestinal tract of gnotobiotic rats.

PubMed

Ben-Yahia, L; Mayeur, C; Rul, F; Thomas, M

2012-09-01

The yoghurt bacteria, Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus, are alleged to have beneficial effects on human health. The objective of this study was to characterise growth, biochemical activity and competitive behaviour of these two bacteria in vitro and in vivo. S. thermophilus LMD-9 and L. bulgaricus ATCC 11842 growth and lactate production were monitored in different media and in the gastrointestinal tract (GIT) of germ-free rats. In vitro, particularly in milk, S. thermophilus had a selective growth advantage over L. bulgaricus. The GIT of germ-free rats not supplemented with lactose was colonised by S. thermophilus but not by L. bulgaricus. Both bacteria were able to colonise the GIT of germ-free rats supplemented with 45 g/l lactose in their drinking water. However, if germ-free rats were inoculated with a mixture of the two bacteria and were supplemented with lactose, S. thermophilus rapidly and extensively colonised the GIT (1010 cfu/g faeces) at the expense of L. bulgaricus, which remained in most cases at levels <102 cfu/g faeces. S. thermophilus specifically produced L-lactate, while L. bulgaricus produced only D-lactate, both in vitro and in vivo. S. thermophilus showed competitive and growth advantage over L. bulgaricus in vitro as well as in vivo in the GIT of germ-free rats and, accordingly, L-lactate was the main lactate isomer produced.

Commensal microbiome effects on mucosal immune system development in the ruminant gastrointestinal tract.

PubMed

Taschuk, Ryan; Griebel, Philip J

2012-06-01

Commensal microflora play many roles within the mammalian gastrointestinal tract (GIT) that benefit host physiology by way of direct or indirect interactions with mucosal surfaces. Commensal flora comprises members across all microbial phyla, although predominantly bacterial, with population dynamics varying with host species, genotype, and environmental factors. Little is known, however, about the complex mechanisms regulating host-commensal interactions that underlie this mutually beneficial relationship and how alterations in the microbiome may influence host development and susceptibility to infection. Research into the gut microbiome has intensified as it becomes increasingly evident that symbiont-host interactions have a significant impact on mucosal immunity and health. Furthermore, evidence that microbial populations vary significantly throughout the GIT suggest that regional differences in the microbiome may also influence immune function within distinct compartments of the GIT. Postpartum colonization of the GIT has been shown to have a direct effect on mucosal immune system development, but information is limited regarding regional effects of the microbiome on the development, activation, and maturation of the mucosal immune system. This review discusses factors influencing the colonization and establishment of the microbiome throughout the GIT of newborn calves and the evidence that regional differences in the microbiome influence mucosal immune system development and maturation. The implications of this complex interaction are also discussed in terms of possible effects on responses to enteric pathogens and vaccines.

A comparative analysis of microbial profile of Guinea fowl and chicken using metagenomic approach

PubMed Central

Bhogoju, Sarayu; Wang, Xiaofei; Darris, Carl; Kilonzo-Nthenge, Agnes

2018-01-01

Probiotics are live microbial feed supplements that promote growth and health to the host by minimizing non-essential and pathogenic microorganisms in the host’s gastrointestinal tract (GIT). The campaign to minimize excessive use of antibiotics in poultry production has necessitated development of probiotics with broad application in multiple poultry species. Design of such probiotics requires understanding of the diversity or similarity in microbial profiles among avian species of economic importance. Therefore, the objective of this research was to establish and compare the microbial profiles of the GIT of Guinea fowl and chicken and to establish the microbial diversity or similarity between the two avian species. A metagenomic approach consisting of the amplification and sequence analysis of the hypervariable regions V1-V9 of the 16S rRNA gene was used to identify the GIT microbes. Collectively, we detected more than 150 microbial families. The total number of microbial species detected in the chicken GIT was higher than that found in the Guinea Fowl GIT. Our studies also revealed phylogenetic diversity among the microbial species found in chicken and guinea fowl. The phylum Firmicutes was most abundant in both avian species whereas Phylum Actinobacteria was most abundant in chickens than Guinea fowls. The diversity of the microbial profiles found in broiler chickens and Guinea fowls suggest that the design of effective avian probiotics would require species specificity. PMID:29494648

Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System.

PubMed

Kourentas, Alexandros; Vertzoni, Maria; Khadra, Ibrahim; Symillides, Mira; Clark, Hugh; Halbert, Gavin; Butler, James; Reppas, Christos

2016-09-01

An in vitro biorelevant gastrointestinal transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipid self-emulsifying vehicles). The in vitro method was also used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately simulated the average albendazole gastrointestinal transfer process and concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation observed in the duodenal compartment was greater than in vivo. Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Technical note: preservation of tissues and gastrointestinal tract portions by plastic coating or plastination.

PubMed

Pond, K R; Holladay, S D; Luginbuhl, J M

1992-04-01

Two methods to preserve gastrointestinal tract (GIT) organs and tissues, plastic coating (PC) and plastination (PN), were investigated and compared. Specimens to be preserved were removed from animals within 2 h of death and immediately cleaned with water. Digesta contents were removed by flushing desired portions of GIT with water until the exiting water was clear. In the PC method, cleaned specimens were dehydrated by immersion in an isopropanol solution, dried with forced air after positioning and orientation as in situ, and finally coated on the outer and inner surfaces with a clear plastic material. In the PN procedure, specimens were filled with, and submerged in, a low-formaldehyde fixative, then dehydrated by immersion in a cold acetone solution. Dehydrated specimens were immersed in silicone and placed in a freeze drier for impregnation under low vacuum, followed by overnight gas curing with a silicone crosslinker. Finally, viewing windows were cut out with a scalpel in GIT preserved by both methods. Preserved GIT and tissues had an appearance similar to their appearance in vivo. The PC method was simple and inexpensive. Plastinated specimens were more flexible, durable, and lifelike than those preserved by the PC method. In addition, many body parts, such as muscles, nerves, bones, ligaments, and central nervous system specimens, were preserved by PN. Both methods were found to be useful tools for postmortem studies of tissues and GIT organs.

Prospective Comparison of QFT-GIT and T-SPOT.TB Assays for Diagnosis of Active Tuberculosis.

PubMed

Du, Fengjiao; Xie, Li; Zhang, Yonghong; Gao, Fei; Zhang, Huibin; Chen, Wei; Sun, Bingqi; Sha, Wei; Fang, Yong; Jia, Hongyan; Xing, Aiying; Du, Boping; Zheng, Li; Gao, Mengqiu; Zhang, Zongde

2018-04-12

T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests, as two commercial blood assays for diagnosing active tuberculosis (ATB), are not yet fully validated. Especially, there are no reports on comparing the efficacy between the two tests in the same population in China. A multicenter, prospective comparison study was undertaken at four hospitals specializing in pulmonary diseases. A total of 746 suspected pulmonary TB were enrolled and categorized, including 185 confirmed TB, 298 probable TB and 263 non-TB. Of 32 patients with indeterminate test results (ITRs), age and underlying disease were associated with the rate of ITRs. Furthermore, the rate of ITRs determined by T-SPOT.TB was lower than QFT-GIT (0.4% vs. 4.3%, P < 0.01). When excluding ITRs, the sensitivities of T-SPOT.TB and QFT-GIT were 85.2% and 84.8%, and specificities of 63.4% and 60.5%, respectively in the diagnosis of ATB. The two assays have an overall agreement of 92.3%, but exhibited a poor linear correlation (r 2  = 0.086) between the levels of interferon-γ release detected by the different assays. Although having some heterogeneity in detecting interferon-γ release, both the QFT-GIT and T-SPOT.TB demonstrated high concordance in diagnosing ATB. However, neither of them showed suitability in the definitive diagnosis of the disease.

[Effects of calcium supplementation during the pregnancy and early infancy stage on the body mass index and gut microbiota in the infants].

PubMed

Chang, X L; Shang, Y; Liu, Y J; Li, P; Wang, Y Y; Liang, A M; Qi, K M

2018-06-06

Objective: To investigate the effects of calcium supplementation during the pregnancy and early infancy stage on body mass index (BMI) and gut microbiota in the infants. Methods: A total of 1 752 healthy pregnant women and their infants (breast feeding) in two maternal and child health care hospitals of Beijing were chosen as the subjects in this study from May to October 2016. Questionnaires were used to obtain the general information and supplementation of calcium and vitamin D in mothers and their infants. The body length and weight of infants at birth and 6 months were recorded to calculate the BMI. The random number table method was used to randomly select 40 infants from each group for gut microbiota analysis (If less than 40 infants were all included in this study, 23 infants in the pregnancy and early infancy would be all treated with calcium supplements. There were 6 infants who was not added calcium during the pregnancy but added in the early infancy). Then it was compared that the effects of calcium supplementation during the pregnancy and early infancy on the BMI and gut microbiota composition of infants were determined at birth and 6 months. Results: Compared to the group with no calcium supplementation during the pregnancy ((12.76±1.23), (17.68±0.76)kg/m(2)), the BMI of infants at birth and 6 months in the group with calcium supplementation during the pregnancy ((13.51±0.47), (17.91±0.23)kg/m(2)) were significantly higher( P< 0.05). In the group with maternal calcium supplementation, the BMI at 6 months ((18.63±0.52)kg/m(2)), BMI increment ((5.71±0.54)kg/m(2)) and the content of lactobacillus (21.04%±3.68%) in the only calcium supplementation subgroup in the early infancy were higher than those in only vitamin D supplementation subgroup ((17.69±0.89) kg/m(2), (4.17±1.01) kg/m(2) and 12.28%±3.86%) ( P< 0.05). In the group without maternal calcium supplementation, the content of lactobacillus (20.15%±4.87%) in the only calcium supplementation subgroup were also higher than those in only vitamin D supplementation subgroup (14.64%±3.71%) ( P< 0.05). Conclusion: Appropriate calcium supplementation during the pregnancy is good for the growth and development of the fetus. Calcium supplementation in the early infancy could increase the BMI of infants, and promote the growth of intestinal lactobacillus.

The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice.

PubMed

Deshmukh, Hitesh S; Liu, Yuhong; Menkiti, Ogechukwu R; Mei, Junjie; Dai, Ning; O'Leary, Claire E; Oliver, Paula M; Kolls, Jay K; Weiser, Jeffrey N; Worthen, G Scott

2014-05-01

Neonatal colonization by microbes, which begins immediately after birth, is influenced by gestational age and the mother's microbiota and is modified by exposure to antibiotics. In neonates, prolonged duration of antibiotic therapy is associated with increased risk of late-onset sepsis (LOS), a disorder controlled by neutrophils. A role for the microbiota in regulating neutrophil development and susceptibility to sepsis in the neonate remains unclear. We exposed pregnant mouse dams to antibiotics in drinking water to limit transfer of maternal microbes to the neonates. Antibiotic exposure of dams decreased the total number and composition of microbes in the intestine of the neonates. This was associated with decreased numbers of circulating and bone marrow neutrophils and granulocyte/macrophage-restricted progenitor cells in the bone marrow of antibiotic-treated and germ-free neonates. Antibiotic exposure of dams reduced the number of interleukin-17 (IL-17)-producing cells in the intestine and production of granulocyte colony-stimulating factor (G-CSF). Granulocytopenia was associated with impaired host defense and increased susceptibility to Escherichia coli K1 and Klebsiella pneumoniae sepsis in antibiotic-treated neonates, which could be partially reversed by administration of G-CSF. Transfer of a normal microbiota into antibiotic-treated neonates induced IL-17 production by group 3 innate lymphoid cells (ILCs) in the intestine, increasing plasma G-CSF levels and neutrophil numbers in a Toll-like receptor 4 (TLR4)- and myeloid differentiation factor 88 (MyD88)-dependent manner and restored IL-17-dependent resistance to sepsis. Specific depletion of ILCs prevented IL-17- and G-CSF-dependent granulocytosis and resistance to sepsis. These data support a role for the intestinal microbiota in regulation of granulocytosis, neutrophil homeostasis and host resistance to sepsis in neonates.

Epidemiology of gastrointestinal nematodes of sheep managed under traditional husbandry system in Kashmir valley.

PubMed

Tariq, K A; Chishti, M Z; Ahmad, F; Shawl, A S

2008-11-25

The present study was conducted with the objective to investigate the seasonal epidemiological prevalence of gastrointestinal tract (GIT) nematodes in different age groups, sexes and breeds (genotypes) of sheep through necropsy and faecal analysis over a period of 2 years in Kashmir valley, India. A total of 1533 sheep were examined [faecal examination: 1035 (year 1: 561, year 2: 474); necropsy: 498 (year 1: 232, year 2: 266)]. Out of these, 945 (61.64%) were found infected [faecal examination: 697 (67.34%, year 1: 390 (69.51%), year 2: 307 (46.99%); necropsy: 248 (49.79%, year 1: 123 (53.01%), year 2: 125 (64.69%)] with GIT nematodes. The over all prevalence of GIT nematodes in sheep in year 1 was 64.76 and 58.37% in year 2 (P=0.04). The parasites in decreasing order of prevalence (%) in sheep were Haemonchus contortus (59.6); Ostertagia circumcincta (38.0); Bunostomum trigonocephalum (37.7); Chabertia ovina (37.7); Trichostrongylus spp. (33.9); Nematodirus spathiger (29.4); Oesophagostomum columbianum (28.4); Trichuris ovis (23.5) and Marshallagia marshalli (22.1). Season, sex, age, and genotype were the factors that influenced the epidemiological prevalence of GIT nematodes in sheep in the present study. The maximum nematode infection was observed in summer season and lowest in winter (P=0.0005). Local Kashmiri breed was less infected as compared to other genotypes (P>0.05). Lower age groups were more infected than adult animals (P>/=0.05). Prevalence was higher in rams (males) than eves (females) (P>0.05). The present study will initially be of great significance to add to the existing knowledge of the epidemiology of GIT nematodes of small ruminants and the findings will be quite helpful to devise the appropriate control and prophylactic strategies for GIT nematodiasis of sheep reared under the temperate agro-climatic conditions.

Diffuse Peritoneal and Bowel Wall Infiltration by Light Chain-AL Amyloidosis with Omental Calcification Mimicking Abdominal Carcinomatosis - An Elderly Female with Incidental Finding of Light Chain Monoclonal Gammopathy of Undetermined Significance (LC-MGUS).

PubMed

Junejo, Shoaib; Ali, Yasir; Singh Lubana, Sandeep; Tuli, Sandeep S

2017-11-25

BACKGROUND Amyloidosis is the extracellular tissue deposition of plasma proteins, which after conformational changes, forms antiparallel beta pleated sheets of fibrils. Amyloid light-chain (AL) is a type of amyloidosis that is due to deposition of proteins derived from immunoglobulin (Ig) light chains. Gastrointestinal tract (GIT) involvement most often found in amyloid A (AA) amyloidosis type. There have been no reports of obstructive GIT AL amyloid patients having monoclonal gammopathy of undetermined significance (MGUS). Our case is the first case to show two coinciding conditions; one is the association of GIT AL amyloidosis with the incidental finding of a rare type of MGUS (LC-MGUS) and the other is the radiologic presentation of GIT amyloidosis with omental calcification mimicking the GIT malignancy. CASE REPORT A 68-year-old female presented with symptoms of partial bowel obstruction, including intermittent diffuse abdominal pain and constipation. After computed tomography (CT) abdomen and pelvis, an exploratory laparotomy was needed because of suspicion of abdominal carcinomatosis due to diffuse omental calcification. The tissue sent for biopsy surprisingly showed AL amyloidosis. The patient did not report any systemic symptoms. Further workup was advised to inquire about the plasma cell dyscrasia which eventually turned into a very rare version of MGUS knows as light chain MGUS (LC-MGUS). Following adequate resection of the involved structures, the patient was then placed on chemotherapy and successfully went into remission. CONCLUSIONS This case report illustrates that in an era of evidence based medicine, it is important to show through case reports the association of GIT AL amyloidosis with LC-MGUS, as the literature on this topic is lacking. It also points to the importance of timely intervention that can greatly enhance, not only the only the chances of remission but also prevention of further complications such as malignant transformation.

Quantiferon-TB Gold Plus is a More Sensitive Screening Tool than Quantiferon-TB Gold In-Tube for Latent Tuberculosis Infection among Older Adults in Long-Term Care Facility.

PubMed

Chien, Jung-Yien; Chiang, Hsiu-Tzy; Lu, Min-Chi; Ko, Wen-Chien; Yu, Chong-Jen; Chen, Yen-Hsu; Hsueh, Po-Ren

2018-05-23

We investigated the prevalence of latent tuberculosis infection (LTBI) among the residents in seven long-term care facilities (LTCFs) located in different regions of Taiwan and compared the performance of two interferon-gamma release assays, i.e. QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold plus (QFT-Plus) for screening LTBI. We also assessed the diagnostic performance against a composite reference standard (subjects with persistent-positive, transient-positive, and negative results of QFTs during reproducibility analysis were classified as definite, possible and not LTBI, respectively). Two hundred and forty-four residents were enrolled and 229 subjects were included into analysis. The median age was 80 years (range, 60-102 years old) and 117 (51.1%) were male. Among them, 66 (28.8%) and 74 (32.3%) subjects had positive results of QFT-GIT and QFT-Plus, respectively, and 215 (93.9%) subjects showed agreement results. Using composite reference standard, 66 (28.8%), 11 (4.8%), and 152 (66.4%) were classified as definite, possible and not LTBI, respectively. For definite LTBI, the sensitivity, specificity, positive predictive value, and negative predictive value of QFT-GIT were 89.4%, 95.7%, 89.4%, and 95.7%, respectively, and those for QFT-Plus were 100.0%, 95.1%, 89.2%, and 100.0%. The sensitivity of QFT-GIT decreased gradually with age. Compared to QFT-GIT, QFT-Plus displayed significantly higher sensitivity (100.0% vs. 89.4%, P =0.013) and similar specificity (95.1% vs. 95.7%). In conclusion, a high prevalence of LTBI was found among elders in LTCFs in Taiwan. The new QFT-Plus test demonstrated a higher sensitivity than QFT-GIT in the older adults in LTCFs. Copyright © 2018 American Society for Microbiology.

Mother’s Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity

PubMed Central

Le Doare, Kirsty; Holder, Beth; Bassett, Aisha; Pannaraj, Pia S.

2018-01-01

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant’s developing mucosal immune system. It is believed that bacteria from the mother’s intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell–cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development. PMID:29599768

High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model

PubMed Central

Ma, Jun; Prince, Amanda L.; Bader, David; Hu, Min; Ganu, Radhika; Baquero, Karalee; Blundell, Peter; Harris, R. Alan; Frias, Antonio E.; Grove, Kevin L.; Aagaard, Kjersti M.

2014-01-01

The intestinal microbiome is a unique ecosystem and an essential mediator of metabolism and obesity in mammals. However, studies investigating the impact of the diet on the establishment of the gut microbiome early in life are generally lacking, and most notably so in primate models. Here we report that a high-fat maternal or postnatal diet, but not obesity per se, structures the offspring’s intestinal microbiome in Macaca fuscata (Japanese macaque). The resultant microbial dysbiosis is only partially corrected by a low-fat, control diet after weaning. Unexpectedly, early exposure to a high-fat diet diminished the abundance of non-pathogenic Campylobacter in the juvenile gut, suggesting a potential role for dietary fat in shaping commensal microbial communities in primates. Our data challenge the concept of an obesity-causing gut microbiome, and rather provide evidence for a contribution of the maternal diet in establishing the microbiota, which in turn affects intestinal maintenance of metabolic health. PMID:24846660

High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model.

PubMed

Ma, Jun; Prince, Amanda L; Bader, David; Hu, Min; Ganu, Radhika; Baquero, Karalee; Blundell, Peter; Alan Harris, R; Frias, Antonio E; Grove, Kevin L; Aagaard, Kjersti M

2014-05-20

The intestinal microbiome is a unique ecosystem and an essential mediator of metabolism and obesity in mammals. However, studies investigating the impact of the diet on the establishment of the gut microbiome early in life are generally lacking, and most notably so in primate models. Here we report that a high-fat maternal or postnatal diet, but not obesity per se, structures the offspring's intestinal microbiome in Macaca fuscata (Japanese macaque). The resultant microbial dysbiosis is only partially corrected by a low-fat, control diet after weaning. Unexpectedly, early exposure to a high-fat diet diminished the abundance of non-pathogenic Campylobacter in the juvenile gut, suggesting a potential role for dietary fat in shaping commensal microbial communities in primates. Our data challenge the concept of an obesity-causing gut microbiome and rather provide evidence for a contribution of the maternal diet in establishing the microbiota, which in turn affects intestinal maintenance of metabolic health.

Fecal Microbiota Transplantation in Gestating Sows and Neonatal Offspring Alters Lifetime Intestinal Microbiota and Growth in Offspring.

PubMed

McCormack, Ursula M; Curião, Tânia; Wilkinson, Toby; Metzler-Zebeli, Barbara U; Reyer, Henry; Ryan, Tomas; Calderon-Diaz, Julia A; Crispie, Fiona; Cotter, Paul D; Creevey, Christopher J; Gardiner, Gillian E; Lawlor, Peadar G

2018-01-01

Previous studies suggest a link between intestinal microbiota and porcine feed efficiency (FE). Therefore, we investigated whether fecal microbiota transplantation (FMT) in sows and/or neonatal offspring, using inocula derived from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were assigned to control or FMT treatments and the subsequent offspring to control treatment, FMT once (at birth), or FMT four times (between birth and weaning). FMT altered sow fecal and colostrum microbiota compositions and resulted in lighter offspring body weight at 70 and 155 days of age when administered to sows and/or offspring. This was accompanied by FMT-associated changes within the offspring's intestinal microbiota, mostly in the ileum. These included transiently higher fecal bacterial diversity and load and numerous compositional differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes at high relative abundances and mostly members of Clostridia , respectively), as well as differences in the abundances of predicted bacterial pathways. In addition, intestinal morphology was negatively impacted, duodenal gene expression altered, and serum protein and cholesterol concentrations reduced due to FMT in sows and/or offspring. Taken together, the results suggest poorer absorptive capacity and intestinal health, most likely explaining the reduced body weight. An additive effect of FMT in sows and offspring also occurred for some parameters. Although these findings have negative implications for the practical use of the FMT regime used here for improving FE in pigs, they nonetheless demonstrate the enormous impact of early-life intestinal microbiota on the host phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel strategy to modulate the porcine intestinal microbiota in an attempt to improve FE in pigs. However, reprogramming the maternal and/or offspring microbiome by using fecal transplants derived from highly feed-efficient pigs did not recapitulate the highly efficient phenotype in the offspring and, in fact, had detrimental effects on lifetime growth. Although these findings may not be wholly attributable to microbiota transplantation, as antibiotic and purgative were also part of the regime in sows, similar effects were also seen in offspring, in which these interventions were not used. Nonetheless, additional work is needed to unravel the effects of each component of the FMT regime and to provide additional mechanistic insights. This may lead to the development of an FMT procedure with practical applications for the improvement of FE in pigs, which could in turn improve the profitability of pig production.

Fecal Microbiota Transplantation in Gestating Sows and Neonatal Offspring Alters Lifetime Intestinal Microbiota and Growth in Offspring

PubMed Central

2018-01-01

ABSTRACT Previous studies suggest a link between intestinal microbiota and porcine feed efficiency (FE). Therefore, we investigated whether fecal microbiota transplantation (FMT) in sows and/or neonatal offspring, using inocula derived from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were assigned to control or FMT treatments and the subsequent offspring to control treatment, FMT once (at birth), or FMT four times (between birth and weaning). FMT altered sow fecal and colostrum microbiota compositions and resulted in lighter offspring body weight at 70 and 155 days of age when administered to sows and/or offspring. This was accompanied by FMT-associated changes within the offspring’s intestinal microbiota, mostly in the ileum. These included transiently higher fecal bacterial diversity and load and numerous compositional differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes at high relative abundances and mostly members of Clostridia, respectively), as well as differences in the abundances of predicted bacterial pathways. In addition, intestinal morphology was negatively impacted, duodenal gene expression altered, and serum protein and cholesterol concentrations reduced due to FMT in sows and/or offspring. Taken together, the results suggest poorer absorptive capacity and intestinal health, most likely explaining the reduced body weight. An additive effect of FMT in sows and offspring also occurred for some parameters. Although these findings have negative implications for the practical use of the FMT regime used here for improving FE in pigs, they nonetheless demonstrate the enormous impact of early-life intestinal microbiota on the host phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel strategy to modulate the porcine intestinal microbiota in an attempt to improve FE in pigs. However, reprogramming the maternal and/or offspring microbiome by using fecal transplants derived from highly feed-efficient pigs did not recapitulate the highly efficient phenotype in the offspring and, in fact, had detrimental effects on lifetime growth. Although these findings may not be wholly attributable to microbiota transplantation, as antibiotic and purgative were also part of the regime in sows, similar effects were also seen in offspring, in which these interventions were not used. Nonetheless, additional work is needed to unravel the effects of each component of the FMT regime and to provide additional mechanistic insights. This may lead to the development of an FMT procedure with practical applications for the improvement of FE in pigs, which could in turn improve the profitability of pig production. PMID:29577087

CT features, mimics and atypical presentations of gastrointestinal stromal tumor (GIST).

PubMed

Sripathi, Smiti; Rajagopal, Kv; Srivastava, Rajendra Kumar; Ayachit, Anurag

2011-07-01

The term stromal tumor was coined in 1983 by Clark and Mazur for smooth muscle neoplasm of the gastrointestinal tract (GIT). Gastrointestinal stromal tumors (GIST) are nonepithelial tumors arising from the interstitial cells of Cajal, which express KIT protein-CD117 on immunohistochemistry. GIST can arise anywhere in the GIT, including the mesentery, omentum, and retroperitoneum.

Maternal intrapartum antibiotics and decreased vertical transmission of Lactobacillus to neonates during birth.

PubMed

Keski-Nisula, Leea; Kyynäräinen, Hanna-Reetta; Kärkkäinen, Ulla; Karhukorpi, Jari; Heinonen, Seppo; Pekkanen, Juha

2013-05-01

To estimate the transmission of maternal vaginal microbiota to neonates during term delivery, focusing on Lactobacillus flora in relation to various obstetric clinical factors. Fifty consecutive pregnant healthy women with singleton term pregnancies and their newborn infants. Vertical transmission of Lactobacillus flora to the newborn during delivery was evaluated in 45 mother-newborn pairs. Lactobacillus-dominant mixed flora was detected in 90% (N = 45) of vaginal samples, but only in 28% (N = 14) of neonatal cultures (transmission rate 31%). All neonates with Lactobacillus-dominant mixed flora had findings similar to those in maternal cultures. Cocci-dominant flora was the most common finding in neonates. Administration of antibiotics to the mother during the intrapartum period before birth and duration of rupture of membranes (ROM), regardless of maternal antibiotic treatment, were associated significantly with a decreased transmission rate of Lactobacillus-dominant mixed flora to neonates. Maternal intrapartum antibiotics and prolonged expectant management after ROM were associated with decreased transmission rate of vaginal Lactobacillus flora to the neonate during birth. As early colonization of Lactobacillus flora may have a preventive role in the development of allergic diseases later, the significance of intrapartum prophylactic antibiotics needs to be highlighted in forthcoming studies, especially as regards immunological development of the offspring. ©2013 The Author(s)/Acta Paediatrica ©2013 Foundation Acta Paediatrica.

Regional Strategic Appraisal of Central America

DTIC Science & Technology

2003-04-07

effective region, to increase its competitiveness in the face of the challenges from globalization . Therefore, I recommend a deepening of the regional...centroamericanos, 1970 a 1999, Mexico City, Mach 2000. 7 Agosin, Bloom and Gitli, Globalization , Liberalization, and Sustainable Human Development in Central...Bloom, and Eduardo Gitli, “ Globalization , Liberalization, and Sustainable Human Development in Central America,” February, 2000; available from <http

CT features, mimics and atypical presentations of gastrointestinal stromal tumor (GIST)

PubMed Central

Sripathi, Smiti; Rajagopal, KV; Srivastava, Rajendra Kumar; Ayachit, Anurag

2011-01-01

The term stromal tumor was coined in 1983 by Clark and Mazur for smooth muscle neoplasm of the gastrointestinal tract (GIT). Gastrointestinal stromal tumors (GIST) are nonepithelial tumors arising from the interstitial cells of Cajal, which express KIT protein-CD117 on immunohistochemistry. GIST can arise anywhere in the GIT, including the mesentery, omentum, and retroperitoneum. PMID:22013291

[Meloxicam: the golden mean of nonsteroidal anti-inflammatory drugs].

PubMed

Karateev, A E

2014-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are most commonly used to treat acute and chronic pain in locomotor system (LMS) diseases. However, their administration may be accompanied by the development of dangerous complications as organic and functional disorders of the cardiovascular system (CVS) and gastrointestinal tract (GIT). Physicians have currently a wide range of NSAIDs at their disposal; but none of the representatives of this group can be considered the best. Thus, highly selective cyclooxygenase-2 inhibitors (Coxibs) are substantially safer for GIT; however, their use is clearly associated with the increased risk of severe cardiovascular events. Nonselective NSAIDs, such as naproxen or ketoprofen, are safer for CVS, but more frequently cause significant GIT organic and functional disorders. Moderately selective NSAIDs, such as meloxicam (movalis), conceivably could be the most acceptable choice for treating the majority of patients in this situation. This drug has been long and extensively used in global clinical practice and has gained the confidence of physicians and patients. The major benefits of meloxicam are its proven efficacy, convenient treatment regimen, relatively low risk of complications as organic and functional disorders of the GIT and CVD and good compatibility with low-dose aspirin.

Understanding the gastrointestinal tract of the elderly to develop dietary solutions that prevent malnutrition

PubMed Central

Rémond, Didier; Shahar, Danit R.; Gille, Doreen; Pinto, Paula; Kachal, Josefa; Peyron, Marie-Agnès; Dos Santos, Claudia Nunes; Walther, Barbara; Bordoni, Alessandra; Dupont, Didier; Tomás-Cobos, Lidia; Vergères, Guy

2015-01-01

Although the prevalence of malnutrition in the old age is increasing worldwide a synthetic understanding of the impact of aging on the intake, digestion, and absorption of nutrients is still lacking. This review article aims at filling the gap in knowledge between the functional decline of the aging gastrointestinal tract (GIT) and the consequences of malnutrition on the health status of elderly. Changes in the aging GIT include the mechanical disintegration of food, gastrointestinal motor function, food transit, chemical food digestion, and functionality of the intestinal wall. These alterations progressively decrease the ability of the GIT to provide the aging organism with adequate levels of nutrients, what contributes to the development of malnutrition. Malnutrition, in turn, increases the risks for the development of a range of pathologies associated with most organ systems, in particular the nervous-, muscoskeletal-, cardiovascular-, immune-, and skin systems. In addition to psychological, economics, and societal factors, dietary solutions preventing malnutrition should thus propose dietary guidelines and food products that integrate knowledge on the functionality of the aging GIT and the nutritional status of the elderly. Achieving this goal will request the identification, validation, and correlative analysis of biomarkers of food intake, nutrient bioavailability, and malnutrition. PMID:26091351

The stability and degradation of dietary DNA in the gastrointestinal tract of mammals: implications for horizontal gene transfer and the biosafety of GMOs.

PubMed

Rizzi, Aurora; Raddadi, Noura; Sorlini, Claudia; Nordgrd, Lise; Nielsen, Kaare Magne; Daffonchio, Daniele

2012-01-01

The fate of dietary DNA in the gastrointestinal tract (GIT) of animals has gained renewed interest after the commercial introduction of genetically modified organisms (GMO). Among the concerns regarding GM food, are the possible consequences of horizontal gene transfer (HGT) of recombinant dietary DNA to bacteria or animal cells. The exposure of the GIT to dietary DNA is related to the extent of food processing, food composition, and to the level of intake. Animal feeding studies have demonstrated that a minor amount of fragmented dietary DNA may resist the digestive process. Mammals have been shown to take up dietary DNA from the GIT, but stable integration and expression of internalized DNA has not been demonstrated. Despite the ability of several bacterial species to acquire external DNA by natural transformation, in vivo transfer of dietary DNA to bacteria in the intestine has not been detected in the few experimental studies conducted so far. However, major methodological limitations and knowledge gaps of the mechanistic aspects of HGT calls for methodological improvements and further studies to understand the fate of various types of dietary DNA in the GIT.

The Implementation of a Geospatial Information Technology (GIT)-Supported Land Use Change Curriculum with Urban Middle School Learners to Promote Spatial Thinking

ERIC Educational Resources Information Center

Bodzin, Alec M.

2011-01-01

This study investigated whether a geospatial information technology (GIT)-supported science curriculum helped students in an urban middle school understand land use change (LUC) concepts and enhanced their spatial thinking. Five 8th grade earth and space science classes in an urban middle school consisting of three different ability level tracks…

Phylesystem: a git-based data store for community-curated phylogenetic estimates.

PubMed

McTavish, Emily Jane; Hinchliff, Cody E; Allman, James F; Brown, Joseph W; Cranston, Karen A; Holder, Mark T; Rees, Jonathan A; Smith, Stephen A

2015-09-01

Phylogenetic estimates from published studies can be archived using general platforms like Dryad (Vision, 2010) or TreeBASE (Sanderson et al., 1994). Such services fulfill a crucial role in ensuring transparency and reproducibility in phylogenetic research. However, digital tree data files often require some editing (e.g. rerooting) to improve the accuracy and reusability of the phylogenetic statements. Furthermore, establishing the mapping between tip labels used in a tree and taxa in a single common taxonomy dramatically improves the ability of other researchers to reuse phylogenetic estimates. As the process of curating a published phylogenetic estimate is not error-free, retaining a full record of the provenance of edits to a tree is crucial for openness, allowing editors to receive credit for their work and making errors introduced during curation easier to correct. Here, we report the development of software infrastructure to support the open curation of phylogenetic data by the community of biologists. The backend of the system provides an interface for the standard database operations of creating, reading, updating and deleting records by making commits to a git repository. The record of the history of edits to a tree is preserved by git's version control features. Hosting this data store on GitHub (http://github.com/) provides open access to the data store using tools familiar to many developers. We have deployed a server running the 'phylesystem-api', which wraps the interactions with git and GitHub. The Open Tree of Life project has also developed and deployed a JavaScript application that uses the phylesystem-api and other web services to enable input and curation of published phylogenetic statements. Source code for the web service layer is available at https://github.com/OpenTreeOfLife/phylesystem-api. The data store can be cloned from: https://github.com/OpenTreeOfLife/phylesystem. A web application that uses the phylesystem web services is deployed at http://tree.opentreeoflife.org/curator. Code for that tool is available from https://github.com/OpenTreeOfLife/opentree. mtholder@gmail.com. © The Author 2015. Published by Oxford University Press.

Early Gut Microbiota Perturbations Following Intrapartum Antibiotic Prophylaxis to Prevent Group B Streptococcal Disease.

PubMed

Mazzola, Giuseppe; Murphy, Kiera; Ross, R Paul; Di Gioia, Diana; Biavati, Bruno; Corvaglia, Luigi T; Faldella, Giacomo; Stanton, Catherine

2016-01-01

The faecal microbiota composition of infants born to mothers receiving intrapartum antibiotic prophylaxis with ampicillin against group B Streptococcus was compared with that of control infants, at day 7 and 30 of life. Recruited newborns were both exclusive breastfed and mixed fed, in order to also study the effect of dietary factors on the microbiota composition. Massive parallel sequencing of the V3-V4 region of the 16S rRNA gene and qPCR analysis were performed. Antibiotic prophylaxis caused the most marked changes on the microbiota in breastfed infants, mainly resulting in a higher relative abundance of Enterobacteriaceae, compared with control infants (52% vs. 14%, p = 0.044) and mixed-fed infants (52% vs. 16%, p = 0.13 NS) at day 7 and in a lower bacterial diversity compared to mixed-fed infants and controls. Bifidobacteria were also particularly vulnerable and abundances were reduced in breastfed (p = 0.001) and mixed-fed antibiotic treated groups compared to non-treated groups. Reductions in bifidobacteria in antibiotic treated infants were also confirmed by qPCR. By day 30, the bifidobacterial population recovered and abundances significantly increased in both breastfed (p = 0.025) and mixed-fed (p = 0.013) antibiotic treated groups, whereas Enterobacteriaceae abundances remained highest in the breastfed antibiotic treated group (44%), compared with control infants (16%) and mixed-fed antibiotic treated group (28%). This study has therefore demonstrated the short term consequences of maternal intrapartum antibiotic prophylaxis on the infant faecal microbial population, particularly in that of breastfed infants.

Analysis of Lactobacillus sakei Mutants Selected after Adaptation to the Gastrointestinal Tracts of Axenic Mice▿ †

PubMed Central

Chiaramonte, Fabrizio; Anglade, Patricia; Baraige, Fabienne; Gratadoux, Jean-Jacques; Langella, Philippe; Champomier-Vergès, Marie-Christine; Zagorec, Monique

2010-01-01

We recently showed that Lactobacillus sakei, a natural meat-borne lactic acid bacterium, can colonize the gastrointestinal tracts (GIT) of axenic mice but that this colonization in the intestinal environment selects L. sakei mutants showing modified colony morphology (small and rough) and cell shape, most probably resulting from the accumulation of various mutations that confer a selective advantage for persistence in the GIT. In the present study, we analyzed such clones, issued from three different L. sakei strains, in order to determine which functions were modified in the mutants. In the elongated filamentous cells of the rough clones, transmission electron microscopy (TEM) analysis showed a septation defect and dotted and slanted black bands, suggesting the presence of a helical structure around the cells. Comparison of the cytoplasmic and cell wall/membrane proteomes of the meat isolate L. sakei 23K and of one of its rough derivatives revealed a modified expression for 38 spots. The expression of six oxidoreductases, several stress proteins, and four ABC transporters was strongly reduced in the GIT-adapted strain, while the actin-like MreB protein responsible for cell shaping was upregulated. In addition, the expression of several enzymes involved in carbohydrate metabolism was modified, which may correlate with the observation of modified growth of mutants on various carbon sources. These results suggest that the modifications leading to a better adaptation to the GIT are pleiotropic and are characterized in a rough mutant by a different stress status, a cell wall modification, and modified use of energy sources, leading to an improved fitness for the colonization of the GIT. PMID:20208026

Disentangling factors that shape the gut microbiota in German Shepherd dogs

PubMed Central

Ramadan, Ziad; Li, Qinghong; Hedhammar, Åke; Reynolds, Arleigh; Spears, Julie; Labuda, Jeff; Pelker, Robyn; Björkstén, Bengt; Dicksved, Johan; Hansson-Hamlin, Helene

2018-01-01

The aim of this study was to explore the development of the gut microbiota in 168 German Shepherd dogs (30 litters) from 7 weeks to 18 months of age and furthermore, to study the effect of relatedness, maternal microbiota composition and living environment in a large and well-defined population of dogs. Using 454 pyrosequencing, we assessed the effects of pre- and postnatal probiotic supplementation (Lactobacillus johnsonii NCC533 (La1)) and analysed whether administration of the probiotic strain influenced fecal microbiota composition in a placebo controlled double-blinded study. The bitches were treated with probiotics or placebo during last trimester of pregnancy and until their puppies were 8 weeks old, the puppies received the same treatment as their mothers between 3–12 weeks of age. Samples from bitches were collected at pregnancy day 42, partum, 4 weeks postpartum and 7 weeks postpartum and from puppies at the age 4 weeks, 7 weeks, 12–13 months and 15–18 months. Serum IgA, total serum IgE, fecal IgA and IgG antibody responses against canine distemper virus were analysed by ELISA in order to detect any immune stimulating effects of the probiotic strain. Analysis of the fecal microbiota composition showed that the predominant phyla were the same in 7 weeks old puppies as in pregnant and lactating bitches (Firmicutes, Fusobacteria, Bacteroidetes). Proportions among different bacteria as well as diversity varied from 7 weeks old puppies up to 15–18 months of age. Litter mates had a more similar fecal microbiota compared to unrelated dogs and 7 weeks old puppies were more similar to their mothers than to unrelated bitches at 7 weeks postpartum but not at partum. We observed a change in the relative abundance of different bacteria during lactation, and an increase in diversity from pregnancy to end of lactation. The microbial diversity was affected by living area where dogs living in big cities had higher diversity compared to dogs living at the countryside. However, we were not able to demonstrate an effect by pre and postnatal exposure to Lactobacillus johnsonii NCC533 (La1) upon the diversity or composition of the microbiota or the levels of serum IgA, total serum IgE, fecal IgA or vaccine response. Our findings provide a better understanding of the canine fecal microbiota in growing dogs as well as in pregnant and lactating bitches. This information forms a basis for further research on the connection between early gut colonization and immune function later in life. PMID:29570709

Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

PubMed

Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

2017-05-19

Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

Investigating different skin and gastrointestinal tract (GIT) pathologies ex vivo by autofluorescence spectroscopy and optical imaging

NASA Astrophysics Data System (ADS)

Zhelyazkova, A.; Kuzmina, I.; Borisova, E.; Penkov, N.; Genova, Ts.; Spigulis, J.; Avramov, L.

2016-01-01

The skin neoplasias are on a second place in the world statistics of cancer incidence, and gastrointestinal tract (GIT) tumours are also in the "top ten" list. For the most of cutaneous and gastrointestinal tumours could be obtained better prognoses for patients, if an earlier and precise diagnostics procedure is applied. One of the most promising approaches for development of improved diagnostic techniques, is based on optical detection, and analysis of the signatures of biological tissues for detecting the presence of pathological alterations in the investigated objects. It is important to develop and combine novel diagnostic techniques for an accurate early stage diagnosis to improve the chances for skin and GIT tumours treatment. Optical techniques are very promising methods for such noninvasive diagnosis of skin and mucosa tumours, possessing the advantages of deep imaging depth, high resolution, fast imaging speed, and noninvasive character of detection. In this study we combine autofluorescence spectroscopy and optical imaging techniques to develop more precise evaluation of the tissue pathologies investigated. We obtain chromophore maps for GIT and cutaneous samples, with better visualization of the tumours borders and margins. In addition, fluorescence spectra give us information about the early changes in chromophores' contents into the tissues during neoplasia growth.

Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life.

PubMed

Forbes, Jessica D; Azad, Meghan B; Vehling, Lorena; Tun, Hein M; Konya, Theodore B; Guttman, David S; Field, Catherine J; Lefebvre, Diana; Sears, Malcolm R; Becker, Allan B; Mandhane, Piushkumar J; Turvey, Stuart E; Moraes, Theo J; Subbarao, Padmaja; Scott, James A; Kozyrskyj, Anita L

2018-06-04

The effect of neonatal and infant feeding practices on childhood obesity is unclear. The gut microbiome is strongly influenced by feeding practices and has been linked to obesity. To characterize the association between breastfeeding, microbiota, and risk of overweight during infancy, accounting for the type and timing of supplementary feeding. In this study of a subset of 1087 infants from the prospective CHILD pregnancy cohort, mothers were recruited between January 1, 2009, and December 31, 2012. Statistical analysis was performed from February 1 to December 20, 2017. Feeding was reported by mothers and documented from hospital records. Fecal microbiota at 3 to 4 months (from 996 infants) and/or 12 months (from 821 infants) were characterized by 16S ribosomal RNA sequencing. Infants with a weight for length exceeding the 85th percentile were considered to be at risk for overweight. There were 1087 infants in the study (507 girls and 580 boys); at 3 months, 579 of 1077 (53.8%) were exclusively breastfed according to maternal report. Infants who were exclusively formula fed at 3 months had an increased risk of overweight in covariate-adjusted models (53 of 159 [33.3%] vs 74 of 386 [19.2%]; adjusted odds ratio, 2.04; 95% CI, 1.25-3.32). This association was attenuated (adjusted odds ratio, 1.33; 95% CI, 0.79-2.24) after further adjustment for microbiota features characteristic of formula feeding at 3 to 4 months, including higher overall richness and enrichment of Lachnospiraceae. A total of 179 of 579 infants who were exclusively breastfed (30.9%) received formula as neonates; this brief supplementation was associated with lower relative abundance of Bifidobacteriaceae and higher relative abundance of Enterobacteriaceae at 3 to 4 months but did not influence the risk of overweight. At 12 months, microbiota profiles differed significantly according to feeding practices at 6 months; among partially breastfed infants, formula supplementation was associated with a profile similar to that of nonbreastfed infants (higher diversity and enrichment of Bacteroidaceae), whereas the introduction of complementary foods without formula was associated with a profile more similar to that of exclusively breastfed infants (lower diversity and enrichment of Bifidobacteriaceae and Veillonellaceae). Microbiota profiles at 3 months were more strongly associated with risk of overweight than were microbiota profiles at 12 months. Breastfeeding may be protective against overweight, and gut microbiota may contribute to this effect. Formula feeding appears to stimulate changes in microbiota that are associated with overweight, whereas other complementary foods do not. Subtle microbiota differences emerge after brief exposure to formula in the hospital. These results identify important areas for future research and distinguish early infancy as a critical period when transient gut dysbiosis may lead to increased risk of overweight.

Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis

PubMed Central

Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

2016-01-01

In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia’s gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus. PMID:26983596

Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.

PubMed

Hsiao, Elaine Y; McBride, Sara W; Hsien, Sophia; Sharon, Gil; Hyde, Embriette R; McCue, Tyler; Codelli, Julian A; Chow, Janet; Reisman, Sarah E; Petrosino, Joseph F; Patterson, Paul H; Mazmanian, Sarkis K

2013-12-19

Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Human breast milk: A review on its composition and bioactivity.

PubMed

Andreas, Nicholas J; Kampmann, Beate; Mehring Le-Doare, Kirsty

2015-11-01

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution, finely attuning it to the requirements of the infant. Breast milk contains many complex proteins, lipids and carbohydrates, the concentrations of which alter dramatically over a single feed, as well as over lactation, to reflect the infant's needs. In addition to providing a source of nutrition for infants, breast milk contains a myriad of biologically active components. These molecules possess diverse roles, both guiding the development of the infants immune system and intestinal microbiota. Orchestrating the development of the microbiota are the human milk oligosaccharides, the synthesis of which are determined by the maternal genotype. In this review, we discuss the composition of breast milk and the factors that affect it during the course of breast feeding. Understanding the components of breast milk and their functions will allow for the improvement of clinical practices, infant feeding and our understanding of immune responses to infection and vaccination in infants. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Toward the identification of methanogenic archaeal groups as targets of methane mitigation in livestock animalsr

PubMed Central

St-Pierre, Benoit; Cersosimo, Laura M.; Ishaq, Suzanne L.; Wright, André-Denis G.

2015-01-01

In herbivores, enteric methane is a by-product from the digestion of plant biomass by mutualistic gastrointestinal tract (GIT) microbial communities. Methane is a potent greenhouse gas that is not assimilated by the host and is released into the environment where it contributes to climate change. Since enteric methane is exclusively produced by methanogenic archaea, the investigation of mutualistic methanogen communities in the GIT of herbivores has been the subject of ongoing research by a number of research groups. In an effort to uncover trends that would facilitate the development of efficient methane mitigation strategies for livestock species, we have in this review summarized and compared currently available results from published studies on this subject. We also offer our perspectives on the importance of pursuing current research efforts on the sequencing of gut methanogen genomes, as well as investigating their cellular physiology and interactions with other GIT microorganisms. PMID:26284054

Heterogeneity across the murine small and large intestine

PubMed Central

Bowcutt, Rowann; Forman, Ruth; Glymenaki, Maria; Carding, Simon Richard; Else, Kathryn Jane; Cruickshank, Sheena Margaret

2014-01-01

The small and large intestine of the gastrointestinal tract (GIT) have evolved to have discrete functions with distinct anatomies and immune cell composition. The importance of these differences is underlined when considering that different pathogens have uniquely adapted to live in each region of the gut. Furthermore, different regions of the GIT are also associated with differences in susceptibility to diseases such as cancer and chronic inflammation. The large and small intestine, given their anatomical and functional differences, should be seen as two separate immunological sites. However, this distinction is often ignored with findings from one area of the GIT being inappropriately extrapolated to the other. Focussing largely on the murine small and large intestine, this review addresses the literature relating to the immunology and biology of the two sites, drawing comparisons between them and clarifying similarities and differences. We also highlight the gaps in our understanding and where further research is needed. PMID:25386070

Heterogeneity across the murine small and large intestine.

PubMed

Bowcutt, Rowann; Forman, Ruth; Glymenaki, Maria; Carding, Simon Richard; Else, Kathryn Jane; Cruickshank, Sheena Margaret

2014-11-07

The small and large intestine of the gastrointestinal tract (GIT) have evolved to have discrete functions with distinct anatomies and immune cell composition. The importance of these differences is underlined when considering that different pathogens have uniquely adapted to live in each region of the gut. Furthermore, different regions of the GIT are also associated with differences in susceptibility to diseases such as cancer and chronic inflammation. The large and small intestine, given their anatomical and functional differences, should be seen as two separate immunological sites. However, this distinction is often ignored with findings from one area of the GIT being inappropriately extrapolated to the other. Focussing largely on the murine small and large intestine, this review addresses the literature relating to the immunology and biology of the two sites, drawing comparisons between them and clarifying similarities and differences. We also highlight the gaps in our understanding and where further research is needed.

Inhibitory Effects of Two Varieties of Tunisian Pomegranate (Punica granatum L.) Extracts on Gastrointestinal Transit in Rat.

PubMed

Souli, Abdelaziz; Sebai, Hichem; Rtibi, Kais; Chehimi, Latifa; Sakly, Mohsen; Amri, Mohamed; El-Benna, Jamel; Marzouki, Lamjed

2015-09-01

The present study was undertaken to determine whether total and methanol juice extracts of two Tunisian Pomegranate (Punica granatum L.) varieties (Garsi and Gabsi) protect against diarrhea as well as their effects on gastrointestinal transit (GIT) in healthy rats. In this respect, male Wistar rats were used and divided into control- and pomegranate-treated groups. The antidiarrheal activity was evaluated using the castor oil-induced diarrhea method and the GIT was assessed using charcoal meal. Our results showed that total and methanol P. granatum juice extracts produced a significant dose-dependent protection against castor oil-induced diarrhea. Pomegranate extracts and juice also decreased the GIT significantly and dose dependently. Importantly, the Garsi variety appeared to be more effective than the Gabsi variety on these two parameters. These findings suggest that pomegranate extracts have a potent antidiarrheal property in rats confirming their efficiency in the Tunisian traditional medicine.

Inhibitory Effects of Two Varieties of Tunisian Pomegranate (Punica granatum L.) Extracts on Gastrointestinal Transit in Rat

PubMed Central

Souli, Abdelaziz; Sebai, Hichem; Rtibi, Kais; Chehimi, Latifa; Sakly, Mohsen; Amri, Mohamed; El-Benna, Jamel; Marzouki, Lamjed

2015-01-01

Abstract The present study was undertaken to determine whether total and methanol juice extracts of two Tunisian Pomegranate (Punica granatum L.) varieties (Garsi and Gabsi) protect against diarrhea as well as their effects on gastrointestinal transit (GIT) in healthy rats. In this respect, male Wistar rats were used and divided into control- and pomegranate-treated groups. The antidiarrheal activity was evaluated using the castor oil-induced diarrhea method and the GIT was assessed using charcoal meal. Our results showed that total and methanol P. granatum juice extracts produced a significant dose-dependent protection against castor oil-induced diarrhea. Pomegranate extracts and juice also decreased the GIT significantly and dose dependently. Importantly, the Garsi variety appeared to be more effective than the Gabsi variety on these two parameters. These findings suggest that pomegranate extracts have a potent antidiarrheal property in rats confirming their efficiency in the Tunisian traditional medicine. PMID:25775227

Early intervention of long-acting nifedipine GITS reduces brachial-ankle pulse wave velocity and improves arterial stiffness in Chinese patients with mild hypertension: a 24-week, single-arm, open-label, prospective study.

PubMed

Zhang, Jidong; Wang, Yan; Hu, Haijuan; Yang, Xiaohong; Tian, Zejun; Liu, Demin; Gu, Guoqiang; Zheng, Hongmei; Xie, Ruiqin; Cui, Wei

2016-01-01

Nifedipine gastrointestinal therapeutic system (GITS) is used to treat angina and hypertension. The authors aimed to study the early intervention impact on arterial stiffness and pulse wave velocity (PWV) independent of its blood-pressure-(BP) lowering effect in mild hypertensive patients. This single-center, single-arm, open-label, prospective, Phase IV study recruited patients with mild hypertension and increased PWV from December 2013 to December 2014 (N=138; age, 18-75 years; systolic blood pressure, 140-160 mmHg; diastolic BP, 90-100 mmHg; increased brachial-ankle pulse wave velocity [baPWV, ≥12 m/s]). Nifedipine GITS (30 mg/d) was administered for 24 weeks to achieve target BP of <140/90 mmHg. The dose was uptitrated at 60 mg/d in case of unsatisfactory BP reduction after 4 weeks. Primary study end point was the change in baPWV after nifedipine GITS treatment. Hemodynamic parameters (office BP, 24-hour ambulatory BP monitoring, and heart rate and adverse events) were evaluated at baseline and followed-up at 2, 4, 8, 12, 18, and 24 weeks. Majority of patients (n=117; 84.8%) completed the study. baPWV decreased significantly at 4 weeks compared with baseline (1,598.87±239.82 vs 1,500.89±241.15 cm/s, P <0.001), was stable at 12 weeks (1,482.24±215.14 cm/s, P <0.001), and remained steady through 24 weeks (1,472.58±205.01 cm/s, P <0.001). Office BP reduced from baseline to week 4 (154/95 vs 136/85 mmHg) and remained steady until 24 weeks. Nifedipine GITS significantly decreased 24-hour ambulatory BP monitoring ( P <0.001) after 24 weeks from baseline. Mean arterial pressure and pulse pressure were lowered significantly after 4, 12, and 24 weeks of treatment ( P <0.001). These changes in baPWV were significantly correlated with changes in systolic blood pressure, diastolic BP, and mean arterial pressure ( P <0.05), but not with changes in pulse pressure ( P >0.05). There were no other drug-related serious adverse events. Nifedipine GITS was considerably effective in reducing baPWV and BP, indicating improvement in arterial stiffness as early as 4 weeks.

Administration of a multistrain probiotic product (VSL#3) to women in the perinatal period differentially affects breast milk beneficial microbiota in relation to mode of delivery.

PubMed

Mastromarino, Paola; Capobianco, Daniela; Miccheli, Alfredo; Praticò, Giulia; Campagna, Giuseppe; Laforgia, Nicola; Capursi, Teresa; Baldassarre, Maria E

2015-01-01

Probiotic supplementation to a mother during the perinatal period can have a positive impact on the breast milk composition. The aim of our study was to evaluate the effect of oral supplementation with the probiotic VSL#3, during late pregnancy and lactation, on breast milk levels of beneficial bacteria and some functional components (oligosaccharides and lactoferrin) potentially able to have a positive influence on the microbiota. Breast milk microbiota was analyzed by conventional and quantitative real-time PCR. In a double-blind, placebo-controlled, randomized trial, 66 women took daily either the probiotic (n=33) or a placebo (n=33). Intergroup analysis demonstrated that the amounts of both lactobacilli and bifidobacteria were significantly higher in the colostrum and mature milk of the mothers taking VSL#3 in comparison to those taking placebo. The analysis of bacterial strains and species present in breast milk of VSL#3 supplemented mothers indicated that the administered probiotic microorganisms did not pass from maternal gut to mammary gland. In women with vaginal delivery, significantly higher amounts of lactobacilli and bifidobacteria were detected in colostrum and mature milk of probiotic treated group in comparison to placebo group, whereas no significant difference was observed between groups in women who had caesarean section, neither in colostrum nor in mature milk. Milk levels of oligosaccharides and lactoferrin were similar in placebo and probiotic supplemented groups at all timepoints and regardless of the mode of delivery. Our results indicate a probiotic-dependent modulation of breast milk microbiota in vaginally delivering women, possibly exerted through a systemic effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gut microbial ecology of lizards: insights into diversity in the wild, effects of captivity, variation across gut regions and transmission.

PubMed

Kohl, Kevin D; Brun, Antonio; Magallanes, Melisa; Brinkerhoff, Joshua; Laspiur, Alejandro; Acosta, Juan Carlos; Caviedes-Vidal, Enrique; Bordenstein, Seth R

2017-02-01

Animals maintain complex associations with a diverse microbiota living in their guts. Our understanding of the ecology of these associations is extremely limited in reptiles. Here, we report an in-depth study into the microbial ecology of gut communities in three syntopic and viviparous lizard species (two omnivores: Liolaemus parvus and Liolaemus ruibali and an herbivore: Phymaturus williamsi). Using 16S rRNA gene sequencing to inventory various bacterial communities, we elucidate four major findings: (i) closely related lizard species harbour distinct gut bacterial microbiota that remain distinguishable in captivity; a considerable portion of gut bacterial diversity (39.1%) in nature overlap with that found on plant material, (ii) captivity changes bacterial community composition, although host-specific communities are retained, (iii) faecal samples are largely representative of the hindgut bacterial community and thus represent acceptable sources for nondestructive sampling, and (iv) lizards born in captivity and separated from their mothers within 24 h shared 34.3% of their gut bacterial diversity with their mothers, suggestive of maternal or environmental transmission. Each of these findings represents the first time such a topic has been investigated in lizard hosts. Taken together, our findings provide a foundation for comparative analyses of the faecal and gastrointestinal microbiota of reptile hosts. © 2016 John Wiley & Sons Ltd.

Biological diversity of yeasts in the gastrointestinal tract of weaned piglets kept under different farm conditions.

PubMed

Urubschurov, Vladimir; Janczyk, Pawel; Pieper, Robert; Souffrant, Wolfgang B

2008-12-01

The study was conducted to determine yeasts present in the gastrointestinal tract (GIT) of piglets kept under experimental farm (EF) and commercial farm (CF) conditions. Ninety five German Landrace full- and half-sibling piglets were sacrificed at 39 days of age. Sixty eight piglets were weaned at 28th day of life, when they were offered one diet ad libitum. Twenty seven piglets remained unweaned by their dams. None of the piglets received any creep feed before weaning. Digesta samples were collected from 1/3 distal small intestine (SI), caecum and proximal colon. One hundred seventy three colonies of isolated yeasts were characterized by sequence analysis of the PCR-amplified D1/D2 domain of the 26S rRNA gene with following alignment of the recovered sequences to GenBank entries. From the 17 phylotypes found, isolates most closely related to Galactomyces geotrichum, Kazachstania slooffiae and Candida catenulata dominated in the GIT of CF piglets. Kazachstania slooffiae and Candida glabrata dominated in GIT of EF piglets. Sørenson and Morisita-Horn similarity indices between farms were low (0.44 and 0.54 respectively) and the Simpson diversity index was higher for EF (7.58) than for CF (4.34). The study brings new data on yeasts composition in the pig GIT and shows differences in yeasts biodiversity between farms operated at different hygiene conditions.

Phylogenetic and genomic analysis of Methanomassiliicoccales in wetlands and animal intestinal tracts reveals clade-specific habitat preferences.

PubMed

Söllinger, Andrea; Schwab, Clarissa; Weinmaier, Thomas; Loy, Alexander; Tveit, Alexander T; Schleper, Christa; Urich, Tim

2016-01-01

Methanogenic Thermoplasmata of the novel order Methanomassiliicoccales were recently discovered in human and animal gastro-intestinal tracts (GITs). However, their distribution in other methanogenic environments has not been addressed systematically. Here, we surveyed Methanomassiliicoccales presence in wetland soils, a globally important source of methane emissions to the atmosphere, and in the GITs of different animals by PCR targeting their 16S rRNA and methyl:coenzyme M reductase (α-subunit) genes. We detected Methanomassiliicoccales in all 16 peat soils investigated, indicating their wide distribution in these habitats. Additionally, we detected their genes in various animal faeces. Methanomassiliicoccales were subdivided in two broad phylogenetic clades designated 'environmental' and 'GIT' clades based on differential, although non-exclusive, habitat preferences of their members. A well-supported cluster within the environmental clade comprised more than 80% of all wetland 16S rRNA gene sequences. Metagenome assembly from bovine rumen fluid enrichments resulted in two almost complete genomes of both Methanomassiliicoccales clades. Comparative genomics revealed that members of the environmental clade contain larger genomes and a higher number of genes encoding anti-oxidative enzymes than animal GIT clade representatives. This study highlights the wide distribution of Methanomassiliicoccales in wetlands, which suggests that they contribute to methane emissions from these climate-relevant ecosystems. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficacy and safety of nifedipine GITS in Chinese patients with hypertension--a post-marketing surveillance study.

PubMed

Huo, Yong; Zhang, Jian; He, Qing; Chen, Hong; Ma, Jishun; Landen, Harald

2007-03-01

This post-marketing surveillance study assessed the efficacy, safety and tolerability of the treatment with nifedipine GITS (gastro-intestinal therapeutic system) in hypertensive patients under normal daily practice conditions in China. A total of 3003 patients were included in 174 outpatient clinics. Patients received 30 mg or 60 mg of nifedipine GITS. Data were collected at up to three follow-up visits. At the end of the observation period, mean treatment duration was 13.3 weeks. Mean blood pressure reduction was 27.6/13.6 mmHg, 62.1% of patients had a systolic blood pressure <140 mmHg, and 82.2% had a diastolic blood pressure <90 mmHg. Blood pressure control according to international guidelines was achieved in 45.0% of all patients. A total of 1515 patients received additional antihypertensive medications, of which angiotensin-converting enzyme (ACE) inhibitors were mostly used (42.2%) followed by beta-blockers (33.7%). Twenty-two patients (0.7%) experienced 27 adverse events. Physicians' assessments of efficacy, tolerability and patient acceptance had ratings of "very good" and "good" in 88.7% (efficacy), 92.8% (tolerability) and 89.1% (patient acceptance) of patients. Nifedipine GITS proved to be effective and well tolerated for the treatment of hypertension in 3003 Chinese patients. The results confirm the findings of previously performed clinical studies.

Effects of dates pulp extract and palm sap (Phoenix dactylifera L.) on gastrointestinal transit activity in healthy rats.

PubMed

Souli, Abdellaziz; Sebai, Hichem; Rtibi, Kaïs; Chehimi, Latifa; Sakly, Mohsen; Amri, Mohamed; El-Benna, Jamel

2014-07-01

The current study was performed to measure the chemical composition and the effects of dates pulp extract and palm sap on gastrointestinal transit (GIT) activity in healthy adult rats. In this respect, male Wistar rats fasted for 24 hours were used and received per orally (p.o.) sodium chloride (NaCl) (0,9%) (control group) or various doses of dates pulp extract (150 and 300 mg/kg, body weight [b.w.]) and palm sap (0.4 and 4 mL/kg, b.w.). Two other groups of rats (batch tests) received, respectively, clonidine (an alpha-2 adrenergic agonist, 1 mg/kg, b.w.) and yohimbine (an alpha-2 adrenergic antagonist, 2mg/kg, b.w.). Chemical analysis showed that the dates pulp extract is more rich in sugars and minerals, especially potassium and sucrose, as compared with palm sap composition. On the other hand, in vivo study showed that the aqueous dates pulp extract significantly, and dose dependently, increased the GIT activity while the palm sap slightly increased it. Moreover, a converse effect has been observed using clonidine (decreased 68%) and yohimbine (increased 33%) on the GIT activity. These findings suggest that dates pulp extract and palm sap have a stimulating effect on GIT activity in rats and confirm their use in traditional Tunisian medicine for the treatment of constipation.

Experimental analysis of tablet properties for discrete element modeling of an active coating process.

PubMed

Just, Sarah; Toschkoff, Gregor; Funke, Adrian; Djuric, Dejan; Scharrer, Georg; Khinast, Johannes; Knop, Klaus; Kleinebudde, Peter

2013-03-01

Coating of solid dosage forms is an important unit operation in the pharmaceutical industry. In recent years, numerical simulations of drug manufacturing processes have been gaining interest as process analytical technology tools. The discrete element method (DEM) in particular is suitable to model tablet-coating processes. For the development of accurate simulations, information on the material properties of the tablets is required. In this study, the mechanical parameters Young's modulus, coefficient of restitution (CoR), and coefficients of friction (CoF) of gastrointestinal therapeutic systems (GITS) and of active-coated GITS were measured experimentally. The dynamic angle of repose of these tablets in a drum coater was investigated to revise the CoF. The resulting values were used as input data in DEM simulations to compare simulation and experiment. A mean value of Young's modulus of 31.9 MPa was determined by the uniaxial compression test. The CoR was found to be 0.78. For both tablet-steel and tablet-tablet friction, active-coated GITS showed a higher CoF compared with GITS. According to the values of the dynamic angle of repose, the CoF was adjusted to obtain consistent tablet motion in the simulation and in the experiment. On the basis of this experimental characterization, mechanical parameters are integrated into DEM simulation programs to perform numerical analysis of coating processes.

Evaluation of water uptake and mechanical properties of blended polymer films for preparing gas-generated multiple-unit floating drug delivery systems.

PubMed

Chen, Ying-Chen; Lee, Lin-Wen; Ho, Hsiu-O; Sha, Chen; Sheu, Ming-Thau

2012-10-01

Among various strategies of gastroretentive drug delivery systems (DDSs) developed to prolong the gastric residence time and to increase the overall bioavailability, effervescent multiple-unit floating DDSs (muFDDSs) were studied here. These systems consist of drug (losartan)- and effervescent (sodium bicarbonate)-containing pellets coated with a blended polymeric membrane, which was a mixture of gastrointestinal tract (GIT)-soluble and GIT-insoluble polymers. The addition of GIT-soluble polymers, such as hydroxypropyl methylcellulose, polyethylene glycol (PEG) 6000, PEG 600, and Kollicoat® IR, greatly increased the water uptake ability of the GIT-insoluble polymers (Eudragit® NE, RS, and RL; Surelease®; and Kollicoat® SR) and caused them to immediately initiate the effervescent reaction and float, but the hydrated films should also be impermeable to the generated CO(2) to maintain floatation and sufficiently flexible to withstand the pressure of carbon dioxide to avoid rupturing. The study demonstrated that the water uptake ability and mechanical properties could be applied as screening tools during the development of effervescent muFDDSs. The optimized system of SRT(5)P600(5) (i.e., a mixture of 5% Kollicoat® SR and 5% PEG 600) with a 20% coating level began to completely float within 15 min and maintained its buoyancy over a period of 12 h with a sustained-release effect. Copyright © 2012 Wiley Periodicals, Inc.

The Significance of Sensitive Interferon Gamma Release Assays for Diagnosis of Latent Tuberculosis Infection in Patients Receiving Tumor Necrosis Factor-α Antagonist Therapy.

PubMed

Jung, Yu Jung; Woo, Hye In; Jeon, Kyeongman; Koh, Won-Jung; Jang, Dong Kyoung; Cha, Hoon Suk; Koh, Eun Mi; Lee, Nam Yong; Kang, Eun-Suk

2015-01-01

We compared two interferon gamma release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, for diagnosis of latent tuberculosis infection (LTBI) in patients before and while receiving tumor necrosis factor (TNF)-α antagonist therapy. This study evaluated the significance of sensitive IGRAs for LTBI screening and monitoring. Before starting TNF-α antagonist therapy, 156 consecutive patients with rheumatic diseases were screened for LTBI using QFT-GIT and T-SPOT.TB tests. According to our study protocol, QFT-GIT-positive patients received LTBI treatment. Patients positive by any IGRAs were subjected to follow-up IGRA tests after completing LTBI-treatment and/or during TNF-α antagonist therapy. At the initial LTBI screening, 45 (28.9%) and 70 (44.9%) patients were positive by QFT-GIT and T-SPOT.TB, respectively. The agreement rate between IGRA results was 78.8% (k = 0.56; 95% confidence interval [95% CI] = 0.43 to 0.68). Of 29 patients who were positive only by T-SPOT.TB in the initial screening, 83% (19/23) were persistently positive by T-SPOT.TB, while QFT-GIT testing showed that 36% (9/25) had conversion during TNF-α antagonist therapy. By the end of the follow-up period (218 to 1,264 days), four patients (4/137, 2.9%) developed active tuberculosis (TB) diseases during receiving TNF-α antagonist therapy. Among them, one was Q-T+, one was Q+T-, and the remaining two were Q-T- at the initial screening (Q, QuantiFERON-TB Gold In-Tube; T, T-SPOT.TB; +, positive; -, negative). Two (2/4, 50%) patients with TB reactivation had at least one prior risk factor consistent with previous TB infection. This study demonstrated the need to capitalize on sensitive IGRAs to monitor for LTBI in at-risk patients for a more sensitive diagnosis in countries with an intermediate TB burden.

Saccharomyces boulardii modifies Salmonella typhimurium traffic and host immune responses along the intestinal tract.

PubMed

Pontier-Bres, Rodolphe; Munro, Patrick; Boyer, Laurent; Anty, Rodolphe; Imbert, Véronique; Terciolo, Chloé; André, Fréderic; Rampal, Patrick; Lemichez, Emmanuel; Peyron, Jean-François; Czerucka, Dorota

2014-01-01

Salmonella enterica serovar Typhimurium (ST) is an enteropathogenic Gram-negative bacterium that causes infection following oral ingestion. ST spreads rapidly along the gastrointestinal tract (GIT) and invades the intestinal epithelium to ultimately reach internal body organs. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is prescribed for prophylaxis of diarrheal infectious diseases. We previously showed that S.b-B prevents weight loss in ST-infected mice and significantly decreases bacterial translocation to the spleen and liver. This study was designed to investigate the effect of S.b-B on ST migration along the GIT and the impact of the yeast on the host's early innate immune responses. Bioluminescent imaging (BLI) was used to evaluate the effect of S.b-B on the progression of luminescent Salmonella Typhimurium (ST-lux) in the GIT of mice pretreated with streptomycin. Photonic emission (PE) was measured in GIT extracts (stomach, small intestine, cecum and colon) at various time periods post-infection (PI). PE analysis revealed that, 45 min PI, ST-lux had migrated slightly faster in the mice treated with S.b-B than in the untreated infected animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice. Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably accounts for (1) the faster elimination of ST-lux in the feces, and (2) reduced translocation of ST to the spleen and liver. In the early phase of infection, S.b-B also modifies the host's immune responses by (1) increasing IFN-γ gene expression and decreasing IL-10 gene expression in the small intestine, and (2) elevating both IFN-γ, and IL-10 mRNA levels in the cecum. BLI revealed that S.b-B modifies ST migration and the host immune response along the GIT. Study findings shed new light on the protective mechanisms of S.b-B during the early phase of Salmonella pathogenesis.

Acupuncture at “Zusanli” (St.36) and “Sanyinjiao” (SP.6) Points on the Gastrointestinal Tract: A Study of the Bioavailability of 99mTc-Sodium Pertechnetate in Rats

PubMed Central

Senna-Fernandes, Vasco; França, Daisy L. M.; de Souza, Deise; Santos, Kelly C. M.; Sousa, Rafael S.; Manoel, Cristiano V.; Santos-Filho, Sebastião D.; Cortez, Célia M.; Bernardo-Filho, Mario; Guimarães, Marco Antonio M.

2011-01-01

The objective of this study is to investigate the differences of acupuncture effect between the Zusanli (St.36) and Sanyinjiao (SP.6) points on the gastrointestinal-tract (GIT) segment performed by the bioavailability of 99mTc-sodium-pertechnetate (Na99mTcO4) in rats. Male Wistar rats (n = 21) were allocated into three groups of seven each. Group 1 was treated by acupuncture bilaterally at St.36; Group 2 at SP.6; and Group 3 was untreated (control). After 10 min of needle insertion in anesthetized rats, 0.3 mL of Na99mTcO4 (7.4 MBq) was injected via ocular-plexus. After 20 min, the exitus of animals was induced by cervical-dislocation and GIT organs isolated. However, immediately before the exitus procedure, blood was collected by cardiac-puncture for blood radio-labeling (BRL). The radioactivity uptake of the blood constituents was calculated together with the GIT organs by a well gamma counter. The percentage of injected dose per gram of tissue (%ID/g) of Na99mTcO4 was calculated for each GIT organs, while BRL was calculated in %ID. According to the one-way ANOVA, the stomach, jejunum, ileum from the treated groups (Group 1 and Group 2) had significant differences compared to the controls (Group 3). However, between the treated groups (Group 1 and Group 2), there were significant differences (P < .05) in the stomach, jejunum, ileum, cecum, transverse and rectum. In BRL analysis, Group 2 showed significant increase and decrease of the insoluble and soluble fractions of the blood cells, respectively (P < .0001). The authors suggest that St.36 may have a tendency of up-regulation effect on GIT, whereas SP.6, down-regulation effect. However, further rigorous experimental studies to examine the effectiveness of acupuncture in either acupuncture points need to be carried out. PMID:19213853

Use of the QuantiFERON-TB Gold In-Tube Test in the Diagnosis and Monitoring of Treatment Efficacy in Active Pulmonary Tuberculosis.

PubMed

Chang, Ping-Chin; Wang, Pin-Hui; Chen, Kow-Tong

2017-02-27

The value of QuantiFERON in the diagnosis of tuberculosis disease and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 133 cases with active PTB and 133 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. PTB patients IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; p < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment.

Maternal exposure to GOS/inulin mixture prevents food allergies and promotes tolerance in offspring in mice.

PubMed

Bouchaud, G; Castan, L; Chesné, J; Braza, F; Aubert, P; Neunlist, M; Magnan, A; Bodinier, M

2016-01-01

Food allergies affect 4-8% of children and are constantly on the rise, thus making allergies a timely issue. Most importantly, prevention strategies are nonexistent, and current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies, particularly during infancy, could consist of modulating maternal immunity and microbiota using nondigestible food ingredients, such as prebiotics. For this purpose, we studied the preventive effects of prebiotics in Balb/c mothers during pregnancy and breastfeeding on food allergy development in offspring mice. After weaning, the offspring from mothers that were exposed to GOS/inulin mixture or fed a control diet were intraperitoneally sensitized to wheat proteins to induce a systemic allergic response and orally exposed to the same allergen. Immunological, physiological, and microbial parameters were analyzed. GOS/inulin mixture diet modified the microbiota of mothers and their offspring. Offspring from mothers that received GOS/inulin prebiotics were protected against food allergies and displayed lower clinical scores, specifically of IgE and histamine levels, compared to offspring from mothers fed a control diet. Moreover, GOS/inulin supplementation for the mother resulted in stronger intestinal permeability in the offspring. Enhancement of the regulatory response to allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response were observed in mice from GOS/inulin mixture-exposed mothers. The treatment of pregnant and lactating mice with nondigestible GOS/inulin prebiotics promotes a long-term protective effect against food allergies in the offspring. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk.

PubMed

Collado, Maria Carmen; Laitinen, Kirsi; Salminen, Seppo; Isolauri, Erika

2012-07-01

Breast milk is an optimal source of nutrition for infants. It contains bioactive components including bacteria that support the microbial colonization and immune system development of the infant. The determinants of human milk composition remain poorly understood, although maternal nutritional and immunological status as well as lifestyle and dietary habits seem to have an impact. The subjects selected were women from a prospective follow-up study categorized by BMI. Milk samples were taken after delivery and at 1 and 6 mo later for analysis of composition in regard to transforming growth factor (TGF)-β2, soluble CD14 (sCD14), cytokines, and microbiota. TGF-β2 and sCD14 levels in the breast milk of overweight mothers tended to be lower than the levels in that of normal-weight mothers. Also, higher levels of Staphylococcus group bacteria and lower levels of Bifidobacterium group bacteria were detected in overweight mothers as compared with normal-weight ones. The prevalence of Akkermansia muciniphila-type bacteria was also higher in overweight mothers, and the numbers of these bacteria were related to the interleukin (IL)-6 concentration in the colostrum, which was in turn related to lower counts of Bifidobacterium group bacteria in the breast milk of overweight women. Complex interactions of cytokines and microbiota in breast milk guide the microbiological, immunological, and metabolic programming of infant health. Our data may indicate the presence of an additional mechanism that may explain the heightened risk of obesity for infants of overweight and excessive weight gain mothers.

Gut Microbiota Composition in Mid-Pregnancy Is Associated with Gestational Weight Gain but Not Prepregnancy Body Mass Index.

PubMed

Aatsinki, Anna-Katariina; Uusitupa, Henna-Maria; Munukka, Eveliina; Pesonen, Henri; Rintala, Anniina; Pietilä, Sami; Lahti, Leo; Eerola, Erkki; Karlsson, Linnea; Karlsson, Hasse

2018-05-14

Pregnancy is a time of numerous hormonal, metabolic, and immunological changes for both the mother and the fetus. Furthermore, maternal gut microbiota composition (GMC) is altered during pregnancy. One major factor affecting GMC in pregnant and nonpregnant populations is obesity. The aim was to analyze associations between maternal overweight/obesity, as well as gestational weight gain (GWG) and GMC. Moreover, the modifying effect of depression and anxiety symptom scores on weight and GMC were investigated. Study included 46 women from the FinnBrain Birth Cohort study, of which 36 were normal weight, and 11 overweight or obese according to their prepregnancy body mass index (BMI). Stool samples were collected in gestational week 24, and the GMC was sequenced with Illumina MiSeq approach. Hierarchical clustering was executed to illuminate group formation according to the GMC. The population was divided according to Firmicutes and Bacteroidetes dominance. Symptoms of depression, general anxiety, and pregnancy-related anxiety were measured by using standardized questionnaires. Excessive GWG was associated with distinct GMC in mid-pregnancy as measured by hierarchical clustering and grouping according to Firmicutes or Bacteroidetes dominance, with Bacteroidetes being prominent and Firmicutes being less prominent in the GMC among those with increased GWG. Reduced alpha diversity was observed among the Bacteroidetes-dominated subjects. There were no zero-order effects between the abundances of bacterial genera or phyla, alpha or beta diversity, and prepregnancy BMI or GWG. Bacteroidetes-dominated GMC in mid-pregnancy is associated with increased GWG and reduced alpha diversity.

Administration of probiotics Lactobacillus rhamnosus GG and Lactobacillus gasseri K7 during pregnancy and lactation changes mouse mesenteric lymph nodes and mammary gland microbiota.

PubMed

Treven, P; Mrak, V; Bogovič Matijašić, B; Horvat, S; Rogelj, I

2015-04-01

The milk and mammary gland (MG) microbiome can be influenced by several factors, such as mode of delivery, breastfeeding, maternal lifestyle, health status, and diet. An increasing number of studies show a variety of positive effects of consumption of probiotics during pregnancy and breastfeeding on the mother and the newborn. The aim of this study was to investigate the effect of oral administration of probiotics Lactobacillus gasseri K7 (LK7) and Lactobacillus rhamnosus GG (LGG) during pregnancy and lactation on microbiota of the mouse mesenteric lymph nodes (MLN), MG, and milk. Pregnant FVB/N mice were fed skim milk or probiotics LGG or LK7 resuspended in skim milk during gestation and lactation. On d 3 and 8 postpartum, blood, feces, MLN, MG, and milk were analyzed for the presence of LGG or LK7. The effects of probiotics on MLN, MG, and milk microbiota was evaluated by real-time PCR and by 16S ribosomal DNA 454-pyrosequencing. In 5 of 8 fecal samples from the LGG group and in 5 of 8 fecal samples from the LK7 group, more than 1 × 10(3) of live LGG or LK7 bacterial cells were detected, respectively, whereas no viable LGG or LK7 cells were detected in the control group. Live lactic acid bacteria but no LGG or LK7 were detected in blood, MLN, and MG. Both probiotics significantly increased the total bacterial load as assessed by copies of 16S ribosomal DNA in MLN, and a similar trend was observed in MG. Metagenomic sequencing revealed that both probiotics increased the abundance of Firmicutes in MG, especially the abundance of lactic acid bacteria. The Lactobacillus genus appeared exclusively in MG from probiotic groups. Both probiotics influenced MLN microbiota by decreasing diversity (Chao1) and increasing the distribution of species (Shannon index). The LGG probiotic also affected the MG microbiota as it increased diversity and distribution of species and proportions of the genera Lactobacillus and Bifidobacterium. These results provide evidence that probiotics can modulate the bacterial composition of MLN and MG microbiota in ways that could improve the health of the MG and, ultimately, the health of the newborn. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Drug-nutrient interactions in enteral feeding: a primary care focus.

PubMed

Varella, L; Jones, E; Meguid, M M

1997-06-01

Drug and nutrient interactions are complex and can take many forms, including malabsorption of either the drug or the nutrient component. Some drugs can stimulate or suppress appetite, whereas others can cause nausea and vomiting resulting in inadequate nutritional intake. Absorption of drugs is a complex process that can be affected by the physical characteristics of the gastrointestinal tract (GIT) as well. Depending on the physical properties of a drug, it may be absorbed in a limited area of the GIT or more diffusely along much of the entire length. Many diseases and conditions are also known to affect the GIT either directly or indirectly. Dietary factors also need to be considered when the "food" is an enteral formula. The widespread use of enteral tubes requires that consideration be given to patients receiving both enteral feedings and medication concurrently. The location of a tube in the gastrointestinal tract, as well as the problems involved in crushing and administering solid dosage forms, creates a unique set of problems.

Influence of Homogenization and Thermal Processing on the Gastrointestinal Fate of Bovine Milk Fat: In Vitro Digestion Study.

PubMed

Liang, Li; Qi, Ce; Wang, Xingguo; Jin, Qingzhe; McClements, David Julian

2017-12-20

Dairy lipids are an important source of energy and nutrients for infants and adults. The dimensions, aggregation state, and interfacial properties of fat globules in raw milk are changed by dairy processing operations, such as homogenization and thermal processing. These changes influence the behavior of fat globules within the human gastrointestinal tract (GIT). The gastrointestinal fate of raw milk, homogenized milk, high temperature short time (HTST) pasteurized milk, and ultrahigh temperature (UHT) pasteurized milk samples was therefore determined using a simulated GIT. The properties of particles in different regions of the GIT depended on the degree of milk processing. Homogenization increased the initial lipid digestion rate but did not influence the final digestion extent. Thermal processing of homogenized milk decreased the initial rate and final extent of lipid digestion, which was attributed to changes in interfacial structure. These results provide insights into the impact of dairy processing on the gastrointestinal fate of milk fat.

A comparative assessment of the duration of action of amlodipine and nifedipine GITS in normotensive subjects.

PubMed

Ueda, S; Meredith, P A; Howie, C A; Elliott, H L

1993-12-01

1 This study in normotensive subjects compared the duration and consistency of action of amlodipine (5 mg) and nifedipine GITS (60 mg) by assessment of the attenuation of pressor responses to noradrenaline and angiotensin II. 2 Both drugs significantly attenuated pressor responses to both vasoconstrictors at 6 and 24 h post-dose with rightward shifts of up to 2.3-fold in the dose-response curves. 3 There was significantly less pharmacokinetic variability with amlodipine: for example, intra-subject variability was 33% with amlodipine and 59% with nifedipine GITS. 4 There were no significant differences in the pressor dose ratios up to 48 h post-dose with amlodipine whereas there was a significant and progressive reduction in the pressor dose ratios with nifedipine. 5 These results suggest that both drugs are broadly comparable as once daily treatments but amlodipine displayed less intra- and inter-subject variability and provided a significantly more sustained effect with a reserve of pharmacological activity up to 48 h post-dose.

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

PubMed

Castleden, C M; Pickles, H

1988-10-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age.

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

PubMed Central

Castleden, C M; Pickles, H

1988-01-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age. PMID:3263875

Evidence-based interventions for improvement of maternal and child nutrition in low-income settings: what's new?

PubMed

Vaivada, Tyler; Gaffey, Michelle F; Das, Jai K; Bhutta, Zulfiqar A

2017-05-01

Maternal and child malnutrition continues to disproportionately affect low and middle-income countries, contributing to high rates of morbidity, mortality, and suboptimal development. This article reviews evidence from recent systematic reviews and studies on the effectiveness of interventions to improve nutritional status in these especially vulnerable populations. Macronutrients provided to expectant mothers in the form of balanced protein energy supplements can improve fetal growth and birth outcomes, and new research suggests that lipid nutrient supplements can reduce both stunting and wasting in newborns. Maternal multiple micronutrient supplementations can also improve fetal growth, and reduce the risk of stillbirth. Nutrition education and supplementation provided to pregnant adolescents can also improve birth outcomes in this vulnerable population. New evidence is broadening our understanding of the development of gut microbiota in malnourished infants, and the possible protective role of breastmilk. The reviewed evidence on nutrition interventions reinforces the importance of packaging interventions delivered within critical windows throughout the life course: before conception, during pregnancy, and throughout childhood. Emerging evidence continues to refine our understanding of which populations and contexts benefit from which intervention components, which should allow for more nuanced and tailored approaches to the implementation of nutrition interventions.

Emerging literature in the Microbiota-Brain Axis and Perinatal Mood and Anxiety Disorders.

PubMed

Rackers, Hannah S; Thomas, Stephanie; Williamson, Kelsey; Posey, Rachael; Kimmel, Mary C

2018-05-17

Perinatal Mood and Anxiety Disorders (PMAD) are common and can cause significant morbidity and mortality for mother and child. A healthy perinatal period requires significant adaptations; however, systems can become imbalanced resulting in depressive and anxiety symptoms. The interface between the microbiome, the immune system, and the stress system may be a model for understanding mechanisms underlying PMAD. Emerging literature from general populations regarding immune, hormone, and HPA axis changes in relation to the microbiome combined with literature on immune, gonadotropin, and stress systems in the perinatal period provides a background. We systematically investigated literature in the developing field of the microbiome in relation to PMAD. Our inclusion criteria were 1) reporting measure of maternal mood, stress, or anxious or depressed behavior; 2) in the perinatal period, defined as pregnancy through one year postpartum; and 3) reporting measure of maternal microbiome including manipulations of the microbiome through prebiotics, probiotics, or interventions with microbial byproducts. The review identified research studying associations between stress and maternal microbiome; dietary impacts on microbial composition, mood, and stress; and the relationship between the microbiome and the immune system through immunoregulatory mechanisms. Important themes identified include: the importance of studying the maternal microbiome and measures of stress, anxiety, and depression and that multi-hit models will be needed as research strives to determine the effects of multiple mechanisms working in concert. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early intervention of long-acting nifedipine GITS reduces brachial–ankle pulse wave velocity and improves arterial stiffness in Chinese patients with mild hypertension: a 24-week, single-arm, open-label, prospective study

PubMed Central

Zhang, Jidong; Wang, Yan; Hu, Haijuan; Yang, Xiaohong; Tian, Zejun; Liu, Demin; Gu, Guoqiang; Zheng, Hongmei; Xie, Ruiqin; Cui, Wei

2016-01-01

Background Nifedipine gastrointestinal therapeutic system (GITS) is used to treat angina and hypertension. The authors aimed to study the early intervention impact on arterial stiffness and pulse wave velocity (PWV) independent of its blood-pressure-(BP) lowering effect in mild hypertensive patients. Methods This single-center, single-arm, open-label, prospective, Phase IV study recruited patients with mild hypertension and increased PWV from December 2013 to December 2014 (N=138; age, 18–75 years; systolic blood pressure, 140–160 mmHg; diastolic BP, 90–100 mmHg; increased brachial–ankle pulse wave velocity [baPWV, ≥12 m/s]). Nifedipine GITS (30 mg/d) was administered for 24 weeks to achieve target BP of <140/90 mmHg. The dose was uptitrated at 60 mg/d in case of unsatisfactory BP reduction after 4 weeks. Primary study end point was the change in baPWV after nifedipine GITS treatment. Hemodynamic parameters (office BP, 24-hour ambulatory BP monitoring, and heart rate and adverse events) were evaluated at baseline and followed-up at 2, 4, 8, 12, 18, and 24 weeks. Results Majority of patients (n=117; 84.8%) completed the study. baPWV decreased significantly at 4 weeks compared with baseline (1,598.87±239.82 vs 1,500.89±241.15 cm/s, P<0.001), was stable at 12 weeks (1,482.24±215.14 cm/s, P<0.001), and remained steady through 24 weeks (1,472.58±205.01 cm/s, P<0.001). Office BP reduced from baseline to week 4 (154/95 vs 136/85 mmHg) and remained steady until 24 weeks. Nifedipine GITS significantly decreased 24-hour ambulatory BP monitoring (P<0.001) after 24 weeks from baseline. Mean arterial pressure and pulse pressure were lowered significantly after 4, 12, and 24 weeks of treatment (P<0.001). These changes in baPWV were significantly correlated with changes in systolic blood pressure, diastolic BP, and mean arterial pressure (P<0.05), but not with changes in pulse pressure (P>0.05). There were no other drug-related serious adverse events. Conclusion Nifedipine GITS was considerably effective in reducing baPWV and BP, indicating improvement in arterial stiffness as early as 4 weeks. PMID:27799740

Interactions between barley grain processing and source of supplemental dietary fat on nitrogen metabolism and urea-nitrogen recycling in dairy cows.

PubMed

Gozho, G N; Hobin, M R; Mutsvangwa, T

2008-01-01

The objective of this study was to determine the effects of methods of barley grain processing and source of supplemental fat on urea-N transfer to the gastrointestinal tract (GIT) and the utilization of this recycled urea-N in lactating dairy cows. Four ruminally cannulated Holstein cows (656.3 +/- 27.7 kg of BW; 79.8 +/- 12.3 d in milk) were used in a 4 x 4 Latin square design with 28-d periods and a 2 x 2 factorial arrangement of dietary treatments. Experimental diets contained dry-rolled barley or pelleted barley in combination with whole canola or whole flaxseed as supplemental fat sources. Nitrogen balance was measured from d 15 to 19, with concurrent measurements of urea-N kinetics using continuous intrajugular infusions of [15N 15N]-urea. Dry matter intake and N intake were higher in cows fed dry-rolled barley compared with those fed pelleted barley. Nitrogen retention was not affected by diet, but fecal N excretion was higher in cows fed dry-rolled barley than in those fed pelleted barley. Actual and energy-corrected milk yield were not affected by diet. Milk fat content and milk fat yield were higher in cows fed dry-rolled barley compared with those fed pelleted barley. Source of supplemental fat did not affect urea-N kinetics. Urea-N production was higher (442.2 vs. 334.3 g of N/d), and urea-N entering the GIT tended to be higher (272.9 vs. 202.0 g of N/d), in cows fed dry-rolled barley compared with those fed pelleted barley. The amount of urea-N entry into the GIT that was returned to the ornithine cycle was higher (204.1 vs. 159.5 g of N/d) in cows fed dry-rolled barley than in pelleted barley-fed cows. The amount of urea-N recycled to the GIT and used for anabolic purposes, and the amounts lost in the urine or feces were not affected by dietary treatment. Microbial nonammonia N supply, estimated using total urinary excretion of purine derivatives, was not affected by diet. These results show that even though barley grain processing altered urea-N entry into the GIT, the utilization of this recycled urea-N for microbial production was unaffected as the additional urea-N, which entered the GIT was returned to ureagenesis.

Microbial transmission from mothers with obesity or diabetes to infants: an innovative opportunity to interrupt a vicious cycle

PubMed Central

Soderborg, Taylor K.; Borengasser, Sarah J.; Barbour, Linda A.; Friedman, Jacob E.

2016-01-01

Maternal obesity and diabetes dramatically increase the long-term risk for obesity in the next generation, and pregnancy and lactation may be critical periods at which to aim primary prevention to break the obesity cycle. It is becoming increasingly clear that the gut microbiome in newborns and infants plays a significant role in gut health and therefore child development. Alteration of the early infant gut microbiome has been correlated with the development of childhood obesity and autoimmune conditions, including asthma, allergies and, more recently, type 1 diabetes. This is likely to be due to complex interactions between mode of delivery, antibiotic use, maternal diet, components of breastfeeding and a network of regulatory events involving both the innate and adaptive immune systems within the infant host. Each of these factors are critical for informing microbiome development and can affect immune signalling, toxin release and metabolic signals, including short-chain fatty acids and bile acids, that regulate appetite, metabolism and inflammation. In several randomised controlled trials, probiotics have been administered with the aim of targeting the microbiome during pregnancy to improve maternal and infant health but the findings have often been confounded by mode of delivery, antibiotic use, ethnicity, infant sex, maternal health and length of exposure. Understanding how nutritional exposure, including breast milk, affects the assembly and development of both maternal and infant microbial communities may help to identify targeted interventions during pregnancy and in infants born to mothers with obesity or diabetes to slow the transmission of obesity risk to the next generation. The aim of this review is to discuss influences on infant microbiota colonisation and the mechanism(s) underlying how alterations due to maternal obesity and diabetes may lead to increased risk of childhood obesity. PMID:26843076

Oral supplements of inulin during gestation offsets rotenone-induced oxidative impairments and neurotoxicity in maternal and prenatal rat brain.

PubMed

Krishna, Gokul; Muralidhara

2018-05-25

Environmental insults including pesticide exposure and their entry into the immature brain are of increased concern due to their developmental neurotoxicity. Several lines of evidence suggest that maternal gut microbiota influences in utero fetal development via modulation of host's microbial composition with prebiotics. Hence we examined the hypothesis if inulin (IN) supplements during pregnancy in rats possess the potential to alleviate brain oxidative response and mitochondrial deficits employing a developmental model of rotenone (ROT) neurotoxicity. Initially, pregnant Sprague-Dawley rats were gavaged during gestational days (GDs) 6-19 with 0 (control), 10 (low), 30 (mid) or 50 (high) mg/kg bw/day of ROT to recapitulate developmental effects on general fetotoxicity (assessed by the number of fetuses, fetal body and placental weights), markers of oxidative stress and cholinergic activities in maternal brain regions and whole fetal-brain. Secondly, dams orally supplemented with inulin (2×/day, 2 g/kg/bw) on GD 0-21 were administered ROT (50 mg/kg, GD 6-19). IN supplements increased maternal cecal bacterial numbers that significantly corresponded with improved exploratory-related behavior among ROT administered rats. In addition, IN supplements improved fetal and placental weight on GD 19. IN diminished gestational ROT-induced increased reactive oxygen species levels, protein and lipid peroxidation biomarkers, and cholinesterase activity in maternal brain regions (cortex, cerebellum, and striatum) and fetal brain. Moreover, in the maternal cortex, mitochondrial assessment revealed IN protected against ROT-induced reduction in NADH cytochrome c oxidoreductase and ATPase activities. These data suggest a potential role for indigestible oligosaccharides in reducing oxidative stress-mediated developmental origins of neurodegenerative disorders. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Microbial transmission from mothers with obesity or diabetes to infants: an innovative opportunity to interrupt a vicious cycle.

PubMed

Soderborg, Taylor K; Borengasser, Sarah J; Barbour, Linda A; Friedman, Jacob E

2016-05-01

Maternal obesity and diabetes dramatically increase the long-term risk for obesity in the next generation, and pregnancy and lactation may be critical periods at which to aim primary prevention to break the obesity cycle. It is becoming increasingly clear that the gut microbiome in newborns and infants plays a significant role in gut health and therefore child development. Alteration of the early infant gut microbiome has been correlated with the development of childhood obesity and autoimmune conditions, including asthma, allergies and, more recently, type 1 diabetes. This is likely to be due to complex interactions between mode of delivery, antibiotic use, maternal diet, components of breastfeeding and a network of regulatory events involving both the innate and adaptive immune systems within the infant host. Each of these factors are critical for informing microbiome development and can affect immune signalling, toxin release and metabolic signals, including short-chain fatty acids and bile acids, that regulate appetite, metabolism and inflammation. In several randomised controlled trials, probiotics have been administered with the aim of targeting the microbiome during pregnancy to improve maternal and infant health but the findings have often been confounded by mode of delivery, antibiotic use, ethnicity, infant sex, maternal health and length of exposure. Understanding how nutritional exposure, including breast milk, affects the assembly and development of both maternal and infant microbial communities may help to identify targeted interventions during pregnancy and in infants born to mothers with obesity or diabetes to slow the transmission of obesity risk to the next generation. The aim of this review is to discuss influences on infant microbiota colonisation and the mechanism(s) underlying how alterations due to maternal obesity and diabetes may lead to increased risk of childhood obesity.

Is the role of human female reproductive tract microbiota underestimated?

PubMed

Kamińska, D; Gajecka, M

2017-05-30

An issue that is currently undergoing extensive study is the influence of human vaginal microbiota (VMB) on the health status of women and their neonates. Healthy women are mainly colonised with lactobacilli such as Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus iners; however, other bacteria may be elements of the VMB, particularly in women with bacterial vaginosis. The implementation of culture-independent molecular methods in VMB characterisation, especially next-generation sequencing, have provided new information regarding bacterial diversity in the vagina, revealing a large number of novel, fastidious, and/or uncultivated bacterial species. These molecular studies have contributed new insights regarding the role of bacterial community composition. In this study, we discuss recent findings regarding the reproductive tract microbiome. Not only bacteria but also viruses and fungi constitute important components of the reproductive tract microbiome. We focus on aspects related to the impact of the maternal microbiome on foetal development, as well as the establishment of the neonatal microbiomes, including the placenta microbiome, and the haematogenous source of intrauterine infection. We also discuss whether the role of the vaginal microbiome is currently understood and appreciated.

Intervention strategies for cesarean section–induced alterations in the microbiota-gut-brain axis

PubMed Central

Moya-Pérez, Angela; Luczynski, Pauline; Renes, Ingrid B.; Wang, Shugui; Borre, Yuliya; Anthony Ryan, C.; Knol, Jan; Stanton, Catherine; Dinan, Timothy G.

2017-01-01

Microbial colonization of the gastrointestinal tract is an essential process that modulates host physiology and immunity. Recently, researchers have begun to understand how and when these microorganisms colonize the gut and the early-life factors that impact their natural ecological establishment. The vertical transmission of maternal microbes to the offspring is a critical factor for host immune and metabolic development. Increasing evidence also points to a role in the wiring of the gut-brain axis. This process may be altered by various factors such as mode of delivery, gestational age at birth, the use of antibiotics in early life, infant feeding, and hygiene practices. In fact, these early exposures that impact the intestinal microbiota have been associated with the development of diseases such as obesity, type 1 diabetes, asthma, allergies, and even neurodevelopmental disorders. The present review summarizes the impact of cesarean birth on the gut microbiome and the health status of the developing infant and discusses possible preventative and restorative strategies to compensate for early-life microbial perturbations. PMID:28379454

L-form bacteria cohabitants in human blood: significance for health and diseases.

PubMed

Markova, Nadya D

2017-05-01

From a historical perspective, intriguing assumptions about unknown "live units" in human blood have attracted the attention of researchers, reflecting their desire to define a new class of microorganisms. Thus, the concept of "blood microbiota" brings about many questions about the nature, origin, and biological significance of the "unusual microbial cohabitants" in human blood. In contrast to current views that bloodstream in healthy humans is sterile, the hypothesis about the existence of microbes as L-forms (cell wall deficient bacteria) in human blood has evolved on the basis of known facts about their unique biology, as observed in our studies and those of other authors. Recently, we reported that bacterial L-forms persist in the human blood and that filterable, self-replicating bodies with a virus-like size of 100 nm are able to cross the maternal-fetal barrier by vertically transmitted pathway, then enter fetus blood circulation and colonize newborns. Subjects discussed here include the following: Is the existence of L-form bacteria in human blood a natural phenomenon? Are L-form bacteria commensal cohabitants in the human body? Since blood is an unfavorable compartment for the classical bacteria and their propagation, how do L-forms survive in blood circulation? How does L-form microbiota in blood influence the host immune system and contribute to systemic inflammatory, autoimmune, and tumor diseases? The current commentary presents the topic of "human microbiota and L-form bacteria" in its microcosm. It contains details of the hypothesis, supporting evidence and important implications.

Probiotics in early life: a preventative and treatment approach.

PubMed

Hashemi, Ashkan; Villa, Christopher R; Comelli, Elena M

2016-04-01

Microbial colonization of the infant gut plays a key role in immunological and metabolic pathways impacting human health. Since the maturation of the gut microbiota coincides with early life development, failure to develop a health compatible microbiota composition may result in pathology and disease in later life. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Maternal transfer of microorganisms is possible during pregnancy and lactation, and the mother's diet and microbiota can influence that of her offspring. Furthermore, pre-term birth, Caesarean section birth, formula feeding, antibiotic use, and malnutrition have been linked to dysbiosis, which in turn is associated with several pathologies such as necrotizing enterocolitis, inflammatory bowel diseases, antibiotic associated diarrhea, colic, and allergies. Thus, early life should represent a preferred stage of life for probiotic interventions. In this context, they could be regarded as a means to 'program' the individual for health maintenance, in order to prevent pathologies associated with dysbiosis. In order to elucidate the mechanisms underlying the benefits of probiotic administration, pre-clinical studies have been conducted and found an array of positive results such as improved microbial composition, intestinal maturation, decreased pathogenic load and infections, and improved immune response. Moreover, specific probiotic strains administered during the perinatal period have shown promise in attenuating severity of necrotizing enterocolitis. The mechanisms elucidated suggest that probiotic interventions in early life can be envisaged for disease prevention in both healthy offspring and offspring at risk of chronic disease.

FFA2 Contribution to Gestational Glucose Tolerance Is Not Disrupted by Antibiotics.

PubMed

Fuller, Miles; Li, Xiaoran; Fisch, Robert; Bughara, Moneb; Wicksteed, Barton; Kovatcheva-Datchary, Petia; Layden, Brian T

2016-01-01

During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during pregnancy. As impaired gestational glucose levels can affect metabolic health of offspring, we aimed to explore the role of maternal Ffar2 expression during pregnancy on the metabolic health of offspring and also the effects of antibiotics, which have been shown to disrupt gut microbiota fermentative activity (the source of the FFA2 ligands) on gestational glucose homeostasis. We found that maternal Ffar2 expression and impaired glucose tolerance during pregnancy had no effect on the growth rates, ad lib glucose and glucose tolerance in the offspring between 3 and 6 weeks of age. To disrupt short chain fatty acid production, we chronically treated WT mice and Ffar2-/- mice with broad range antibiotics and further compared their glucose tolerance prior to pregnancy and at gestational day 15, and also quantified cecum and plasma SCFAs. We found that during pregnancy antibiotic treatment reduced the levels of SCFAs in the cecum of the mice, but resulted in elevated levels of plasma SCFAs and altered concentrations of individual SCFAs. Along with these changes, gestational glucose tolerance in WT mice, but not Ffar2-/- mice improved while on antibiotics. Additional data showed that gestational glucose tolerance worsened in Ffar2-/- mice during a second pregnancy. Together, these results indicate that antibiotic treatment alone is inadequate to deplete plasma SCFA concentrations, and that modulation of gut microbiota by antibiotics does not disrupt the contribution of FFA2 to gestational glucose tolerance.

Neutral oligosaccharides in feces of breastfed and formula-fed infants at different ages.

PubMed

Dotz, Viktoria; Adam, Rüdiger; Lochnit, Günter; Schroten, Horst; Kunz, Clemens

2016-12-01

Beneficial effects have been proposed for human milk oligosaccharides (HMO), as deduced from in vitro and animal studies. To date, in vivo evidence of the link between certain oligosaccharide structures in milk and their consumption by infant gut microbiota is still missing, although likely. Whereas many studies have described HMO patterns in human milk from larger cohorts, data on the excretion of HMO and possible metabolites produced in the infant gut are still very limited. From smaller-scale studies, an age-dependency according to infant gut maturation and microbiota adaptation has previously been hypothesized. To further investigate this, we profiled neutral fecal oligosaccharides from term-born infants who were exclusively breastfed, formula-fed or mixed-fed at the age of 2 months, and from a follow-up of a subgroup at 7 months of age (INFABIO study). Data on maternal antibiotic exposure was also included. Automated matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analyses revealed the presence of HMO and metabolites in the feces of most, but not all breastfed infants at 2 months, with highly varying patterns that appeared not to differ with maternal antibiotics exposure. Formula-fed infants at 2 months and most of the breastfed infants at 7 months did not excrete HMO-like structures in their feces, the latter corresponding to the hypothesis of age-dependency. Together with our previous results that were partly contradictory to what has been proposed by others, here, we suggest alternative explanations for the described association of oligosaccharide excretion with age and feeding type in infants below 7 months of age. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Breast Milk Transforming Growth Factor β Is Associated With Neonatal Gut Microbial Composition.

PubMed

Sitarik, Alexandra R; Bobbitt, Kevin R; Havstad, Suzanne L; Fujimura, Kei E; Levin, Albert M; Zoratti, Edward M; Kim, Haejin; Woodcroft, Kimberley J; Wegienka, Ganesa; Ownby, Dennis R; Joseph, Christine L M; Lynch, Susan V; Johnson, Christine C

2017-09-01

Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota. A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)β1, TGFβ2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing. Individually, immunomodulators TGFβ1 and TGFβ2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFβ1 and TGFβ2, however, were not independent of one another, and the effect of TGFβ2 was stronger than that of TGFβ1. Higher levels of TGFβ2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa. Breast milk TGFβ concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFβ acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.

Randomized trial comparing the effects of a low-dose combination of nifedipine GITS and valsartan versus high-dose monotherapy on central hemodynamics in patients with inadequately controlled hypertension: FOCUS study.

PubMed

Park, Jeong Bae; Ha, Jong-Won; Jung, Hae-Ok; Rhee, Moo-Yong

2014-10-01

Measurement of central blood pressure provides prognostic information beyond conventional peripheral blood pressure (BP). However, few studies have directly compared the effects of antihypertensives on central hemodynamics. This study investigated the effects of a low-dose combination of nifedipine Gastrointestinal Therapeutic System (GITS) and valsartan versus high-dose monotherapy with either agent in reducing central BP in essential hypertension inadequately controlled by low-dose monotherapy. In this prospective, open-label, randomized, active-controlled, multicenter 8-week study, patients not meeting the target BP after 4 weeks of treatment with low-dose monotherapy were randomized to receive nifedipine GITS 30 mg plus valsartan 80 mg (N30+V80), nifedipine GITS 60 mg (N60), or valsartan 160 mg (V160) for a further 4 weeks. Central hemodynamics were measured by applanation tonometry. A total of 391 patients were enrolled. Reduction in central systolic BP from baseline to week 8, the primary efficacy variable, was significantly greater in the N30+V80 group (-27.2±14.7 mmHg) and the N60 group (-27.1±16.5 mmHg) compared with V160 group (-14.4±16.6 mmHg). Decrease in the augmentation index in the N60 group was significantly greater compared with V160 alone, without differences between combination therapy and either high-dose monotherapy. Decreases in brachial systolic BP were significantly greater in the N30+V80 and N60 groups than in the V160 group. By multiple regression analysis, most differences in drug effects on central hemodynamics disappeared after controlling for changes in peripheral BP. A low rate of adverse events occurred in all treatment groups. A low-dose combination of nifedipine GITS plus valsartan or high-dose nifedipine was more effective in improving central hemodynamics than high-dose valsartan in patients with hypertension, mostly because of the improvement in peripheral (brachial) hemodynamics.

Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca

Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable andmore » stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.« less

Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii

DOE PAGES

Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca; ...

2015-04-21

Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable andmore » stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.« less

Antituberculosis IgG Antibodies as a Marker of Active Mycobacterium tuberculosis Disease

PubMed Central

Welch, Ryan J.; Lawless, Kathleen M.

2012-01-01

Anti-Mycobacterium tuberculosis IgG antibodies may aid in the diagnosis of active M. tuberculosis disease. We studied whether anti-M. tuberculosis IgG antibodies are elevated in active M. tuberculosis disease and assessed factors contributing to false-positive and -negative results. A retrospective study of 2,150 individuals tested by the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was conducted at the University of Utah, ARUP Laboratories, November 2008 to December 2010. All samples were tested with the InBios Active TbDetect antituberculosis (anti-TB) IgG antibody assay. Of 1,044 patients with a positive QFT-GIT, 59 (5.7%) were positive for M. tuberculosis antibodies. Fourteen of 1,106 (1.3%) with a negative or indeterminate QFT-GIT were positive for M. tuberculosis antibodies. M. tuberculosis antibody tests were positive in 61.5% with confirmed active M. tuberculosis disease and other mycobacterial infections. Over half of the false-negative M. tuberculosis antibody tests occurred in patients ≥90 years of age. False positives were seen in 12.9% of autoimmune patients. The odds ratio of being positive by the QFT-GIT and the InBios TB IgG assay increased with confirmed M. tuberculosis disease or highly suspected M. tuberculosis disease and was 86.7 (95% confidence interval [CI], 34.4 to 218.5) in these two groups compared to patients negative by both tests. Although anti-M. tuberculosis antibodies can be detected in patients with active M. tuberculosis disease, caution should be used with patients where immunoglobulin levels may be decreased or patients with autoantibodies. PMID:22301692

Glycosulfatase-Encoding Gene Cluster in Bifidobacterium breve UCC2003.

PubMed

Egan, Muireann; Jiang, Hao; O'Connell Motherway, Mary; Oscarson, Stefan; van Sinderen, Douwe

2016-11-15

Bifidobacteria constitute a specific group of commensal bacteria typically found in the gastrointestinal tract (GIT) of humans and other mammals. Bifidobacterium breve strains are numerically prevalent among the gut microbiota of many healthy breastfed infants. In the present study, we investigated glycosulfatase activity in a bacterial isolate from a nursling stool sample, B. breve UCC2003. Two putative sulfatases were identified on the genome of B. breve UCC2003. The sulfated monosaccharide N-acetylglucosamine-6-sulfate (GlcNAc-6-S) was shown to support the growth of B. breve UCC2003, while N-acetylglucosamine-3-sulfate, N-acetylgalactosamine-3-sulfate, and N-acetylgalactosamine-6-sulfate did not support appreciable growth. By using a combination of transcriptomic and functional genomic approaches, a gene cluster designated ats2 was shown to be specifically required for GlcNAc-6-S metabolism. Transcription of the ats2 cluster is regulated by a repressor open reading frame kinase (ROK) family transcriptional repressor. This study represents the first description of glycosulfatase activity within the Bifidobacterium genus. Bifidobacteria are saccharolytic organisms naturally found in the digestive tract of mammals and insects. Bifidobacterium breve strains utilize a variety of plant- and host-derived carbohydrates that allow them to be present as prominent members of the infant gut microbiota as well as being present in the gastrointestinal tract of adults. In this study, we introduce a previously unexplored area of carbohydrate metabolism in bifidobacteria, namely, the metabolism of sulfated carbohydrates. B. breve UCC2003 was shown to metabolize N-acetylglucosamine-6-sulfate (GlcNAc-6-S) through one of two sulfatase-encoding gene clusters identified on its genome. GlcNAc-6-S can be found in terminal or branched positions of mucin oligosaccharides, the glycoprotein component of the mucous layer that covers the digestive tract. The results of this study provide further evidence of the ability of this species to utilize mucin-derived sugars, a trait which may provide a competitive advantage in both the infant gut and adult gut. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Glycosulfatase-Encoding Gene Cluster in Bifidobacterium breve UCC2003

PubMed Central

Egan, Muireann; Jiang, Hao; O'Connell Motherway, Mary; Oscarson, Stefan

2016-01-01

ABSTRACT Bifidobacteria constitute a specific group of commensal bacteria typically found in the gastrointestinal tract (GIT) of humans and other mammals. Bifidobacterium breve strains are numerically prevalent among the gut microbiota of many healthy breastfed infants. In the present study, we investigated glycosulfatase activity in a bacterial isolate from a nursling stool sample, B. breve UCC2003. Two putative sulfatases were identified on the genome of B. breve UCC2003. The sulfated monosaccharide N-acetylglucosamine-6-sulfate (GlcNAc-6-S) was shown to support the growth of B. breve UCC2003, while N-acetylglucosamine-3-sulfate, N-acetylgalactosamine-3-sulfate, and N-acetylgalactosamine-6-sulfate did not support appreciable growth. By using a combination of transcriptomic and functional genomic approaches, a gene cluster designated ats2 was shown to be specifically required for GlcNAc-6-S metabolism. Transcription of the ats2 cluster is regulated by a repressor open reading frame kinase (ROK) family transcriptional repressor. This study represents the first description of glycosulfatase activity within the Bifidobacterium genus. IMPORTANCE Bifidobacteria are saccharolytic organisms naturally found in the digestive tract of mammals and insects. Bifidobacterium breve strains utilize a variety of plant- and host-derived carbohydrates that allow them to be present as prominent members of the infant gut microbiota as well as being present in the gastrointestinal tract of adults. In this study, we introduce a previously unexplored area of carbohydrate metabolism in bifidobacteria, namely, the metabolism of sulfated carbohydrates. B. breve UCC2003 was shown to metabolize N-acetylglucosamine-6-sulfate (GlcNAc-6-S) through one of two sulfatase-encoding gene clusters identified on its genome. GlcNAc-6-S can be found in terminal or branched positions of mucin oligosaccharides, the glycoprotein component of the mucous layer that covers the digestive tract. The results of this study provide further evidence of the ability of this species to utilize mucin-derived sugars, a trait which may provide a competitive advantage in both the infant gut and adult gut. PMID:27590817

Epstein Barr virus-positive mucocutaneous ulcer of the colon associated Hodgkin lymphoma in Crohn's disease.

PubMed

Moran, Neil R; Webster, Bradley; Lee, Kenneth M; Trotman, Judith; Kwan, Yiu-Lam; Napoli, John; Leong, Rupert W

2015-05-21

Epstein Barr virus (EBV) positive mucocutaneous ulcers (EBVMCU) form part of a spectrum of EBV-associated lymphoproliferative disease. They have been reported in the setting of immunosenescence and iatrogenic immunosuppression, affecting the oropharyngeal mucosa, skin and gastrointestinal tract (GIT). Case reports and series to date suggest a benign natural history responding to conservative management, particularly in the GIT. We report an unusual case of EBVMCU in the colon, arising in the setting of immunosuppression in the treatment of Crohn's disease, with progression to Hodgkin lymphoma 18 mo after cessation of infliximab. The patient presented with multiple areas of segmental colonic ulceration, histologically showing a polymorphous infiltrate with EBV positive Reed-Sternberg-like cells. A diagnosis of EBVMCU was made. The ulcers failed to regress upon cessation of infliximab and methotrexate for 18 mo. Following commencement of prednisolone for her Crohn's disease, the patient developed widespread Hodgkin lymphoma which ultimately presented as a life-threatening lower GIT bleed requiring emergency colectomy. This is the first report of progression of EBVMCU to Hodgkin lymphoma, in the setting of ongoing iatrogenic immunosuppression and inflammatory bowel disease.

Magnetic resonance imaging and relaxometry to study water transport mechanisms in a commercially available gastrointestinal therapeutic system (GITS) tablet.

PubMed

Broadbent, Amber L; Fell, Rob J; Codd, Sarah L; Lightley, Kim A; Konagurthu, Sanjay; Koehler-King, Dory G; Seymour, Joseph D

2010-09-15

The hydration of 4 mg Cardura XL (Pfizer), a commercially available gastrointestinal therapeutic system (GITS) tablet, was investigated using magnetic resonance imaging (MRI). A short echo time (T(e)=2.81 ms) technique for MRI of the hydration of a GITS tablet was implemented. From the MR images, signal intensity profiles were generated and interpreted in the context of diffusive and osmotic transport mechanisms. A distinct transition from diffusive to osmotic transport was measured at a timescale relevant to the measured drug release time. Diffusion and osmotic rate coefficients for water in the drug and polymer sweller layers of the tablet were quantified. Spin-lattice T(1) and spin-spin T(2) relaxation times of the water signal from within the tablet were measured as a function of hydration time in order to incorporate the effects of relaxation into interpretation of signal intensity and provide unique information on the distribution of water in different physical and chemical environments within the tablet. Copyright 2010 Elsevier B.V. All rights reserved.

Starch-based nanocapsules fabricated through layer-by-layer assembly for oral delivery of protein to lower gastrointestinal tract.

PubMed

Zhang, Yiping; Chi, Chengdeng; Huang, Xiaoyi; Zou, Qin; Li, Xiaoxi; Chen, Ling

2017-09-01

Anionic carboxymethyl starch (CMS) and cationic quaternary ammonium starch (QAS), were used to fabricate nanocapsules through electrostatic layer by layer (LbL) alternate deposition onto colloidal BSA particles. An ideal starch-based colloidal nanocapsule was achieved by adjusting the degree of substitution (DS) and weight average molecular molar mass (M w ) of CMS. The nanocapsules fabricated by CMS with lower DS or M w possessed more compact and stable core-shell structure, which favoured the BSA delivery from the upper gastrointestinal tract (GIT) to the colon. In particular, CMS/QAS nanocapsules constructed by CMS with lower DS and M w showed better colon-specific delivery and release performance in simulated GIT fluid after 7days' storage in different kinds of beverage (33.04%-46.35% in upper GIT, 52.70%-64.97% in colon, respectively). These findings demonstrated that CMS/QAS nanocapsules constructed by CMS with lower DS and M w can be further exploited as a potential oral delivery system for protein to colon. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of oral food-grade delivery systems: current knowledge and future challenges.

PubMed

Benshitrit, Revital Cohen; Levi, Carmit Shani; Tal, Sharon Levi; Shimoni, Eyal; Lesmes, Uri

2012-01-01

In recent years there has been an increasing interest in the development of new and efficient oral food delivery systems as tools to prevent disease and promote human health and well-being. Such vehicles are sought to protect bioactive ingredients added to food while controlling and targeting their release as they pass through the human gastrointestinal tract (GIT). This review aims to summarize the key concepts of food delivery systems, their characterization and evaluation. Particularly, evaluation of their performance within the human GIT is discussed. To this end an overview of several in vivo and in vitro methods currently applied for the study of such systems is given. Although considered to be still in its infancy, this promising field of research is likely to infiltrate into real products through rational design. In order for such efforts to materialize into real products some challenges still need to be met and are discussed herein. Overall, it seems that adopting a comprehensive pharmacological approach and relevant cutting edge tools are likely to facilitate innovations and help elucidate and perhaps tailor delivery systems' behavior in the human GIT.

Prenatal Androgen Exposure Causes Hypertension and Gut Microbiota Dysbiosis.

PubMed

Sherman, Shermel; Sarsour, Nadeen; Salehi, Marziyeh; Schroering, Allen; Mell, Blair; Joe, Bina; Hill, Jennifer W

2018-02-22

Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring. The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs). We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in metabolite production of short chain fatty acids. These results suggest that early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead to long-term alterations in gut microbiota and cardiometabolic function.

Exposure to household furry pets influences the gut microbiota of infant at 3-4 months following various birth scenarios.

PubMed

Tun, Hein M; Konya, Theodore; Takaro, Tim K; Brook, Jeffrey R; Chari, Radha; Field, Catherine J; Guttman, David S; Becker, Allan B; Mandhane, Piush J; Turvey, Stuart E; Subbarao, Padmaja; Sears, Malcolm R; Scott, James A; Kozyrskyj, Anita L

2017-04-06

Early-life exposure to household pets has the capacity to reduce risk for overweight and allergic disease, especially following caesarean delivery. Since there is some evidence that pets also alter the gut microbial composition of infants, changes to the gut microbiome are putative pathways by which pet exposure can reduce these risks to health. To investigate the impact of pre- and postnatal pet exposure on infant gut microbiota following various birth scenarios, this study employed a large subsample of 746 infants from the Canadian Healthy Infant Longitudinal Development Study (CHILD) cohort, whose mothers were enrolled during pregnancy between 2009 and 2012. Participating mothers were asked to report on household pet ownership at recruitment during the second or third trimester and 3 months postpartum. Infant gut microbiota were profiled with 16S rRNA sequencing from faecal samples collected at the mean age of 3.3 months. Two categories of pet exposure (i) only during pregnancy and (ii) pre- and postnatally were compared to no pet exposure under different birth scenarios. Over half of studied infants were exposed to at least one furry pet in the prenatal and/or postnatal periods, of which 8% were exposed in pregnancy alone and 46.8% had exposure during both time periods. As a common effect in all birth scenarios, pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus (P < 0.05) with more than a twofold greater likelihood of high abundance. Among vaginally born infants with maternal intrapartum antibiotic prophylaxis exposure, Streptococcaceae were substantially and significantly reduced by pet exposure (P < 0.001, FDRp = 0.03), reflecting an 80% decreased likelihood of high abundance (OR 0.20, 95%CI, 0.06-0.70) for pet exposure during pregnancy alone and a 69% reduced likelihood (OR 0.31, 95%CI, 0.16-0.58) for exposure in the pre- and postnatal time periods. All of these associations were independent of maternal asthma/allergy status, siblingship, breastfeeding exclusivity and other home characteristics. The impact of pet ownership varies under different birth scenarios; however, in common, exposure to pets increased the abundance of two bacteria, Ruminococcus and Oscillospira, which have been negatively associated with childhood atopy and obesity.

Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT.TB on active tuberculosis in Japan.

PubMed

Takasaki, Jin; Manabe, Toshie; Morino, Eriko; Muto, Yoshikazu; Hashimoto, Masao; Iikura, Motoyasu; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro

2018-03-01

The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934-0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929-0.998) and T-SPOT (96.9%; 95% CI, 0.914-0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934-0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

A field survey on the status of gastrointestinal helminth parasites in hangul (Cervus elaphus hanglu) in Dachigam National Park of Kashmir.

PubMed

Lone, Bashir A; Chishti, M Z; Ahmad, Fayaz; Tak, Hidayatullah; Bandh, Suhaib A; Khan, Abida

2016-09-01

One year crossectional survey was carried out to determine and describe the prevalence and intensity of gastrointestinal parasite infections in hangul (Cervus elaphus hanglu) in Dachigam National Park of Kashmir through faecal examinations. Out of 153 faecal samples examined, 82 (53.59 %) were found infected with GIT helminthes. In present study seven helminth species were found, including five nematode [Haemonchus contortus (55.39 %), Trichuris ovis (39.75 %), Dictyocaulus viviparus (28.4.00 %), Oesophogostomum circumcincta (13.7 %) and Chabertia ovina (4.02 %)] one trematode [Fasciola hepatica (17.3 %)] and one cestode species [Moneizia expansa (6.05 %)]. Based on the severity of infection 81.7 % of hangul positive samples were severely infected (epg > 1,500), 8.3 % heavily infected (epg = 1,100-1,500), 3.8 % moderately infected (epg = 800-1,000) and 7.2 % mildly infected (epg = 500). Season, sex and age were the factors that influenced the epidemiological prevalence of GIT helminths in hangul in the present study. The maximum helminth infection was observed in summer season and lowest in winter (P = 0.003). Lower age groups were more infected than adult animals (P > 0.05). Prevalence was higher in males than females (P > 0.05). The present study will initially be of great significance to add to existing knowledge of the epidemiology of GIT helminth of hangul which is the pioneering study on this animal in the valley and the findings will be quite helpful to devise the appropriate control and prophylactic strategies for GIT helminthiasis of hangul in the Dachigam national park.

Glycoside hydrolase family 13 α-glucosidases encoded by Bifidobacterium breve UCC2003; A comparative analysis of function, structure and phylogeny.

PubMed

Kelly, Emer D; Bottacini, Francesca; O'Callaghan, John; Motherway, Mary O'Connell; O'Connell, Kerry Joan; Stanton, Catherine; van Sinderen, Douwe

2016-05-02

Bifidobacterium breve is a noted inhabitant and one of the first colonizers of the human gastro intestinal tract (GIT). The ability of this bacterium to persist in the GIT is reflected by the abundance of carbohydrate-active enzymes that are encoded by its genome. One such family of enzymes is represented by the α-glucosidases, of which three, Agl1, Agl2 and MelD, have previously been identified and characterized in the prototype B. breve strain UCC2003. In this report, we describe an additional B. breve UCC2003-encoded α-glucosidase, along with a B. breve UCC2003-encoded α-glucosidase-like protein, designated here as Agl3 and Agl4, respectively, which together with the three previously described enzymes belong to glycoside hydrolase (GH) family 13. Agl3 was shown to exhibit hydrolytic specificity towards the α-(1→6) linkage present in palatinose; the α-(1→3) linkage present in turanose; the α-(1→4) linkages found in maltotriose and maltose; and to a lesser degree, the α-(1→2) linkage found in sucrose and kojibiose; and the α-(1→5) linkage found in leucrose. Surprisingly, based on the substrates analyzed, Agl4 did not exhibit biologically relevant α-glucosidic activity. With the presence of four functionally active GH13 α-glucosidases, B. breve UCC2003 is capable of hydrolyzing all α-glucosidic linkages that can be expected in glycan substrates in the lower GIT. This abundance of α-glucosidases provides B. breve UCC2003 with an adaptive ability and metabolic versatility befitting the transient nature of growth substrates in the GIT. Copyright © 2016 Elsevier B.V. All rights reserved.

Screening of latent tuberculosis infection among health care workers working in Hajj pilgrimage area in Saudi Arabia, using interferon gamma release assay and tuberculin skin test.

PubMed

Bukhary, Zakeya A; Amer, Soliman M; Emara, Magdy M; Abdalla, Mohammad E; Ali, Sahar A

2018-01-01

Interferon gamma release assays (IGRA) is highly specific for Mycobacterium tuberculosis and is the preferred test in BCG-vaccinated individuals. The few studies that have screened health care workers (HCWs) in Saudi Arabia for latent tuberculosis infection (LTBI) using IGRA have varied in agreement with the traditional tuberculin skin test (TST). Assess the prevalence of LTBI among HCWs working in the Hajj pilgrimage using IGRA and TST and measuring their agreement. Cross-sectional prospective. Multiple non-tertiary care hospitals. HCWs who worked during the Hajj pilgrimage in Saudi Arabia in December 2015. Data was collected by standarized questionnaire. Samples were drawn and analyzed by standard methods. The prevalence of LTBI among HCW and the agreement by kappa statistic between QFT-GIT and TST. 520 subjects. Nurses accounted for 30.7% of the sample and physicians, 19.2%. The majority were BCG vaccinated (98.5%). There were a total of 56 positive by QFT-GIT and the LTBI rate was 10.8%. In 50 QFT positive/476 TST negative the LTBI rate was 10.5% in discordant tests, and in 6 QFT positive/44 TST positive it was 13.6% in concordant tests. The overall agreement between both tests was poor-83% and kappa was 0.02. LTBI prevalence was associated with longer employment (13.1 [9.2] years). The QFT-GIT positive test was significantly higher in physicians (P=.02) and in HCWs working in chest hospitals 16/76 (21.05%) (P=.001). Agreement between the tests was poor. QFT-GIT detected LTBI when TST was negative in HCWs who had a history of close contact with TB patients. A second step TST was not feasible within 2-3 weeks. None.

In-vitro GIT Tolerance of Microencapsulated Bifidobacterium bifidum ATCC 35914 Using Polysaccharide-Protein Matrix.

PubMed

Iqbal, Rabia; Zahoor, Tahir; Huma, Nuzhat; Jamil, Amer; Ünlü, Gülhan

2018-03-12

Longevity of probiotic is the main concern for getting maximum benefits when added in food product. Bifidobacterium, a probiotic, tends to lose its viability during gastrointestinal track (GIT) transit and storage of food. Their viability can be enhanced through microencapsulation technology. In this study, Bifidobacterium bifidum (B. bifidum) ATCC 35914 was encapsulated by using two experimental plans. In the first plan, chitosan (CH) at 0.6, 0.8, and 1.0% and sodium alginate (SA) at 4, 5, and 6% were used. Based on encapsulation efficiency, 6% sodium alginate and 0.8% chitosan were selected for single coating of the bacteria, and the resulting micro beads were double coated with different concentrations (5, 7.5, and 10%) of whey protein concentrate (WPC) in the second plan. Encapsulation efficiency and GIT tolerance were determined by incubating the micro beads in simulated gastrointestinal juices (SIJ) at variable pH and exposure times, and their release (liberation of bacterial cells) profile was also observed in SIJ. The microencapsulated bacterial cells showed significantly (P < 0.01) higher viability as compared to the unencapsulated (free) cells during GIT assay. The double-coated micro beads SA 6%-WPC 5% and CH 0.8%-WPC 5% were proven to have the higher survival at pH 3.0 after 90 min of incubation time and at pH 7.0 after 3-h exposure in comparison to free cells in simulated conditions of the stomach and intestine, respectively. Moreover, double coating with whey protein concentrate played a significant role in the targeted (10 6-9  CFU/mL) delivery under simulated intestinal conditions.

Improving the efficiency of feed utilization in poultry by selection. 2. Genetic parameters of excretion traits and correlations with anatomy of the gastro-intestinal tract and digestive efficiency.

PubMed

de Verdal, Hugues; Narcy, Agnès; Bastianelli, Denis; Chapuis, Hervé; Même, Nathalie; Urvoix, Séverine; Le Bihan-Duval, Elisabeth; Mignon-Grasteau, Sandrine

2011-08-17

Poultry production has been widely criticized for its negative environmental impact related to the quantity of manure produced and to its nitrogen and phosphorus content. In this study, we investigated which traits related to excretion could be used to select chickens for lower environmental pollution.The genetic parameters of several excretion traits were estimated on 630 chickens originating from 2 chicken lines divergently selected on apparent metabolisable energy corrected for zero nitrogen (AMEn) at constant body weight. The quantity of excreta relative to feed consumption (CDUDM), the nitrogen and phosphorus excreted, the nitrogen to phosphorus ratio and the water content of excreta were measured, and the consequences of such selection on performance and gastro-intestinal tract (GIT) characteristics estimated. The genetic correlations between excretion, GIT and performance traits were established. Heritability estimates were high for CDUDM and the nitrogen excretion rate (0.30 and 0.29, respectively). The other excretion measurements showed low to moderate heritability estimates, ranging from 0.10 for excreta water content to 0.22 for the phosphorus excretion rate. Except for the excreta water content, the CDUDM was highly correlated with the excretion traits, ranging from -0.64 to -1.00. The genetic correlations between AMEn or CDUDM and the GIT characteristics were very similar and showed that a decrease in chicken excretion involves an increase in weight of the upper part of the GIT, and a decrease in the weight of the small intestine. In order to limit the environmental impact of chicken production, AMEn and CDUDM seem to be more suitable criteria to include in selection schemes than feed efficiency traits.

Mother-to-Infant Transmission of Intestinal Bifidobacterial Strains Has an Impact on the Early Development of Vaginally Delivered Infant's Microbiota

PubMed Central

Makino, Hiroshi; Kushiro, Akira; Ishikawa, Eiji; Kubota, Hiroyuki; Gawad, Agata; Sakai, Takafumi; Oishi, Kenji; Martin, Rocio; Ben-Amor, Kaouther; Knol, Jan; Tanaka, Ryuichiro

2013-01-01

Objectives Bifidobacterium species are one of the major components of the infant's intestine microbiota. Colonization with bifidobacteria in early infancy is suggested to be important for health in later life. However, information remains limited regarding the source of these microbes. Here, we investigated whether specific strains of bifidobacteria in the maternal intestinal flora are transmitted to their infant's intestine. Materials and Methods Fecal samples were collected from healthy 17 mother and infant pairs (Vaginal delivery: 12; Cesarean section delivery: 5). Mother's feces were collected twice before delivery. Infant's feces were collected at 0 (meconium), 3, 7, 30, 90 days after birth. Bifidobacteria isolated from feces were genotyped by multilocus sequencing typing, and the transitions of bifidobacteria counts in infant's feces were analyzed by quantitative real-time PCR. Results Stains belonging to Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium catenulatum, Bifidobacterium longum subsp. longum, and Bifidobacterium pseudocatenulatum, were identified to be monophyletic between mother's and infant's intestine. Eleven out of 12 vaginal delivered infants carried at least one monophyletic strain. The bifidobacterial counts of the species to which the monophyletic strains belong, increased predominantly in the infant's intestine within 3 days after birth. Among infants delivered by C-section, monophyletic strains were not observed. Moreover, the bifidobacterial counts were significantly lower than the vaginal delivered infants until 7 days of age. Conclusions Among infants born vaginally, several Bifidobacterium strains transmit from the mother and colonize the infant's intestine shortly after birth. Our data suggest that the mother's intestine is an important source for the vaginal delivered infant's intestinal microbiota. PMID:24244304

The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.

PubMed

Barthow, Christine; Wickens, Kristin; Stanley, Thorsten; Mitchell, Edwin A; Maude, Robyn; Abels, Peter; Purdie, Gordon; Murphy, Rinki; Stone, Peter; Kang, Janice; Hood, Fiona; Rowden, Judy; Barnes, Phillipa; Fitzharris, Penny; Craig, Jeffrey; Slykerman, Rebecca F; Crane, Julian

2016-06-03

Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum. The PiP Study is a two-centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14-16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 × 10(9) colony-forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding. Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35-37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action. The study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum. Australian New Zealand Clinical Trials Registration: ACTRN12612000196842. Date Registered: 15/02/12.

Intervention strategies for cesarean section-induced alterations in the microbiota-gut-brain axis.

PubMed

Moya-Pérez, Angela; Luczynski, Pauline; Renes, Ingrid B; Wang, Shugui; Borre, Yuliya; Anthony Ryan, C; Knol, Jan; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

2017-04-01

Microbial colonization of the gastrointestinal tract is an essential process that modulates host physiology and immunity. Recently, researchers have begun to understand how and when these microorganisms colonize the gut and the early-life factors that impact their natural ecological establishment. The vertical transmission of maternal microbes to the offspring is a critical factor for host immune and metabolic development. Increasing evidence also points to a role in the wiring of the gut-brain axis. This process may be altered by various factors such as mode of delivery, gestational age at birth, the use of antibiotics in early life, infant feeding, and hygiene practices. In fact, these early exposures that impact the intestinal microbiota have been associated with the development of diseases such as obesity, type 1 diabetes, asthma, allergies, and even neurodevelopmental disorders. The present review summarizes the impact of cesarean birth on the gut microbiome and the health status of the developing infant and discusses possible preventative and restorative strategies to compensate for early-life microbial perturbations. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute.

Effects of occupational stress on the gastrointestinal tract

PubMed Central

Huerta-Franco, María-Raquel; Vargas-Luna, Miguel; Tienda, Paola; Delgadillo-Holtfort, Isabel; Balleza-Ordaz, Marco; Flores-Hernandez, Corina

2013-01-01

The aim of this review is to provide a general overview of the relationship between occupational stress and gastrointestinal alterations. The International Labour Organization suggests occupational health includes psychological aspects to achieve mental well-being. However, the definition of health risks for an occupation includes biological, chemical, physical and ergonomic factors but does not address psychological stress or other affective disorders. Nevertheless, multiple investigations have studied occupational stress and its physiological consequences, focusing on specific risk groups and occupations considered stressful. Among the physiological effects of stress, gastrointestinal tract (GIT) alterations are highly prevalent. The relationship between occupational stress and GIT diseases is evident in everyday clinical practice; however, the usual strategy is to attack the effects but not the root of the problem. That is, in clinics, occupational stress is recognized as a source of GIT problems, but employers do not ascribe it enough importance as a risk factor, in general, and for gastrointestinal health, in particular. The identification, stratification, measurement and evaluation of stress and its associated corrective strategies, particularly for occupational stress, are important topics to address in the near future to establish the basis for considering stress as an important risk factor in occupational health. PMID:24244879

Requirement of Treg-intrinsic CTLA4/PKCη signaling pathway for suppressing tumor immunity

PubMed Central

Pedros, Christophe; Canonigo-Balancio, Ann J.; Kong, Kok-Fai

2017-01-01

The ability of Tregs to control the development of immune responses is essential for maintaining immune system homeostasis. However, Tregs also inhibit the development of efficient antitumor responses. Here, we explored the characteristics and mechanistic basis of the Treg-intrinsic CTLA4/PKCη signaling pathway that we recently found to be required for contact-dependent Treg-mediated suppression. We show that PKCη is required for the Treg-mediated suppression of tumor immunity in vivo. The presence of PKCη-deficient (Prkch–/–) Tregs in the tumor microenvironment was associated with a significantly increased expression of the costimulatory molecule CD86 on intratumoral CD103+ DCs, enhanced priming of antigen-specific CD8+ T cells, and greater levels of effector cytokines produced by these cells. Similar to mouse Tregs, the GIT/PAK/PIX complex also operated downstream of CTLA4 and PKCη in human Tregs, and GIT2 knockdown in Tregs promoted antitumor immunity. Collectively, our data suggest that targeting the CTLA4/PKCη/GIT/PAK/PIX signaling pathway in Tregs could represent a novel immunotherapeutic strategy to alleviate the negative impact of Tregs on antitumor immune responses. PMID:29212947

The Role of Cell Surface Architecture of Lactobacilli in Host-Microbe Interactions in the Gastrointestinal Tract

PubMed Central

Altermann, Eric; Anderson, Rachel C.; McNabb, Warren C.; Moughan, Paul J.; Roy, Nicole C.

2013-01-01

Lactobacillus species can exert health promoting effects in the gastrointestinal tract (GIT) through many mechanisms, which include pathogen inhibition, maintenance of microbial balance, immunomodulation, and enhancement of the epithelial barrier function. Different species of the genus Lactobacillus can evoke different responses in the host, and not all strains of the same species can be considered beneficial. Strain variations may be related to diversity of the cell surface architecture of lactobacilli and the bacteria's ability to express certain surface components or secrete specific compounds in response to the host environment. Lactobacilli are known to modify their surface structures in response to stress factors such as bile and low pH, and these adaptations may help their survival in the face of harsh environmental conditions encountered in the GIT. In recent years, multiple cell surface-associated molecules have been implicated in the adherence of lactobacilli to the GIT lining, immunomodulation, and protective effects on intestinal epithelial barrier function. Identification of the relevant bacterial ligands and their host receptors is imperative for a better understanding of the mechanisms through which lactobacilli exert their beneficial effects on human health. PMID:23576850

Histo-FISH protocol to detect bacterial compositions and biofilms formation in vivo.

PubMed

Madar, M; Slizova, M; Czerwinski, J; Hrckova, G; Mudronova, D; Gancarcikova, S; Popper, M; Pistl, J; Soltys, J; Nemcova, R

2015-01-01

The study of biofilm function in vivo in various niches of the gastrointestinal tract (GIT) is rather limited. It is more frequently used in in vitro approaches, as an alternative to the studies focused on formation mechanisms and function of biofilms, which do not represent the actual in vivo complexity of microbial structures. Additionally, in vitro tests can sometimes lead to unreliable results. The goal of this study was to develop a simple approach to detect bacterial populations, particularly Lactobacillus and Bifidobacterium in biofilms, in vivo by the fluorescent in situ hybridisation (FISH) method. We standardised a new Histo-FISH method based on specific fluorochrome labelling probes which are able to detect Lactobacillus spp. and Bifidobacterium spp. within biofilms on the mucosal surface of the GIT embedded in paraffin in histological slices. This method is also suitable for visualisation of bacterial populations in the GIT internal content. Depending on the labelling probes, the Histo-FISH method has the potential to detect other probiotic strains or pathogenic bacteria. This original approach permits us to analyse bacterial colonisation processes as well as biofilm formation in stomach and caecum of BALB/c and germ-free mice.

Poor agreement between interferon-gamma release assays and the tuberculin skin test among HIV-infected individuals in the country of Georgia.

PubMed

Chkhartishvili, Nikoloz; Kempker, Russell R; Dvali, Natia; Abashidze, Lela; Sharavdze, Lali; Gabunia, Pati; Blumberg, Henry M; Del Rio, Carlos; Tsertsvadze, Tengiz

2013-11-01

Improved tests to diagnose latent TB infection (LTBI) are needed. We sought to evaluate the performance of two commercially available interferon-gamma release assays (IGRAs) compared to the tuberculin skin test (TST) for the diagnosis of LTBI and to identify risk factors for LTBI among HIV-infected individuals in Georgia, a country with high rates of TB. HIV-patients were enrolled from the National AIDS Center in Tbilisi, Georgia. After providing informed consent, each participant completed a questionnaire, had blood drawn for QuantiFERON-TB Gold in-Tube (QFT-GIT) and T-SPOT.TB testing and had a TST placed. The TST was read at 48-72 hrs with ≥ 5 mm induration considered positive. Between 2009-2011, 240 HIV-infected persons (66% male) with a median age of 38 years and a median CD4 count of 255 cells/μl (IQR: 124-412) had diagnostic testing for LTBI performed. 94% had visible evidence of a BCG scar. The TST was positive in 41 (17%) patients; QFT-GIT in 70 (29%); and T-SPOT.TB in 56 (24%). At least one diagnostic test was positive in 109 (45%) patients and only among 13 (5%) patients were all three tests positive. Three (1%) QFT-GIT and 19 (8%) T-SPOT.TB test results were indeterminate. The agreement among all pairs of tests was poor: QFT-GIT vs. T-SPOT.TB (κ = 0.18, 95% CI .07-.30), QFT-GIT vs. TST (κ = 0.29, 95% CI .16-.42), and TST vs. T-SPOT.TB (κ = 0.22, 95% CI .07-.29). Risk factors for LTBI varied by diagnostic test and none showed associations between positive test results and well-known risk factors for TB, such as imprisonment, drug abuse and immunological status. A high proportion of HIV patients had at least one positive diagnostic test for LTBI; however, there was very poor agreement among all tests. This lack of agreement makes it difficult to know which test is superior and most appropriate for LTBI testing among HIV-infected patients. While further follow-up studies will help determine the predictive ability of different LTBI tests, improved modalities are needed for accurate detection of LTBI and assessment of risk of developing active TB among HIV-infected patients.

Prevalence of latent tuberculosis infection among foreign students in Lübeck, Germany tested with QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus.

PubMed

Gallegos Morales, Elia Noemi; Knierer, Johannes; Schablon, Anja; Nienhaus, Albert; Kersten, Jan Felix

2017-01-01

The tuberculosis (TB) incidence rate in foreign-born individuals has been increasing in Germany in recent years. Foreign students may be an important source of latent tuberculosis infection (LTBI) in low-incidence countries. In Germany, there are no guidelines for LTBI screening of foreign students. The aim of the study was to estimate LTBI prevalence and evaluate associated risk factors among foreign students in Germany. The second purpose of our study was to compare the results of the new generation of QuantiFERON-TB Gold Plus (QFT-Plus) to those of its predecessor QuantiFERON-TB Gold In-Tube (QFT-GIT). This cross - sectional study was conducted between February 2016 and March 2016. Foreign students and young professionals attending the university and higher education institutes in Lübeck, Germany were tested with QFT-Plus and QFT-GIT. Participants filled out a questionnaire for the purpose of LTBI risk assessment and analysis. Variables associated with a positive test result were analyzed using logistic regression. One hundred thirty four students participated in the study. The overall prevalence as regards positive results from both tests, QFT-Plus and QFT-GIT, was 9.7%, and the prevalence of positive QFT-Plus results was 8.2%. The main independent variables associated with a positive QFT-Plus result were a) being born in a high-incidence country (OR = 6.7, 95% CI: 1.3-34.3) and b) previous contact with a person with active TB (OR = 4.5, 95% CI: 1.1-18.3). Higher age (OR = 2.8, 95% CI: 0.7-11.3) and male gender (OR = 1.6, 95% CI: 0.4-6.7) showed a tendency toward positive QFT-Plus results but this was not statistically significant. Agreement between QFT-Plus and QFT-GIT results was κ = 0.85, p  < 0.001. The LTBI prevalence among foreign students was about 10%. We recommend implementing a policy whereby all foreign students are screened by means of a questionnaire about LTBI risk factors, so that only students with present risk factors are tested for LTBI. The agreement between the new QFT-Plus and the QFT-GIT (κ = 0.85) was good. QFT-Plus might be used in the same format as its predecessor.

Community-based evaluation of immigrant tuberculosis screening using interferon γ release assays and tuberculin skin testing: observational study and economic analysis

PubMed Central

Pareek, Manish; Bond, Marion; Shorey, Jennifer; Seneviratne, Suranjith; Guy, Margaret; White, Peter; Lalvani, Ajit; Kon, Onn Min

2017-01-01

Background UK tuberculosis (TB) notifications are rising due to disease in the immigrant population. National screening guidelines have been revised but cost-effectiveness analyses are hampered by the lack of data on the comparative performance of tuberculin skin tests (TSTs) and interferon γ release assays (IGRAs) in immigrants. Methods Three-way evaluation of TSTs and two IGRAs (QuantiFERON Gold in-tube (QFN-GIT) and T-SPOT.TB) in immigrants aged ≥16 years to quantify test positivity, concordance and factors associated with positivity. Yields were computed at different incidence thresholds and the relative cost-effectiveness of screening was estimated using different latent TB infection (LTBI) screening modalities at varying incidence thresholds with or without port-of-arrival chest x-ray (CXR). Results 231 immigrants were included; median age 29 (IQR 24–37). TSTs were accepted by 80.9%, read in 93.5% and 30.3% were positive – QFN-GIT and T-SPOT.TB positive in 16.6% and 22.5% respectively. Positive TSTs, QFN-GIT and T-SPOT.TB were independently associated with increasing TB incidence in immigrants’ countries of origin (p=0.007, 0.007, 0.037 respectively). Implementing current guidance (threshold 40/100 000 per year) would identify 98–100% of LTBIs (depending on test) but entail testing 97–99% of the cohort; screening at 150/100 000 per year would identify 49–71% of LTBIs but only entail screening half the cohort. The two most cost-effective screening strategies were no port-of-entry chest radiography and screen with single-step QFN-GIT at 250/100 000 per year (incremental cost-effectiveness ratio (ICER)) £21 565.3/case averted); and no port-of-entry CXR and screen with single-step QFN-GIT at 150/100 000 per year (averted additional 7.8 TB cases; ICER £31 867.1/case averted). Conclusions UK immigrant screening could cost-effectively and safely eliminate mandatory CXR on arrival by emphasising systematic screening for LTBI with single-step IGRA. Intermediate incidence thresholds balance the need to identify as many imported LTBIs as possible against limited service capacity. PMID:22693179

Honey - A Novel Antidiabetic Agent

PubMed Central

Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd S. Ab

2012-01-01

Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT), on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise) of these experimental data in diabetic human subjects. PMID:22811614

Human Milk Bacterial and Glycosylation Patterns Differ by Delivery Mode.

PubMed

Hoashi, Marina; Meche, Lawrence; Mahal, Lara K; Bakacs, Elizabeth; Nardella, Deanna; Naftolin, Frederick; Bar-Yam, Naomi; Dominguez-Bello, Maria G

2016-07-01

Mammals have evolved to nourish their offspring exclusively with maternal milk for around half of the lactation period, a crucial developmental window. In view of oral-breast contact during lactation and the differences in oral microbiota between cesarean section (C-section) and vaginally delivered infants, we expected differences in milk composition by delivery mode. We performed a cross-sectional study of banked human milk and found changes related to time since delivery in bacterial abundance and glycosylation patterns only in milk from women who delivered vaginally. The results warrant further research into the effects of delivery mode on milk microbes, milk glycosylation, and postpartum infant development. © The Author(s) 2015.

Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring.

PubMed

Miyoshi, Jun; Bobe, Alexandria M; Miyoshi, Sawako; Huang, Yong; Hubert, Nathaniel; Delmont, Tom O; Eren, A Murat; Leone, Vanessa; Chang, Eugene B

2017-07-11

Factors affecting the developing neonatal gut microbiome and immune networks may increase the risk of developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence is lacking. Therefore, we examined the temporal impact of the commonly used antibiotic cefoperazone on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10-deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact of increased IBD risk on genetically susceptible offspring. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Optimisation of 16S rRNA gut microbiota profiling of extremely low birth weight infants.

PubMed

Alcon-Giner, Cristina; Caim, Shabhonam; Mitra, Suparna; Ketskemety, Jennifer; Wegmann, Udo; Wain, John; Belteki, Gusztav; Clarke, Paul; Hall, Lindsay J

2017-11-02

Infants born prematurely, particularly extremely low birth weight infants (ELBW) have altered gut microbial communities. Factors such as maternal health, gut immaturity, delivery mode, and antibiotic treatments are associated with microbiota disturbances, and are linked to an increased risk of certain diseases such as necrotising enterocolitis. Therefore, there is a requirement to optimally characterise microbial profiles in this at-risk cohort, via standardisation of methods, particularly for studying the influence of microbiota therapies (e.g. probiotic supplementation) on community profiles and health outcomes. Profiling of faecal samples using the 16S rRNA gene is a cost-efficient method for large-scale clinical studies to gain insights into the gut microbiota and additionally allows characterisation of cohorts were sample quantities are compromised (e.g. ELBW infants). However, DNA extraction method, and the 16S rRNA region targeted can significantly change bacterial community profiles obtained, and so confound comparisons between studies. Thus, we sought to optimise a 16S rRNA profiling protocol to allow standardisation for studying ELBW infant faecal samples, with or without probiotic supplementation. Using ELBW faecal samples, we compared three different DNA extraction methods, and subsequently PCR amplified and sequenced three hypervariable regions of the 16S rRNA gene (V1 + V2 + V3), (V4 + V5) and (V6 + V7 + V8), and compared two bioinformatics approaches to analyse results (OTU and paired end). Paired shotgun metagenomics was used as a 'gold-standard'. Results indicated a longer bead-beating step was required for optimal bacterial DNA extraction and that sequencing regions (V1 + V2 + V3) and (V6 + V7 + V8) provided the most representative taxonomic profiles, which was confirmed via shotgun analysis. Samples sequenced using the (V4 + V5) region were found to be underrepresented in specific taxa including Bifidobacterium, and had altered diversity profiles. Both bioinformatics 16S rRNA pipelines used in this study (OTU and paired end) presented similar taxonomic profiles at genus level. We determined that DNA extraction from ELBW faecal samples, particularly those infants receiving probiotic supplementation, should include a prolonged beat-beating step. Furthermore, use of the 16S rRNA (V1 + V2 + V3) and (V6 + V7 + V8) regions provides reliable representation of ELBW microbiota profiles, while inclusion of the (V4 + V5) region may not be appropriate for studies where Bifidobacterium constitutes a resident microbiota member.

Cell-free DNA fragment-size distribution analysis for non-invasive prenatal CNV prediction.

PubMed

Arbabi, Aryan; Rampášek, Ladislav; Brudno, Michael

2016-06-01

Non-invasive detection of aneuploidies in a fetal genome through analysis of cell-free DNA circulating in the maternal plasma is becoming a routine clinical test. Such tests, which rely on analyzing the read coverage or the allelic ratios at single-nucleotide polymorphism (SNP) loci, are not sensitive enough for smaller sub-chromosomal abnormalities due to sequencing biases and paucity of SNPs in a genome. We have developed an alternative framework for identifying sub-chromosomal copy number variations in a fetal genome. This framework relies on the size distribution of fragments in a sample, as fetal-origin fragments tend to be smaller than those of maternal origin. By analyzing the local distribution of the cell-free DNA fragment sizes in each region, our method allows for the identification of sub-megabase CNVs, even in the absence of SNP positions. To evaluate the accuracy of our method, we used a plasma sample with the fetal fraction of 13%, down-sampled it to samples with coverage of 10X-40X and simulated samples with CNVs based on it. Our method had a perfect accuracy (both specificity and sensitivity) for detecting 5 Mb CNVs, and after reducing the fetal fraction (to 11%, 9% and 7%), it could correctly identify 98.82-100% of the 5 Mb CNVs and had a true-negative rate of 95.29-99.76%. Our source code is available on GitHub at https://github.com/compbio-UofT/FSDA CONTACT: : brudno@cs.toronto.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Streptococcal Adhesin P (SadP) contributes to Streptococcus suis adhesion to the human intestinal epithelium.

PubMed

Ferrando, Maria Laura; Willemse, Niels; Zaccaria, Edoardo; Pannekoek, Yvonne; van der Ende, Arie; Schultsz, Constance

2017-01-01

Streptococcus suis is a zoonotic pathogen, causing meningitis and septicemia. We previously demonstrated that the gastrointestinal tract (GIT) is an entry site for zoonotic S. suis infection. Here we studied the contribution of Streptococcal adhesin Protein (SadP) to host-pathogen interaction at GIT level. SadP expression in presence of Intestinal Epithelial Cells (IEC) was compared with expression of other virulence factors by measuring transcript levels using quantitative Real Time PCR (qRT-PCR). SadP variants were identified by phylogenetic analysis of complete DNA sequences. The interaction of SadP knockout and complementation mutants with IEC was tested in vitro. Expression of sadP was significantly increased in presence of IEC. Sequence analysis of 116 invasive strains revealed five SadP sequence variants, correlating with genotype. SadP1, present in zoonotic isolates of clonal complex 1, contributed to binding to both human and porcine IEC and translocation across human IEC. Antibodies against the globotriaosylceramide Gb3/CD77 receptor significantly inhibited adhesion to human IEC. SadP is involved in the host-pathogen interaction in the GIT. Differences between SadP variants may determine different affinities to the Gb3/CD77 host-receptor, contributing to variation in adhesion capacity to host IEC and thus to S. suis zoonotic potential.

SWRT: A package for semi-analytical solutions of surface wave propagation, including mode conversion, across transversely aligned vertical discontinuities

NASA Astrophysics Data System (ADS)

Datta, Arjun

2018-03-01

We present a suite of programs that implement decades-old algorithms for computation of seismic surface wave reflection and transmission coefficients at a welded contact between two laterally homogeneous quarter-spaces. For Love as well as Rayleigh waves, the algorithms are shown to be capable of modelling multiple mode conversions at a lateral discontinuity, which was not shown in the original publications or in the subsequent literature. Only normal incidence at a lateral boundary is considered so there is no Love-Rayleigh coupling, but incidence of any mode and coupling to any (other) mode can be handled. The code is written in Python and makes use of SciPy's Simpson's rule integrator and NumPy's linear algebra solver for its core functionality. Transmission-side results from this code are found to be in good agreement with those from finite-difference simulations. In today's research environment of extensive computing power, the coded algorithms are arguably redundant but SWRT can be used as a valuable testing tool for the ever evolving numerical solvers of seismic wave propagation. SWRT is available via GitHub (https://github.com/arjundatta23/SWRT.git).

Decades of research in drug targeting to the upper gastrointestinal tract using gastroretention technologies: where do we stand?

PubMed

Awasthi, Rajendra; Kulkarni, Giriraj T

2016-01-01

A major constraint in oral controlled release drug delivery is that not all the drug candidates are absorbed uniformly throughout the gastrointestinal tract (GIT). Drugs having "absorption window" are absorbed in a particular portion of GIT only or are absorbed to a different extent in various segments of the GIT. Thus, only the drug released in the region preceding and in close vicinity to the absorption window is available for absorption. The drug must be released from the dosage form in solution form; otherwise, it is generally not absorbed. Hence, much research has been dedicated to the development of gastroretentive drug delivery systems that may optimize the bioavailability and subsequent therapeutic efficacy of such drugs, as these systems have unique properties to bypass the gastric emptying process. These systems show excellent in vitro results but fail to give desirable in vivo performance. During the last 2-3 decades, researchers from the academia and industries are giving considerable importance in this field. Unfortunately, till date, few so-called gastroretentive dosage forms have been brought to the market in spite of numerous academic publications. The manuscript considers strategies that are commonly used in the development of gastroretentive drug delivery systems with a special attention on various parameters, which needs to be monitored during formulation development.

Multicenter study of QuantiFERON®-TB Gold Plus in patients with active tuberculosis.

PubMed

Horne, D J; Jones, B E; Kamada, A; Fukushima, K; Winthrop, K L; Siegel, S A R; Kovacs, A; Anthony, P; Meekin, K A; Bhat, S; Kerndt, P; Chang, A; Koelle, D M; Narita, M

2018-06-01

QuantiFERON®-TB Gold Plus (QFT-Plus), recently approved for use in the United States, is a new-generation QuantiFERON assay that differs from its predecessors in that it uses an additional antigen tube containing peptides to elicit both CD8+ and CD4+ T-lymphocyte responses. To assess the sensitivity of QFT-Plus compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) in participants with active TB. Adult patients with active TB at three US and two Japanese sites were eligible for this study if they had culture-confirmed TB and were either untreated or had received 14 days of anti-tuberculosis treatment. We enrolled 164 participants, nine of whom had indeterminate results. Excluding indeterminate values, there were 150 QFT-GIT-positive results among 159 tests and 146 QFT-Plus-positive results among 157 tests, with sensitivities of respectively 94.3% (95%CI 89.5-97.4) and 93.02% (95%CI 87.8-96.5%). The estimated sensitivities for the two tests were not significantly different (P = 0.16). Overall test agreement was 98.7%, with a κ statistic of 0.89 (95%CI 0.75-1.00). In this multisite study, we found that QFT-Plus had similar sensitivity to QFT-GIT in adult patients with active TB.

Detection of bovine papilloma viruses in wart-like lesions of upper gastrointestinal tract of cattle and buffaloes.

PubMed

Kumar, P; Nagarajan, N; Saikumar, G; Arya, R S; Somvanshi, R

2015-06-01

In present investigation, etiopathological characterization of upper gastrointestinal tract (GIT) tumours of cattle and buffaloes was undertaken. A total of 27 GIT wart-like lesions in rumen, reticulum, mouth and oesophagus of cattle and buffaloes revealed the presence of small nodular to larger spherical or slender growths with thin base present on mucosa and ruminal pillar. Histopathologically, these cases were diagnosed as fibropapilloma/papilloma. This is the first world record on ruminal papillomatosis in buffaloes. Ruminal warts of cattle and buffaloes revealed the presence of BPV-5, -1 & -2, which is the first report of presence of these BPVs in the ruminal warts from India. Quantitative real-time PCR revealed that DNA samples of different GIT wart-like lesions contained varying amount of BPV DNA copy numbers. Immunohistochemistry revealed that the PCNA and Ki67 immunopositivity was present in the basal and spinosum layer of the fibropapilloma/papilloma, indicating these as the cellular proliferation site. In conclusion, the present investigation revealed that BPV-5, -1 & -2 are associated with certain ruminal wart-like lesions/growths in cattle and buffaloes, and the basal and spinosum layer of the ruminal fibropapilloma/papilloma were cellular proliferation sites. © 2013 Blackwell Verlag GmbH.

Prevalence of Latent Mycobacterium Tuberculosis Infection (LTBI) in Saudi Arabia; Population based survey.

PubMed

Balkhy, Hanan H; El Beltagy, Kamel; El-Saed, Aiman; Aljasir, Badr; Althaqafi, Abdulhakeem; Alothman, Adel F; Alshalaan, Mohammad; Al-Jahdali, Hamdan

2017-07-01

The annual risk of tuberculosis infection (ARTI) data in Saudi Arabia has not been updated since 1993. To estimate the prevalence of latent TB infection (LTBI) and ARTI in a population-based sample in Saudi Arabia using Tuberculin skin test (TST) and QuantiFERON TB Gold in tube (QFT-GIT) test. A population-based cross sectional study was conducted between July 2010 and March 2013. Participants were randomly selected from the population served by the primary healthcare centers of the Ministry of National Guard Health Affairs in Riyadh, Jeddah, Alhassa and Dammam, Saudi Arabia. A total of 1369 participants were included. The overall prevalence of LTBI was similar using TST and QFT-GIT (9.3% and 9.1% respectively, p=0.872) but stratified prevalence rates were variable in all sociodemographic groups except marital status. Additionally, the prevalence rates of LTBI using either test alone showed significant differences by several sociodemographic and behavioral characteristics. The overall ARTI was 0.36% using TST and 0.35% using QFT-GIT. We are reporting much lower estimates for the prevalence of LTBI and the ARTI in a population-based sample in Saudi Arabia relative to the data that have been used for more than two decades. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Phosphorylation of tyrosine 285 of PAK1 facilitates βPIX/GIT1 binding and adhesion turnover

PubMed Central

Hammer, Alan; Oladimeji, Peter; De Las Casas, Luis E.; Diakonova, Maria

2015-01-01

The p21-activated serine-threonine kinase (PAK1) regulates cell motility and adhesion. We have previously shown that the prolactin (PRL)-activated tyrosine kinase JAK2 phosphorylates PAK1 in vivo and in vitro and identified tyrosines 153, 201, and 285 in PAK1 as sites of JAK2 tyrosyl phosphorylation. Here, we further investigate the role of the tyrosyl phosphorylated PAK1 (pTyr-PAK1) in regulation of cell adhesion. We use human breast cancer T47D cell lines that stably overexpress PAK1 wild type or PAK1 Y3F mutant in which these 3 JAK2 phosphorylation sites were mutated to phenylalanine. We demonstrate that PRL/JAK2-dependent phosphorylation of these tyrosines promotes a motile phenotype in the cells upon adhesion, participates in regulation of cell adhesion on collagen IV, and is required for maximal PAK1 kinase activity. Down-regulation of PAK1 abolishes the effect of PAK1 on cell adhesion. We show that the tyrosyl phosphorylation of PAK1 promotes PAK1 binding to β-PAK1-interacting guanine-nucleotide exchange factor (βPIX) and G protein-coupled receptor kinase-interacting target 1 (GIT1), phosphorylation of paxillin on Ser273, and formation and distribution of adhesion complexes. Using phosphospecific antibodies (Abs) directed to single phosphorylated tyrosines on PAK1, we identified Tyr285 as a site of PRL-dependent phosphorylation of PAK1 by JAK2. Furthermore, using PAK1 Y285F mutant, we provide evidence for a role of pTyr285 in cell adhesion, enhanced βPIX/GIT1 binding, and adhesion turnover. Our immunohistochemistry analysis demonstrates that pTyr285- PAK1 may modulate PAK1 signaling during tumor progression.—Hammer, A., Oladimeji, P., De La Casas, L. E., Diakonova, M. Phosphorylation of tyrosine 285 of PAK1 facilitates bPIX/GIT1 binding and adhesion turnover. PMID:25466889

Isoenergetic Replacement of Fat by Starch in Diets for African Catfish (Clarias gariepinus): Effect on Water Fluxes in the Gastro Intestinal Tract

PubMed Central

Harter, Till S.; Verreth, Johan A. J.; Heinsbroek, Leon T. N.; Schrama, Johan W.

2013-01-01

The effect of an isoenergetic replacement of dietary fat by starch, on chyme characteristics and water fluxes in the gastro intestinal tract (GIT) was assessed. Adult African catfish (Clarias gariepinus) were fed a starch (SD) or fat (FD) diet and groups of fish were dissected at 2, 5 and 8 h after the consumption of a single meal. Chyme was collected quantitatively and was analysed for osmolality and dry matter (DM) content. Postprandial water fluxes were calculated, while using yttrium oxide (Y2O3) as an inert marker to account for the absorption of DM along the GIT. The largest differences in chyme characteristics between diets were observed in the stomach and decreased towards subsequent compartments. A high initial osmotic pressure was measured in the stomach for both diets (up to 498±2 mOsm kg−1) and was likely the driver for the endogeneous water influx to this compartment. Large additions of water were recorded to the stomach and proximal intestine for both diets and absorption of water took place in the mid- and distal intestine. Interestingly, the dietary treatment had an impact on water balance in the stomach and proximal intestine of the fish, but not in the mid- and distal intestine. A strong complementary relationship suggested that 59% of the water fluxes in the proximal intestine could be explained by previous additions to the stomach. Therefore, a higher dietary inclusion of starch led to a shift in water additions from the proximal intestine to the stomach. However, the sum of water additions to the GIT was not different between diets and was on average 6.52±0.85 ml water g−1 DM. The interactions between osmoregulation and digestion, in the GIT of fed freshwater fish, deserve further attention in future research. PMID:23372842

Variability of the QuantiFERON®-TB gold in-tube test using automated and manual methods.

PubMed

Whitworth, William C; Goodwin, Donald J; Racster, Laura; West, Kevin B; Chuke, Stella O; Daniels, Laura J; Campbell, Brandon H; Bohanon, Jamaria; Jaffar, Atheer T; Drane, Wanzer; Sjoberg, Paul A; Mazurek, Gerald H

2014-01-01

The QuantiFERON®-TB Gold In-Tube test (QFT-GIT) detects Mycobacterium tuberculosis (Mtb) infection by measuring release of interferon gamma (IFN-γ) when T-cells (in heparinized whole blood) are stimulated with specific Mtb antigens. The amount of IFN-γ is determined by enzyme-linked immunosorbent assay (ELISA). Automation of the ELISA method may reduce variability. To assess the impact of ELISA automation, we compared QFT-GIT results and variability when ELISAs were performed manually and with automation. Blood was collected into two sets of QFT-GIT tubes and processed at the same time. For each set, IFN-γ was measured in automated and manual ELISAs. Variability in interpretations and IFN-γ measurements was assessed between automated (A1 vs. A2) and manual (M1 vs. M2) ELISAs. Variability in IFN-γ measurements was also assessed on separate groups stratified by the mean of the four ELISAs. Subjects (N = 146) had two automated and two manual ELISAs completed. Overall, interpretations were discordant for 16 (11%) subjects. Excluding one subject with indeterminate results, 7 (4.8%) subjects had discordant automated interpretations and 10 (6.9%) subjects had discordant manual interpretations (p = 0.17). Quantitative variability was not uniform; within-subject variability was greater with higher IFN-γ measurements and with manual ELISAs. For subjects with mean TB Responses ±0.25 IU/mL of the 0.35 IU/mL cutoff, the within-subject standard deviation for two manual tests was 0.27 (CI95 = 0.22-0.37) IU/mL vs. 0.09 (CI95 = 0.07-0.12) IU/mL for two automated tests. QFT-GIT ELISA automation may reduce variability near the test cutoff. Methodological differences should be considered when interpreting and using IFN-γ release assays (IGRAs).

Is secretion of IFN-gamma in response to Mycobacterium tuberculosis antigens in youngest children sufficient to play a role in TB diagnostics?

PubMed

Bielecka, Teresa; Komorowska-Piotrowska, Anna; Krenke, Katarzyna; Feleszko, Wojciech; Kulus, Marek

2018-02-01

To assess whether children ≤5 years of age, produce sufficient amounts of interferon gamma (IFN-ɣ) in response to phytohaemagglutinin (mitogen), and Mycobacterium tuberculosis antigens (TB antigens) in the QuantiFERON-TB Gold in-Tube test (QFT-GIT), (Cellestis Ltd., Australia). Is TB-antigen-induced IFN-ɣ response in children ≤5 years sufficient to consider QFT-GIT a possible tool for TB diagnostics? Study design, patient-subject selection, and methods: We recruited children 0-17 years old suspected of TB infection to this cross-sectional study, in whom QFT-GIT and TST were performed. We analyzed the median IFN-ɣ levels in mitogen and TB antigen tubes in children ≤5 years and >5 years, and the correlation between IFN-ɣ level in both tubes and age. A total of 153 children were enrolled, age median was 7.8 (IQR:8), 45 (29.4%) aged ≤5 years (median 3.4, IQR:1.7), 108 > 5 years (median 10.55, IQR:5.93). In the mitogen tubes, the median IFN-ɣ level was higher in children >5 years (median 17.87, IQR:2.1 vs 16.77, IQR:7.6), but surprisingly in the TB antigen tubes it was higher in the younger group (median 0.12, IQR:0.21vs 0.06, IQR:0.09, P = 0.04). We proved a positive correlation between IFN-ɣ level and age in mitogen tubes (r = 0.18, P = 0.03) and a negative correlation in TB antigen tubes (r = -0.17, P = 0.04). In latent tuberculosis infection patients, the latter correlation was found to be even stronger (r = -0.39, P = 0.01). The youngest children release sufficient amount of IFN-ɣ in response to TB antigens thus QFT-GIT might be a useful tool for TB diagnostics in this age group. © 2017 Wiley Periodicals, Inc.

Inclusion of psyllium in milk replacer for neonatal calves. 2. Effects on volatile fatty acid concentrations, microbial populations, and gastrointestinal tract size.

PubMed

Cannon, S J; Fahey, G C; Pope, L L; Bauer, L L; Wallace, R L; Miller, B L; Drackley, J K

2010-10-01

Fermentable fibers such as psyllium increase volatile fatty acid (VFA) concentrations in the lower digestive tract and increase the gastrointestinal tract (GIT) mass of many mammals. We reasoned that psyllium inclusion in milk replacer might produce similar effects in neonatal dairy calves, which could lead to improved growth and health. Male Holstein calves were fed a milk replacer (22% crude protein, 20% fat) either without or with psyllium (1.1% of dry matter, DM) from 2 d through 28 d of age. Milk replacer was reconstituted to 12.5% DM and fed at 12% of calf body weight, adjusted weekly. Water was offered ad libitum but no starter was fed. Three calves per treatment were harvested weekly to sample digesta from the reticulo-rumen, abomasum, jejunum, proximal colon, and distal colon, and to determine length and mass of GIT components. Psyllium in milk replacer increased the proportion of butyrate in reticulo-rumen contents from 2.4 to 3.2% of total but did not affect total VFA concentrations. Total VFA concentrations were very low in the jejunum but psyllium tended to increase total VFA, acetate, and valerate concentrations; valerate accounted for 15.9 and 16.7% of total VFA (molar basis) for control and psyllium calves, respectively. Psyllium increased total VFA concentrations in the proximal and distal colon by 104.4 and 45.6%, respectively, but had little effect on the profile of VFA. Psyllium in milk replacer increased populations of bifidobacteria (from 9.7 to 10.3 log(10) cfu/g of DM) and lactobacilli (from 8.2 to 9.4 log(10) cfu/g of DM) in the reticulo-rumen, but did not affect populations in jejunum or colon. Calves fed psyllium had 12.0% greater total GIT mass and 9.4% greater GIT as a percentage of body weight. Psyllium tended to increase mass of the reticulo-rumen and significantly increased mass of duodenum (34.2%), jejunum (14.5%), and colon (14.6%). Density of intestinal tissues from calves fed psyllium-supplemented milk replacer was 25.9% greater in the jejunum and 25.3% greater in the ileum, and tended to be greater in duodenum and colon than tissue from control calves. Supplementation of psyllium to milk replacer increased fermentation in the colon, mass of the total GIT, and populations of bifidobacteria and lactobacilli in the reticulo-rumen. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Determinants and Duration of Impact of Early Gut Bacterial Colonization.

PubMed

Edwards, Christine Ann

2017-01-01

An increasing number of studies show low diversity of the gut microbiome in those with chronic diseases such as obesity, inflammatory bowel disease, and allergy. Manipulation of the microbiota may promote health. However, the adult microbiota is stable and may be difficult to change. Understanding the fixed and modifiable factors, which determine colonization in early life, may provide strategies for acquisition of a health-promoting microbiome. Not enough is known about the long-term effects of established determinants of gut colonization, including delivery mode, perinatal antibiotics, and infant diet. It has been suggested that weaning onto solid diet containing non-digestible carbohydrates and cessation of breastfeeding are key stages in the colonization process. In addition, the microbiome of the placenta, amniotic fluid, and breast milk, alongside vaginal and fecal bacteria, may aid the transfer of maternal bacteria to the infant. However, methodological issues such as contamination during collection and/or analysis should be considered. Key Messages: The factors determining early colonization are becoming more evident. However, longitudinal studies of microbiome maturation into late childhood and adulthood are required. The nutrition and health status of the mother before, during, and after birth may be major factors in the early colonization of the infant. © 2017 S. Karger AG, Basel.

Clawpack: Building an open source ecosystem for solving hyperbolic PDEs

USGS Publications Warehouse

Iverson, Richard M.; Mandli, K.T.; Ahmadia, Aron J.; Berger, M.J.; Calhoun, Donna; George, David L.; Hadjimichael, Y.; Ketcheson, David I.; Lemoine, Grady L.; LeVeque, Randall J.

2016-01-01

Clawpack is a software package designed to solve nonlinear hyperbolic partial differential equations using high-resolution finite volume methods based on Riemann solvers and limiters. The package includes a number of variants aimed at different applications and user communities. Clawpack has been actively developed as an open source project for over 20 years. The latest major release, Clawpack 5, introduces a number of new features and changes to the code base and a new development model based on GitHub and Git submodules. This article provides a summary of the most significant changes, the rationale behind some of these changes, and a description of our current development model. Clawpack: building an open source ecosystem for solving hyperbolic PDEs.

Dismicrobism in inflammatory bowel disease and colorectal cancer: Changes in response of colocytes

PubMed Central

Tomasello, Giovanni; Tralongo, Pietro; Damiani, Provvidenza; Sinagra, Emanuele; Di Trapani, Benedetto; Zeenny, Marie Noelle; Hajj Hussein, Inaya; Jurjus, Abdo; Leone, Angelo

2014-01-01

Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health. The gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. In utero, the intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). The healthy human gut harbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC. In healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. The microbiota exerts diverse physiological functions to include: growth inhibition of pathogenic microorganisms, synthesis of compounds useful for the trophism of colonic mucosa, regulation of intestinal lymphoid tissue and synthesis of amino acids. Furthermore, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. Changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn’s disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis. PMID:25561781

Dismicrobism in inflammatory bowel disease and colorectal cancer: changes in response of colocytes.

PubMed

Tomasello, Giovanni; Tralongo, Pietro; Damiani, Provvidenza; Sinagra, Emanuele; Di Trapani, Benedetto; Zeenny, Marie Noelle; Hussein, Inaya Hajj; Jurjus, Abdo; Leone, Angelo

2014-12-28

Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health. The gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. In utero, the intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). The healthy human gut harbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC. In healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. The microbiota exerts diverse physiological functions to include: growth inhibition of pathogenic microorganisms, synthesis of compounds useful for the trophism of colonic mucosa, regulation of intestinal lymphoid tissue and synthesis of amino acids. Furthermore, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. Changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn's disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.

In Silico Analysis of the Small Molecule Content of Outer Membrane Vesicles Produced by Bacteroides thetaiotaomicron Indicates an Extensive Metabolic Link between Microbe and Host

PubMed Central

Bryant, William A.; Stentz, Régis; Le Gall, Gwenaelle; Sternberg, Michael J. E.; Carding, Simon R.; Wilhelm, Thomas

2017-01-01

The interactions between the gut microbiota and its host are of central importance to the health of the host. Outer membrane vesicles (OMVs) are produced ubiquitously by Gram-negative bacteria including the gut commensal Bacteroides thetaiotaomicron. These vesicles can interact with the host in various ways but until now their complement of small molecules has not been investigated in this context. Using an untargeted high-coverage metabolomic approach we have measured the small molecule content of these vesicles in contrasting in vitro conditions to establish what role these metabolites could perform when packed into these vesicles. B. thetaiotaomicron packs OMVs with a highly conserved core set of small molecules which are strikingly enriched with mouse-digestible metabolites and with metabolites previously shown to be associated with colonization of the murine GIT. By use of an expanded genome-scale metabolic model of B. thetaiotaomicron and a potential host (the mouse) we have established many possible metabolic pathways between the two organisms that were previously unknown, and have found several putative novel metabolic functions for mouse that are supported by gene annotations, but that do not currently appear in existing mouse metabolic networks. The lipidome of these OMVs bears no relation to the mouse lipidome, so the purpose of this particular composition of lipids remains unclear. We conclude from this analysis that through intimate symbiotic evolution OMVs produced by B. thetaiotaomicron are likely to have been adopted as a conduit for small molecules bound for the mammalian host in vivo. PMID:29276507

In Silico Analysis of the Small Molecule Content of Outer Membrane Vesicles Produced by Bacteroides thetaiotaomicron Indicates an Extensive Metabolic Link between Microbe and Host.

PubMed

Bryant, William A; Stentz, Régis; Le Gall, Gwenaelle; Sternberg, Michael J E; Carding, Simon R; Wilhelm, Thomas

2017-01-01

The interactions between the gut microbiota and its host are of central importance to the health of the host. Outer membrane vesicles (OMVs) are produced ubiquitously by Gram-negative bacteria including the gut commensal Bacteroides thetaiotaomicron . These vesicles can interact with the host in various ways but until now their complement of small molecules has not been investigated in this context. Using an untargeted high-coverage metabolomic approach we have measured the small molecule content of these vesicles in contrasting in vitro conditions to establish what role these metabolites could perform when packed into these vesicles. B. thetaiotaomicron packs OMVs with a highly conserved core set of small molecules which are strikingly enriched with mouse-digestible metabolites and with metabolites previously shown to be associated with colonization of the murine GIT. By use of an expanded genome-scale metabolic model of B. thetaiotaomicron and a potential host (the mouse) we have established many possible metabolic pathways between the two organisms that were previously unknown, and have found several putative novel metabolic functions for mouse that are supported by gene annotations, but that do not currently appear in existing mouse metabolic networks. The lipidome of these OMVs bears no relation to the mouse lipidome, so the purpose of this particular composition of lipids remains unclear. We conclude from this analysis that through intimate symbiotic evolution OMVs produced by B. thetaiotaomicron are likely to have been adopted as a conduit for small molecules bound for the mammalian host in vivo .

Quantification of FITC-labelled probiotic Lactobacillus salivarius DSPV 001P during gastrointestinal transit in broilers.

PubMed

Blajman, J E; Astesana, D M; Zimmermann, J A; Rossler, E; Scharpen, A Romero; Berisvil, A P; Zbrun, M V; Soto, L P; Rosmini, M R; Frizzo, L S

2017-02-07

The knowledge related to the fate of probiotics in the complex environment of the intestinal microbiota in broilers is just beginning to be elucidated; however, it is not yet well understood. A good method to investigate the mechanisms by which probiotics mediate their effects is to mark probiotic bacteria and trace them. The aim of this research was to develop a new method to estimate in vivo fluorescein isothiocyanate (FITC)-labelled Lactobacillus salivarius DSPV 001P counts during passage through the gastrointestinal tract (GIT) of broilers. Forty-five, 1 d old Cobb broilers were used in this trial. Programmed necropsies were performed 30 min, 6 h, and 12 h after the administration of the probiotic bacterium, and samples of liver, crop, duodenum, caecum, and bursa of fabricius were collected. To determine the spatial and temporal transit of L. salivarius DSPV 001P in broilers, the number of bacteria as well as its respective fluorescent signal produced by FITC were measured. In order to observe the relationship between the variables, a logistic regression analysis was applied. The amount of fluorescence could be used as an indicator of fluorescent probiotic bacteria in the crop and duodenum 30 min after probiotic bacterium supplementation. In addition, the fluorescent signal could be used to estimate bacterial counts in caecum 6 and 12 h after L. salivarius DSPV 001P administration. To the best of our knowledge, this research is the first in vivo trial to employ the bacterial FITC-labelling technique in order to enumerate probiotic bacteria during gastrointestinal transit in broilers.

The underexposed role of food matrices in probiotic products: Reviewing the relationship between carrier matrices and product parameters.

PubMed

Flach, Joost; van der Waal, Mark B; van den Nieuwboer, Maurits; Claassen, Eric; Larsen, Olaf F A

2017-06-13

Probiotic microorganisms are increasingly incorporated into food matrices in order to confer proposed health benefits on the consumer. It is important that the health benefits, sensory properties, shelf-life and probiotic gastrointestinal tract (GIT) survival of these products are carefully balanced as they determine functionality and drive consumer acceptance. The strain-specific effects of probiotic species are imperative in this process but carrier matrices may play a pivotal role as well. This study therefore recapitulates the wealth of knowledge on carrier matrices and their interaction with probiotic strains. The most substantiated carrier matrices, factors that influence probiotic functionality and matrix effects on shelf-life, GIT survival and clinical efficacy are reviewed. Results indicate that carrier matrices have a significant impact on the quality of probiotic products. Matrix components, such as proteins, carbohydrates and flavoring agents are shown to alter probiotic efficacy and viability. In vivo studies furthermore revealed strain-dependent matrix effects on the GIT survival of probiotic bacteria. However, only a limited number of studies have specifically addressed the effects of carrier matrices on the aforementioned product-parameters; most studies seem to focus solely on the strain-specific effects of probiotic microorganisms. This hampers the innovation of probiotic products. More human studies, comparing not only different probiotic strains but different carrier matrices as well, are needed to drive the innovation cycle.

Global gas chromatography/time-of-flight mass spectrometry (GC/TOFMS)-based metabonomic profiling of lyophilized human feces.

PubMed

Phua, Lee Cheng; Koh, Poh Koon; Cheah, Peh Yean; Ho, Han Kiat; Chan, Eric Chun Yong

2013-10-15

Gas chromatography mass spectrometry (GC/MS)-based fecal metabonomics represents a powerful systems biology approach for elucidating metabolic biomarkers of lower gastrointestinal tract (GIT) diseases. Unlike metabolic profiling of fecal water, the profiling of complete fecal material remains under-explored. Here, a gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) method was developed and validated for the global metabonomic profiling of human feces. Fecal and fecal water metabotypes were also profiled and compared. Additionally, the unclear influence of blood in stool on the fecal metabotype was investigated unprecedentedly. Eighty milligram of lyophilized feces was ultrasonicated with 1mL of methanol:water (8:2) for 30min, followed by centrifugation, drying of supernatant, oximation and trimethylsilylation for 45min. Lyophilized feces demonstrated a more comprehensive metabolic coverage than fecal water, based on the number of chromatographic peaks. Principal component analysis (PCA) indicated occult blood (1mgHb/g feces) exerted a negligible effect on the fecal metabotype. Conversely, a unique metabotype related to feces spiked with gross blood (100mgHb/g feces) was revealed (PCA, R(2)X=0.837, Q(2)=0.794), confirming the potential confounding effect of gross GIT bleeding on the fecal metabotype. This pertinent finding highlights the importance of prudent interpretation of fecal metabonomic data, particularly in GIT diseases where bleeding is prevalent. Copyright © 2013 Elsevier B.V. All rights reserved.

NASA's Earth Imagery Service as Open Source Software

NASA Astrophysics Data System (ADS)

De Cesare, C.; Alarcon, C.; Huang, T.; Roberts, J. T.; Rodriguez, J.; Cechini, M. F.; Boller, R. A.; Baynes, K.

2016-12-01

The NASA Global Imagery Browse Service (GIBS) is a software system that provides access to an archive of historical and near-real-time Earth imagery from NASA-supported satellite instruments. The imagery itself is open data, and is accessible via standards such as the Open Geospatial Consortium (OGC)'s Web Map Tile Service (WMTS) protocol. GIBS includes three core software projects: The Imagery Exchange (TIE), OnEarth, and the Meta Raster Format (MRF) project. These projects are developed using a variety of open source software, including: Apache HTTPD, GDAL, Mapserver, Grails, Zookeeper, Eclipse, Maven, git, and Apache Commons. TIE has recently been released for open source, and is now available on GitHub. OnEarth, MRF, and their sub-projects have been on GitHub since 2014, and the MRF project in particular receives many external contributions from the community. Our software has been successful beyond the scope of GIBS: the PO.DAAC State of the Ocean and COVERAGE visualization projects reuse components from OnEarth. The MRF source code has recently been incorporated into GDAL, which is a core library in many widely-used GIS software such as QGIS and GeoServer. This presentation will describe the challenges faced in incorporating open software and open data into GIBS, and also showcase GIBS as a platform on which scientists and the general public can build their own applications.

Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy.

PubMed

Hoffmann, Christine; Ziegler, Ute; Buschmann, Anne; Weber, Artur; Kupfer, Leila; Oelschlegel, Anja; Hammerschmidt, Baerbel; Groschup, Martin H

2007-03-01

To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.

The comparative gastrointestinal morphology of Jaculus jaculus (Rodentia) and Paraechinus aethiopicus (Erinaceomorpha).

PubMed

Pereira, Daniella L; Walters, Jacklynn; Bennett, Nigel C; Alagaili, Abdulaziz N; Mohammed, Osama B; Kotzé, Sanet H

2016-05-01

Jaculus jaculus (Lesser Egyptian jerboa) and Paraechinus aethiopicus (Desert hedgehog) are small mammals which thrive in desert conditions and are found, among others, in the Arabian Peninsula. Jaculus jaculus is omnivorous while P. aethiopicus is described as being insectivorous. The study aims to describe the gastrointestinal tract (GIT) morphology of these animals which differ in diet and phylogeny. The GITs of J. jaculus (n = 8) and P. aethiopicus (n = 7) were weighed, photographed, and the length, basal surface areas, and luminal surface areas of each of the anatomically distinct gastrointestinal segments were determined. The internal aspects of each area were examined and photographed while representative histological sections of each area were processed to wax and stained using haematoxylin and eosin. Both species had a simple unilocular stomach which was confirmed as wholly glandular on histology sections. Paraechinus aethiopicus had a relatively simple GIT which lacked a caecum. The caecum of J. jaculus was elongated, terminating in a narrow cecal appendix which contained lymphoid tissue on histological examination. The internal aspect of the proximal colon of J. jaculus revealed distinct V-shaped folds. Stomach content analysis of J. jaculus revealed mostly plant and seed material and some insects, whereas P. aethiopicus samples showed plant material in addition to insects, indicating omnivorous feeding tendencies in areas where insects may be scarce. © 2016 Wiley Periodicals, Inc.

High doses of lercanidipine are better tolerated than other dihydropyridines in hypertensive patients with metabolic syndrome: results from the TOLERANCE study

PubMed Central

Barrios, V; Escobar, C; de la Figuera, M; Honorato, J; Llisterri, J L; Segura, J; Calderón, A

2008-01-01

Aims/Introduction The TOlerabilidad de LERcanidipino 20 mg frente a Amlodipino y Nifedipino en CondicionEs normales de uso study was aimed to compare the tolerability of high doses of lercanidipine with amlodipine and nifedipine gastro-intestinal therapeutic system (GITS) in the treatment of hypertension in daily clinical practice. Patients/methods Essential hypertensives ≥ 18 years, treated during at least 1 month with lercanidipine 20 mg, amlodipine 10 mg or nifedipine GITS 60 mg, after a previous treatment course of at least 1 month with half the dose of the corresponding drugs were included. We present the data of the subgroup of patients with metabolic syndrome (MetS). Results Three hundred and thirty-seven of the 650 study population fulfilled criteria of MetS, 233 (69.1%) on lercanidipine and 104 (30.9%) on amlodipine/nifedipine GITS. Overall, a significantly lower proportion of lercanidipine-treated patients showed adverse reactions (ARs) when compared with patients receiving other-dihydropyridines (DHPs) (60.1% vs. 73.1%, p = 0.003). Similarly, the most common vasodilation-related ARs (oedema, swelling, flushing and headache) were significantly less frequent in lercanidipine group (all p < 0.01). Conclusion In conclusion, lercanidipine appears to exhibit a better tolerability profile and less vasodilation-related ARs compared with other DHPs in hypertensive patients with MetS. PMID:18355238

The mother-offspring dyad: microbial transmission, immune interactions and allergy development.

PubMed

Jenmalm, M C

2017-12-01

The increasing prevalence of allergy in affluent countries may be caused by reduced intensity and diversity of microbial stimulation, resulting in abnormal postnatal immune maturation. Most studies investigating the underlying immunomodulatory mechanisms have focused on postnatal microbial exposure, for example demonstrating that the gut microbiota differs in composition and diversity during the first months of life in children who later do or do not develop allergic disease. However, it is also becoming increasingly evident that the maternal microbial environment during pregnancy is important in childhood immune programming, and the first microbial encounters may occur already in utero. During pregnancy, there is a close immunological interaction between the mother and her offspring, which provides important opportunities for the maternal microbial environment to influence the immune development of the child. In support of this theory, combined pre- and postnatal supplementations seem to be crucial for the preventive effect of probiotics on infant eczema. Here, the influence of microbial and immune interactions within the mother-offspring dyad on childhood allergy development will be discussed. In addition, how perinatal transmission of microbes and immunomodulatory factors from mother to offspring may shape appropriate immune maturation during infancy and beyond, potentially via epigenetic mechanisms, will be examined. Deeper understanding of these interactions between the maternal and offspring microbiome and immunity is needed to identify efficacious preventive measures to combat the allergy epidemic. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Jussara (Euterpe edulis Mart.) Supplementation during Pregnancy and Lactation Modulates the Gene and Protein Expression of Inflammation Biomarkers Induced by trans-Fatty Acids in the Colon of Offspring

PubMed Central

Almeida Morais, Carina; Oyama, Lila Missae; de Oliveira, Juliana Lopez; Carvalho Garcia, Márcia; de Rosso, Veridiana Vera; Sousa Mendes Amigo, Laís; do Nascimento, Claudia Maria Oller; Pisani, Luciana Pellegrini

2014-01-01

Maternal intake of trans-fatty acids (TFAs) in the perinatal period triggers a proinflammatory state in offspring. Anthocyanins contained in fruit are promising modulators of inflammation. This study investigated the effect of Jussara supplementation in the maternal diet on the proinflammatory state of the colon in offspring exposed to perinatal TFAs. On the first day of pregnancy rats were divided into four groups: control diet (C), control diet with 0.5% Jussara supplementation (CJ), diet enriched with hydrogenated vegetable fat, rich in TFAs (T), or T diet supplemented with 0.5% Jussara (TJ) during pregnancy and lactation. We showed that Jussara supplementation in maternal diet (CJ and TJ groups) reduced carcass lipid/protein ratios, serum lipids, glucose, IL-6, TNF-α, gene expression of IL-6R, TNF-αR (P < 0.05), TLR-4 (P < 0.01), and increase Lactobacillus spp. (P < 0.05) in the colon of offspring compared to the T group. The IL-10 (P = 0.035) and IL-10/TNF-α ratio (P < 0.01) was higher in the CJ group than in the T group. The 0.5% Jussara supplementation reverses the adverse effects of perinatal TFAs, improving lipid profiles, glucose levels, body composition, and gut microbiota and reducing low-grade inflammation in the colon of 21-day-old offspring, and could contribute to reducing chronic disease development. PMID:25276060

The Perinatal Microbiome and Pregnancy: Moving Beyond the Vaginal Microbiome

PubMed Central

Prince, Amanda L.; Chu, Derrick M.; Seferovic, Maxim D.; Antony, Kathleen M.; Ma, Jun; Aagaard, Kjersti M.

2015-01-01

The human microbiome, the collective genome of the microbial community that is on and within us, has recently been mapped. The initial characterization of healthy subjects has provided investigators with a reference population for interrogating the microbiome in metabolic, intestinal, and reproductive health and disease states. Although it is known that bacteria can colonize the vagina, recent metagenomic studies have shown that the vaginal microbiome varies among reproductive age women. Similarly, the richness and diversity of intestinal microbiota also naturally fluctuate among gravidae in both human and nonhuman primates, as well as mice. Moreover, recent evidence suggests that microbiome niches in pregnancy are not limited to maternal body sites, as the placenta appears to harbor a low biomass microbiome that is presumptively established in early pregnancy and varies in association with a remote history of maternal antenatal infection as well as preterm birth. In this article, we will provide a brief overview on metagenomics science as a means to investigate the microbiome, observations pertaining to both variation and the presumptive potential role of a varied microbiome during pregnancy, and how future studies of the microbiome in pregnancy may lend to a better understanding of human biology, reproductive health, and parturition. PMID:25775922

Preterm Birth Affects the Risk of Developing Immune-Mediated Diseases

PubMed Central

Goedicke-Fritz, Sybelle; Härtel, Christoph; Krasteva-Christ, Gabriela; Kopp, Matthias V.; Meyer, Sascha; Zemlin, Michael

2017-01-01

Prematurity affects approximately 10% of all children, resulting in drastically altered antigen exposure due to premature confrontation with microbes, nutritional antigens, and other environmental factors. During the last trimester of pregnancy, the fetal immune system adapts to tolerate maternal and self-antigens, while also preparing for postnatal immune defense by acquiring passive immunity from the mother. Since the perinatal period is regarded as the most important “window of opportunity” for imprinting metabolism and immunity, preterm birth may have long-term consequences for the development of immune-mediated diseases. Intriguingly, preterm neonates appear to develop bronchial asthma more frequently, but atopic dermatitis less frequently in comparison to term neonates. The longitudinal study of preterm neonates could offer important insights into the process of imprinting for immune-mediated diseases. On the one hand, preterm birth may interrupt influences of the intrauterine environment on the fetus that increase or decrease the risk of later immune disease (e.g., maternal antibodies and placenta-derived factors), whereas on the other hand, it may lead to the premature exposure to protective or harmful extrauterine factors such as microbiota and nutritional antigen. Solving this puzzle may help unravel new preventive and therapeutic approaches for immune diseases. PMID:29062316

A streptococcal NRAMP homologue is crucial for the survival of Streptococcus agalactiae under low pH conditions.

PubMed

Shabayek, Sarah; Bauer, Richard; Mauerer, Stefanie; Mizaikoff, Boris; Spellerberg, Barbara

2016-05-01

Streptococcus agalactiae or Group B Streptococcus (GBS) is a commensal bacterium of the human gastrointestinal and urogenital tracts as well as a leading cause of neonatal sepsis, pneumonia and meningitis. Maternal vaginal carriage is the main source for GBS transmission and thus the most important risk factor for neonatal disease. Several studies in eukaryotes identified a group of proteins natural resistance-associated macrophage protein (NRAMP) that function as divalent cation transporters for Fe(2+) and Mn(2+) and confer on macrophages the ability to control replication of bacterial pathogens. Genome sequencing predicted potential NRAMP homologues in several prokaryotes. Here we describe for the first time, a pH-regulated NRAMP Mn(2+) /Fe(2+) transporter in GBS, designated MntH, which confers resistance to reactive oxygen species (ROS) and is crucial for bacterial growth and survival under low pH conditions. Our investigation implicates MntH as an important colonization determinant for GBS in the maternal vagina as it helps bacteria to adapt to the harsh acidic environment, facilitates bacterial adherence, contributes to the coexistence with the vaginal microbiota and plays a role in GBS intracellular survival inside macrophages. © 2016 John Wiley & Sons Ltd.

Upper gastrointestinal barium evaluation of duodenal pathology: A pictorial review

PubMed Central

Gupta, Pankaj; Debi, Uma; Sinha, Saroj Kant; Prasad, Kaushal Kishor

2014-01-01

Like other parts of the gastrointestinal tract (GIT), duodenum is subject to a variety of lesions both congenital and acquired. However, unlike other parts of the GIT viz. esophagus, rest of the small intestine and large intestine, barium evaluation of duodenal lesions is technically more challenging and hence not frequently reported. With significant advances in computed tomography technology, a thorough evaluation including intraluminal, mural and extramural is feasible in a single non-invasive examination. Notwithstanding, barium evaluation still remains the initial and sometimes the only imaging study in several parts of the world. Hence, a thorough acquaintance with the morphology of various duodenal lesions on upper gastrointestinal barium examination is essential in guiding further evaluation. We reviewed our experience with various common and uncommon barium findings in duodenal abnormalities. PMID:25170399

Benchmark solutions for the galactic ion transport equations: Energy and spatially dependent problems

NASA Technical Reports Server (NTRS)

Ganapol, Barry D.; Townsend, Lawrence W.; Wilson, John W.

1989-01-01

Nontrivial benchmark solutions are developed for the galactic ion transport (GIT) equations in the straight-ahead approximation. These equations are used to predict potential radiation hazards in the upper atmosphere and in space. Two levels of difficulty are considered: (1) energy independent, and (2) spatially independent. The analysis emphasizes analytical methods never before applied to the GIT equations. Most of the representations derived have been numerically implemented and compared to more approximate calculations. Accurate ion fluxes are obtained (3 to 5 digits) for nontrivial sources. For monoenergetic beams, both accurate doses and fluxes are found. The benchmarks presented are useful in assessing the accuracy of transport algorithms designed to accommodate more complex radiation protection problems. In addition, these solutions can provide fast and accurate assessments of relatively simple shield configurations.

A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease.

PubMed

Marin, R; Ruilope, L M; Aljama, P; Aranda, P; Segura, J; Diez, J

2001-10-01

To investigate in a random comparison the capacity of an angiotensin converting enzyme inhibitor (fosinopril), and that of a long-acting dihydropiridine (nifedipine GITS) to modify the decay in renal function in patients with primary renal disease, exhibiting a progressive increase in serum creatinine during the previous 2 years. A randomized, open-label, multicenter study with a minimum follow-up of 3 years. A total of 241 patients were included in the study. All of them were hypertensive and had a 25% or at least 0.5 mg/dl increase in the value of serum creatinine during the 24 months prior to entering the study. Initial doses of fosinopril and nifedipine GITS were 10 and 30 mg respectively, and titration to 30 and 60 mg was performed if needed to obtain the expected blood pressure goal (< 140/90 mmHg). Furosemide, atenolol, and doxazosin were added as second, third, and fourth drugs if necessary, for blood pressure control. The primary end-point of the study was the appearance of double the serum creatinine values and/or the need to enter a dialysis programme. Secondary end-points were cardiovascular events, death, changes in 24 h proteinuria, and the evolution of serum creatinine. Data reflect the analysis performed by intention to treat. Mean age of the group was 54 +/- 14, and 59% were males. Primary glomerulonephritis (31%), nephrosclerosis (26%) and polycystic kidney disease (19%) were the three most frequent diagnostic findings. After 3 years of follow-up, 21% (27/127) of patients treated with fosinopril, and 36% (40/112) of those receiving nifedipine GITS presented a primary end-point, (OR 0.47, 95% confidence intervals 0.26-0.84, P = 0.01). Renal survival was significantly better when fosinopril constituted the first step therapy (P = 0.002). These results did not seem to be influenced by the type of primary renal disease. Proteinuria decreased at the end of the study by a mean of 57% in the fosinopril group and increased by 7% in the group receiving dihydropiridine. Blood pressure control did not differ among groups for diastolic values. During follow-up, however, the patients receiving ACEi showed systolic blood pressure values 4-6 mmHg lower. In patients with chronic renal failure and hypertension due to primary renal disease, fosinopril significantly differed from nifedipine GITS by its capacity to slow the progressive decay in renal function. The drugs also differed by their capacity to lower blood pressure. The better control, in particular of systolic blood pressure, in the fosinopril arm could have contributed in a relevant manner to the attainment of a better outcome when the ACEi was employed.

Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

PubMed

Park, Jeong Bae; Shin, Joon-Han; Kim, Dong-Soo; Youn, Ho-Joong; Park, Seung Woo; Shim, Wan Joo; Park, Chang Gyu; Kim, Dong-Woon; Lee, Hae-Young; Choi, Dong-Ju; Rim, Se-Joong; Lee, Sung-Yun; Kim, Ju-Han

2016-04-01

Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Ecological Restoration of Antibiotic-Disturbed Gastrointestinal Microbiota in Foregut and Hindgut of Cows

PubMed Central

Ji, Shoukun; Jiang, Tao; Yan, Hui; Guo, Chunyan; Liu, Jingjing; Su, Huawei; Alugongo, Gibson M.; Shi, Haitao; Wang, Yajing; Cao, Zhijun; Li, Shengli

2018-01-01

Antibiotically disturbed gastrointestinal microbiota needs a long period time to be restored to normal, which may cause a series of problems to the host. The understanding of restoration of the biased microbiota by antibiotics remains largely unknown. Here, we investigated the microbiota shift in foregut (rumen) and hindgut (rectum) of lactating cows after antibiotics exposure as well as after antibiotics withdrawal with (Microbiota transplantation, MT group) or without (Control, CON group) microbiota transplantation. We were able to demonstrate that microbiota in both foregut and hindgut significantly changed after 3 or 14 days of antibiotics exposure, and the changes persisted over long period of time (>18 days) after withdrawing the antibiotics. We further observed a faster restoration of microbiota in both foregut and hindgut of MT group than CON group, microbiota in foregut was mainly benefited from microbiota transplantation by restoring the alpha-diversity as well as within-group similarity, while microbiota in hindgut was primarily benefited from microbiota transplantation by reestablishing the co-occurrence network (nodes number, edges number, density, modularity as well as closeness centrality). These results together expanded our understanding of restoration of the biased microbiota by antibiotics, and may also be instructive to deal with the delayed microbiota restoration at least in cows. PMID:29594071

Probiotics in human milk and probiotic supplementation in infant nutrition: a workshop report.

PubMed

Bergmann, Henrike; Rodríguez, Juan Miguel; Salminen, Seppo; Szajewska, Hania

2014-10-14

Probiotics in human milk are a very recent field of research, as the existence of the human milk microbiome was discovered only about a decade ago. Current research is focusing on bacterial diversity and the influence of the maternal environment as well as the mode of delivery on human milk microbiota, the pathways of bacterial transfer to milk ducts, possible benefits of specific bacterial strains for the treatment of mastitis in mothers, and disease prevention in children. Recent advances in the assessment of early host-microbe interactions suggest that early colonisation may have an impact on later health. This review article summarises a scientific workshop on probiotics in human milk and their implications for infant health as well as future perspectives for infant feeding.

Effects of infant cereals with different carbohydrate profiles on colonic function--randomised and double-blind clinical trial in infants aged between 6 and 12 months--pilot study.

PubMed

Bernal, María José; Periago, María Jesús; Martínez, Rosario; Ortuño, Inmaculada; Sánchez-Solís, Manuel; Ros, Gaspar; Romero, Fernando; Abellán, Pedro

2013-11-01

Infant cereals are often the elected foodstuff for beginning complementary feeding and provide carbohydrates which are different to those found in maternal milk. The objective of this preliminary study was to ascertain the colonic effects of two infant cereals, with different carbohydrate profiles, in a randomised and double-blind trial in healthy infants. Nineteen term infants between 6.3 and 9.8 months of age were enrolled, after written informed consent was obtained from parents. Ten subjects were allocated to take infant cereal A and nine, infant cereal B. An intervention period was 2 months, with five visits every 15 days, to take anthropometric measurements and faeces samples for the analysis of microbiota, short-chain fatty acids concentration (SCFA), pH value and secretory immunoglobulin A (sIgA). An adequate growth and stool frequency was registered in both intervention groups. Faecal counts of Bifidobacterium, Lactobacillus, Enterobacteriaceae, Enterococcus, Clostridium and Bacteroides did not show any statistical differences. However, a significantly (P < 0.05) higher butyric acid and sIgA, and lower faecal pH were observed in infants who had ingested infant cereal A, with a higher ratio complex/simple carbohydrates. In conclusion, small changes in the carbohydrate profile of infant cereals could lead to significant differences in parameters related to fermentative activity of intestinal microbiota.

Building Successful GitHub Communities

NASA Astrophysics Data System (ADS)

Smith, A.

2014-12-01

Building successful online communities is hard, whether it's in open source software or web-based citizen science. In this presentation I'll share some lessons learned and outline some techniques employed by successful open source projects.

Small cell carcinomas of the gastrointestinal tract: clinicopathological features and treatment approach.

PubMed

Brenner, Baruch; Tang, Laura H; Shia, Jinruh; Klimstra, David S; Kelsen, David P

2007-02-01

Small cell undifferentiated carcinoma (SmCC) of the gastrointestinal tract (GIT) is a rare and highly aggressive malignancy. To date, fewer than 1,000 cases have been reported, with an estimated prevalence of 0.1% to 1% of all gastrointestinal (GI) tumors. Data on the disease are scarce due to its rarity and the fact that most authors have focused on one site within the GIT. In light of the limited data and its perceived similarity to SmCC of the lung, the disease has usually been treated as the latter. Nevertheless, recent clinicopathologic and molecular data imply several differences between the two entities, questioning the extent to which extrapolations from one to the other can be made. We review the available data on GI SmCC with emphasis on outlining its clinicopathologic features and the recommended treatment approach.

Alarmins as biomarkers of gastrointestinal surgical injury - a pilot study.

PubMed

Maca, Jan; Holub, Michal; Bursa, Filip; Ihnat, Peter; Reimer, Petr; Svagera, Zdenek; Burda, Michal; Sevcik, Pavel

2018-02-01

The dysregulation of inflammatory response to surgical injury affects outcomes. Alarmins, the earliest bioactive substances from damaged cells, play a crucial role in initiating the inflammation. We analyzed serum levels of alarmins (S100A8, S100A12, high mobility group box, and heat shock protein 70) after major abdominal surgery (MAS) in surgical (S) (n = 82) and nonsurgical (NS) groups (n = 35). The main objective was determining a role of selected alarmins in host response to MAS. The secondary objectives were (i) evaluation of the relationship among alarmins and selected biomarkers (C-reactive protein, interleukin-6), (ii) influence of the place of gastrointestinal resection, and (iii) role of alarmins in MAS for cancer. Except for HMGB1, the levels of all alarmins were higher in the S group compared with the NS group. In the S group, positive correlations were found between S100A8 and both IL-6 and CRP. Additionally, the S100A8 level was higher (p < 0.01) in patients who underwent upper gastrointestinal tract (GIT) surgery compared to middle and lower GIT resections. Alarmins levels did not differ between cancer and noncancer patients. MAS is able to elicit increase in alarmin levels. S100A8 can be considered a potential biomarker of surgical injury, especially in the upper part of the GIT. © 2018 APMIS. Published by John Wiley & Sons Ltd.

Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization.

PubMed

Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Coussa-Charley, Michael; Kahouli, Imen; Jones, Mitchell L; Labbé, Alain; Prakash, Satya

2012-02-16

Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT) which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA) microcapsules to encapsulate Lactobacillus fermentum NCIMB 5221 and characterize its enzymatic activity and viability through a simulated GIT. This specific strain, in previous research, was characterized for its inherent ferulic acid esterase (FAE) activity which could prove beneficial in the development of a therapeutic for the treatment and prevention of cancers and metabolic disorders. Our findings demonstrate that the APA microcapsule does not slow the mass transfer of substrate into and that of the FA product out of the microcapsule, while also not impairing bacterial cell viability. The use of simulated gastrointestinal conditions led to a significant 2.5 log difference in viability between the free (1.10 × 104 ± 1.00 × 103 cfu/mL) and the microencapsulated (5.50 × 106 ± 1.00 × 105 cfu/mL) L. fermentum NCIMB 5221 following exposure. The work presented here suggests that APA microencapsulation can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a FAE-active probiotic strain.

Snapshot of Quantiferon TB gold testing in Northern Mexico.

PubMed

González-Salazar, F; Vargas-Villarreal, J; Garcialuna-Martínez, F J; Rivera, G; Moreno-Treviño, M G; Montfort-Gardeazabal, J M; Garcialuna-Martínez, E

2011-12-01

Most people infected with Mycobacterium tuberculosis have an asymptomatic condition named latent tuberculosis. These people do not have bacilli in the corporal secretions and are hard to diagnose by conventional laboratory tests. Diagnosis of latent tuberculosis infection (LTBI) in México is based on the tuberculin skin test (TST). This test has disadvantages, principally because the vaccine containing the Bacille Calmette-Guérin (BCG) is applied to 99% of this population and causes false positive TST outcomes. Recently, interferon-gamma release assays (IGRA) have been demonstrated to be a good test to detect latent tuberculosis with equal or better sensitivity to TST and without interference from BCG. However, in México the IGRA are an uncommon test due to the higher cost compared to TST. The main objective of this work was demonstrate the potential utility of the Quantiferon TB(®) gold in tube (QTB(®)-GIT) test to detect latent TB in a population from northern México. Samples from 106 subjects with close contact, or without contact, with actively infected TB patients were tested to detect LTBI. Our results show a significant difference between individuals in close contact with active TB patients (39.7%) compared to those without contact (3.2%), p < 0.01. The concordance between TST and QTB(®)-GIT was poor (κ = 0.31). Our preliminary results show that the QTB(®)-GIT has better capacity than TST to detect latent tuberculosis infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sucralose, a synthetic organochlorine sweetener: overview of biological issues.

PubMed

Schiffman, Susan S; Rother, Kristina I

2013-01-01

Sucralose is a synthetic organochlorine sweetener (OC) that is a common ingredient in the world's food supply. Sucralose interacts with chemosensors in the alimentary tract that play a role in sweet taste sensation and hormone secretion. In rats, sucralose ingestion was shown to increase the expression of the efflux transporter P-glycoprotein (P-gp) and two cytochrome P-450 (CYP) isozymes in the intestine. P-gp and CYP are key components of the presystemic detoxification system involved in first-pass drug metabolism. The effect of sucralose on first-pass drug metabolism in humans, however, has not yet been determined. In rats, sucralose alters the microbial composition in the gastrointestinal tract (GIT), with relatively greater reduction in beneficial bacteria. Although early studies asserted that sucralose passes through the GIT unchanged, subsequent analysis suggested that some of the ingested sweetener is metabolized in the GIT, as indicated by multiple peaks found in thin-layer radiochromatographic profiles of methanolic fecal extracts after oral sucralose administration. The identity and safety profile of these putative sucralose metabolites are not known at this time. Sucralose and one of its hydrolysis products were found to be mutagenic at elevated concentrations in several testing methods. Cooking with sucralose at high temperatures was reported to generate chloropropanols, a potentially toxic class of compounds. Both human and rodent studies demonstrated that sucralose may alter glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels. Taken together, these findings indicate that sucralose is not a biologically inert compound.

Methodological factors influencing inhalation bioaccessibility of metal(loid)s in PM2.5 using simulated lung fluid.

PubMed

Kastury, Farzana; Smith, E; Karna, Ranju R; Scheckel, Kirk G; Juhasz, A L

2018-06-07

In this study, methodological factors influencing the dissolution of metal(loid)s in simulated lung fluid (SLF) was assessed in order to develop a standardised method for the assessment of inhalation bioaccessibility in PM 2.5 . To achieve this aim, the effects of solid to liquid (S/L) ratio (1:100 to 1:5000), agitation (magnetic agitation, occasional shaking, orbital and end-over-end rotation), composition of SLF (artificial lysosomal fluid: ALF; phagolysosomal simulant fluid: PSF) and extraction time (1-120 h) on metal(loid) bioaccessibility were investigated using PM 2.5 from three Australian mining/smelting impacted soils and a certified reference material. The results highlighted that SLF composition significantly (p < 0.001) influenced metal(loid) bioaccessibility and that when a S/L ratio of 1:5000 and end-over-end rotation was used, metal(loid) solubility plateaued after approximately 24 h. Additionally, in order to assess the exposure of metal(loid)s via incidental ingestion of surface dust, PM 2.5 was subjected to simulated gastro-intestinal tract (GIT) solutions and the results were compared to extraction using SLF. Although As bioaccessibility in SLF (24 h) was significantly lower than in simulated GIT solutions (p < 0.05), Pb bioaccessibility was equal to or significantly higher than that extracted using simulated GIT solutions (p < 0.05). Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of sub-lethal stresses on the survival of lactic acid bacteria after spray-drying in orange juice.

PubMed

Barbosa, J; Borges, S; Teixeira, P

2015-12-01

The demand for new functional non-dairy based products makes the production of a probiotic orange juice powder an encouraging challenge. However, during drying process and storage, loss of viability of the dried probiotic cultures can occur, since the cells are exposed to various stresses. The influence of sub-lethal conditions of temperature, acidic pH and hydrogen peroxide on the viability of Pediococcus acidilactici HA-6111-2 and Lactobacillus plantarum 299v during spray drying in orange juice and subsequent storage under different conditions was investigated. At the end of storage, the survival of both microorganisms through simulated gastro-intestinal tract (GIT) conditions was also determined. The viability of cells previously exposed to each stress was not affected by the drying process. However, during 180 days of storage at room temperature, unlike P. acidilactici HA-6111-2, survival of L. plantarum 299v was enhanced by prior exposure to sub-lethal conditions. Previous exposure to sub-lethal stresses of each microorganism did not improve their viability after passage through simulated GIT. Nevertheless, as cellular inactivation during 180 days of storage was low, both microorganisms were present in numbers of ca. 10(7) cfu/mL at the end of GIT. This is an indication that both bacteria are good candidates for use in the development of an orange juice powder with functional characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization

PubMed Central

Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Coussa-Charley, Michael; Kahouli, Imen; Jones, Mitchell L.; Labbé, Alain; Prakash, Satya

2012-01-01

Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT) which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA) microcapsules to encapsulate Lactobacillus fermentum NCIMB 5221 and characterize its enzymatic activity and viability through a simulated GIT. This specific strain, in previous research, was characterized for its inherent ferulic acid esterase (FAE) activity which could prove beneficial in the development of a therapeutic for the treatment and prevention of cancers and metabolic disorders. Our findings demonstrate that the APA microcapsule does not slow the mass transfer of substrate into and that of the FA product out of the microcapsule, while also not impairing bacterial cell viability. The use of simulated gastrointestinal conditions led to a significant 2.5 log difference in viability between the free (1.10 × 104 ± 1.00 × 103 cfu/mL) and the microencapsulated (5.50 × 106 ± 1.00 × 105 cfu/mL) L. fermentum NCIMB 5221 following exposure. The work presented here suggests that APA microencapsulation can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a FAE-active probiotic strain. PMID:24288090

A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules.

PubMed

Choonara, Bibi F; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Pillay, Viness

2014-11-15

The oral delivery of proteins and peptides is a dynamic research field despite the numerous challenges limiting their effective delivery. Successful oral delivery of proteins and peptides requires the accomplishment of three key tasks: protection of the macromolecules from degradation in the gastrointestinal tract (GIT), permeation through the intestinal barrier and absorption of molecules into the systemic circulation. Currently, no clinically useful oral formulations have been developed but several attempts have been made to overcome the challenges of low oral bioavailability resulting from poor absorption, poor permeation and enzymatic degradation of the proteins and peptides in the GIT. Present strategies attempt to provide structural protection of the proteins and peptides and improved absorption through the use of enzyme inhibitors, absorption enhancers, novel polymeric delivery systems and chemical modification. However, each of these technologies has their limitations despite showing positive results. This review attempts to discuss the physical and chemical barriers of the GIT with particular emphasis on the current approaches employed to overcome these barriers, including the evaluation of other non-parenteral routes of protein and peptide delivery. In addition, this review assimilates oral formulation strategies under development and within the clinical trial stage in relation to their benefits and drawbacks with regard to facilitating optimal protection and absorption of proteins and peptides, as well as pertinent future challenges and opportunities governing oral drug delivery. Copyright © 2014 Elsevier Inc. All rights reserved.

Sucralose, A Synthetic Organochlorine Sweetener: Overview of Biological Issues

PubMed Central

Schiffman, Susan S.; Rother, Kristina I.

2013-01-01

Sucralose is a synthetic organochlorine sweetener (OC) that is a common ingredient in the world's food supply. Sucralose interacts with chemosensors in the alimentary tract that play a role in sweet taste sensation and hormone secretion. In rats, sucralose ingestion was shown to increase the expression of the efflux transporter P-glycoprotein (P-gp) and two cytochrome P-450 (CYP) isozymes in the intestine. P-gp and CYP are key components of the presystemic detoxification system involved in first-pass drug metabolism. The effect of sucralose on first-pass drug metabolism in humans, however, has not yet been determined. In rats, sucralose alters the microbial composition in the gastrointestinal tract (GIT), with relatively greater reduction in beneficial bacteria. Although early studies asserted that sucralose passes through the GIT unchanged, subsequent analysis suggested that some of the ingested sweetener is metabolized in the GIT, as indicated by multiple peaks found in thin-layer radiochromatographic profiles of methanolic fecal extracts after oral sucralose administration. The identity and safety profile of these putative sucralose metabolites are not known at this time. Sucralose and one of its hydrolysis products were found to be mutagenic at elevated concentrations in several testing methods. Cooking with sucralose at high temperatures was reported to generate chloropropanols, a potentially toxic class of compounds. Both human and rodent studies demonstrated that sucralose may alter glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels. Taken together, these findings indicate that sucralose is not a biologically inert compound. PMID:24219506

High fat diet drives obesity regardless the composition of gut microbiota in mice

PubMed Central

Rabot, Sylvie; Membrez, Mathieu; Blancher, Florence; Berger, Bernard; Moine, Déborah; Krause, Lutz; Bibiloni, Rodrigo; Bruneau, Aurélia; Gérard, Philippe; Siddharth, Jay; Lauber, Christian L.; Chou, Chieh Jason

2016-01-01

The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1st week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice. PMID:27577172

High fat diet drives obesity regardless the composition of gut microbiota in mice.

PubMed

Rabot, Sylvie; Membrez, Mathieu; Blancher, Florence; Berger, Bernard; Moine, Déborah; Krause, Lutz; Bibiloni, Rodrigo; Bruneau, Aurélia; Gérard, Philippe; Siddharth, Jay; Lauber, Christian L; Chou, Chieh Jason

2016-08-31

The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1(st) week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice.

Nutrition meets the microbiome: micronutrients and the microbiota.

PubMed

Biesalski, Hans K

2016-05-01

There is increasing evidence that food is an important factor that influences and shapes the composition and configuration of the gut microbiota. Most studies have focused on macronutrients (fat, carbohydrate, protein) in particular and their effects on the gut microbiota. Although the microbiota can synthesize different water-soluble vitamins, the effects of vitamins synthesized within the microbiota on systemic vitamin status are unclear. Few studies exist on the shuttling of vitamins between the microbiota and intestine and the impact of luminal vitamins on the microbiota. Studying the interactions between vitamins and the microbiota may help to understand the effects of vitamins on the barrier function and immune system of the intestinal tract. Furthermore, understanding the impact of malnutrition, particularly low micronutrient supply, on microbiota development, composition, and metabolism may help in implementing new strategies to overcome the deleterious effects of malnutrition on child development. This article reviews data on the synthesis of different micronutrients and their effects on the human microbiota, and further discusses the consequences of malnutrition on microbiota composition. © 2016 New York Academy of Sciences.

Doing It Right: 366 answers to computing questions you didn't know you had

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herring, Stuart Davis

Slides include information on history: version control, version control: branches, version control: Git, releases, requirements, readability, readability control flow, global variables, architecture, architecture redundancy, processes, input/output, unix, etcetera.

Interrelations between the microbiotas in the litter and in the intestines of commercial broiler chickens.

PubMed

Cressman, Michael D; Yu, Zhongtang; Nelson, Michael C; Moeller, Steven J; Lilburn, Michael S; Zerby, Henry N

2010-10-01

The intestinal microbiota of broiler chickens and the microbiota in the litter have been well studied, but the interactions between these two microbiotas remain to be determined. Therefore, we examined their reciprocal effects by analyzing the intestinal microbiotas of broilers reared on fresh pine shavings versus reused litter, as well as the litter microbiota over a 6-week cycle. Composite ileal mucosal and cecal luminal samples from birds (n = 10) reared with both litter conditions (fresh versus reused) were collected at 7, 14, 21, and 42 days of age. Litter samples were also collected at days 7, 14, 21, and 42. The microbiotas were profiled and compared within sample types based on litter condition using PCR and denaturing gradient gel electrophoresis (PCR-DGGE). The microbiotas were further analyzed using 16S rRNA gene clone libraries constructed from microbiota DNA extracted from both chick intestinal and litter samples collected at day 7. Results showed significant reciprocal effects between the microbiotas present in the litter and those in the intestines of broilers. Fresh litter had more environmental bacteria, while reused litter contained more bacteria of intestinal origin. Lactobacillus spp. dominated the ileal mucosal microbiota of fresh-litter chicks, while a group of bacteria yet to be classified within Clostridiales dominated in the ileal mucosal microbiota in the reused-litter chicks. The Litter condition (fresh versus reused) seemed to have a more profound impact on the ileal microbiota than on the cecal microbiota. The data suggest that the influence of fresh litter on ileal microbiota decreased as broilers grew, compared with temporal changes observed under reused-litter rearing conditions.

The gut microbiota and its relationship to diet and obesity

PubMed Central

Clarke, Siobhan F.; Murphy, Eileen F.; Nilaweera, Kanishka; Ross, Paul R.; Shanahan, Fergus; O’Toole, Paul W.; Cotter, Paul D.

2012-01-01

Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain. PMID:22572830

Gut microbiota and obesity.

PubMed

Gérard, Philippe

2016-01-01

The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.

Gut Microbiota and IGF-1.

PubMed

Yan, Jing; Charles, Julia F

2018-04-01

Microbiota and their hosts have coevolved for millions of years. Microbiota are not only critical for optimal development of the host under normal physiological growth, but also important to ensure proper host development during nutrient scarcity or disease conditions. A large body of research has begun to detail the mechanism(s) of how microbiota cooperate with the host to maintain optimal health status. One crucial host pathway recently demonstrated to be modulated by microbiota is that of the growth factor insulin like growth factor 1 (IGF-1). Gut microbiota are capable of dynamically modulating circulating IGF-1 in the host, with the majority of data suggesting that microbiota induce host IGF-1 synthesis to influence growth. Microbiota-derived metabolites such as short chain fatty acids are sufficient to induce IGF-1. Whether microbiota induction of IGF-1 is mediated by the difference in growth hormone expression or the host sensitivity to growth hormone is still under investigation. This review summarizes the current data detailing the interaction between gut microbiota, IGF-1 and host development.

Gut microbiota composition correlates with diet and health in the elderly.

PubMed

Claesson, Marcus J; Jeffery, Ian B; Conde, Susana; Power, Susan E; O'Connor, Eibhlís M; Cusack, Siobhán; Harris, Hugh M B; Coakley, Mairead; Lakshminarayanan, Bhuvaneswari; O'Sullivan, Orla; Fitzgerald, Gerald F; Deane, Jennifer; O'Connor, Michael; Harnedy, Norma; O'Connor, Kieran; O'Mahony, Denis; van Sinderen, Douwe; Wallace, Martina; Brennan, Lorraine; Stanton, Catherine; Marchesi, Julian R; Fitzgerald, Anthony P; Shanahan, Fergus; Hill, Colin; Ross, R Paul; O'Toole, Paul W

2012-08-09

Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.

Gut microbiota dictates the metabolic response of Drosophila to diet

PubMed Central

Wong, Adam C.-N.; Dobson, Adam J.; Douglas, Angela E.

2014-01-01

Animal nutrition is profoundly influenced by the gut microbiota, but knowledge of the scope and core mechanisms of the underlying animal–microbiota interactions is fragmentary. To investigate the nutritional traits shaped by the gut microbiota of Drosophila, we determined the microbiota-dependent response of multiple metabolic and performance indices to systematically varied diet composition. Diet-dependent differences between Drosophila bearing its unmanipulated microbiota (conventional flies) and experimentally deprived of its microbiota (axenic flies) revealed evidence for: microbial sparing of dietary B vitamins, especially riboflavin, on low-yeast diets; microbial promotion of protein nutrition, particularly in females; and microbiota-mediated suppression of lipid/carbohydrate storage, especially on high sugar diets. The microbiota also sets the relationship between energy storage and body mass, indicative of microbial modulation of the host signaling networks that coordinate metabolism with body size. This analysis identifies the multiple impacts of the microbiota on the metabolism of Drosophila, and demonstrates that the significance of these different interactions varies with diet composition and host sex. PMID:24577449

Streptococcus pneumoniae Colonization Is Required To Alter the Nasal Microbiota in Cigarette Smoke-Exposed Mice

PubMed Central

Shen, Pamela; Whelan, Fiona J.; Schenck, L. Patrick; McGrath, Joshua J. C.; Vanderstocken, Gilles; Bowdish, Dawn M. E.; Surette, Michael G.

2017-01-01

ABSTRACT Smokers have nasal microbiota dysbiosis, with an increased frequency of colonizing bacterial pathogens. It is possible that cigarette smoke increases pathogen acquisition by perturbing the microbiota and decreasing colonization resistance. However, it is difficult to disentangle microbiota dysbiosis due to cigarette smoke exposure from microbiota changes caused by increased pathogen acquisition in human smokers. Using an experimental mouse model, we investigated the impact of cigarette smoke on the nasal microbiota in the absence and presence of nasal pneumococcal colonization. We observed that cigarette smoke exposure alone did not alter the nasal microbiota composition. The microbiota composition was also unchanged at 12 h following low-dose nasal pneumococcal inoculation, suggesting that the ability of the microbiota to resist initial nasal pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal microbiota dysbiosis occurred as a consequence of established high-dose nasal pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical reports on human smokers, an enrichment of potentially pathogenic bacterial genera such as Fusobacterium, Gemella, and Neisseria was observed. Our findings suggest that cigarette smoke exposure predisposes to pneumococcal colonization independent of changes to the nasal microbiota and that microbiota dysbiosis observed in smokers may occur as a consequence of established pathogen colonization. PMID:28760931

Streptococcus pneumoniae Colonization Is Required To Alter the Nasal Microbiota in Cigarette Smoke-Exposed Mice.

PubMed

Shen, Pamela; Whelan, Fiona J; Schenck, L Patrick; McGrath, Joshua J C; Vanderstocken, Gilles; Bowdish, Dawn M E; Surette, Michael G; Stämpfli, Martin R

2017-10-01

Smokers have nasal microbiota dysbiosis, with an increased frequency of colonizing bacterial pathogens. It is possible that cigarette smoke increases pathogen acquisition by perturbing the microbiota and decreasing colonization resistance. However, it is difficult to disentangle microbiota dysbiosis due to cigarette smoke exposure from microbiota changes caused by increased pathogen acquisition in human smokers. Using an experimental mouse model, we investigated the impact of cigarette smoke on the nasal microbiota in the absence and presence of nasal pneumococcal colonization. We observed that cigarette smoke exposure alone did not alter the nasal microbiota composition. The microbiota composition was also unchanged at 12 h following low-dose nasal pneumococcal inoculation, suggesting that the ability of the microbiota to resist initial nasal pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal microbiota dysbiosis occurred as a consequence of established high-dose nasal pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical reports on human smokers, an enrichment of potentially pathogenic bacterial genera such as Fusobacterium , Gemella , and Neisseria was observed. Our findings suggest that cigarette smoke exposure predisposes to pneumococcal colonization independent of changes to the nasal microbiota and that microbiota dysbiosis observed in smokers may occur as a consequence of established pathogen colonization. Copyright © 2017 American Society for Microbiology.

Antibiotic and Modulation of Microbiota: A New Paradigm?

PubMed

Rizzatti, Gianenrico; Ianiro, Gianluca; Gasbarrini, Antonio

2018-06-16

Recently new insights on gut microbiota have revolutionized many concepts of the modern medicine. The alteration of microbiota, which is called dysbiosis, has been associated with an expanding list of diseases and conditions. The development of next-generation sequencing techniques allowed comprehensive analysis of gut microbiota composition without the limitations of classic culture methods. Furthermore, introduction of functional techniques such as metabolomics and proteomics allowed for integrated analysis thus obtaining more robust insights on microbiota functions in health and disease. These tools allow to address the role of factors able to modify the gut microbiota, the so called "microbiota influencers." These data are useful to explain the physiopathology of several disease and thus to identify new potential therapeutic targets. Among microbiota influencers, many studies focused on the impact of antibiotic administration on the gut microbiota, because of their widespread use. Notably, beside the known beneficial effect of antibiotic in treating infectious diseases, these drugs have shown detrimental effects on gut microbiota which, in turn, might have long-term consequences on the host. Finally, therapeutic modulation of gut microbiota, by means of selected antibiotics with eubiotic effects, probiotics and with fecal microbiota transplantation seems of great interest as it might be able to prevent or even revert antibiotic-induced dysbiosis.

Earthworms are associated with subpopulations of Gammaproteobacteria irrespective of the total soil microbiota composition and stability.

PubMed

Fjøsne, Trine; Myromslien, Frøydis D; Wilson, Robert C; Rudi, Knut

2018-05-01

Soil represents one of the most complex microbial ecosystems on earth. It is well-known that invertebrates such as earthworms have a major impact on transformations of organic material in soil, while their effect on the soil microbiota remains largely unknown. The aim of our work was therefore to investigate the association of earthworms with temporal stability, composition and diversity in two soil microbiota experimental series. We found that earthworms were consistently associated with an increase in subgroups of Gammaproteobacteria, despite major differences in microbiota composition and temporal stability across the experimental series. Our results therefore suggest that earthworms can affect subpopulation dynamics in the soil microbiota, irrespective of the total microbiota composition. If the soil microbiota is comprised of independent microbiota components, this can contribute to our general understanding of the complexity of the soil microbiota.

Characterization of Gastric Microbiota in Twins.

PubMed

Dong, Quanjiang; Xin, Yongning; Wang, Lili; Meng, Xinying; Yu, Xinjuan; Lu, Linlin; Xuan, Shiying

2017-02-01

Contribution of host genetic backgrounds in the development of gastric microbiota has not been clearly defined. This study was aimed to characterize the biodiversity, structure and composition of gastric microbiota among twins. A total of four pairs of twins and eight unrelated individuals were enrolled in the study. Antral biopsies were obtained during endoscopy. The bacterial 16S rRNA gene was amplified and pyrosequenced. Sequences were analyzed for the composition, structure, and α and β diversities of gastric microbiota. Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria were the most predominant phyla of gastric microbiota. Each individual, twins as well as unrelated individuals, harbored a microbiota of distinct composition. There was no evidence of additional similarity in the richness and evenness of gastric microbiota among co-twins as compared to unrelated individuals. Calculations of θ YC and PCoA demonstrated that the structure similarity of gastric microbial community between co-twins did not increase compared to unrelated individuals. In contrast, the structure of microbiota was altered enormously by Helicobacter pylori infection. These results suggest that host genetic backgrounds had little effect in shaping the gastric microbiota. This property of gastric microbiota could facilitate the studies discerning the role of microbiota from genetic grounds in the pathogenesis.

Housing Systems Influence Gut Microbiota Composition of Sows but Not of Their Piglets.

PubMed

Kubasova, Tereza; Davidova-Gerzova, Lenka; Merlot, Elodie; Medvecky, Matej; Polansky, Ondrej; Gardan-Salmon, Delphine; Quesnel, Helene; Rychlik, Ivan

2017-01-01

Different housing systems can be used in pig production and little is known about their effect on gut microbiota composition. In this study we characterized fecal microbiota by sequencing the rRNA genes in sows kept during gestation in conventional pens with a slatted floor and in enriched pens with a floor covered with deep straw. After farrowing, microbiota of 1- and 4-day-old piglets were also monitored. Microbiota of sows from the enriched system contained significantly more Prevotella, Parabacteroides, CF231, Phascolarctobacterium, Fibrobacter, Anaerovibrio and YRC22 and significantly less Lactobacillus, Bulleidia, Lachnospira, Dorea, Ruminococcus and Oscillospira than microbiota of sows from the conventional system. The Firmicutes to Bacteroidetes ratio was 0.96 in the microbiota of sows kept in the enriched pens and this increased to 1.66 in the microbiota of sows kept in the conventional system. The production system therefore influenced microbiota composition, most likely due the ingestion of the straw. The microbiota of 1- and 4-day-old piglets differed from the microbiota of sows and sows therefore did not represent the most important source for their colonization in early days of life.

Housing Systems Influence Gut Microbiota Composition of Sows but Not of Their Piglets

PubMed Central

Kubasova, Tereza; Davidova-Gerzova, Lenka; Merlot, Elodie; Medvecky, Matej; Polansky, Ondrej; Gardan-Salmon, Delphine; Quesnel, Helene; Rychlik, Ivan

2017-01-01

Different housing systems can be used in pig production and little is known about their effect on gut microbiota composition. In this study we characterized fecal microbiota by sequencing the rRNA genes in sows kept during gestation in conventional pens with a slatted floor and in enriched pens with a floor covered with deep straw. After farrowing, microbiota of 1- and 4-day-old piglets were also monitored. Microbiota of sows from the enriched system contained significantly more Prevotella, Parabacteroides, CF231, Phascolarctobacterium, Fibrobacter, Anaerovibrio and YRC22 and significantly less Lactobacillus, Bulleidia, Lachnospira, Dorea, Ruminococcus and Oscillospira than microbiota of sows from the conventional system. The Firmicutes to Bacteroidetes ratio was 0.96 in the microbiota of sows kept in the enriched pens and this increased to 1.66 in the microbiota of sows kept in the conventional system. The production system therefore influenced microbiota composition, most likely due the ingestion of the straw. The microbiota of 1- and 4-day-old piglets differed from the microbiota of sows and sows therefore did not represent the most important source for their colonization in early days of life. PMID:28085934

Microbiota regulate the development and function of the immune cells.

PubMed

Yu, Qing; Jia, Anna; Li, Yan; Bi, Yujing; Liu, Guangwei

2018-03-04

Microbiota is a group of microbes coexisting and co-evolving with the immune system in the host body for millions of years. There are mutual interaction between microbiota and the immune system. Immune cells can shape the populations of microbiota in the gut of animals and humans, and the presence of microbiota and the microbial products can regulate the development and function of the immune cells in the host. Although microbiota resides mainly at the mucosa, the effect of microbiota on the immune system can be both local at the mucosa and systemic through the whole body. At the mucosal sites, the presences of microbiota and microbial products have a direct effect on the immune cells. Microbiota induces production of effectors from immune cells, such as cytokines and inflammatory factors, influencing the further development and function of the immune cells. Experimental data have shown that microbial products can influence the activity of some key factors in signaling pathways. At the nonmucosal sites, such as the bone marrow, peripheral lymph nodes, and spleen, microbiota can also regulate the development and function of the immune cells via several mechanisms in mice, such as introduction of chromatin-level changes through histone acetylation and DNA methylation. Given the important effect of microbiota on the immune system, many immunotherapies that are mediated by immune system rely on gut microbiota. Thus, the study of how microbiota influences immune system bring a potential therapy prospect in preventing and treating diseases.

Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass.

PubMed

Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

2017-09-01

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.

Effect of Maternal Probiotic Intervention on HPA Axis, Immunity and Gut Microbiota in a Rat Model of Irritable Bowel Syndrome

PubMed Central

Barouei, Javad; Moussavi, Mahta; Hodgson, Deborah M.

2012-01-01

Objective To examine whether maternal probiotic intervention influences the alterations in the brain-immune-gut axis induced by neonatal maternal separation (MS) and/or restraint stress in adulthood (AS) in Wistar rats. Design Dams had free access to drinking water supplemented with Bifidobacterium animalis subsp lactis BB-12® (3×109 CFU/mL) and Propionibacterium jensenii 702 (8.0×108 CFU/mL) from 10 days before conception until postnatal day (PND) 22 (weaning day), or to control ad lib water. Offspring were subjected to MS from PND 2 to 14 or left undisturbed. From PND 83 to 85, animals underwent 30 min/day AS, or were left undisturbed as controls. On PND 24 and 86, blood samples were collected for corticosterone, ACTH and IgA measurement. Colonic contents were analysed for the composition of microflora and luminal IgA levels. Results Exposure to MS significantly increased ACTH levels and neonatal fecal counts of aerobic and anaerobic bacteria, E. coli, enterococci and clostridia, but reduced plasma IgA levels compared with non-MS animals. Animals exposed to AS exhibited significantly increased ACTH and corticosterone levels, decreased aerobic bacteria and bifidobacteria, and increased Bacteroides and E. coli counts compared to non-AS animals. MS coupled with AS induced significantly decreased anaerobes and clostridia compared with the non-stress adult controls. Maternal probiotic intervention significantly increased neonatal corticosterone levels which persisted until at least week 12 in females only, and also resulted in elevated adult ACTH levels and altered neonatal microflora comparable to that of MS. However, it improved plasma IgA responses, increased enterococci and clostridia in MS adults, increased luminal IgA levels, and restored anaerobes, bifidobacteria and E. coli to normal in adults. Conclusion Maternal probiotic intervention induced activation of neonatal stress pathways and an imbalance in gut microflora. Importantly however, it improved the immune environment of stressed animals and protected, in part, against stress-induced disturbances in adult gut microflora. PMID:23071537

Immunomodulatory effects of phytogenics in chickens and pigs — A review

PubMed Central

2018-01-01

Environmental stressors like pathogens and toxins may depress the animal immune system through invasion of the gastrointestinal tract (GIT) tract, where they may impair performance and production, as well as lead to increased mortality rates. Therefore, protection of the GIT tract and improving animal health are top priorities in animal production. Being natural-sourced materials, phytochemicals are potential feed additives possessing multiple functions, including: anti-inflammatory, anti-fungal, anti-viral and antioxidative properties. This paper focuses on immunity-related physiological parameters regulated by phytochemicals, such as carvacrol, cinnamaldehyde, curcumin, and thymol; many studies have proven that these phytochemicals can improve animal performance and production. On the molecular level, the impact of inflammatory gene expression on underlying mechanisms was also examined, as were the effects of environmental stimuli and phytochemicals in initiating nuclear factor kappa B and mitogen-activated protein kinases signaling pathways and improving health conditions. PMID:29268586

Experimental research of neutron yield and spectrum from deuterium gas-puff z-pinch on the GIT-12 generator at current above 2 MA

NASA Astrophysics Data System (ADS)

Cherdizov, R. K.; Fursov, F. I.; Kokshenev, V. A.; Kurmaev, N. E.; Labetsky, A. Yu; Ratakhin, N. A.; Shishlov, A. V.; Cikhardt, J.; Cikhardtova, B.; Klir, D.; Kravarik, J.; Kubes, P.; Rezac, K.; Dudkin, G. N.; Garapatsky, A. A.; Padalko, V. N.; Varlachev, V. A.

2017-05-01

The Z-pinch experiments with deuterium gas-puff surrounded by an outer plasma shell were carried out on the GIT-12 generator (Tomsk, Russia) at currents of 2 MA. The plasma shell consisting of hydrogen and carbon ions was formed by 48 plasma guns. The deuterium gas-puff was created by a fast electromagnetic valve. This configuration provides an efficient mode of the neutron production in DD reaction, and the neutron yield reaches a value above 1012 neutrons per shot. Neutron diagnostics included scintillation TOF detectors for determination of the neutron energy spectrum, bubble detectors BD-PND, a silver activation detector, and several activation samples for determination of the neutron yield analysed by a Sodium Iodide (NaI) and a high-purity Germanium (HPGe) detectors. Using this neutron diagnostic complex, we measured the total neutron yield and amount of high-energy neutrons.

Endoscopic submucosal dissection in the West: Current status and future directions.

PubMed

Ma, Michael X; Bourke, Michael J

2018-05-01

Endoscopic submucosal dissection (ESD) was first conceptually described almost 30 years ago in Japan and is now widely practiced throughout East Asia. ESD expands the boundaries of endoscopic resection (ER) by allowing en bloc resection of large early neoplastic lesions within the gastrointestinal tract (GIT). This offers advantages over other ER techniques by facilitating definitive histological staging and curative treatment of early cancer in selected cases. Indeed, the experience of ESD in Eastern countries is significant, and excellent outcomes from high-volume centers are reported. The potential benefits of ESD are recognized by Western endoscopists, but its adoption has been limited. A number of factors contribute to this, including epidemiological differences in GIT neoplasia between Western and Eastern populations and limitations in training opportunities. In this review, we discuss the role of ESD, its current status and the future in Western endoscopic practice. © 2017 Japan Gastroenterological Endoscopy Society.

A hypothetical model of host-pathogen interaction of Streptococcus suis in the gastro-intestinal tract

PubMed Central

Ferrando, Maria Laura; Schultsz, Constance

2016-01-01

ABSTRACT Streptococcus suis (SS) is a zoonotic pathogen that can cause systemic infection in pigs and humans. The ingestion of contaminated pig meat is a well-established risk factor for zoonotic S. suis disease. In our studies, we provide experimental evidence that S. suis is capable to translocate across the host gastro-intestinal tract (GIT) using in vivo and in vitro models. Hence, S. suis should be considered an emerging foodborne pathogen. In this addendum, we give an overview of the complex interactions between S. suis and host-intestinal mucosa which depends on the host origin, the serotype and genotype of S. suis, as well as the presence and expression of virulence factors involved in host-pathogen interaction. Finally, we propose a hypothetical model of S. suis interaction with the host-GIT taking in account differences in conditions between the porcine and human host. PMID:26900998

CRISPR-DAV: CRISPR NGS data analysis and visualization pipeline.

PubMed

Wang, Xuning; Tilford, Charles; Neuhaus, Isaac; Mintier, Gabe; Guo, Qi; Feder, John N; Kirov, Stefan

2017-12-01

The simplicity and precision of CRISPR/Cas9 system has brought in a new era of gene editing. Screening for desired clones with CRISPR-mediated genomic edits in a large number of samples is made possible by next generation sequencing (NGS) due to its multiplexing. Here we present CRISPR-DAV (CRISPR Data Analysis and Visualization) pipeline to analyze the CRISPR NGS data in a high throughput manner. In the pipeline, Burrows-Wheeler Aligner and Assembly Based ReAlignment are used for small and large indel detection, and results are presented in a comprehensive set of charts and interactive alignment view. CRISPR-DAV is available at GitHub and Docker Hub repositories: https://github.com/pinetree1/crispr-dav.git and https://hub.docker.com/r/pinetree1/crispr-dav/. xuning.wang@bms.com. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Characteristics of Emergency Gastrointestinal Stromal Tumor (GIST).

PubMed

Uçar, Ahmet Deniz; Oymaci, Erkan; Carti, Erdem Bariş; Yakan, Savaş; Vardar, Enver; Erkan, Nazif; Mehmet, Yildirim

2015-05-01

Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT). Importance of GISTs is increasing while surgeons are facing with more frequent either in emergency setting of elective cases. Delineating the presentation and management of emergency GIST is important. From 2005 to 2014, emergency cases with final diagnosis of GIST were examined retrospectively. Total of 13 operated cases were evaluated by patients characteristics, clinical presentation, operational findings and postoperative prognosis. There were 9 male and 4 female with the mean age of 48.15 years. The most frequent presentations are ileus and GIT hemorrhage both covering the 84% of patients. Small bowel was the dominating site with ileus. Stomach was the second frequent site of the disease with the finding of hemorrhage. Emergency patients are more likely to come with small bowel GIST and obstruction symptoms. Hemorrhage is the most frequent symptom for emergency GIST of stomach and duodenum.

Long-term exposure to zero-g and the gastro-intestinal tract function

NASA Technical Reports Server (NTRS)

Mccormack, Percial D.

1989-01-01

The gastrointestinal tract (GIT) function is described with emphasis placed on its important role to smooth, delay, and modify sudden fluid load stress applied to the fluid distribution control system in the body. Two basic components of the GIT are considered: stomach dynamics, which involves storage, mixing, and discharge of food into the intestine after addition of gastric juices; and absorption of water and electrolytes from the small intestine. A dynamic model of these components is described, along with performance characteristics computed consecutively for one g and zero g conditions. The main impact of the zero g condition appears to be through a change in osmotic driven transport across the gut wall. A dramatic change in transport characteristics is predicted with implication for many body systems (the immune system in particular) during long-term exposure to zero g. Experimental measurements in zero g are needed to evaluate these predictions.

The Drosophila transcriptional network is structured by microbiota.

PubMed

Dobson, Adam J; Chaston, John M; Douglas, Angela E

2016-11-25

Resident microorganisms (microbiota) have far-reaching effects on the biology of their animal hosts, with major consequences for the host's health and fitness. A full understanding of microbiota-dependent gene regulation requires analysis of the overall architecture of the host transcriptome, by identifying suites of genes that are expressed synchronously. In this study, we investigated the impact of the microbiota on gene coexpression in Drosophila. Our transcriptomic analysis, of 17 lines representative of the global genetic diversity of Drosophila, yielded a total of 11 transcriptional modules of co-expressed genes. For seven of these modules, the strength of the transcriptional network (defined as gene-gene coexpression) differed significantly between flies bearing a defined gut microbiota (gnotobiotic flies) and flies reared under microbiologically sterile conditions (axenic flies). Furthermore, gene coexpression was uniformly stronger in these microbiota-dependent modules than in both the microbiota-independent modules in gnotobiotic flies and all modules in axenic flies, indicating that the presence of the microbiota directs gene regulation in a subset of the transcriptome. The genes constituting the microbiota-dependent transcriptional modules include regulators of growth, metabolism and neurophysiology, previously implicated in mediating phenotypic effects of microbiota on Drosophila phenotype. Together these results provide the first evidence that the microbiota enhances the coexpression of specific and functionally-related genes relative to the animal's intrinsic baseline level of coexpression. Our system-wide analysis demonstrates that the presence of microbiota enhances gene coexpression, thereby structuring the transcriptional network in the animal host. This finding has potentially major implications for understanding of the mechanisms by which microbiota affect host health and fitness, and the ways in which hosts and their resident microbiota coevolve.

Therapeutic modulation of gut microbiota: current clinical applications and future perspectives.

PubMed

Ianiro, Gianluca; Bibbò, Stefano; Gasbarrini, Antonio; Cammarota, Giovanni

2014-01-01

Human beings and gut microbiota are in a symbiotic relationship, and the hypothesis of a "super organism" composed of the human organism and microbes has been recently proposed. The gut microbiota fulfills important metabolic and immunological tasks, and the impairment of its composition might alter homeostasis and lead to the development of microbiota-related diseases. The most common illnesses associated with alterations of the gut microbiota include inflammatory bowel disease, gastroenteric infections, irritable bowel syndrome and other gastrointestinal functional diseases, colorectal cancer, metabolic syndrome and obesity, liver diseases, allergic diseases, and neurological diseases such as autism. In theory, every disease associated with the impairment of intestinal microflora might benefit from the therapeutic modulation of the gut microbiota. A number of attempts to manipulate the microbiota have not produced identical results for every disease. Although antibiotics and probiotics have been available for a long time, the so-called fecal microbiota transplantation, which is a very old remedy, was only recently re-evaluated as a promising therapeutic approach for microbiota impairment. A comprehensive understanding of the gut microbiota composition, in states of both health and various diseases, is needed for the development of future approaches for microbiota modulation and for developing targeted therapies. In this review, we describe the role of the microbiota in several diseases and the related treatment options that are currently available.

Gut Microbiota-brain Axis

PubMed Central

Wang, Hong-Xing; Wang, Yu-Ping

2016-01-01

Objective: To systematically review the updated information about the gut microbiota-brain axis. Data Sources: All articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of “gut microbiota”, “gut-brain axis”, and “neuroscience”. Study Selection: All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design. Results: It is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gut microbiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gut microbiota, and metagenomics is an appropriate technique to characterize gut microbiota. Conclusions: Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain, which may provide a new way to protect the brain in the near future. PMID:27647198

Dietary Factors Modulate Colonic Tumorigenesis Through the Interaction of Gut Microbiota and Host Chloride Channels.

PubMed

Zhang, Yong; Kang, Chao; Wang, Xiao-Lan; Zhou, Min; Chen, Meng-Ting; Zhu, Xiao-Hui; Liu, Kai; Wang, Bin; Zhang, Qian-Yong; Zhu, Jun-Dong; Mi, Man-Tian

2018-03-01

In recent decades, the association among diet, gut microbiota, and the risk of colorectal cancer (CRC) has been established. Gut microbiota and associated metabolites, such as bile acids and butyrate, are now known to play a key role in CRC development. The aim of this study is to identify that the progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat diet, or different dose of dihydromyricetin (DMY) interacted with gut microbiota. An AOM/DSS (azoxymethan/dextran sodium sulfate) model is established to study the gut microbiota compsition before and after tumor formation during colitis-induced tumorigenesis. All above dietary factors profoundly influence the composition of gut microbiota and host colonic tumorigenesis. In addition, mice with DMY-modified initial microbiota display different degrees of chemically induced tumorigenesis. Mechanism analysis reveals that gut microbiota-associated chloride channels participated in colon tumorigenesis. Gut microbiota changes occur in the hyperproliferative stage before tumor formation. Gut microbiota and host chloride channels, both of which are regulated by dietary factors, are associated with CRC development. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of Microbiota in Sexually Dimorphic Immunity.

PubMed

Elderman, Marlies; de Vos, Paul; Faas, Marijke

2018-01-01

Sex differences in peripheral immune responses are well recognized. This is associated with sex differences in many immunological diseases. As the intestinal microbiota is known to influence the immune system, such sex differences in immune responses may be a consequence of sex-specific microbiota. Therefore, this mini-review discusses sex differences in intestinal microbiota and the possible role of microbiota in shaping sexually dimorphic immunity. Sex differences in microbiota composition are clearly found in mice studies and also in human studies. However, the lack of standardization in human studies may mask the sexual dimorphism in microbiota composition in human studies, since many factors such as age, genetic background, BMI, diet, and sex hormones appear to interfere with the sexual dimorphism in microbiota composition. Only a few mice studies found that differences in gut microbiota composition are causative for some aspects of sexually dimorphic immunity. Therefore, future studies should focus on a causal relationship between sexually dimorphic immunity and microbiota, considering the abovementioned interfering confounding factors. This would benefit the development of more sex-specific effective treatment options for immunological diseases.

Maternal Weaning Modulates Emotional Behavior and Regulates the Gut-Brain Axis

PubMed Central

Farshim, Pamela; Walton, Gemma; Chakrabarti, Bhismadev; Givens, Ian; Saddy, Doug; Kitchen, Ian; R. Swann, Jonathan; Bailey, Alexis

2016-01-01

Evidence shows that nutritional and environmental stress stimuli during postnatal period influence brain development and interactions between gut and brain. In this study we show that in rats, prevention of weaning from maternal milk results in depressive-like behavior, which is accompanied by changes in the gut bacteria and host metabolism. Depressive-like behavior was studied using the forced-swim test on postnatal day (PND) 25 in rats either weaned on PND 21, or left with their mother until PND 25 (non-weaned). Non-weaned rats showed an increased immobility time consistent with a depressive phenotype. Fluorescence in situ hybridization showed non-weaned rats to harbor significantly lowered Clostridium histolyticum bacterial groups but exhibit marked stress-induced increases. Metabonomic analysis of urine from these animals revealed significant differences in the metabolic profiles, with biochemical phenotypes indicative of depression in the non-weaned animals. In addition, non-weaned rats showed resistance to stress-induced modulation of oxytocin receptors in amygdala nuclei, which is indicative of passive stress-coping mechanism. We conclude that delaying weaning results in alterations to the gut microbiota and global metabolic profiles which may contribute to a depressive phenotype and raise the issue that mood disorders at early developmental ages may reflect interplay between mammalian host and resident bacteria. PMID:26903212

Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation

PubMed Central

Parthasarathy, Gopanandan; Chen, Jun; Chen, Xianfeng; Chia, Nicholas; O'Connor, Helen M.; Wolf, Patricia G.; Gaskins, H. Rex; Bharucha, Adil E.

2015-01-01

Background & Aims In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. Methods Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average of 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). Results Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P<.05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P<.05) and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. Conclusions After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation. PMID:26460205

New frontiers in nanotoxicology: Gut microbiota/microbiome-mediated effects of engineered nanomaterials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pietroiusti, Antonio, E-mail: pietroiu@uniroma2.it

It has been recently recognized that the gut microbiota, the community of organisms living within the gastrointestinal tract is an integral part of the human body, and that its genoma (the microbiome) interacts with the genes expressed by the cells of the host organism. Several important physiological functions require the cooperation of microbiota/microbiome, whose alterations play an important role in several human diseases. On this basis, it is probable that microbiota/microbiome may in part be involved in many biological effects of engineered nanomaterials (ENMs). There are still few reports on the possible toxicological effects of ENMs on microbiota/microbiome, and onmore » their possible clinical consequences. Available data suggest that several ENMs, including carbon nanotubes (CNTs), titanium dioxide, cerium dioxide, zinc oxide, nanosilica and nanosilver may affect the microbiota and that clinical disorders such as colitis, obesity and immunological dysfunctions might follow. On the other hand, other ENMs such as iron nanoparticles may show advantages over traditional iron-based supplemental treatment because they do not interfere with the microbiota/microbiome, and some ENM-based therapeutic interventions might be employed for treating intestinal infections, while sparing the microbiota. The final section of the review is focused on the possible future developments of the research in this field: new in vitro and in vivo models, possible biomarkers and new pathophysiological pathways are proposed and discussed, as well as the possibility that metabolic changes following ENMs/microbiota interactions might be exploited as a fingerprint of ENM exposure. The potential toxicological relevance of physico-chemical modifications of ENMs induced by the microbiota is also highlighted. - Highlights: • Interactions between ENMs and microbiota are largely unexplored. • Microbiota probably mediates several ENMs' biological actions. • ENMs/microbiota interactions might provide new specific biomarkers. • ENM/microbiota interactions may be exploited in nanomedicine. • We propose new experimental models and new targets for ENMs/microbiota.« less

Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation.

PubMed

Parthasarathy, Gopanandan; Chen, Jun; Chen, Xianfeng; Chia, Nicholas; O'Connor, Helen M; Wolf, Patricia G; Gaskins, H Rex; Bharucha, Adil E

2016-02-01

In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average, 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P < .05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P < .05), and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

PubMed

Gautier, Yentl; Luneau, Isabelle; Coquery, Nicolas; Meurice, Paul; Malbert, Charles-Henri; Guerin, Sylvie; Kemp, Bas; Bolhuis, J Elizabeth; Clouard, Caroline; Le Huërou-Luron, Isabelle; Blat, Sophie; Val-Laillet, David

2018-06-13

This study explores the long-term effects of exposure to a maternal Western diet (WD) vs. standard diet (SD) in the Yucatan minipig, on the adult progeny at lean status ( n = 32), and then overweight status. We investigated eating behavior, cognitive abilities, brain basal glucose metabolism, dopamine transporter availability, microbiota activity, blood lipids, and glucose tolerance. Although both groups demonstrated similar cognitive abilities in a holeboard test, WD pigs expressed a higher stress level than did SD pigs (immobility, P < 0.05) and lower performance in an alley maze ( P = 0.06). WD pigs demonstrated lower dopamine transporter binding potential in the hippocampus and parahippocampal cortex ( P < 0.05 for both), as well as a trend in putamen ( P = 0.07), associated with lower basal brain activity in the prefrontal cortex and nucleus accumbens ( P < 0.05) compared with lean SD pigs. Lean WD pigs demonstrated a lower glucose tolerance than did SD animals (higher glucose peak, P < 0.05) and a tendency to a higher incremental area under the curve of insulin from 0 to 30 minutes after intravenous glucose injection ( P < 0.1). Both groups developed glucose intolerance with overweight, but WD animals were less impacted than SD animals. These results demonstrate that maternal diet shaped the offspring's brain functions and cognitive responses long term, even after being fed a balanced diet from weaning, but behavioral effects were only revealed in WD pigs under anxiogenic situation; however, WD animals seemed to cope better with the obesogenic diet from a metabolic standpoint.-Gautier, Y., Luneau, I., Coquery, N., Meurice, P., Malbert, C.-H., Guerin, S., Kemp, B., Bolhuis, J. E., Clouard, C., Le Huërou-Luron, I., Blat, S., Val-Laillet, D. Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

[Host-microbiota crosstalk and cardiovascular diseases].

PubMed

Amar, Jacques

2018-06-13

When analyzing the microbiota-host crosstalk, we have to consider three participants in this dialogue: the gut microbiota, the intestinal barrier and bacterial translocation. Experimental data demonstrate that host microbiota crosstalk plays a causal on the regulation of blood pressure, glucose metabolism and the development of atherosclerosis. Host microbiota crosstalk is associated in humans with main cardiovascular risk factors notably hypertension and type 2 diabetes. Host microbiota crosstalk is associated in humans with the onset of cardiovascular diseases. The Mediterranean diet has proven as proven to be an effective strategy in improving cardiovascular prognosis and in changing gut microbiota. Copyright © 2018. Published by Elsevier Masson SAS.

Could the gut microbiota reconcile the oral bioavailability conundrum of traditional herbs?

PubMed

Chen, Feng; Wen, Qi; Jiang, Jun; Li, Hai-Long; Tan, Yin-Feng; Li, Yong-Hui; Zeng, Nian-Kai

2016-02-17

A wealth of information is emerging about the impact of gut microbiota on human health and diseases such as cardiovascular diseases, obesity and diabetes. As we learn more, we find out the gut microbiota has the potential as new territory for drug targeting. Some novel therapeutic approaches could be developed through reshaping the commensal microbial structure using combinations of different agents. The gut microbiota also affects drug metabolism, directly and indirectly, particularly towards the orally administered drugs. Herbal products have become the basis of traditional medicines such as traditional Chinese medicine and also been being considered valuable materials in modern drug discovery. Of note, low oral bioavailability but high bioactivity is a conundrum not yet solved for some herbs. Since most of herbal products are orally administered, the herbs' constituents are inevitably exposed to the intestinal microbiota and the interplays between herbal constituents and gut microbiota are expected. Emerging explorations of herb-microbiota interactions have an opportunity to revolutionize the way we view herbal therapeutics. The present review aims to provide information regarding the health promotion and/or disease prevention by the interplay between traditional herbs with low bioavailability and gut microbiota through gut microbiota via two different types of mechanisms: (1) influencing the composition of gut microbiota by herbs and (2) metabolic reactions of herbal constituents by gut microbiota. The major data bases (PubMed and Web of Science) were searched using "gut microbiota", "intestinal microbiota", "gut flora", "intestinal flora", "gut microflora", "intestinal microflora", "herb", "Chinese medicine", "traditional medicine", or "herbal medicine" as keywords to find out studies regarding herb-microbiota interactions. The Chinese Pharmacopoeia (2010 edition, Volume I) was also used to collect the data of commonly used medicinal herbs and their quality control approaches. Among the 474 monographs of herbs usually used in the Chinese Pharmacopoeia, the quality control approach of 284 monographs is recommended to use high-performance liquid chromatography approach. Notably, the major marker compounds (>60%) for quality control are polyphenols, polysaccharides and saponins, with significant oral bioavailability conundrum. Results from preclinical and clinical studies on herb-microbiota interactions showed that traditional herbs could exert heath promotion and disease prevention roles via influencing the gut microbiota structure. On the other hand, herb constituents such as ginsenoside C-K, hesperidin, baicalin, daidzin and glycyrrhizin could exert their therapeutic effects through gut microbiota-mediated bioconversion. Herb-microbiota interaction studies provide novel mechanistic understanding of the traditional herbs that exhibit poor oral bioavailability. "Microbiota availability" could be taken consideration into describing biological measurements in the therapeutic assessment of herbal medicine. Our review should be of value in stimulating discussions among the scientific community on this relevant theme and prompting more efforts to complement herb-microbiota interactions studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Intestinal microbiota composition is altered according to nutritional biorhythms in the leopard coral grouper (Plectropomus leopardus).

PubMed

Mekuchi, Miyuki; Asakura, Taiga; Sakata, Kenji; Yamaguchi, Tomofumi; Teruya, Kazuhisa; Kikuchi, Jun

2018-01-01

Aquaculture is currently a major source of fish and has the potential to become a major source of protein in the future. These demands require efficient aquaculture. The intestinal microbiota plays an integral role that benefits the host, providing nutrition and modulating the immune system. Although our understanding of microbiota in fish gut has increased, comprehensive studies examining fish microbiota and host metabolism remain limited. Here, we investigated the microbiota and host metabolism in the coral leopard grouper, which is traded in Asian markets as a superior fish and has begun to be produced via aquaculture. We initially examined the structural changes of the gut microbiota using next-generation sequencing and found that the composition of microbiota changed between fasting and feeding conditions. The dominant phyla were Proteobacteria in fasting and Firmicutes in feeding; interchanging the dominant bacteria required 12 hours. Moreover, microbiota diversity was higher under feeding conditions than under fasting conditions. Multivariate analysis revealed that Proteobacteria are the key bacteria in fasting and Firmicutes and Fusobacteria are the key bacteria in feeding. Subsequently, we estimated microbiota functional capacity. Microbiota functional structure was relatively stable throughout the experiment; however, individual function activity changed according to feeding conditions. Taken together, these findings indicate that the gut microbiota could be a key factor to understanding fish feeding conditions and play a role in interactions with host metabolism. In addition, the composition of microbiota in ambient seawater directly affects the fish; therefore, it is important to monitor the microbiota in rearing tanks and seawater circulating systems.

The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia

PubMed Central

Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom

2016-01-01

Objective Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. Design We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. Results We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. Conclusions This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut–lung axis in bacterial infections. PMID:26511795

Fecal microbiota variation across the lifespan of the healthy laboratory rat.

PubMed

Flemer, Burkhardt; Gaci, Nadia; Borrel, Guillaume; Sanderson, Ian R; Chaudhary, Prem P; Tottey, William; O'Toole, Paul W; Brugère, Jean-François

2017-09-03

Laboratory rats are commonly used in life science research as a model for human biology and disease, but the composition and development of their gut microbiota during life is poorly understood. We determined the fecal microbiota composition of healthy Sprague Dawley laboratory rats from 3 weeks to 2 y of age, kept under controlled environmental and dietary conditions. Additionally, we determined fecal short-chain fatty acid profiles, and we compared the rat fecal microbiota with that of mice and humans. Gut microbiota and to a lesser extent SCFAs profiles separated rats into 3 different clusters according to age: before weaning, first year of life (12- to 26-week-old animals) and second year of life (52- to 104-week-old). A core of 46 bacterial species was present in all rats but its members' relative abundance progressively decreased with age. This was accompanied by an increase of microbiota α-diversity, likely due to the acquisition of environmental microorganisms during the lifespan. Contrastingly, the functional profile of the microbiota across animal species became more similar upon aging. Lastly, the microbiota of rats and mice were most similar to each other but at the same time the microbiota profile of rats was more similar to that of humans than was the microbiota profile of mice. These data offer an explanation as to why germ-free rats are more efficient recipients and retainers of human microbiota than mice. Furthermore, experimental design should take into account dynamic changes in the microbiota of model animals considering that their changing gut microbiota interacts with their physiology.

Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass

PubMed Central

Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

2017-01-01

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB. PMID:28524868

Structure of Manila Clam (Ruditapes philippinarum) Microbiota at the Organ Scale in Contrasting Sets of Individuals.

PubMed

Meisterhans, Guillaume; Raymond, Natalie; Girault, Emilie; Lambert, Christophe; Bourrasseau, Line; de Montaudouin, Xavier; Garabetian, Frédéric; Jude-Lemeilleur, Florence

2016-01-01

Marine invertebrate microbiota has a key function in host physiology and health. To date, knowledge about bivalve microbiota is poorly documented except public health concerns. This study used a molecular approach to characterize the microbiota associated with the bivalve Manila clam (Ruditapes philippinarum) by determining (1) the difference among organs either or not under the influence of host habitat, (2) small-scale variability of microbiota, and (3) the experimental response of the Manila clam microbiota submitted to different lateral transmissions. These questions were investigated by sampling two groups of individuals living in contrasting habitats and carrying out a transplant experiment. Manila clam microbiota (i.e., bacterial community structure) was determined at organ-scale (gills, gut, and a pool of remaining tissues) by capillary electrophoresis DNA fingerprinting (CE fingerprinting). The Manila clam microbiota structure differed among organs indicating a selection of Manila clam microbiota at organ scale. Habitat strongly influenced gill and gut microbiota. In contrast, microbiota associated with remaining tissues was similar between group individuals suggesting that these communities are mostly autochthonous, i.e., Manila clam specific. Transplant experiment showed that improving living condition did not induce any change in microbiota associated with remaining tissues. In contrast, the reduction in individual habitat quality led to individuals in declining health as strongly suggested by the increase in phagocytosis activity and decrease in condition index together with the change in internal organ microbiota. This study provides a first description of the Manila clam holobiont which can withstand disturbance and respond opportunistically to improved environmental conditions.

Potential impact of inorganic nanoparticles on macronutrient digestion: titanium dioxide nanoparticles slightly reduce lipid digestion under simulated gastrointestinal conditions.

PubMed

Li, Qian; Li, Ti; Liu, Chengmei; DeLoid, Glen; Pyrgiotakis, Georgios; Demokritou, Philip; Zhang, Ruojie; Xiao, Hang; McClements, David Julian

Titanium dioxide (TiO 2 ) particles are used in some food products to alter their optical properties, such as whiteness or brightness. These additives typically contain a population of TiO 2 nanoparticles (d < 100 nm), which has led to concern about their potential toxicity. The objective of this study was to examine the impact of TiO 2 particles on the gastrointestinal fate of oil-in-water emulsions using a simulated gastrointestinal tract (GIT) that includes mouth, stomach, and small intestine phases. Theoretical predictions suggested that TiO 2 nanoparticles might inhibit lipid digestion through two physicochemical mechanisms: (i) a fraction of the lipase adsorbs to TiO 2 particle surfaces, thereby reducing the amount available to hydrolyze lipid droplets; (ii) some TiO 2 particles adsorb to the surfaces of lipid droplets, thereby reducing the lipid surface area exposed to lipase. The importance of these mechanisms was tested by passing protein-coated lipid droplets (2%, w/w) through the simulated GIT in the absence and presence of TiO 2 (0.5%, w/w) nanoparticles (18 nm) and fine particles (167 nm). Changes in particle characteristics (size, organization, and charge) and lipid digestion were then measured. Both TiO 2 nanoparticles and fine particles had little impact on the aggregation state and charge of the lipid droplets in the different GIT regions, as well as on the rate and extent of lipid digestion. This suggests that the theoretically predicted impact of particle size on lipid digestion was not seen in practice.

International consensus statement regarding the use of animal models for research on anastomoses in the lower gastrointestinal tract.

PubMed

Bosmans, Joanna W A M; Moossdorff, Martine; Al-Taher, Mahdi; van Beek, Lotte; Derikx, Joep P M; Bouvy, Nicole D

2016-05-01

This project aimed to reach consensus on the most appropriate animal models and outcome measures in research on anastomoses in the lower gastrointestinal tract (GIT). The physiology of anastomotic healing remains an important research topic in gastrointestinal surgery. Recent results from experimental studies are limited with regard to comparability and clinical translation. PubMed and EMBASE were searched for experimental studies investigating anastomotic healing in the lower GIT published between January 1, 2000 and December 31, 2014 to assess currently used models. All corresponding authors were invited for a Delphi-based analysis that consisted of two online survey rounds followed by a final online recommendation survey to reach consensus on the discussed topics. Two hundred seventy-seven original articles were retrieved and 167 articles were included in the systematic review. Mice, rats, rabbits, pigs, and dogs are currently being used as animal models, with a large variety in surgical techniques and outcome measures. Forty-four corresponding authors participated in the Delphi analysis. In the first two rounds, 39/44 and 35/39 participants completed the survey. In the final meeting, 35 experts reached consensus on 76/122 items in six categories. Mouse, rat, and pig are considered appropriate animal models; rabbit and dog should be abandoned in research regarding bowel anastomoses. ARRIVE guidelines should be followed more strictly. Consensus was reached on several recommendations for the use of animal models and outcome measurements in research on anastomoses of the lower GIT. Future research should take these suggestions into account to facilitate comparison and clinical translation of results.

Production of bioactive substances by intestinal bacteria as a basis for explaining probiotic mechanisms: bacteriocins and conjugated linoleic acid.

PubMed

O'Shea, Eileen F; Cotter, Paul D; Stanton, Catherine; Ross, R Paul; Hill, Colin

2012-01-16

The mechanisms by which intestinal bacteria achieve their associated health benefits can be complex and multifaceted. In this respect, the diverse microbial composition of the human gastrointestinal tract (GIT) provides an almost unlimited potential source of bioactive substances (pharmabiotics) which can directly or indirectly affect human health. Bacteriocins and fatty acids are just two examples of pharmabiotic substances which may contribute to probiotic functionality within the mammalian GIT. Bacteriocin production is believed to confer producing strains with a competitive advantage within complex microbial environments as a consequence of their associated antimicrobial activity. This has the potential to enable the establishment and prevalence of producing strains as well as directly inhibiting pathogens within the GIT. Consequently, these antimicrobial peptides and the associated intestinal producing strains may be exploited to beneficially influence microbial populations. Intestinal bacteria are also known to produce a diverse array of health-promoting fatty acids. Indeed, certain strains of intestinal bifidobacteria have been shown to produce conjugated linoleic acid (CLA), a fatty acid which has been associated with a variety of systemic health-promoting effects. Recently, the ability to modulate the fatty acid composition of the liver and adipose tissue of the host upon oral administration of CLA-producing bifidobacteria and lactobacilli was demonstrated in a murine model. Importantly, this implies a potential therapeutic role for probiotics in the treatment of certain metabolic and immunoinflammatory disorders. Such examples serve to highlight the potential contribution of pharmabiotic production to probiotic functionality in relation to human health maintenance. Copyright © 2011 Elsevier B.V. All rights reserved.

GaN transistors on Si for switching and high-frequency applications

NASA Astrophysics Data System (ADS)

Ueda, Tetsuzo; Ishida, Masahiro; Tanaka, Tsuyoshi; Ueda, Daisuke

2014-10-01

In this paper, recent advances of GaN transistors on Si for switching and high-frequency applications are reviewed. Novel epitaxial structures including superlattice interlayers grown by metal organic chemical vapor deposition (MOCVD) relieve the strain and eliminate the cracks in the GaN over large-diameter Si substrates up to 8 in. As a new device structure for high-power switching application, Gate Injection Transistors (GITs) with a p-AlGaN gate over an AlGaN/GaN heterostructure successfully achieve normally-off operations maintaining high drain currents and low on-state resistances. Note that the GITs on Si are free from current collapse up to 600 V, by which the drain current would be markedly reduced after the application of high drain voltages. Highly efficient operations of an inverter and DC-DC converters are presented as promising applications of GITs for power switching. The high efficiencies in an inverter, a resonant LLC converter, and a point-of-load (POL) converter demonstrate the superior potential of the GaN transistors on Si. As for high-frequency transistors, AlGaN/GaN heterojuction field-effect transistors (HFETs) on Si designed specifically for microwave and millimeter-wave frequencies demonstrate a sufficiently high output power at these frequencies. Output powers of 203 W at 2.5 GHz and 10.7 W at 26.5 GHz are achieved by the fabricated GaN transistors. These devices for switching and high-frequency applications are very promising as future energy-efficient electronics because of their inherent low fabrication cost and superior device performance.

The novel orally active guanylhydrazone CPSI-2364 prevents postoperative ileus in mice independently of anti-inflammatory vagus nerve signaling.

PubMed

Wehner, S; Vilz, T O; Sommer, N; Sielecki, T; Hong, G S; Lysson, M; Stoffels, B; Pantelis, D; Kalff, J C

2012-10-01

Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). Previously, we demonstrated that intravenous application of the tetravalent guanylhydrazone semapimod (CNI-1493) prevents POI, but the underlying mode of action could not definitively be confirmed. Herein, we investigated the effect of a novel orally active salt of semapimod (CPSI-2364) on POI in rodents and distinguished between its inhibitory peripheral and stimulatory central nervous effects on anti-inflammatory vagus nerve signaling. Distribution of radiolabeled orally administered CPSI-2364 was analyzed by whole body autoradiography and liquid scintillation counting. POI was induced by intestinal manipulation with or without preoperative vagotomy. CPSI-2364 was administered preoperatively via gavage in a dose- and time-dependent manner. ME specimens were assessed for p38-MAP kinase activity by immunoblotting, neutrophil extravasation, and nitric oxide production. Furthermore, in vivo gastrointestinal (GIT) and colonic transit were measured. Autoradiography demonstrated a near-exclusive detection of CPSI-2364 within the gastrointestinal wall and contents. Preoperative CPSI-2364 application significantly reduced postoperative neutrophil counts, nitric oxide release, GIT deceleration, and delay of colonic transit time, while intraoperatively administered CPSI-2364 failed to improve POI. CPSI-2364 also prevents postoperative neutrophil increase and GIT deceleration in vagotomized mice. Orally administered CPSI-2364 shows a near-exclusive dispersal in the gastrointestinal tract and effectively reduces POI independently of central vagus nerve stimulation. Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI.

Impact of Environmental Factors on Bacteriocin Promoter Activity in Gut-Derived Lactobacillus salivarius.

PubMed

Guinane, Caitriona M; Piper, Clare; Draper, Lorraine A; O'Connor, Paula M; Hill, Colin; Ross, R Paul; Cotter, Paul D

2015-11-01

Bacteriocin production is regarded as a desirable probiotic trait that aids in colonization and persistence in the gastrointestinal tract (GIT). Strains of Lactobacillus salivarius, a species associated with the GIT, are regarded as promising probiotic candidates and have a number of associated bacteriocins documented to date. These include multiple class IIb bacteriocins (salivaricin T, salivaricin P, and ABP-118) and the class IId bacteriocin bactofencin A, which show activity against medically important pathogens. However, the production of a bacteriocin in laboratory media does not ensure production under stressful environmental conditions, such as those encountered within the GIT. To allow this issue to be addressed, the promoter regions located upstream of the structural genes encoding the L. salivarius bacteriocins mentioned above were fused to a number of reporter proteins (green fluorescent protein [GFP], red fluorescent protein [RFP], and luciferase [Lux]). Of these, only transcriptional fusions to GFP generated signals of sufficient strength to enable the study of promoter activity in L. salivarius. While analysis of the class IIb bacteriocin promoter regions indicated relatively weak GFP expression, assessment of the promoter of the antistaphylococcal bacteriocin bactofencin A revealed a strong promoter that is most active in the absence of the antimicrobial peptide and is positively induced in the presence of mild environmental stresses, including simulated gastric fluid. Taken together, these data provide information on factors that influence bacteriocin production, which will assist in the development of strategies to optimize in vivo and in vitro production of these antimicrobials. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease.

PubMed

Wang, Zi-Kai; Yang, Yun-Sheng; Chen, Ye; Yuan, Jing; Sun, Gang; Peng, Li-Hua

2014-10-28

The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.

Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease

PubMed Central

Wang, Zi-Kai; Yang, Yun-Sheng; Chen, Ye; Yuan, Jing; Sun, Gang; Peng, Li-Hua

2014-01-01

The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models. PMID:25356041

The Role of Microbiota on the Gut Immunology.

PubMed

Min, Yang Won; Rhee, Poong-Lyul

2015-05-01

The human gut contains >100 trillion microbes. This microbiota plays a crucial role in the gut homeostasis. Importantly, the microbiota contributes to the development and regulation of the gut immune system. Dysbiosis of the gut microbiota could also cause several intestinal and extraintestinal diseases. Many experimental studies help us to understand the complex interplay between the host and microbiota. This review presents our current understanding of the mucosal immune system and the role of gut microbiota for the development and functionality of the mucosal immunity, with a particular focus on gut-associated lymphoid tissues, mucosal barrier, TH17 cells, regulatory T cells, innate lymphoid cells, dendritic cells, and IgA-producing B cells and plasma cells. Comparative studies using germ-free and conventionally-raised animals reveal that the presence of microbiota is important for the development and regulation of innate and adaptive immune systems. The host-microbial symbiosis seems necessary for gut homeostasis. However, the precise mechanisms by which microbiota contributes to development and functionality of the immune system remain to be elucidated. Understanding the complex interplay between the host and microbiota and further investigation of the host-microbiota relationship could provide us the insight into the therapeutic and/or preventive strategy for the disorders related to dysbiosis of the gut microbiota. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Can We Prevent Obesity-Related Metabolic Diseases by Dietary Modulation of the Gut Microbiota?1

PubMed Central

2016-01-01

Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity-related metabolic diseases and the potential of dietary modulation of the gut microbiota in metabolic disease prevention and treatment. PMID:26773017

Human Gut Microbiota: Toward an Ecology of Disease

PubMed Central

Selber-Hnatiw, Susannah; Rukundo, Belise; Ahmadi, Masoumeh; Akoubi, Hayfa; Al-Bizri, Hend; Aliu, Adelekan F.; Ambeaghen, Tanyi U.; Avetisyan, Lilit; Bahar, Irmak; Baird, Alexandra; Begum, Fatema; Ben Soussan, Hélène; Blondeau-Éthier, Virginie; Bordaries, Roxane; Bramwell, Helene; Briggs, Alicia; Bui, Richard; Carnevale, Matthew; Chancharoen, Marisa; Chevassus, Talia; Choi, Jin H.; Coulombe, Karyne; Couvrette, Florence; D'Abreau, Samantha; Davies, Meghan; Desbiens, Marie-Pier; Di Maulo, Tamara; Di Paolo, Sean-Anthony; Do Ponte, Sabrina; dos Santos Ribeiro, Priscyla; Dubuc-Kanary, Laure-Anne; Duncan, Paola K.; Dupuis, Frédérique; El-Nounou, Sara; Eyangos, Christina N.; Ferguson, Natasha K.; Flores-Chinchilla, Nancy R.; Fotakis, Tanya; Gado Oumarou H D, Mariam; Georgiev, Metodi; Ghiassy, Seyedehnazanin; Glibetic, Natalija; Grégoire Bouchard, Julien; Hassan, Tazkia; Huseen, Iman; Ibuna Quilatan, Marlon-Francis; Iozzo, Tania; Islam, Safina; Jaunky, Dilan B.; Jeyasegaram, Aniththa; Johnston, Marc-André; Kahler, Matthew R.; Kaler, Kiranpreet; Kamani, Cedric; Karimian Rad, Hessam; Konidis, Elisavet; Konieczny, Filip; Kurianowicz, Sandra; Lamothe, Philippe; Legros, Karina; Leroux, Sebastien; Li, Jun; Lozano Rodriguez, Monica E.; Luponio-Yoffe, Sean; Maalouf, Yara; Mantha, Jessica; McCormick, Melissa; Mondragon, Pamela; Narayana, Thivaedee; Neretin, Elizaveta; Nguyen, Thi T. T.; Niu, Ian; Nkemazem, Romeo B.; O'Donovan, Martin; Oueis, Matthew; Paquette, Stevens; Patel, Nehal; Pecsi, Emily; Peters, Jackie; Pettorelli, Annie; Poirier, Cassandra; Pompa, Victoria R.; Rajen, Harshvardhan; Ralph, Reginald-Olivier; Rosales-Vasquez, Josué; Rubinshtein, Daria; Sakr, Surya; Sebai, Mohammad S.; Serravalle, Lisa; Sidibe, Fily; Sinnathurai, Ahnjana; Soho, Dominique; Sundarakrishnan, Adithi; Svistkova, Veronika; Ugbeye, Tsolaye E.; Vasconcelos, Megan S.; Vincelli, Michael; Voitovich, Olga; Vrabel, Pamela; Wang, Lu; Wasfi, Maryse; Zha, Cong Y.; Gamberi, Chiara

2017-01-01

Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics. PMID:28769880

Captive bottlenose dolphins and killer whales harbor a species-specific skin microbiota that varies among individuals.

PubMed

Chiarello, M; Villéger, S; Bouvier, C; Auguet, J C; Bouvier, T

2017-11-10

Marine animals surfaces host diverse microbial communities, which play major roles for host's health. Most inventories of marine animal surface microbiota have focused on corals and fishes, while cetaceans remain overlooked. The few studies focused on wild cetaceans, making difficult to distinguish intrinsic inter- and/or intraspecific variability in skin microbiota from environmental effects. We used high-throughput sequencing to assess the skin microbiota from 4 body zones of 8 bottlenose dolphins (Tursiops truncatus) and killer whales (Orcinus orca), housed in captivity (Marineland park, France). Overall, cetacean skin microbiota is more diverse than planktonic communities and is dominated by different phylogenetic lineages and functions. In addition, the two cetacean species host different skin microbiotas. Within each species, variability was higher between individuals than between body parts, suggesting a high individuality of cetacean skin microbiota. Overall, the skin microbiota of the assessed cetaceans related more to the humpback whale and fishes' than to microbiotas of terrestrial mammals.

Saliva Microbiota Carry Caries-Specific Functional Gene Signatures

PubMed Central

Chang, Xingzhi; Yuan, Xiao; Tu, Qichao; Yuan, Tong; Deng, Ye; Hemme, Christopher L.; Van Nostrand, Joy; Cui, Xinping; He, Zhili; Chen, Zhenggang; Guo, Dawei; Yu, Jiangbo; Zhang, Yue; Zhou, Jizhong; Xu, Jian

2014-01-01

Human saliva microbiota is phylogenetically divergent among host individuals yet their roles in health and disease are poorly appreciated. We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults. Saliva microbiota in the pilot population featured a vast diversity of functional genes. No significant distinction in gene number or diversity indices was observed between healthy and caries-active microbiota. However, co-presence network analysis of functional genes revealed that caries-active microbiota was more divergent in non-core genes than healthy microbiota, despite both groups exhibited a similar degree of conservation at their respective core genes. Furthermore, functional gene structure of saliva microbiota could potentially distinguish caries-active patients from healthy hosts. Microbial functions such as Diaminopimelate epimerase, Prephenate dehydrogenase, Pyruvate-formate lyase and N-acetylmuramoyl-L-alanine amidase were significantly linked to caries. Therefore, saliva microbiota carried disease-associated functional signatures, which could be potentially exploited for caries diagnosis. PMID:24533043

Saliva microbiota carry caries-specific functional gene signatures.

PubMed

Yang, Fang; Ning, Kang; Chang, Xingzhi; Yuan, Xiao; Tu, Qichao; Yuan, Tong; Deng, Ye; Hemme, Christopher L; Van Nostrand, Joy; Cui, Xinping; He, Zhili; Chen, Zhenggang; Guo, Dawei; Yu, Jiangbo; Zhang, Yue; Zhou, Jizhong; Xu, Jian

2014-01-01

Human saliva microbiota is phylogenetically divergent among host individuals yet their roles in health and disease are poorly appreciated. We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults. Saliva microbiota in the pilot population featured a vast diversity of functional genes. No significant distinction in gene number or diversity indices was observed between healthy and caries-active microbiota. However, co-presence network analysis of functional genes revealed that caries-active microbiota was more divergent in non-core genes than healthy microbiota, despite both groups exhibited a similar degree of conservation at their respective core genes. Furthermore, functional gene structure of saliva microbiota could potentially distinguish caries-active patients from healthy hosts. Microbial functions such as Diaminopimelate epimerase, Prephenate dehydrogenase, Pyruvate-formate lyase and N-acetylmuramoyl-L-alanine amidase were significantly linked to caries. Therefore, saliva microbiota carried disease-associated functional signatures, which could be potentially exploited for caries diagnosis.

The microbiota in bronchoalveolar lavage from young children with chronic lung disease includes taxa present in both the oropharynx and nasopharynx.

PubMed

Marsh, R L; Kaestli, M; Chang, A B; Binks, M J; Pope, C E; Hoffman, L R; Smith-Vaughan, H C

2016-07-07

Invasive methods requiring general anaesthesia are needed to sample the lung microbiota in young children who do not expectorate. This poses substantial challenges to longitudinal study of paediatric airway microbiota. Non-invasive upper airway sampling is an alternative method for monitoring airway microbiota; however, there are limited data describing the relationship of such results with lung microbiota in young children. In this study, we compared the upper and lower airway microbiota in young children to determine whether non-invasive upper airway sampling procedures provide a reliable measure of either lung microbiota or clinically defined differences. The microbiota in oropharyngeal (OP) swabs, nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) from 78 children (median age 2.2 years) with and without lung disease were characterised using 16S rRNA gene sequencing. Permutational multivariate analysis of variance (PERMANOVA) detected significant differences between the microbiota in BAL and those in both OP swabs (p = 0.0001, Pseudo-F = 12.2, df = 1) and NP swabs (p = 0.0001; Pseudo-F = 21.9, df = 1) with the NP and BAL microbiota more different than the OP and BAL, as indicated by a higher Pseudo-F value. The microbiota in combined OP and NP data (upper airways) provided a more comprehensive representation of BAL microbiota, but significant differences between the upper airway and BAL microbiota remained, albeit with a considerably smaller Pseudo-F (PERMANOVA p = 0.0001; Pseudo-F = 4.9, df = 1). Despite this overall difference, paired BAL and upper airway (OP and NP) microbiota were >50 % similar among 69 % of children. Furthermore, canonical analysis of principal coordinates (CAP analysis) detected significant differences between the microbiota from clinically defined groups when analysing either BAL (eigenvalues >0.8; misclassification rate 26.5 %) or the combined OP and NP data (eigenvalues >0.8; misclassification rate 12.2 %). Upper airway sampling provided an imperfect, but reliable, representation of the BAL microbiota for most children in this study. We recommend inclusion of both OP and NP specimens when non-invasive upper airway sampling is needed to assess airway microbiota in young children who do not expectorate. The results of the CAP analysis suggest lower and upper airway microbiota profiles may differentiate children with chronic suppurative lung disease from those with persistent bacterial bronchitis; however, further research is needed to confirm this observation.

The human microbiota associated with overall health.

PubMed

Xu, Xiaofei; Wang, Zhujun; Zhang, Xuewu

2015-03-01

Human body harbors diverse microbes, the main components include bacteria, eukaryotes and viruses. Emerging evidences show that the human microbiota is intrinsically linked with overall health. The development of next-generation sequencing provides an unprecedented opportunity to investigate the complex microbial communities that are associated with the human body. Many factors like host genetics and environmental factors have a major impact on the composition and dynamic changes of human microbiota. The purpose of this paper is to present an overview of the relationship between human health and human microbiota (skin, nasal, throat, oral, vaginal and gut microbiota), then to focus on the factors modulating the composition of the microbiota and the future challenges to manipulate the microbiota for personalized health.

Starving our Microbial Self: The Deleterious Consequences of a Diet Deficient in Microbiota-Accessible Carbohydrates

PubMed Central

Sonnenburg, Erica D.; Sonnenburg, Justin L.

2016-01-01

The gut microbiota of a healthy person may not be equivalent to a healthy microbiota. It is possible that the Western microbiota is actually dysbiotic and predisposes individuals to a variety of diseases. The asymmetric plasticity between the relatively stable human genome and the more malleable gut microbiome suggests that incompatibilities between the two could rapidly arise. The Western lifestyle, which includes a diet low in microbiota-accessible carbohydrates (MACs), has selected for a microbiota with altered membership and functionality compared to those of groups living traditional lifestyles. Interactions between resident microbes and host leading to immune dysregulation may explain several diseases that share inflammation as a common basis. The low-MAC Western diet results in poor production of gut microbiota-generated short-chain fatty acids (SCFAs), which attenuate inflammation through a variety of mechanisms in mouse models. Studies focused on modern and traditional societies, combined with animal models, are needed to characterize the connection between diet, microbiota composition, and function. Differentiating between an optimal microbiota, one that increases disease risk, and one that is causative or potentiates disease will be required to further understand both the etiology and possible treatments for health problems related to microbiota dysbiosis. PMID:25156449

Microbiota and metabolic diseases.

PubMed

Pascale, Alessia; Marchesi, Nicoletta; Marelli, Cristina; Coppola, Adriana; Luzi, Livio; Govoni, Stefano; Giustina, Andrea; Gazzaruso, Carmine

2018-05-02

The microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi, living in different districts of the human body, such as the gastro-enteric tube, skin, mouth, respiratory system, and the vagina. Over 70% of the microbiota lives in the gastrointestinal tract in a mutually beneficial relationship with its host. The microbiota plays a major role in many metabolic functions, including modulation of glucose and lipid homeostasis, regulation of satiety, production of energy and vitamins. It exerts a role in the regulation of several biochemical and physiological mechanisms through the production of metabolites and substances. In addition, the microbiota has important anti-carcinogenetic and anti-inflammatory actions. There is growing evidence that any modification in the microbiota composition can lead to several diseases, including metabolic diseases, such as obesity and diabetes, and cardiovascular diseases. This is because alterations in the microbiota composition can cause insulin resistance, inflammation, vascular, and metabolic disorders. The causes of the microbiota alterations and the mechanisms by which microbiota modifications can act on the development of metabolic and cardiovascular diseases have been reported. Current and future preventive and therapeutic strategies to prevent these diseases by an adequate modulation of the microbiota have been also discussed.

Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort.

PubMed

Org, Elin; Blum, Yuna; Kasela, Silva; Mehrabian, Margarete; Kuusisto, Johanna; Kangas, Antti J; Soininen, Pasi; Wang, Zeneng; Ala-Korpela, Mika; Hazen, Stanley L; Laakso, Markku; Lusis, Aldons J

2017-04-13

The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. We investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gut microbiota composition and microbiota-metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state. Our study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host-gut microbiota relationships.

The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia.

PubMed

Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

2016-04-01

Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut-lung axis in bacterial infections. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

PubMed

Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

2018-01-09

Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that aspiration is a source of the COPD lung microbiota.

Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence.

PubMed

Lamas, Bruno; Michel, Marie-Laure; Waldschmitt, Nadine; Pham, Hang-Phuong; Zacharioudaki, Vassiliki; Dupraz, Louise; Delacre, Myriam; Natividad, Jane M; Costa, Gregory Da; Planchais, Julien; Sovran, Bruno; Bridonneau, Chantal; Six, Adrien; Langella, Philippe; Richard, Mathias L; Chamaillard, Mathias; Sokol, Harry

2017-08-08

In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 ( CARD9 ), a key innate immunity gene, is required to shape a normal gut microbiota. Card9 -/- mice are more susceptible to the enteric mouse pathogen Citrobacter rodentium that mimics human infections with enteropathogenic and enterohaemorrhagic Escherichia coli . Here, we examined how CARD9 controls C. rodentium infection susceptibility through microbiota-dependent and microbiota-independent mechanisms. C. rodentium infection was assessed in conventional and germ-free (GF) wild-type (WT) and Card9 -/- mice. To explore the impact of Card9 -/- microbiota in infection susceptibility, GF WT mice were colonised with WT (WT→GF) or Card9 -/- ( Card9 -/- →GF) microbiota before C. rodentium infection. Microbiota composition was determined by 16S rDNA gene sequencing. Inflammation severity was determined by histology score and lipocalin level. Microbiota-host immune system interactions were assessed by quantitative PCR analysis. CARD9 controls pathogen virulence in a microbiota-independent manner by supporting a specific humoral response. Higher susceptibility to C. rodentium -induced colitis was observed in Card9 -/- →GF mice. The microbiota of Card9 -/- mice failed to outcompete the monosaccharide-consuming C. rodentium , worsening the infection severity. A polysaccharide-enriched diet counteracted the ecological advantage of C. rodentium and the defective pathogen-specific antibody response in Card9 -/- mice. CARD9 modulates the susceptibility to intestinal infection by controlling the pathogen virulence in a microbiota-dependent and microbiota-independent manner. Genetic susceptibility to intestinal pathogens can be overridden by diet intervention that restores humoural immunity and a competing microbiota. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Fecal Microbiota Transplantation: A Review of Emerging Indications Beyond Relapsing Clostridium difficile Toxin Colitis

PubMed Central

Lee, Woo Jung; Lattimer, Lakshmi D. N.; Stephen, Sindu; Borum, Marie L.

2015-01-01

The symbiotic relationship between gut microbiota and humans has been forged over many millennia. This relationship has evolved to establish an intimate partnership that we are only beginning to understand. Gut microbiota were once considered pathogenic, but the concept of gut microbiota and their influence in human health is undergoing a major paradigm shift, as there is mounting evidence of their impact in the homeostasis of intestinal development, metabolic activities, and the immune system. The disruption of microbiota has been associated with many gastrointestinal and nongastrointestinal diseases, and the reconstitution of balanced microbiota has been postulated as a potential therapeutic strategy. Fecal microbiota transplantation (FMT), a unique method to reestablish a sustained balance in the disrupted microbiota of diseased intestine, has demonstrated great success in the treatment of recurrent Clostridium difficile infection and has gained increasing acceptance in clinical use. The possibility of dysfunctional micro-biota playing a causative role in other gastrointestinal and nongas-trointestinal diseases, therefore, has also been raised, and there are an increasing number of studies supporting this hypothesis. FMT is emerging as a feasible therapeutic option for several diseases; however, its efficacy remains in question, given the lack of clinical trial data. Altering microbiota with FMT holds great promise, but much research is needed to further define FMT’s therapeutic role and optimize the microbiota delivery system. PMID:27099570

Fecal Microbiota Transplantation: A Review of Emerging Indications Beyond Relapsing Clostridium difficile Toxin Colitis.

PubMed

Jung Lee, Woo; Lattimer, Lakshmi D N; Stephen, Sindu; Borum, Marie L; Doman, David B

2015-01-01

The symbiotic relationship between gut microbiota and humans has been forged over many millennia. This relationship has evolved to establish an intimate partnership that we are only beginning to understand. Gut microbiota were once considered pathogenic, but the concept of gut microbiota and their influence in human health is undergoing a major paradigm shift, as there is mounting evidence of their impact in the homeostasis of intestinal development, metabolic activities, and the immune system. The disruption of microbiota has been associated with many gastrointestinal and nongastrointestinal diseases, and the reconstitution of balanced microbiota has been postulated as a potential therapeutic strategy. Fecal microbiota transplantation (FMT), a unique method to reestablish a sustained balance in the disrupted microbiota of diseased intestine, has demonstrated great success in the treatment of recurrent Clostridium difficile infection and has gained increasing acceptance in clinical use. The possibility of dysfunctional micro-biota playing a causative role in other gastrointestinal and nongas-trointestinal diseases, therefore, has also been raised, and there are an increasing number of studies supporting this hypothesis. FMT is emerging as a feasible therapeutic option for several diseases; however, its efficacy remains in question, given the lack of clinical trial data. Altering microbiota with FMT holds great promise, but much research is needed to further define FMT's therapeutic role and optimize the microbiota delivery system.

Microbiota fingerprints lose individually identifying features over time.

PubMed

Wilkins, David; Leung, Marcus H Y; Lee, Patrick K H

2017-01-09

Humans host individually unique skin microbiota, suggesting that microbiota traces transferred from skin to surfaces could serve as forensic markers analogous to fingerprints. While it is known that individuals leave identifiable microbiota traces on surfaces, it is not clear for how long these traces persist. Moreover, as skin and surface microbiota change with time, even persistent traces may lose their forensic potential as they would cease to resemble the microbiota of the person who left them. We followed skin and surface microbiota within households for four seasons to determine whether accurate microbiota-based matching of individuals to their households could be achieved across long time delays. While household surface microbiota traces could be matched to the correct occupant or occupants with 67% accuracy, accuracy decreased substantially when skin and surface samples were collected in different seasons, and particularly when surface samples were collected long after skin samples. Most OTUs persisted on skin or surfaces for less than one season, indicating that OTU loss was the major cause of decreased matching accuracy. OTUs that were more useful for individual identification persisted for less time and were less likely to be deposited from skin to surface, suggesting a trade-off between the longevity and identifying value of microbiota traces. While microbiota traces have potential forensic value, unlike fingerprints they are not static and may degrade in a way that preferentially erases features useful in identifying individuals.

The role of adaptive immunity as an ecological filter on the gut microbiota in zebrafish.

PubMed

Stagaman, Keaton; Burns, Adam R; Guillemin, Karen; Bohannan, Brendan Jm

2017-07-01

All animals live in intimate association with communities of microbes, collectively referred to as their microbiota. Certain host traits can influence which microbial taxa comprise the microbiota. One potentially important trait in vertebrate animals is the adaptive immune system, which has been hypothesized to act as an ecological filter, promoting the presence of some microbial taxa over others. Here we surveyed the intestinal microbiota of 68 wild-type zebrafish, with functional adaptive immunity, and 61 rag1 - zebrafish, lacking functional B- and T-cell receptors, to test the role of adaptive immunity as an ecological filter on the intestinal microbiota. In addition, we tested the robustness of adaptive immunity's filtering effects to host-host interaction by comparing the microbiota of fish populations segregated by genotype to those containing both genotypes. The presence of adaptive immunity individualized the gut microbiota and decreased the contributions of neutral processes to gut microbiota assembly. Although mixing genotypes led to increased phylogenetic diversity in each, there was no significant effect of adaptive immunity on gut microbiota composition in either housing condition. Interestingly, the most robust effect on microbiota composition was co-housing within a tank. In all, these results suggest that adaptive immunity has a role as an ecological filter of the zebrafish gut microbiota, but it can be overwhelmed by other factors, including transmission of microbes among hosts.

Dysbiosis of gut microbiota and microbial metabolites in Parkinson's Disease.

PubMed

Sun, Meng-Fei; Shen, Yan-Qin

2018-04-26

Gut microbial dysbiosis and alteration of microbial metabolites in Parkinson's disease (PD) have been increasingly reported. Dysbiosis in the composition and abundance of gut microbiota can affect both the enteric nervous system and the central nervous system (CNS), indicating the existence of a microbiota-gut-brain axis and thereby causing CNS diseases. Disturbance of the microbiota-gut-brain axis has been linked to specific microbial products that are related to gut inflammation and neuroinflammation. Future directions should therefore focus on the exploration of specific gut microbes or microbial metabolites that contribute to the development of PD. Microbiota-targeted interventions, such as antibiotics, probiotics and fecal microbiota transplantation, have been shown to favorably affect host health. In this review, recent findings regarding alterations and the role of gut microbiota and microbial metabolites in PD are summarized, and potential molecular mechanisms and microbiota-targeted interventions in PD are discussed. Copyright © 2018. Published by Elsevier B.V.

Core fecal microbiota of domesticated herbivorous ruminant, hindgut fermenters, and monogastric animals.

PubMed

O' Donnell, Michelle M; Harris, Hugh M B; Ross, R Paul; O'Toole, Paul W

2017-10-01

In this pilot study, we determined the core fecal microbiota composition and overall microbiota diversity of domesticated herbivorous animals of three digestion types: hindgut fermenters, ruminants, and monogastrics. The 42 animals representing 10 animal species were housed on a single farm in Ireland and all the large herbivores consumed similar feed, harmonizing two of the environmental factors that influence the microbiota. Similar to other mammals, the fecal microbiota of all these animals was dominated by the Firmicutes and Bacteroidetes phyla. The fecal microbiota spanning all digestion types comprised 42% of the genera identified. Host phylogeny and, to a lesser extent, digestion type determined the microbiota diversity in these domesticated herbivores. This pilot study forms a platform for future studies into the microbiota of nonbovine and nonequine domesticated herbivorous animals. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Possibilities of electrical impedance tomography in gynecology

NASA Astrophysics Data System (ADS)

V, Trokhanova O.; A, Chijova Y.; B, Okhapkin M.; V, Korjenevsky A.; S, Tuykin T.

2013-04-01

The paper describes results of comprehensive EIT diagnostics of mammary glands and cervix. The data were obtained from examinations of 170 patients by EIT system MEM (multi-frequency electrical impedance mammograph) and EIT system GIT (gynecological impedance tomograph). Mutual dependence is discussed.

Depletion of Cultivatable Gut Microbiota by Broad-Spectrum Antibiotic Pretreatment Worsens Outcome After Murine Stroke

PubMed Central

Winek, Katarzyna; Engel, Odilo; Koduah, Priscilla; Heimesaat, Markus M.; Fischer, André; Bereswill, Stefan; Dames, Claudia; Kershaw, Olivia; Gruber, Achim D.; Curato, Caterina; Oyama, Naoki; Meisel, Christian; Meisel, Andreas

2016-01-01

Background and Purpose— Antibiotics disturbing microbiota are often used in treatment of poststroke infections. A bidirectional brain–gut microbiota axis was recently suggested as a modulator of nervous system diseases. We hypothesized that gut microbiota may be an important player in the course of stroke. Methods— We investigated the outcome of focal cerebral ischemia in C57BL/6J mice after an 8-week decontamination with quintuple broad-spectrum antibiotic cocktail. These microbiota-depleted animals were subjected to 60 minutes middle cerebral artery occlusion or sham operation. Infarct volume was measured using magnetic resonance imaging, and mice were monitored clinically throughout the whole experiment. At the end point, tissues were preserved for further analysis, comprising histology and immunologic investigations using flow cytometry. Results— We found significantly decreased survival in the middle cerebral artery occlusion microbiota-depleted mice when the antibiotic cocktail was stopped 3 days before surgery (compared with middle cerebral artery occlusion specific pathogen-free and sham-operated microbiota-depleted mice). Moreover, all microbiota-depleted animals in which antibiotic treatment was terminated developed severe acute colitis. This phenotype was rescued by continuous antibiotic treatment or colonization with specific pathogen-free microbiota before surgery. Further, infarct volumes on day one did not differ between any of the experimental groups. Conclusions— Conventional microbiota ensures intestinal protection in the mouse model of experimental stroke and prevents development of acute and severe colitis in microbiota-depleted mice not given antibiotic protection after cerebral ischemia. Our experiments raise the clinically important question as to whether microbial colonization or specific microbiota are crucial for stroke outcome. PMID:27056982

Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease.

PubMed

Weingarden, Alexa R; Vaughn, Byron P

2017-05-04

Inflammatory bowel disease (IBD) is a complex set of diseases that lead to chronic inflammation in the gastrointestinal tract. Although the etiology of IBD is not fully understood, it is well-known that the intestinal microbiota is associated with the development and maintenance of IBD. Manipulation of the gut microbiota, therefore, may represent a target for IBD therapy. Fecal microbiota transplantation (FMT), where fecal microbiota from a healthy donor is transplanted into a patient's GI tract, is already a successful therapy for Clostridium difficile infection. FMT is currently being explored as a potential therapy for IBD as well. In this review, the associations between the gut microbiota and IBD and the emerging data on FMT for IBD will be discussed.

The Reciprocal Interactions between Polyphenols and Gut Microbiota and Effects on Bioaccessibility

PubMed Central

Ozdal, Tugba; Sela, David A.; Xiao, Jianbo; Boyacioglu, Dilek; Chen, Fang; Capanoglu, Esra

2016-01-01

As of late, polyphenols have increasingly interested the scientific community due to their proposed health benefits. Much of this attention has focused on their bioavailability. Polyphenol–gut microbiota interactions should be considered to understand their biological functions. The dichotomy between the biotransformation of polyphenols into their metabolites by gut microbiota and the modulation of gut microbiota composition by polyphenols contributes to positive health outcomes. Although there are many studies on the in vivo bioavailability of polyphenols, the mutual relationship between polyphenols and gut microbiota is not fully understood. This review focuses on the biotransformation of polyphenols by gut microbiota, modulation of gut microbiota by polyphenols, and the effects of these two-way mutual interactions on polyphenol bioavailability, and ultimately, human health. PMID:26861391

Gut microbiota and obesity: role in aetiology and potential therapeutic target.

PubMed

Moran, Carthage P; Shanahan, Fergus

2014-08-01

Obesity is epidemic; chronic energy surplus is clearly important in obesity development but other factors are at play. Indigenous gut microbiota are implicated in the aetiopathogenesis of obesity and obesity-related disorders. Evidence from murine models initially suggested a role for the gut microbiota in weight regulation and the microbiota has been shown to contribute to the low grade inflammation that characterises obesity. The microbiota and its metabolites mediate some of the alterations of the microbiota-gut-brain axis, the endocannabinoid system, and bile acid metabolism, found in obesity-related disorders. Modulation of the gut microbiota is an attractive proposition for prevention or treatment of obesity, particularly as traditional measures have been sub-optimal. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanisms and Therapy

PubMed Central

Ma, Junli; Zhou, Qihang; Li, Houkai

2017-01-01

The gut microbiota plays critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes(T2D), and insulin resistance(IR), highlighting the potential of gut microbiota-targeted therapies in these diseases. There are various ways that gut microbiota can be manipulated, including through use of probiotics, prebiotics, synbiotics, antibiotics, and some active components from herbal medicines. In this review, we review the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies for NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future. PMID:29035308

Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota.

PubMed

Xu, Jun; Chen, Hu-Biao; Li, Song-Lin

2017-09-01

Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever-increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs. More advanced experimental designs are recommended for future study, such as overall chemical characterization of gut microbiota-metabolized HMs, direct microbial analysis of HM-targeted gut microbiota, and precise gut microbiota research model development. The outcomes of such research can further elucidate the interactions between HMs and gut microbiota, thereby opening a new window for defining the scientific basis of HMs and for guiding HM-based drug discovery. © 2016 Wiley Periodicals, Inc.

Molecular diversity of the faecal microbiota of Toy Poodles in Japan.

PubMed

Omatsu, Tsutomu; Omura, Miki; Katayama, Yukie; Kimura, Toru; Okumura, Maho; Okumura, Atsushi; Murata, Yoshiteru; Mizutani, Tetsuya

2018-05-18

The intestinal microbiota was revealed with the recent advances in molecular techniques, such as high-throughput sequencing analysis. As a result, the microbial changes are thought to influence the health of humans and animals and such changes are affected by several factors including diet, genetics, age, sex, and diseases. Similar studies are being conducted in dogs, and the knowledge of intestinal microbiota in dogs is expanding. Nonetheless, basic information on intestinal microbiota in dogs is less than that of humans. Our aim was to study toy poodles (n=21), a popular companion dog, in terms of basic characteristics of the faecal microbiota by 16S rRNA gene barcoding analysis. In the faecal microbiota, Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria were the dominant phyla (over 93.4% of faecal microbiota) regardless of the attributes of the dogs. In family level, Enterobacteriaceae, Bacteroidaceae, and Lachnospiraceae were most prevalent. In case of a dog with protein-losing enteropathy, the diversity of faecal microbiota was different between before and after treatment. This study provides basic information for studying on faecal microbiota in toy poodles.

Application of NMR-based metabolomics to the study of gut microbiota in obesity.

PubMed

Calvani, Riccardo; Brasili, Elisa; Praticò, Giulia; Sciubba, Fabio; Roselli, Marianna; Finamore, Alberto; Marini, Federico; Marzetti, Emanuele; Miccheli, Alfredo

2014-01-01

Lifestyle habits, host gene repertoire, and alterations in the intestinal microbiota concur to the development of obesity. A great deal of research has recently been focused on investigating the role gut microbiota plays in the pathogenesis of metabolic dysfunctions and increased adiposity. Altered microbiota can affect host physiology through several pathways, including enhanced energy harvest, and perturbations in immunity, metabolic signaling, and inflammatory pathways. A broad range of "omics" technologies is now available to help decipher the interactions between the host and the gut microbiota at detailed genetic and functional levels. In particular, metabolomics--the comprehensive analysis of metabolite composition of biological fluids and tissues--could provide breakthrough insights into the links among the gut microbiota, host genetic repertoire, and diet during the development and progression of obesity. Here, we briefly review the most insightful findings on the involvement of gut microbiota in the pathogenesis of obesity. We also discuss how metabolomic approaches based on nuclear magnetic resonance spectroscopy could help understand the activity of gut microbiota in relation to obesity, and assess the effects of gut microbiota modulation in the treatment of this condition.

A review of metabolic potential of human gut microbiome in human nutrition.

PubMed

Yadav, Monika; Verma, Manoj Kumar; Chauhan, Nar Singh

2018-03-01

The human gut contains a plethora of microbes, providing a platform for metabolic interaction between the host and microbiota. Metabolites produced by the gut microbiota act as a link between gut microbiota and its host. These metabolites act as messengers having the capacity to alter the gut microbiota. Recent advances in the characterization of the gut microbiota and its symbiotic relationship with the host have provided a platform to decode metabolic interactions. The human gut microbiota, a crucial component for dietary metabolism, is shaped by the genetic, epigenetic and dietary factors. The metabolic potential of gut microbiota explains its significance in host health and diseases. The knowledge of interactions between microbiota and host metabolism, as well as modification of microbial ecology, is really beneficial to have effective therapeutic treatments for many diet-related diseases in near future. This review cumulates the information to map the role of human gut microbiota in dietary component metabolism, the role of gut microbes derived metabolites in human health and host-microbe metabolic interactions in health and diseases.

The Impact of Gut Microbiota on Gender-Specific Differences in Immunity

PubMed Central

Fransen, Floris; van Beek, Adriaan A.; Borghuis, Theo; Meijer, Ben; Hugenholtz, Floor; van der Gaast-de Jongh, Christa; Savelkoul, Huub F.; de Jonge, Marien I.; Faas, Marijke M.; Boekschoten, Mark V.; Smidt, Hauke; El Aidy, Sahar; de Vos, Paul

2017-01-01

Males and females are known to have gender-specific differences in their immune system and gut microbiota composition. Whether these differences in gut microbiota composition are a cause or consequence of differences in the immune system is not known. To investigate this issue, gut microbiota from conventional males or females was transferred to germ-free (GF) animals of the same or opposing gender. We demonstrate that microbiota-independent gender differences in immunity are already present in GF mice. In particular, type I interferon signaling was enhanced in the intestine of GF females. Presumably, due to these immune differences bacterial groups, such as Alistipes, Rikenella, and Porphyromonadaceae, known to expand in the absence of innate immune defense mechanism were overrepresented in the male microbiota. The presence of these bacterial groups was associated with induction of weight loss, inflammation, and DNA damage upon transfer of the male microbiota to female GF recipients. In summary, our data suggest that microbiota-independent gender differences in the immune system select a gender-specific gut microbiota composition, which in turn further contributes to gender differences in the immune system. PMID:28713378

[Research advances in the relationship between childhood malnutrition and gut microbiota].

PubMed

Wang, Hui-Hui; Wen, Fei-Qiu; Wei, Ju-Rong

2016-11-01

Childhood malnutrition is an important disease threatening healthy growth of children worldwide. Gut microbiota has close links to food digestion, absorption and intestinal function. Current research considers that alterations in gut microbiota have been strongly implicated in childhood malnutrition. This review article addresses the latest understanding and evidence of interrelationship between gut microbiota and individual nutrition status, the changes of gut microbiota in different types of malnutrition, and the attribution of gut microbiota in the treatment and prognosis of malnutrition. It provides in depth understanding of childhood malnutrition from the perspective of microbiome.

Root microbiota shift in rice correlates with resident time in the field and developmental stage.

PubMed

Zhang, Jingying; Zhang, Na; Liu, Yong-Xin; Zhang, Xiaoning; Hu, Bin; Qin, Yuan; Xu, Haoran; Wang, Hui; Guo, Xiaoxuan; Qian, Jingmei; Wang, Wei; Zhang, Pengfan; Jin, Tao; Chu, Chengcai; Bai, Yang

2018-06-01

Land plants in natural soil form intimate relationships with the diverse root bacterial microbiota. A growing body of evidence shows that these microbes are important for plant growth and health. Root microbiota composition has been widely studied in several model plants and crops; however, little is known about how root microbiota vary throughout the plant's life cycle under field conditions. We performed longitudinal dense sampling in field trials to track the time-series shift of the root microbiota from two representative rice cultivars in two separate locations in China. We found that the rice root microbiota varied dramatically during the vegetative stages and stabilized from the beginning of the reproductive stage, after which the root microbiota underwent relatively minor changes until rice ripening. Notably, both rice genotype and geographical location influenced the patterns of root microbiota shift that occurred during plant growth. The relative abundance of Deltaproteobacteria in roots significantly increased overtime throughout the entire life cycle of rice, while that of Betaproteobacteria, Firmicutes, and Gammaproteobacteria decreased. By a machine learning approach, we identified biomarker taxa and established a model to correlate root microbiota with rice resident time in the field (e.g., Nitrospira accumulated from 5 weeks/tillering in field-grown rice). Our work provides insights into the process of rice root microbiota establishment.

Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates.

PubMed

Sonnenburg, Erica D; Sonnenburg, Justin L

2014-11-04

The gut microbiota of a healthy person may not be equivalent to a healthy microbiota. It is possible that the Western microbiota is actually dysbiotic and predisposes individuals to a variety of diseases. The asymmetric plasticity between the relatively stable human genome and the more malleable gut microbiome suggests that incompatibilities between the two could rapidly arise. The Western lifestyle, which includes a diet low in microbiota-accessible carbohydrates (MACs), has selected for a microbiota with altered membership and functionality compared to those of groups living traditional lifestyles. Interactions between resident microbes and host leading to immune dysregulation may explain several diseases that share inflammation as a common basis. The low-MAC Western diet results in poor production of gut microbiota-generated short-chain fatty acids (SCFAs), which attenuate inflammation through a variety of mechanisms in mouse models. Studies focused on modern and traditional societies, combined with animal models, are needed to characterize the connection between diet, microbiota composition, and function. Differentiating between an optimal microbiota, one that increases disease risk, and one that is causative or potentiates disease will be required to further understand both the etiology and possible treatments for health problems related to microbiota dysbiosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Root microbiota dynamics of perennial Arabis alpina are dependent on soil residence time but independent of flowering time.

PubMed

Dombrowski, Nina; Schlaeppi, Klaus; Agler, Matthew T; Hacquard, Stéphane; Kemen, Eric; Garrido-Oter, Ruben; Wunder, Jörg; Coupland, George; Schulze-Lefert, Paul

2017-01-01

Recent field and laboratory experiments with perennial Boechera stricta and annual Arabidopsis thaliana suggest that the root microbiota influences flowering time. Here we examined in long-term time-course experiments the bacterial root microbiota of the arctic-alpine perennial Arabis alpina in natural and controlled environments by 16S rRNA gene profiling. We identified soil type and residence time of plants in soil as major determinants explaining up to 15% of root microbiota variation, whereas environmental conditions and host genotype explain maximally 11% of variation. When grown in the same soil, the root microbiota composition of perennial A. alpina is largely similar to those of its annual relatives A. thaliana and Cardamine hirsuta. Non-flowering wild-type A. alpina and flowering pep1 mutant plants assemble an essentially indistinguishable root microbiota, thereby uncoupling flowering time from plant residence time-dependent microbiota changes. This reveals the robustness of the root microbiota against the onset and perpetual flowering of A. alpina. Together with previous studies, this implies a model in which parts of the root microbiota modulate flowering time, whereas, after microbiota acquisition during vegetative growth, the established root-associated bacterial assemblage is structurally robust to perturbations caused by flowering and drastic changes in plant stature.

Stable engraftment of human microbiota into mice with a single oral gavage following antibiotic conditioning.

PubMed

Staley, Christopher; Kaiser, Thomas; Beura, Lalit K; Hamilton, Matthew J; Weingarden, Alexa R; Bobr, Aleh; Kang, Johnthomas; Masopust, David; Sadowsky, Michael J; Khoruts, Alexander

2017-08-01

Human microbiota-associated (HMA) animal models relying on germ-free recipient mice are being used to study the relationship between intestinal microbiota and human disease. However, transfer of microbiota into germ-free animals also triggers global developmental changes in the recipient intestine, which can mask disease-specific attributes of the donor material. Therefore, a simple model of replacing microbiota into a developmentally mature intestinal environment remains highly desirable. Here we report on the development of a sequential, three-course antibiotic conditioning regimen that allows sustained engraftment of intestinal microorganisms following a single oral gavage with human donor microbiota. SourceTracker, a Bayesian, OTU-based algorithm, indicated that 59.3 ± 3.0% of the fecal bacterial communities in treated mice were attributable to the donor source. This overall degree of microbiota engraftment was similar in mice conditioned with antibiotics and germ-free mice. Limited surveys of systemic and mucosal immune sites did not show evidence of immune activation following introduction of human microbiota. The antibiotic treatment protocol described here followed by a single gavage of human microbiota may provide a useful, complimentary HMA model to that established in germ-free facilities. The model has the potential for further in-depth translational investigations of microbiota in a variety of human disease states.

Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

PubMed

Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

2017-07-20

Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

Diet, gut microbiota and cognition.

PubMed

Proctor, Cicely; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-02-01

The consumption of a diet high in fat and sugar can lead to the development of obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease and cognitive decline. In the human gut, the trillions of harmless microorganisms harboured in the host's gastrointestinal tract are called the 'gut microbiota'. Consumption of a diet high in fat and sugar changes the healthy microbiota composition which leads to an imbalanced microbial population in the gut, a phenomenon known as "gut dysbiosis". It has been shown that certain types of gut microbiota are linked to the pathogenesis of obesity. In addition, long-term consumption of a high fat diet is associated with cognitive decline. It has recently been proposed that the gut microbiota is part of a mechanistic link between the consumption of a high fat diet and the impaired cognition of an individual, termed "microbiota-gut-brain axis". In this complex relationship between the gut, the brain and the gut microbiota, there are several types of gut microbiota and host mechanisms involved. Most of these mechanisms are still poorly understood. Therefore, this review comprehensively summarizes the current evidence from mainly in vivo (rodent and human) studies of the relationship between diet, gut microbiota and cognition. The possible mechanisms that the diet and the gut microbiota have on cognition are also presented and discussed.

Microbiota-induced obesity requires farnesoid X receptor

PubMed Central

Parséus, Ava; Sommer, Nina; Sommer, Felix; Caesar, Robert; Molinaro, Antonio; Ståhlman, Marcus; Greiner, Thomas U; Perkins, Rosie; Bäckhed, Fredrik

2017-01-01

Objective The gut microbiota has been implicated as an environmental factor that modulates obesity, and recent evidence suggests that microbiota-mediated changes in bile acid profiles and signalling through the bile acid nuclear receptor farnesoid X receptor (FXR) contribute to impaired host metabolism. Here we investigated if the gut microbiota modulates obesity and associated phenotypes through FXR. Design We fed germ-free (GF) and conventionally raised (CONV-R) wild-type and Fxr−/− mice a high-fat diet (HFD) for 10 weeks. We monitored weight gain and glucose metabolism and analysed the gut microbiota and bile acid composition, beta-cell mass, accumulation of macrophages in adipose tissue, liver steatosis, and expression of target genes in adipose tissue and liver. We also transferred the microbiota of wild-type and Fxr-deficient mice to GF wild-type mice. Results The gut microbiota promoted weight gain and hepatic steatosis in an FXR-dependent manner, and the bile acid profiles and composition of faecal microbiota differed between Fxr−/− and wild-type mice. The obese phenotype in colonised wild-type mice was associated with increased beta-cell mass, increased adipose inflammation, increased steatosis and expression of genes involved in lipid uptake. By transferring the caecal microbiota from HFD-fed Fxr−/− and wild-type mice into GF mice, we showed that the obesity phenotype was transferable. Conclusions Our results indicate that the gut microbiota promotes diet-induced obesity and associated phenotypes through FXR, and that FXR may contribute to increased adiposity by altering the microbiota composition. PMID:26740296

Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior.

PubMed

Lyte, Mark

2014-01-01

The ability of microorganisms, whether present as commensals within the microbiota or introduced as part of a therapeutic regimen, to influence behavior has been demonstrated by numerous laboratories over the last few years. Our understanding of the mechanisms that are responsible for microbiota-gut-brain interactions is, however, lacking. The complexity of the microbiota is, of course, a contributing factor. Nonetheless, while microbiologists approaching the issue of microbiota-gut-brain interactions in the behavior well recognize such complexity, what is often overlooked is the equal complexity of the host neurophysiological system, especially within the gut which is differentially innervated by the enteric nervous system. As such, in the search for common mechanisms by which the microbiota may influence behavior one may look for mechanisms which are shared by both host and microbiota. Such interkingdom signaling can be found in the shared production of neurochemical mediators that are found in both eukaryotes and prokaryotes. The study of the production and recognition of neurochemicals that are exactly the same in structure to those produced in the vertebrate organisms is known as microbial endocrinology. The examination of the microbiota from the vantage point of host-microbiota neuroendocrine interactions cannot only identify new microbial endocrinology-based mechanisms by which the microbiota can influence host behavior, but also lead to the design of interventions in which the composition of the microbiota may be modulated in order to achieve a specific microbial endocrinology-based profile beneficial to overall host behavior.

Linking microbiota and respiratory disease.

PubMed

Hauptmann, Matthias; Schaible, Ulrich E

2016-11-01

An increasing body of evidence indicates the relevance of microbiota for pulmonary health and disease. Independent investigations recently demonstrated that the lung harbors a resident microbiota. Therefore, it is intriguing that a lung microbiota can shape pulmonary immunity and epithelial barrier functions. Here, we discuss the ways how the composition of the microbial community in the lung may influence pulmonary health and vice versa, factors that determine community composition. Prominent microbiota at other body sites such as the intestinal one may also contribute to pulmonary health and disease. However, it is difficult to discriminate between influences of lung vs. gut microbiota due to systemic mutuality between both communities. With focuses on asthma and respiratory infections, we discuss how microbiota of lung and gut can determine pulmonary immunity and barrier functions. © 2016 Federation of European Biochemical Societies.

Molecular Insight into Gut Microbiota and Rheumatoid Arthritis.

PubMed

Wu, Xiaohao; He, Bing; Liu, Jin; Feng, Hui; Ma, Yinghui; Li, Defang; Guo, Baosheng; Liang, Chao; Dang, Lei; Wang, Luyao; Tian, Jing; Zhu, Hailong; Xiao, Lianbo; Lu, Cheng; Lu, Aiping; Zhang, Ge

2016-03-22

Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gut microbiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gut microbiota difference between RA patients and healthy individuals provides an updated overview of the association between gut microbiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gut microbiota, the immune system, and RA. It has become known that gut microbiota contribute to the pathogenesis of RA via multiple molecular mechanisms. The progressive understanding of the dynamic interaction between gut microbiota and their host will help in establishing a highly individualized management for each RA patient, and achieve a better efficacy in clinical practice, or even discovering new drugs for RA.

Understanding biological mechanisms underlying adverse birth outcomes in developing countries: protocol for a prospective cohort (AMANHI bio-banking) study.

PubMed

Baqui, Abdullah H; Khanam, Rasheda; Rahman, Mohammad Sayedur; Ahmed, Aziz; Rahman, Hasna Hena; Moin, Mamun Ibne; Ahmed, Salahuddin; Jehan, Fyezah; Nisar, Imran; Hussain, Atiya; Ilyas, Muhammad; Hotwani, Aneeta; Sajid, Muhammad; Qureshi, Shahida; Zaidi, Anita; Sazawal, Sunil; Ali, Said M; Deb, Saikat; Juma, Mohammed Hamad; Dhingra, Usha; Dutta, Arup; Ame, Shaali Makame; Hayward, Caroline; Rudan, Igor; Zangenberg, Mike; Russell, Donna; Yoshida, Sachiyo; Polašek, Ozren; Manu, Alexander; Bahl, Rajiv

2017-12-01

The AMANHI study aims to seek for biomarkers as predictors of important pregnancy-related outcomes, and establish a biobank in developing countries for future research as new methods and technologies become available. AMANHI is using harmonised protocols to enrol 3000 women in early pregnancies (8-19 weeks of gestation) for population-based follow-up in pregnancy up to 42 days postpartum in Bangladesh, Pakistan and Tanzania, with collection taking place between August 2014 and June 2016. Urine pregnancy tests will be used to confirm reported or suspected pregnancies for screening ultrasound by trained sonographers to accurately date the pregnancy. Trained study field workers will collect very detailed phenotypic and epidemiological data from the pregnant woman and her family at scheduled home visits during pregnancy (enrolment, 24-28 weeks, 32-36 weeks & 38+ weeks) and postpartum (days 0-6 or 42-60). Trained phlebotomists will collect maternal and umbilical blood samples, centrifuge and obtain aliquots of serum, plasma and the buffy coat for storage. They will also measure HbA1C and collect a dried spot sample of whole blood. Maternal urine samples will also be collected and stored, alongside placenta, umbilical cord tissue and membrane samples, which will both be frozen and prepared for histology examination. Maternal and newborn stool (for microbiota) as well as paternal and newborn saliva samples (for DNA extraction) will also be collected. All samples will be stored at -80°C in the biobank in each of the three sites. These samples will be linked to numerous epidemiological and phenotypic data with unique study identification numbers. AMANHI biobank proves that biobanking is feasible to implement in LMICs, but recognises that biobank creation is only the first step in addressing current global challenges.

OVERVIEW OF THE 1999 ATLANTA SUPERSITE PROJECT

EPA Science Inventory

This paper presents an overview of the 1999 Atlanta Supersite Project coordinated through the Southern Oxidants Study and the Georgia Institute of Technology (GIT) and funded by the US EPA along with other sponsors who provided in-kind support primarily through existing studies. ...

Salmonella Typhimurium and Multidirectional Communication in the Gut

PubMed Central

Gart, Elena V.; Suchodolski, Jan S.; Welsh, Thomas H.; Alaniz, Robert C.; Randel, Ronald D.; Lawhon, Sara D.

2016-01-01

The mammalian digestive tract is home to trillions of microbes, including bacteria, archaea, protozoa, fungi, and viruses. In monogastric mammals the stomach and small intestine harbor diverse bacterial populations but are typically less populated than the colon. The gut bacterial community (microbiota hereafter) varies widely among different host species and individuals within a species. It is influenced by season of the year, age of the host, stress and disease. Ideally, the host and microbiota benefit each other. The host provides nutrients to the microbiota and the microbiota assists the host with digestion and nutrient metabolism. The resident microbiota competes with pathogens for space and nutrients and, through this competition, protects the host in a phenomenon called colonization resistance. The microbiota participates in development of the host immune system, particularly regulation of autoimmunity and mucosal immune response. The microbiota also shapes gut–brain communication and host responses to stress; and, indeed, the microbiota is a newly recognized endocrine organ within mammalian hosts. Salmonella enterica serovar Typhimurium (S. Typhimurium hereafter) is a food-borne pathogen which adapts to and alters the gastrointestinal (GI) environment. In the GI tract, S. Typhimurium competes with the microbiota for nutrients and overcomes colonization resistance to establish infection. To do this, S. Typhimurium uses multiple defense mechanisms to resist environmental stressors, like the acidic pH of the stomach, and virulence mechanisms which allow it to invade the intestinal epithelium and disseminate throughout the host. To coordinate gene expression and disrupt signaling within the microbiota and between host and microbiota, S. Typhimurium employs its own chemical signaling and may regulate host hormone metabolism. This review will discuss the multidirectional interaction between S. Typhimurium, host and microbiota as well as mechanisms that allow S. Typhimurium to succeed in the gut. PMID:27920756

Short- and long-term effects of oral vancomycin on the human intestinal microbiota.

PubMed

Isaac, Sandrine; Scher, Jose U; Djukovic, Ana; Jiménez, Nuria; Littman, Dan R; Abramson, Steven B; Pamer, Eric G; Ubeda, Carles

2017-01-01

Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown. We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation. The clinical relevance of the observed microbiota perturbations was studied in mice. During vancomycin therapy, most intestinal microbiota genera and operational taxonomic units (OTUs) were depleted in all analysed subjects, including all baseline OTUs from the phylum Bacteroidetes. This was accompanied by a vast expansion of genera associated with infections, including Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked differences in microbiota resilience were observed among subjects. While some individuals recovered a microbiota close to baseline composition, in others, up to 89% of abundant OTUs could no longer be detected. The clinical relevance of the observed microbiota changes was further demonstrated in mice, which developed analogous microbiota alterations. During vancomycin treatment, mice were highly susceptible to intestinal colonization by an antibiotic-resistant pathogen and, upon antibiotic cessation, a less-resilient microbiota allowed higher levels of pathogen colonization. Oral vancomycin induces drastic and consistent changes in the human intestinal microbiota. Upon vancomycin cessation, the microbiota recovery rate varied considerably among subjects, which could influence, as validated in mice, the level of susceptibility to pathogen intestinal colonization. Our results demonstrate the negative long-term effects of vancomycin, which should be considered as a fundamental aspect of the cost-benefit equation for antibiotic prescription. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Short- and long-term effects of oral vancomycin on the human intestinal microbiota

PubMed Central

Isaac, Sandrine; Scher, Jose U.; Djukovic, Ana; Jiménez, Nuria; Littman, Dan R.; Abramson, Steven B.; Pamer, Eric G.; Ubeda, Carles

2017-01-01

Background Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown. Methods We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation. The clinical relevance of the observed microbiota perturbations was studied in mice. Results During vancomycin therapy, most intestinal microbiota genera and operational taxonomic units (OTUs) were depleted in all analysed subjects, including all baseline OTUs from the phylum Bacteroidetes. This was accompanied by a vast expansion of genera associated with infections, including Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked differences in microbiota resilience were observed among subjects. While some individuals recovered a microbiota close to baseline composition, in others, up to 89% of abundant OTUs could no longer be detected. The clinical relevance of the observed microbiota changes was further demonstrated in mice, which developed analogous microbiota alterations. During vancomycin treatment, mice were highly susceptible to intestinal colonization by an antibiotic-resistant pathogen and, upon antibiotic cessation, a less-resilient microbiota allowed higher levels of pathogen colonization. Conclusions Oral vancomycin induces drastic and consistent changes in the human intestinal microbiota. Upon vancomycin cessation, the microbiota recovery rate varied considerably among subjects, which could influence, as validated in mice, the level of susceptibility to pathogen intestinal colonization. Our results demonstrate the negative long-term effects of vancomycin, which should be considered as a fundamental aspect of the cost–benefit equation for antibiotic prescription. PMID:27707993

Seasonal and algal diet-driven patterns of the digestive microbiota of the European abalone Haliotis tuberculata, a generalist marine herbivore.

PubMed

Gobet, Angélique; Mest, Laëtitia; Perennou, Morgan; Dittami, Simon M; Caralp, Claire; Coulombet, Céline; Huchette, Sylvain; Roussel, Sabine; Michel, Gurvan; Leblanc, Catherine

2018-03-27

Holobionts have a digestive microbiota with catabolic abilities allowing the degradation of complex dietary compounds for the host. In terrestrial herbivores, the digestive microbiota is known to degrade complex polysaccharides from land plants while in marine herbivores, the digestive microbiota is poorly characterized. Most of the latter are generalists and consume red, green, and brown macroalgae, three distinct lineages characterized by a specific composition in complex polysaccharides, which represent half of their biomass. Subsequently, each macroalga features a specific epiphytic microbiota, and the digestive microbiota of marine herbivores is expected to vary with a monospecific algal diet. We investigated the effect of four monospecific diets (Palmaria palmata, Ulva lactuca, Saccharina latissima, Laminaria digitata) on the composition and specificity of the digestive microbiota of a generalist marine herbivore, the abalone, farmed in a temperate coastal area over a year. The microbiota from the abalone digestive gland was sampled every 2 months and explored using metabarcoding. Diversity and multivariate analyses showed that patterns of the microbiota were significantly linked to seasonal variations of contextual parameters but not directly to a specific algal diet. Three core genera: Psychrilyobacter, Mycoplasma, and Vibrio constantly dominated the microbiota in the abalone digestive gland. Additionally, a less abundant and diet-specific core microbiota featured genera representing aerobic primary degraders of algal polysaccharides. This study highlights the establishment of a persistent core microbiota in the digestive gland of the abalone since its juvenile state and the presence of a less abundant and diet-specific core community. While composed of different microbial taxa compared to terrestrial herbivores, the digestive gland constitutes a particular niche in the abalone holobiont, where bacteria (i) may cooperate to degrade algal polysaccharides to products assimilable by the host or (ii) may have acquired these functions through gene transfer from the aerobic algal microbiota.

Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

PubMed

Quigley, Eamonn M M

2017-10-17

The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

Oral Microbiota Distinguishes Acute Lymphoblastic Leukemia Pediatric Hosts from Healthy Populations

PubMed Central

Zhou, Xuedong; You, Meng; Du, Qin; Yang, Xue; He, Jingzhi; Zou, Jing; Cheng, Lei; Li, Mingyun; Li, Yuqing; Zhu, Yiping; Li, Jiyao; Shi, Wenyuan; Xu, Xin

2014-01-01

In leukemia, oral manifestations indicate aberrations in oral microbiota. Microbiota structure is determined by both host and environmental factors. In human hosts, how health status shapes the composition of oral microbiota is largely unknown. Taking advantage of advances in high-throughput sequencing, we compared the composition of supragingival plaque microbiota of acute lymphoblastic leukemia (ALL) pediatric patients with healthy controls. The oral microbiota of leukemia patients had lower richness and less diversity compared to healthy controls. Microbial samples clustered into two major groups, one of ALL patients and another of healthy children, with different structure and composition. Abundance changes of certain taxa including the Phylum Firmicutes, the Class Bacilli, the Order Lactobacillales, the Family Aerococcaceae and Carnobacteriaceae, as well as the Genus Abiotrophia and Granulicatella were associated with leukemia status. ALL patients demonstrated a structural imbalance of the oral microbiota, characterized by reduced diversity and abundance alterations, possibly involved in systemic infections, indicating the importance of immune status in shaping the structure of oral microbiota. PMID:25025462

Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress.

PubMed

Karl, J Philip; Margolis, Lee M; Madslien, Elisabeth H; Murphy, Nancy E; Castellani, John W; Gundersen, Yngvar; Hoke, Allison V; Levangie, Michael W; Kumar, Raina; Chakraborty, Nabarun; Gautam, Aarti; Hammamieh, Rasha; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

2017-06-01

The magnitude, temporal dynamics, and physiological effects of intestinal microbiome responses to physiological stress are poorly characterized. This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers ( n = 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ± 57% (mean ± SD, P < 0.001) during STRESS independent of diet group and was associated with increased inflammation. Intestinal microbiota responses were characterized by increased α-diversity and changes in the relative abundance of >50% of identified genera, including increased abundance of less dominant taxa at the expense of more dominant taxa such as Bacteroides Changes in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Together, pre-STRESS Actinobacteria relative abundance and changes in serum IL-6 and stool cysteine concentrations accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation and with intestinal microbiota composition and metabolism. Associations between IP, the pre-STRESS microbiota, and microbiota metabolites suggest that targeting the intestinal microbiota could provide novel strategies for preserving IP during physiological stress. NEW & NOTEWORTHY Military training, a unique model for studying temporal dynamics of intestinal barrier and intestinal microbiota responses to stress, resulted in increased intestinal permeability concomitant with changes in intestinal microbiota composition and metabolism. Prestress intestinal microbiota composition and changes in fecal concentrations of metabolites linked to the microbiota were associated with increased intestinal permeability. Findings suggest that targeting the intestinal microbiota could provide novel strategies for mitigating increases in intestinal permeability during stress.

Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke.

PubMed

Singh, Vikramjeet; Roth, Stefan; Llovera, Gemma; Sadler, Rebecca; Garzetti, Debora; Stecher, Bärbel; Dichgans, Martin; Liesz, Arthur

2016-07-13

Acute brain ischemia induces a local neuroinflammatory reaction and alters peripheral immune homeostasis at the same time. Recent evidence has suggested a key role of the gut microbiota in autoimmune diseases by modulating immune homeostasis. Therefore, we investigated the mechanistic link among acute brain ischemia, microbiota alterations, and the immune response after brain injury. Using two distinct models of acute middle cerebral artery occlusion, we show by next-generation sequencing that large stroke lesions cause gut microbiota dysbiosis, which in turn affects stroke outcome via immune-mediated mechanisms. Reduced species diversity and bacterial overgrowth of bacteroidetes were identified as hallmarks of poststroke dysbiosis, which was associated with intestinal barrier dysfunction and reduced intestinal motility as determined by in vivo intestinal bolus tracking. Recolonizing germ-free mice with dysbiotic poststroke microbiota exacerbates lesion volume and functional deficits after experimental stroke compared with the recolonization with a normal control microbiota. In addition, recolonization of mice with a dysbiotic microbiome induces a proinflammatory T-cell polarization in the intestinal immune compartment and in the ischemic brain. Using in vivo cell-tracking studies, we demonstrate the migration of intestinal lymphocytes to the ischemic brain. Therapeutic transplantation of fecal microbiota normalizes brain lesion-induced dysbiosis and improves stroke outcome. These results support a novel mechanism in which the gut microbiome is a target of stroke-induced systemic alterations and an effector with substantial impact on stroke outcome. We have identified a bidirectional communication along the brain-gut microbiota-immune axis and show that the gut microbiota is a central regulator of immune homeostasis. Acute brain lesions induced dysbiosis of the microbiome and, in turn, changes in the gut microbiota affected neuroinflammatory and functional outcome after brain injury. The microbiota impact on immunity and stroke outcome was transmissible by microbiota transplantation. Our findings support an emerging concept in which the gut microbiota is a key regulator in priming the neuroinflammatory response to brain injury. These findings highlight the key role of microbiota as a potential therapeutic target to protect brain function after injury. Copyright © 2016 the authors 0270-6474/16/367428-13$15.00/0.

The Open Spectral Database: an open platform for sharing and searching spectral data.

PubMed

Chalk, Stuart J

2016-01-01

A number of websites make available spectral data for download (typically as JCAMP-DX text files) and one (ChemSpider) that also allows users to contribute spectral files. As a result, searching and retrieving such spectral data can be time consuming, and difficult to reuse if the data is compressed in the JCAMP-DX file. What is needed is a single resource that allows submission of JCAMP-DX files, export of the raw data in multiple formats, searching based on multiple chemical identifiers, and is open in terms of license and access. To address these issues a new online resource called the Open Spectral Database (OSDB) http://osdb.info/ has been developed and is now available. Built using open source tools, using open code (hosted on GitHub), providing open data, and open to community input about design and functionality, the OSDB is available for anyone to submit spectral data, making it searchable and available to the scientific community. This paper details the concept and coding, internal architecture, export formats, Representational State Transfer (REST) Application Programming Interface and options for submission of data. The OSDB website went live in November 2015. Concurrently, the GitHub repository was made available at https://github.com/stuchalk/OSDB/, and is open for collaborators to join the project, submit issues, and contribute code. The combination of a scripting environment (PHPStorm), a PHP Framework (CakePHP), a relational database (MySQL) and a code repository (GitHub) provides all the capabilities to easily develop REST based websites for ingestion, curation and exposure of open chemical data to the community at all levels. It is hoped this software stack (or equivalent ones in other scripting languages) will be leveraged to make more chemical data available for both humans and computers.

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

PubMed

Mancia, G; Cha, G; Gil-Extremera, B; Harvey, P; Lewin, A J; Villa, G; Kjeldsen, S E

2017-03-01

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min -1 , n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.

Food and symptom generation in functional gastrointestinal disorders: physiological aspects.

PubMed

Farré, Ricard; Tack, Jan

2013-05-01

The response of the gastrointestinal tract (GIT) to ingestion of food is a complex and closely controlled process, which allows optimization of propulsion, digestion, absorption of nutrients, and removal of indigestible remnants. This review summarizes current knowledge on the mechanisms that control the response of the GIT to food intake. During the cephalic phase, triggered by cortical food-related influences, the GIT prepares for receiving nutrients. The gastric phase is dominated by the mechanical effect of the meal volume. Accumulation of food in the stomach activates tension-sensitive mechanoreceptors, which in turn stimulate gastric accommodation and gastric acid secretion through the intrinsic and vago-vagal reflex pathways. After meal ingestion, the tightly controlled process of gastric emptying starts, with arrival of nutrients in the duodenum triggering negative feedback on emptying and stimulating secretion of digestive enzymes through the neural (mainly vago-vagal reflex, but also intrinsic) and endocrine (release of peptides from entero-endocrine cells) pathways. Several types of specialized receptors detect the presence of all main categories of nutrients. In addition, the gastrointestinal mucosa expresses receptors of the T1R and T2R families (taste receptors) and several members of the transient receptor potential channel family, all of which are putatively involved in the detection of specific tastants in the lumen. Activation of nutrient and taste sensors also activates the extrinsic and intrinsic neural, as well as entero-endocrine, pathways. During passage through the small bowel, nutrients are progressively extracted, and electrolyte-rich liquid intestinal content with non-digestible residue is delivered to the colon. The colon provides absorption of the water and electrolytes, storage of non-digestible remnants of food, aboral propulsion of contents, and finally evacuation through defecation.

Integration of lncRNA and mRNA Transcriptome Analyses Reveals Genes and Pathways Potentially Involved in Calf Intestinal Growth and Development during the Early Weeks of Life

PubMed Central

Do, Duy N.; Dudemaine, Pier-Luc; Fomenky, Bridget E.

2018-01-01

A better understanding of the factors that regulate growth and immune response of the gastrointestinal tract (GIT) of calves will promote informed management practices in calf rearing. This study aimed to explore genomics (messenger RNA (mRNA)) and epigenomics (long non-coding RNA (lncRNA)) mechanisms regulating the development of the rumen and ileum in calves. Thirty-two calves (≈5-days-old) were reared for 96 days following standard procedures. Sixteen calves were humanely euthanized on experiment day 33 (D33) (pre-weaning) and another 16 on D96 (post-weaning) for collection of ileum and rumen tissues. RNA from tissues was subjected to next generation sequencing and 3310 and 4217 mRNAs were differentially expressed (DE) between D33 and D96 in ileum and rumen tissues, respectively. Gene ontology and pathways enrichment of DE genes confirmed their roles in developmental processes, immunity and lipid metabolism. A total of 1568 (63 known and 1505 novel) and 4243 (88 known and 4155 novel) lncRNAs were detected in ileum and rumen tissues, respectively. Cis target gene analysis identified BMPR1A, an important gene for a GIT disease (juvenile polyposis syndrome) in humans, as a candidate cis target gene for lncRNAs in both tissues. LncRNA cis target gene enrichment suggested that lncRNAs might regulate growth and development in both tissues as well as posttranscriptional gene silencing by RNA or microRNA processing in rumen, or disease resistance mechanisms in ileum. This study provides a catalog of bovine lncRNAs and set a baseline for exploring their functions in calf GIT development. PMID:29510583

Integration of lncRNA and mRNA Transcriptome Analyses Reveals Genes and Pathways Potentially Involved in Calf Intestinal Growth and Development during the Early Weeks of Life.

PubMed

Ibeagha-Awemu, Eveline M; Do, Duy N; Dudemaine, Pier-Luc; Fomenky, Bridget E; Bissonnette, Nathalie

2018-03-05

A better understanding of the factors that regulate growth and immune response of the gastrointestinal tract (GIT) of calves will promote informed management practices in calf rearing. This study aimed to explore genomics (messenger RNA (mRNA)) and epigenomics (long non-coding RNA (lncRNA)) mechanisms regulating the development of the rumen and ileum in calves. Thirty-two calves (≈5-days-old) were reared for 96 days following standard procedures. Sixteen calves were humanely euthanized on experiment day 33 (D33) (pre-weaning) and another 16 on D96 (post-weaning) for collection of ileum and rumen tissues. RNA from tissues was subjected to next generation sequencing and 3310 and 4217 mRNAs were differentially expressed (DE) between D33 and D96 in ileum and rumen tissues, respectively. Gene ontology and pathways enrichment of DE genes confirmed their roles in developmental processes, immunity and lipid metabolism. A total of 1568 (63 known and 1505 novel) and 4243 (88 known and 4155 novel) lncRNAs were detected in ileum and rumen tissues, respectively. Cis target gene analysis identified BMPR1A , an important gene for a GIT disease (juvenile polyposis syndrome) in humans, as a candidate cis target gene for lncRNAs in both tissues. LncRNA cis target gene enrichment suggested that lncRNAs might regulate growth and development in both tissues as well as posttranscriptional gene silencing by RNA or microRNA processing in rumen, or disease resistance mechanisms in ileum. This study provides a catalog of bovine lncRNAs and set a baseline for exploring their functions in calf GIT development.

Comparison of QuantiFERON-TB gold in-tube test with tuberculin skin test in children who had no contact with active tuberculosis case.

PubMed

Metin Timur, Özge; Tanir, Gönül; Öz, Fatma Nur; Bayhan, Gülsüm İclal; Aydin Teke, Türkan; Tuygun, Nilden

2014-01-01

In this study, we aimed to compare QuantiFERON-TB gold in-tube test (QFT-GIT) and tuberculin skin test (TST) as a diagnosis of latent tuberculosis infection in the children with Bacille Calmette-Guerin (BCG) vaccine. We evaluated 81 children in the study who have positive TST result without a known history of tuberculosis contact from 2008 to 2011 prospectively. Patients were separated into groups according to their ages, the reason of TST application, number of BCG vaccination scars and diameter of TST induration. Posteroanterior, lateral chest radiographies and computerized tomography, if necessary, were performed. The study consists of 48 (59.3%) boys and 33 (40.7%) girls with a mean age of 94.8 ± 51.9 months (ranged from 6 to 193 months). Sixty nine (85.2%) children had one and 12 (14.8%) had two BCG vaccination scars. The TST induration diameters were 15-19 mm in 65 (80.2%) children and ≥ 20 mm in 16 (19.8%) children. QFT-GIT positivity was found in 12 (14.8%) of the evaluated patients. QFT-GIT positive patients were treated with triple anti-tuberculosis regime or isoniazid (INH). In three years period of study, there were no tuberculosis disease observed among the children who had not been treated with anti-tuberculosis drugs. As a result of the study it is suggested to confirm positive TST results with tests based on interferon-gamma (IFN-γ) because it can reduce false positive diagnosis and treatment of latent tuberculosis infection, thus adverse reactions of drugs, in countries where BCG vaccination is routinely recommended especially for low risk children.

Gastro-intestinal tract perforation in neonates.

PubMed

Kuremu, R T; Hadley, G P; Wiersma, R

2003-09-01

Gastro-intestinal tract (GIT) perforation in neonates is a serious problem associated with high mortality due to resulting sepsis. Co-morbid factors, eg. prematurity, respiratory problems, low birth weight, and nutritional factors, negatively affect the outcome. To review the management outcome of gastro-intestinal tract perforation in neonates in KwaZulu-Natal and identify factors that require attention for better survival of neonates with GIT perforation. Retrospective study of consecutive complete data sets of patients presenting with a diagnosis of GIT perforation. Department of Paediatric Surgery, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa. Fifty four neonates treated for gastro-intestinal tract perforation between January 1998 and January 2003. Morbidity as determined by complications and mortality. More males (69%) were affected than females (31%). The median birth weight was 2.3 kg and median age at presentation was four days. Eighty nine percent were referred from peripheral hospitals. Abdominal distension was the leading symptom and sign (74%). Co-morbid factors were present in 89%, with prematurity as the leading factor (52%). Necrotising enterocolitis (NEC) was the main cause of perforation (33%) and the terminal ileum was the most common site. Most (56%) were treated by excision and primary repair of perforations. Sepsis was the leading complication (44%) and major cause of death (72%). Mortality was highest (56%) in perforations due to other primary pathology followed by NEC (53%). Overall mortality was 46%. It is essential to prevent secondary perforations by early recognition and management of primary pathology. Management of pneumoperitoneum in neonates with respiratory difficulties should be included in resuscitation before transfer. Rectal temperature monitoring and herbal enemas should be strongly discouraged.

Effects of forage provision to young calves on rumen fermentation and development of the gastrointestinal tract.

PubMed

Castells, L; Bach, A; Aris, A; Terré, M

2013-08-01

Fifteen Holstein male calves were randomly assigned to 1 of 3 dietary treatments according to age and body weight (BW) to determine the effects of feeding different forages sources on rumen fermentation and gastrointestinal tract (GIT) development. Treatments consisted of a starter (20% crude protein, 21% neutral detergent fiber) fed alone (CON) or supplemented with alfalfa (AH) or with oat hay (OH). All calves received 2L of milk replacer (MR) at 12.5% dry matter twice daily until 49 d of age. Calves received 2L of the same MR from 50 to 56 d of age and were weaned at 57 d of age. Individual starter, forage, and MR intakes were recorded daily and BW was recorded weekly. A rumen sample was taken weekly to determine rumen pH and volatile fatty acid concentrations. Three weeks after weaning, animals were harvested and each anatomical part of the GIT was separated and weighed with and without contents. Rumen pH was lower in CON than in OH and AH calves. Furthermore, acetate proportion in the rumen liquid tended to be greater in AH than in CON and OH treatments. Total GIT weight, expressed as a percentage of BW, tended to be greater in AH compared with the other 2 treatments. Rumen tissue tended to weigh more in CON than in OH animals. Animals with access to forage tended to have a greater expression of monocarboxylate transporter 1 than CON calves. In conclusion, calves supplemented with oat hay have a better rumen environment than calves offered no forage and do not have an increased gut fill. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Dose-dependent effects on sphingoid bases and cytokines in chickens fed diets prepared with fusarium verticillioides culture material containing fumonisins.

PubMed

Grenier, Bertrand; Schwartz-Zimmermann, Heidi E; Caha, Sylvia; Moll, Wulf Dieter; Schatzmayr, Gerd; Applegate, Todd J

2015-04-13

In chickens, the effect of mycotoxins, especially fumonisins (FB), in the gastrointestinal tract (GIT) is not well documented. Thus, this study in broiler chicks determined the effects of consuming diets prepared with Fusarium verticillioides culture material containing FB on intestinal gene expression and on the sphinganine (Sa)/sphingosine (So) ratio (Sa/So; a biomarker of FB effect due to disruption of sphingolipid metabolism). Male broilers were assigned to 6 diets (6 cages/diet; 6 birds/cage) from hatch to 20 days containing 0.4, 5.6, 11.3, 17.5, 47.8, or 104.8 mg FB/kg diet. Exposure to FB altered the Sa/So ratio in all tissues analyzed, albeit to varying extents. Linear dose-responses were observed in the kidney, jejunum and cecum. The liver and the ileum were very sensitive and data fit a cubic and quadratic polynomial model, respectively. Gene expression in the small intestine revealed low but significant upregulations of cytokines involved in the pro-inflammatory, Th1/Th17 and Treg responses, especially at 10 days of age. Interestingly, the cecal tonsils exhibited a biphasic response. Unlike the sphingolipid analysis, the effects seen on gene expression were not dose dependent, even showing more effects when birds were exposed to 11.3 mg FB/kg. In conclusion, this is the first report on the disruption of the sphingolipid metabolism by FB in the GIT of poultry. Further studies are needed to reach conclusions on the biological meaning of the immunomodulation observed in the GIT, but the susceptibility of chickens to intestinal pathogens when exposed to FB, at doses lower than those that would cause overt clinical symptoms, should be addressed.

Psoriasis and Microbiota: A Systematic Review.

PubMed

Benhadou, Farida; Mintoff, Dillon; Schnebert, Benjamin; Thio, Hok Bing

2018-06-02

Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy, unaffected skin. Through an extensive review of the literature, we aim to discuss the skin and gut microbiota and redefine their role in the pathogenesis of psoriasis. Unfortunately, the direct link between the skin microbiota and the pathogenesis of psoriasis remains to be clearly established. Apart from improving the course of psoriasis, selective modulation of the microbiota may increase the efficacy of medical treatments as well as attenuate their side effects.

Gut Microbiota and Metabolic Disorders

PubMed Central

Hur, Kyu Yeon

2015-01-01

Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders. PMID:26124989

Gut Microbiota as a Therapeutic Target for Metabolic Disorders.

PubMed

Okubo, Hirofumi; Nakatsu, Yusuke; Kushiyama, Akifumi; Yamamotoya, Takeshi; Matsunaga, Yasuka; Inoue, Masa-Ki; Fujishiro, Midori; Sakoda, Hideaki; Ohno, Haruya; Yoneda, Masayasu; Ono, Hiraku; Asano, Tomoichiro

2018-01-01

Gut microbiota play a vital role not only in the digestion and absorption of nutrients, but also in homeostatic maintenance of host immunity, metabolism and the gut barrier. Recent evidence suggests that gut microbiota alterations contribute to the pathogenesis of metabolic disorders. In this review, we discuss the association between the gut microbiota and metabolic disorders, such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease, and the contribution of relevant modulating interventions, focusing on recent human studies. Several studies have identified potential causal associations between gut microbiota and metabolic disorders, as well as the underlying mechanisms. The effects of modulating interventions, such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities on these metabolic disorders have also been reported. A growing body of evidence highlights the role of gut microbiota in the development of dysbiosis, which in turn influences host metabolism and disease phenotypes. Further studies are required to elucidate the precise mechanisms by which gut microbiota-derived mediators induce metabolic disorders and modulating interventions exert their beneficial effects in humans. The gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Structural modulation of gut microbiota by chondroitin sulfate and its oligosaccharide.

PubMed

Shang, Qingsen; Shi, Jingjing; Song, Guanrui; Zhang, Meifang; Cai, Chao; Hao, Jiejie; Li, Guoyun; Yu, Guangli

2016-08-01

Chondroitin sulfate (CS) as a dietary supplement and a symptomatic slow acting (SYSA) drug has been used for years. Recently, CS has been demonstrated to be readily degraded and fermented in vitro by specific human gut microbes, hinting that dietary CS may pose a potential effect on gut microbiota composition in vivo. However, until now, little information is available on modulations of gut microbiota by CS. In the present study, modulations of gut microbiota in Kunming mice by CS and its oligosaccharide (CSO) were investigated by high-throughput sequencing. As evidenced by Heatmap and principal component analysis (PCA), the female microbiota were more vulnerable than the male microbiota to CS and CSO treatment. Besides, it is of interest to found that CS and CSO had differing effects on the abundance of Bacteroidales S24-7, Bacteroides, Helicobacter, Odoribacter, Prevotellaceae and Lactobacillus in male mice versus female mice. Collectively, we demonstrated a sex-dependent effect on gut microbiota of CS and CSO. In addition, since gut microbiota exerts a major effect on host physiology, our study highlighted that certain beneficial effects of CS may be associated with modulations of gut microbiota, which merits further investigation. Copyright © 2016 Elsevier B.V. All rights reserved.

Intestinal microbiota in pathophysiology and management of irritable bowel syndrome

PubMed Central

Lee, Kang Nyeong; Lee, Oh Young

2014-01-01

Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 1014 cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS. PMID:25083061

The developing hypopharyngeal microbiota in early life.

PubMed

Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael; Abu Al-Soud, Waleed; Balle, Christina; Krogfelt, Karen Angeliki; Stokholm, Jakob; Thorsen, Jonathan; Waage, Johannes; Rasmussen, Morten Arendt; Bisgaard, Hans; Sørensen, Søren Johannes

2016-12-30

The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC 2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. Our analysis shows that majority of the hypopharyngeal microbiota of healthy infants belong to each individual's core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we show temporal pneumotype changes suggesting a rapid development towards maturation of the hypopharyngeal microbiota and a significant effect from older siblings. Despite an overall common trajectory towards maturation, individual infants' microbiota are more similar to their own, than to others, over time. Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota.

The microbiota revolution: Excitement and caution.

PubMed

Rescigno, Maria

2017-09-01

Scientific progress is characterized by important technological advances. Next-generation DNA sequencing has, in the past few years, led to a major scientific revolution: the microbiome revolution. It has become possible to generate a fingerprint of the whole microbiota of any given environment. As it becomes clear that the microbiota affects several aspects of our lives, each new scientific finding should ideally be analyzed in light of these communities. For instance, animal experimentation should consider animal sources and husbandry; human experimentation should include analysis of microenvironmental cues that might affect the microbiota, including diet, antibiotic, and drug use, genetics. When analyzing the activity of a drug, we should remember that, according to the microbiota of the host, different drug activities might be observed, either due to modification or degradation by the microbiota, or because the microbiota changes the immune system of the host in a way that makes that drug more or less effective. This minireview will not be a comprehensive review on the interaction between the host and microbiota, but it will aim at creating awareness on why we should not forget the contribution of the microbiota in any single aspect of biology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variation in faecal microbiota in a group of horses managed at pasture over a 12-month period.

PubMed

Salem, Shebl E; Maddox, Thomas W; Berg, Adam; Antczak, Philipp; Ketley, Julian M; Williams, Nicola J; Archer, Debra C

2018-05-31

Colic (abdominal pain) is a common cause of mortality in horses. Change in management of horses is associated with increased colic risk and seasonal patterns of increased risk have been identified. Shifts in gut microbiota composition in response to management change have been proposed as one potential underlying mechanism for colic. However, the intestinal microbiota in normal horses and how this varies over different seasons has not previously been investigated. In this study the faecal microbiota composition was studied over 12 months in a population of horses managed at pasture with minimal changes in management. We hypothesised that gut microbiota would be stable in this population over time. Faecal samples were collected every 14 days from 7 horses for 52 weeks and the faecal microbiota was characterised by next-generation sequencing of 16S rRNA genes. The faecal microbiota was dominated by members of the phylum Firmicutes and Bacteroidetes throughout. Season, supplementary forage and ambient weather conditions were significantly associated with change in the faecal microbiota composition. These results provide important baseline information demonstrating physiologic variation in the faecal microbiota of normal horses over a 12-month period without development of colic.

[Oral microbiota: a promising predictor of human oral and systemic diseases].

PubMed

Xin, Xu; Junzhi, He; Xuedong, Zhou

2015-12-01

A human oral microbiota is the ecological community of commensal, symbiotic, and pathogenic microorganisms found in human oral cavity. Oral microbiota exists mostly in the form of a biofilm and maintains a dynamic ecological equilibrium with the host body. However, the disturbance of this ecological balance inevitably causes oral infectious diseases, such as dental caries, apical periodontitis, periodontal diseases, pericoronitis, and craniofacial bone osteomyelitis. Oral microbiota is also correlated with many systemic diseases, including cancer, diabetes mellitus, rheumatoid arthritis, cardiovascular diseases, and preterm birth. Hence, oral microbiota has been considered as a potential biomarker of human diseases. The "Human Microbiome Project" and other metagenomic projects worldwide have advanced our knowledge of the human oral microbiota. The integration of these metadata has been the frontier of oral microbiology to improve clinical translation. By reviewing recent progress on studies involving oral microbiota-related oral and systemic diseases, we aimed to propose the essential role of oral microbiota in the prediction of the onset, progression, and prognosis of oral and systemic diseases. An oral microbiota-based prediction model helps develop a new paradigm of personalized medicine and benefits the human health in the post-metagenomics era.

Mice harboring pathobiont-free microbiota do not develop intestinal inflammation that normally results from an innate immune deficiency

PubMed Central

Gewirtz, Andrew T.

2018-01-01

Background Inability to maintain a stable and beneficial microbiota is associated with chronic gut inflammation, which classically manifests as colitis but may more commonly exist as low-grade inflammation that promotes metabolic syndrome. Alterations in microbiota, and associated inflammation, can originate from dysfunction in host proteins that manage the microbiota, such as the flagellin receptor TLR5. That the complete absence of a microbiota (i.e. germfree conditions) eliminates all evidence of inflammation in TLR5-deficient mice demonstrates that this model of gut inflammation is microbiota-dependent. We hypothesize that such microbiota dependency reflects an inability to manage pathobionts, such as Adherent-Invasive E. coli (AIEC). Herein, we examined the extent to which microbiota mismanagement and associated inflammation in TLR5-deficient mice would manifest in a limited and pathobiont-free microbiota. For this purpose, WT and TLR5-deficient mice were generated and maintained with the 8-member consortium of bacteria referred to as “Altered Schaedler Flora” (ASF). Such ASF animals were subsequently inoculated with AIEC reference strain LF82. Feces were assayed for bacterial loads, fecal lipopolysaccharide and flagellin loads, fecal inflammatory marker lipocalin-2 and microbiota composition. Results Relative to similarly maintained WT mice, mice lacking TLR5 (T5KO) did not display low-grade intestinal inflammation nor metabolic syndrome under ASF conditions. Concomitantly, the ASF microbial community was similar between WT and T5KO mice, while inoculation with AIEC strain LF82 resulted in alteration of the ASF community in T5KO mice compared to WT control animals. AIEC LF82 inoculation in ASF T5KO mice resulted in microbiota components having elevated levels of bioactive lipopolysaccharide and flagellin, a modest level of low-grade inflammation and increased adiposity. Conclusions In a limited-complexity pathobiont-free microbiota, loss of the flagellin receptor TLR5 does not impact microbiota composition nor its ability to promote inflammation. Addition of AIEC to this ecosystem perturbs microbiota composition, increases levels of lipopolysaccharide and flagellin, but only modestly promotes gut inflammation and adiposity, suggesting that the phenotypes previously associated with loss of this innate immune receptor require disruption of complex microbiota. PMID:29617463

Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children

USDA-ARS?s Scientific Manuscript database

Undernourished children exhibit impaired development of their gut microbiota. Transplanting microbiota from 6- and 18-month-old healthy or undernourished Malawian donors into young germ-free mice that were fed a Malawian diet revealed that immature microbiota from undernourished infants and children...

The Gut Microbiota from Lean and Obese Subjects Contribute Differently to the Fermentation of Arabinogalactan and Inulin

PubMed Central

Aguirre, Marisol; Bussolo de Souza, Carlota; Venema, Koen

2016-01-01

Background An aberrant metabolic activity or a compositional alteration of the gut microbiota has been proposed as a factor that makes us more prone to disease. Therefore, we explored the effect of two dietary fibers (arabinogalactan and inulin) on the microbiota from lean and obese subjects during 72 h in vitro fermentation experiments using the validated TNO dynamic in vitro model of the proximal colon: TIM-2. Metabolically, arabinogalactan fermentation showed a higher production of propionate when compared to n-butyrate in the obese microbiota fermentations. In general, lean microbiota produced more n-butyrate from the fermentation of both substrates when compared to the obese microbiota. Furthermore, the obese microbiota extracted more energy from the fermentation of both fibers. Results Compositionally, bacteria belonging to Gemmiger, Dorea, Roseburia, Alistipes, Lactobacillus and Bifidobacterium genera were found to be highly abundant or stimulated by the prebiotics in the lean microbiota suggesting a potential role in leanness. Furthermore, a significant correlation between known butyrogenic strains including B. adolescentis, an unclassified Bifidobacterium and F. prausnitzii with this metabolite in the fermentation of inulin in both microbiotas was found. Conclusions Although supplementary in vivo studies are needed, the current study provides more evidence for the consumption of specific ingredients with the aim of modulating the gut microbiota in the context of obesity. PMID:27410967

GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION

PubMed Central

Yang, Tao; Santisteban, Monica M.; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J.; Raizada, Mohan K.; Mohamadzadeh, Mansour

2015-01-01

Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. The present study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension since genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of two rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes to Bacteroidetes ratio. These changes were accompanied with decreases in acetate- and butyrate-producing bacteria. Additionally, the microbiota of a small cohort of human hypertension patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes to Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes to Bacteroidetes ratio. These observations demonstrate that high BP is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

Diet-induced extinction in the gut microbiota compounds over generations

PubMed Central

Sonnenburg, Erica D.; Smits, Samuel A.; Tikhonov, Mikhail; Higginbottom, Steven K.; Wingreen, Ned S.; Sonnenburg, Justin L.

2015-01-01

The gut is home to trillions of microbes that play a fundamental role in many aspects of human biology including immune function and metabolism 1,2. The reduced diversity of the Western microbiota compared to populations living traditional lifestyles presents the question of which factors have driven microbiota change during modernization. Microbiota accessible carbohydrates (MACs) found in dietary fiber, play a key role in shaping this microbial ecosystem, and are strikingly reduced in the Western diet relative to more traditional diets 3. Here we show that changes in the microbiota of mice consuming a low-MAC diet and harboring a human microbiota are largely reversible within a single generation, however over multiple generations a low-MAC diet results in a progressive loss of diversity, which is not recoverable upon the reintroduction of dietary MACs. To restore the microbiota to its original state requires the administration of missing taxa in combination with dietary MAC consumption. Our data illustrate that taxa driven to low abundance when dietary MACs are scarce are inefficiently transferred to the next generation and are at increased risk of becoming extinct within an isolated population. As more diseases are linked to the Western microbiota and the microbiota is targeted therapeutically, microbiota reprogramming may need to involve strategies that incorporate dietary MACs as well as taxa not currently present in the Western gut. PMID:26762459

Interactions between multiple helminths and the gut microbiota in wild rodents.

PubMed

Kreisinger, Jakub; Bastien, Géraldine; Hauffe, Heidi C; Marchesi, Julian; Perkins, Sarah E

2015-08-19

The gut microbiota is vital to host health and, as such, it is important to elucidate the mechanisms altering its composition and diversity. Intestinal helminths are host immunomodulators and have evolved both temporally and spatially in close association with the gut microbiota, resulting in potential mechanistic interplay. Host-helminth and host-microbiota interactions are comparatively well-examined, unlike microbiota-helminth relationships, which typically focus on experimental infection with a single helminth species in laboratory animals. Here, in addition to a review of the literature on helminth-microbiota interactions, we examined empirically the association between microbiota diversity and composition and natural infection of multiple helminth species in wild mice (Apodemus flavicollis), using 16S rRNA gene catalogues (metataxonomics). In general, helminth presence is linked with high microbiota diversity, which may confer health benefits to the host. Within our wild rodent system variation in the composition and abundance of gut microbial taxa associated with helminths was specific to each helminth species and occurred both up- and downstream of a given helminth's niche (gut position). The most pronounced helminth-microbiota association was between the presence of tapeworms in the small intestine and increased S24-7 (Bacteroidetes) family in the stomach. Helminths clearly have the potential to alter gut homeostasis. Free-living rodents with a diverse helminth community offer a useful model system that enables both correlative (this study) and manipulative inference to elucidate helminth-microbiota interactions.

Bacterial microbiota assemblage in Aedes albopictus mosquitoes and its impacts on larval development.

PubMed

Wang, Xiaoming; Liu, Tong; Wu, Yang; Zhong, Daibin; Zhou, Guofa; Su, Xinghua; Xu, Jiabao; Sotero, Charity F; Sadruddin, Adnan A; Wu, Kun; Chen, Xiao-Guang; Yan, Guiyun

2018-05-30

Interactions between bacterial microbiota and mosquitoes play an important role in mosquitoes' capacity to transmit pathogens. However, microbiota assemblages within mosquitoes and the impact of microbiota in environments on mosquito development and survival remain unclear. This study examined microbiota assemblages and the effects of aquatic environment microbiota on the larval development of the Aedes albopictus mosquito, an important dengue virus vector. Life table studies have found that reducing bacterial load in natural aquatic habitats through water filtering and treatment with antibiotics significantly reduced the larva-to-adult emergence rate. This finding was consistent in two types of larval habitats examined-discarded tires and flowerpots, suggesting that bacteria play a crucial role in larval development. Pyrosequencing of the bacterial 16S rRNA gene was used to determine the diversity of bacterial communities in larval habitats and the resulting numbers of mosquitoes under both laboratory and field conditions. The microbiota profiling identified common shared bacteria among samples from different years; further studies are needed to determine whether these bacteria represent a core microbiota. The highest microbiota diversity was found in aquatic habitats, followed by mosquito larvae, and the lowest in adult mosquitoes. Mosquito larvae ingested their bacterial microbiota and nutrients from aquatic habitats of high microbiota diversity. Taken together, the results support the observation that Ae. albopictus larvae are able to utilize diverse bacteria from aquatic habitats and that live bacteria from aquatic habitats play an important role in larval mosquito development and survival. These findings provide new insights into bacteria's role in mosquito larval ecology. © 2018 John Wiley & Sons Ltd.

Intestinal Microbiota of White Shrimp Penaeus vannamei Under Intensive Cultivation Conditions in Ecuador.

PubMed

Gainza, Oreste; Ramírez, Carolina; Ramos, Alfredo Salinas; Romero, Jaime

2018-04-01

The goal of the study was to characterize the intestinal tract bacterial microbiota composition of Penaeus vannamei in intensive commercial ponds in Ecuador, comparing two shrimp-farming phases: nursery and harvest. Bacterial microbiota was examined by sequencing amplicons V2-V3 of the 16S rRNA using Ion Torrent technology. Archaea sequences were detected in both phases. Sequence analyses revealed quantitative and qualitative differences between the nursery phase and the harvest phase in shrimp intestinal microbiota composition. The main differences were observed at the phylum level during the nursery phase, and the prevailing phyla were CKC4 (37.3%), Proteobacteria (29.8%), Actinobacteria (11.6%), and Firmicutes (10.1%). In the harvest phase, the prevailing phyla were Proteobacteria (28.4%), Chloroflexi (19.9%), and Actinobacteria (15.1%). At the genus level, microbiota from the nursery phase showed greater relative abundances of CKC4 uncultured bacterium (37%) and Escherichia-Shigella (18%). On the contrary, in the microbiota of harvested shrimp, the prevailing genera were uncultured Caldilinea (19%) and Alphaproteobacteria with no other assigned rate (10%). The analysis of similarity ANOSIM test (beta diversity) indicated significant differences between the shrimp microbiota for these two farming phases. Similarly, alfa-diversity analysis (Chao1) indicated that the microbiota at harvest was far more diverse than the microbiota during the nursery phase, which showed a homogeneous composition. These results suggest that shrimp microbiota diversify their composition during intensive farming. The present work offers the most detailed description of the microbiota of P. vannamei under commercial production conditions to date.

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

PubMed Central

Temko, Jamie E.; Bouhlal, Sofia; Farokhnia, Mehdi; Lee, Mary R.; Cryan, John F.; Leggio, Lorenzo

2017-01-01

Abstract Aims Accumulating evidence for the influence of the gut microbiota on the bidirectional communication along the gut-brain axis suggests a role of the gut microbiota in eating disorders (EDs) and alcohol and substance use disorders. The potential influence of altered gut microbiota (dysbiosis) on behaviors associated with such disorders may have implications for developing therapeutic interventions. Methods A systematic review of preclinical and clinical studies evaluating the gut microbiota, EDs and alcohol and substance use disorders was conducted using MEDLINE, Embase and Web of Science databases with the objective being to examine the role of the gut microbiota in behavioral correlates of these disorders. Original papers focused on the gut microbiota and potential behavioral implications were deemed eligible for consideration. Results The resulting 12 publications were limited to gut microbiota studies related to EDs and alcohol and substance use disorders. Some studies suggest that dysbiosis and gut microbial byproducts may influence the pathophysiology of EDs via direct and indirect interference with peptide hormone signaling. Additionally, dysbiosis was shown to be correlated with alcohol use disorder-related symptoms, i.e. craving, depression and anxiety. Finally, a mouse study suggests that manipulations in the gut microbiota may affect cocaine-related behaviors. Conclusions Promising, albeit preliminary, findings suggest a potential role of the gut microbiota in behavioral correlates of EDs and alcohol and substance use disorders. Short summary Preliminary evidence exists supporting the role of the gut microbiota in eating disorders and alcohol and substance use disorders, although additional investigation is needed to determine what is causative versus epiphenomenological. PMID:28482009

Enteric microbiota leads to new therapeutic strategies for ulcerative colitis.

PubMed

Chen, Wei-Xu; Ren, Li-Hua; Shi, Rui-Hua

2014-11-14

Ulcerative colitis (UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not achieve remission, there is a pressing need for the development of more effective therapies. The human gut contains a large, diverse, and dynamic population of microorganisms, collectively referred to as the enteric microbiota. There is a symbiotic relationship between the human host and the enteric microbiota, which provides nutrition, protection against pathogenic organisms, and promotes immune homeostasis. An imbalance of the normal enteric microbiota composition (termed dysbiosis) underlies the pathogenesis of UC. A reduction of enteric microbiota diversity has been observed in UC patients, mainly affecting the butyrate-producing bacteria, such as Faecalibacterium prausnitzii, which can repress pro-inflammatory cytokines. Many studies have shown that enteric microbiota plays an important role in anti-inflammatory and immunoregulatory activities, which can benefit UC patients. Therefore, manipulation of the dysbiosis is an attractive approach for UC therapy. Various therapies targeting a restoration of the enteric microbiota have shown efficacy in treating patients with active and chronic forms of UC. Such therapies include fecal microbiota transplantation, probiotics, prebiotics, antibiotics, helminth therapy, and dietary polyphenols, all of which can alter the abundance and composition of the enteric microbiota. Although there have been many large, randomized controlled clinical trials assessing these treatments, the effectiveness and safety of these bacteria-driven therapies need further evaluation. This review focuses on the important role that the enteric microbiota plays in maintaining intestinal homeostasis and discusses new therapeutic strategies targeting the enteric microbiota for UC.

Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.

PubMed

Yadava, Koshika; Pattaroni, Céline; Sichelstiel, Anke K; Trompette, Aurélien; Gollwitzer, Eva S; Salami, Olawale; von Garnier, Christophe; Nicod, Laurent P; Marsland, Benjamin J

2016-05-01

Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified. Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.

Maturation of the Infant Respiratory Microbiota, Environmental Drivers, and Health Consequences. A Prospective Cohort Study.

PubMed

Bosch, Astrid A T M; de Steenhuijsen Piters, Wouter A A; van Houten, Marlies A; Chu, Mei Ling J N; Biesbroek, Giske; Kool, Jolanda; Pernet, Paula; de Groot, Pieter-Kees C M; Eijkemans, Marinus J C; Keijser, Bart J F; Sanders, Elisabeth A M; Bogaert, Debby

2017-12-15

Perinatal and postnatal influences are presumed important drivers of the early-life respiratory microbiota composition. We hypothesized that the respiratory microbiota composition and development in infancy is affecting microbiota stability and thereby resistance against respiratory tract infections (RTIs) over time. To investigate common environmental drivers, including birth mode, feeding type, antibiotic exposure, and crowding conditions, in relation to respiratory tract microbiota maturation and stability, and consecutive risk of RTIs over the first year of life. In a prospectively followed cohort of 112 infants, we characterized the nasopharyngeal microbiota longitudinally from birth on (11 consecutive sample moments and the maximum three RTI samples per subject; in total, n = 1,121 samples) by 16S-rRNA gene amplicon sequencing. Using a microbiota-based machine-learning algorithm, we found that children experiencing a higher number of RTIs in the first year of life already demonstrate an aberrant microbial developmental trajectory from the first month of life on as compared with the reference group (0-2 RTIs/yr). The altered microbiota maturation process coincided with decreased microbial community stability, prolonged reduction of Corynebacterium and Dolosigranulum, enrichment of Moraxella very early in life, followed by later enrichment of Neisseria and Prevotella spp. Independent drivers of these aberrant developmental trajectories of respiratory microbiota members were mode of delivery, infant feeding, crowding, and recent antibiotic use. Our results suggest that environmental drivers impact microbiota development and, consequently, resistance against development of RTIs. This supports the idea that microbiota form the mediator between early-life environmental risk factors for and susceptibility to RTIs over the first year of life.