Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis

PubMed Central

Giannelli, Valerio; Di Gregorio, Vincenza; Iebba, Valerio; Giusto, Michela; Schippa, Serena; Merli, Manuela; Thalheimer, Ulrich

2014-01-01

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis. PMID:25492994

Bacterial growth, flow, and mixing shape human gut microbiota density and composition.

PubMed

Arnoldini, Markus; Cremer, Jonas; Hwa, Terence

2018-03-13

The human gut microbiota is highly dynamic, and host physiology and diet exert major influences on its composition. In our recent study, we integrated new quantitative measurements on bacterial growth physiology with a reanalysis of published data on human physiology to build a comprehensive modeling framework. This can generate predictions of how changes in different host factors influence microbiota composition. For instance, hydrodynamic forces in the colon, along with colonic water absorption that manifests as transit time, exert a major impact on microbiota density and composition. This can be mechanistically explained by their effect on colonic pH which directly affects microbiota competition for food. In this addendum, we describe the underlying analysis in more detail. In particular, we discuss the mixing dynamics of luminal content by wall contractions and its implications for bacterial growth and density, as well as the broader implications of our insights for the field of gut microbiota research.

Altered gut microbiota in Rett syndrome.

PubMed

Strati, Francesco; Cavalieri, Duccio; Albanese, Davide; De Felice, Claudio; Donati, Claudio; Hayek, Joussef; Jousson, Olivier; Leoncini, Silvia; Pindo, Massimo; Renzi, Daniela; Rizzetto, Lisa; Stefanini, Irene; Calabrò, Antonio; De Filippo, Carlotta

2016-07-30

The human gut microbiota directly affects human health, and its alteration can lead to gastrointestinal abnormalities and inflammation. Rett syndrome (RTT), a progressive neurological disorder mainly caused by mutations in MeCP2 gene, is commonly associated with gastrointestinal dysfunctions and constipation, suggesting a link between RTT's gastrointestinal abnormalities and the gut microbiota. The aim of this study was to evaluate the bacterial and fungal gut microbiota in a cohort of RTT subjects integrating clinical, metabolomics and metagenomics data to understand if changes in the gut microbiota of RTT subjects could be associated with gastrointestinal abnormalities and inflammatory status. Our findings revealed the occurrence of an intestinal sub-inflammatory status in RTT subjects as measured by the elevated values of faecal calprotectin and erythrocyte sedimentation rate. We showed that, overall, RTT subjects harbour bacterial and fungal microbiota altered in terms of relative abundances from those of healthy controls, with a reduced microbial richness and dominated by microbial taxa belonging to Bifidobacterium, several Clostridia (among which Anaerostipes, Clostridium XIVa, Clostridium XIVb) as well as Erysipelotrichaceae, Actinomyces, Lactobacillus, Enterococcus, Eggerthella, Escherichia/Shigella and the fungal genus Candida. We further observed that alterations of the gut microbiota do not depend on the constipation status of RTT subjects and that this dysbiotic microbiota produced altered short chain fatty acids profiles. We demonstrated for the first time that RTT is associated with a dysbiosis of both the bacterial and fungal component of the gut microbiota, suggesting that impairments of MeCP2 functioning favour the establishment of a microbial community adapted to the costive gastrointestinal niche of RTT subjects. The altered production of short chain fatty acids associated with this microbiota might reinforce the constipation status of RTT subjects and contribute to RTT gastrointestinal physiopathology.

May the Force Be With You: The Light and Dark Sides of the Microbiota-Gut-Brain Axis in Neuropsychiatry.

PubMed

Sherwin, Eoin; Sandhu, Kiran V; Dinan, Timothy G; Cryan, John F

2016-11-01

The role of the gut microbiota in health and disease is becoming increasingly recognized. The microbiota-gut-brain axis is a bi-directional pathway between the brain and the gastrointestinal system. The bacterial commensals in our gut can signal to the brain through a variety of mechanisms, which are slowly being resolved. These include the vagus nerve, immune mediators and microbial metabolites, which influence central processes such as neurotransmission and behaviour. Dysregulation in the composition of the gut microbiota has been identified in several neuropsychiatric disorders, such as autism, schizophrenia and depression. Moreover, preclinical studies suggest that they may be the driving force behind the behavioural abnormalities observed in these conditions. Understanding how bacterial commensals are involved in regulating brain function may lead to novel strategies for development of microbiota-based therapies for these neuropsychiatric disorders.

The role of gut microbiota in health and disease: In vitro modeling of host-microbe interactions at the aerobe-anaerobe interphase of the human gut.

PubMed

von Martels, Julius Z H; Sadaghian Sadabad, Mehdi; Bourgonje, Arno R; Blokzijl, Tjasso; Dijkstra, Gerard; Faber, Klaas Nico; Harmsen, Hermie J M

2017-04-01

The microbiota of the gut has many crucial functions in human health. Dysbiosis of the microbiota has been correlated to a large and still increasing number of diseases. Recent studies have mostly focused on analyzing the associations between disease and an aberrant microbiota composition. Functional studies using (in vitro) gut models are required to investigate the precise interactions that occur between specific bacteria (or bacterial mixtures) and gut epithelial cells. As most gut bacteria are obligate or facultative anaerobes, studying their effect on oxygen-requiring human gut epithelial cells is technically challenging. Still, several (anaerobic) bacterial-epithelial co-culture systems have recently been developed that mimic host-microbe interactions occurring in the human gut, including 1) the Transwell "apical anaerobic model of the intestinal epithelial barrier", 2) the Host-Microbiota Interaction (HMI) module, 3) the "Human oxygen-Bacteria anaerobic" (HoxBan) system, 4) the human gut-on-a-chip and 5) the HuMiX model. This review discusses the role of gut microbiota in health and disease and gives an overview of the characteristics and applications of these novel host-microbe co-culture systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Underlying Ecological Processes of Gut Microbiota Among Cohabitating Retarded, Overgrown and Normal Shrimp.

PubMed

Xiong, Jinbo; Dai, Wenfang; Zhu, Jinyong; Liu, Keshao; Dong, Chunming; Qiu, Qiongfen

2017-05-01

Increasing evidence of tight links among the gut microbiota, obesity, and host health has emerged, but knowledge of the ecological processes that shape the variation in microbial assemblages across growth rates remains elusive. Moreover, inadequately control for differences in factors that profoundly affect the gut microbial community, hampers evaluation of the gut microbiota roles in regulating growth rates. To address this gap, we evaluated the composition and ecological processes of the gut bacterial community in cohabitating retarded, overgrown, and normal shrimps from identically managed ponds. Gut bacterial community structures were distinct (P = 0.0006) among the shrimp categories. Using a structural equation modeling (SEM), we found that changes in the gut bacterial community were positively related to digestive activities, which subsequently affected shrimp growth rate. This association was further supported by intensified interspecies interaction and enriched lineages with high nutrient intake efficiencies in overgrown shrimps. However, the less phylogenetic clustering of gut microbiota in overgrown and retarded subjects may offer empty niches for pathogens invasion, as evidenced by higher abundances of predicted functional pathways involved in disease infection. Given no differences in biotic and abiotic factors among the cohabitating shrimps, we speculated that the distinct gut community assembly could be attributed to random colonization in larval shrimp (e.g., priority effects) and that an altered microbiota could be a causative factor in overgrowth or retardation in shrimp. To our knowledge, this is the first study to provide an integrated overview of the direct roles of gut microbiota in shaping shrimp growth rate and the underlying ecological mechanisms.

Beyond 16S rRNA Community Profiling: Intra-Species Diversity in the Gut Microbiota

PubMed Central

Ellegaard, Kirsten M.; Engel, Philipp

2016-01-01

Interactions with microbes affect many aspects of animal biology, including immune system development, nutrition and health. In vertebrates, the gut microbiota is dominated by a small subset of phyla, but the species composition within these phyla is typically not conserved. Moreover, several recent studies have shown that bacterial species in the gut are composed of a multitude of strains, which frequently co-exist in their host, and may be host-specific. However, since the study of intra-species diversity is challenging, particularly in the setting of complex, host-associated microbial communities, our current understanding of the distribution, evolution and functional relevance of intra-species diversity in the gut is scarce. In order to unravel how genomic diversity translates into phenotypic diversity, community analyses going beyond 16S rRNA profiling, in combination with experimental approaches, are needed. Recently, the honeybee has emerged as a promising model for studying gut bacterial communities, particularly in terms of strain-level diversity. Unlike most other invertebrates, the honeybee gut is colonized by a remarkably consistent and specific core microbiota, which is dominated by only eight bacterial species. As for the vertebrate gut microbiota, these species are composed of highly diverse strains suggesting that similar evolutionary forces shape gut community structures in vertebrates and social insects. In this review, we outline current knowledge on the evolution and functional relevance of strain diversity within the gut microbiota, including recent insights gained from mammals and other animals such as the honeybee. We discuss methodological approaches and propose possible future avenues for studying strain diversity in complex bacterial communities. PMID:27708630

Beyond 16S rRNA Community Profiling: Intra-Species Diversity in the Gut Microbiota.

PubMed

Ellegaard, Kirsten M; Engel, Philipp

2016-01-01

Interactions with microbes affect many aspects of animal biology, including immune system development, nutrition and health. In vertebrates, the gut microbiota is dominated by a small subset of phyla, but the species composition within these phyla is typically not conserved. Moreover, several recent studies have shown that bacterial species in the gut are composed of a multitude of strains, which frequently co-exist in their host, and may be host-specific. However, since the study of intra-species diversity is challenging, particularly in the setting of complex, host-associated microbial communities, our current understanding of the distribution, evolution and functional relevance of intra-species diversity in the gut is scarce. In order to unravel how genomic diversity translates into phenotypic diversity, community analyses going beyond 16S rRNA profiling, in combination with experimental approaches, are needed. Recently, the honeybee has emerged as a promising model for studying gut bacterial communities, particularly in terms of strain-level diversity. Unlike most other invertebrates, the honeybee gut is colonized by a remarkably consistent and specific core microbiota, which is dominated by only eight bacterial species. As for the vertebrate gut microbiota, these species are composed of highly diverse strains suggesting that similar evolutionary forces shape gut community structures in vertebrates and social insects. In this review, we outline current knowledge on the evolution and functional relevance of strain diversity within the gut microbiota, including recent insights gained from mammals and other animals such as the honeybee. We discuss methodological approaches and propose possible future avenues for studying strain diversity in complex bacterial communities.

Introduction to the human gut microbiota.

PubMed

Thursby, Elizabeth; Juge, Nathalie

2017-05-16

The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host-microbe interactions. © 2017 The Author(s).

Introduction to the human gut microbiota

PubMed Central

Thursby, Elizabeth

2017-01-01

The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions. PMID:28512250

Insect Gut Bacterial Diversity Determined by Environmental Habitat, Diet, Developmental Stage, and Phylogeny of Host

PubMed Central

Yun, Ji-Hyun; Roh, Seong Woon; Whon, Tae Woong; Jung, Mi-Ja; Kim, Min-Soo; Park, Doo-Sang; Yoon, Changmann; Nam, Young-Do; Kim, Yun-Ji; Choi, Jung-Hye; Kim, Joon-Yong; Shin, Na-Ri; Kim, Sung-Hee; Lee, Won-Jae

2014-01-01

Insects are the most abundant animals on Earth, and the microbiota within their guts play important roles by engaging in beneficial and pathological interactions with these hosts. In this study, we comprehensively characterized insect-associated gut bacteria of 305 individuals belonging to 218 species in 21 taxonomic orders, using 454 pyrosequencing of 16S rRNA genes. In total, 174,374 sequence reads were obtained, identifying 9,301 bacterial operational taxonomic units (OTUs) at the 3% distance level from all samples, with an average of 84.3 (±97.7) OTUs per sample. The insect gut microbiota were dominated by Proteobacteria (62.1% of the total reads, including 14.1% Wolbachia sequences) and Firmicutes (20.7%). Significant differences were found in the relative abundances of anaerobes in insects and were classified according to the criteria of host environmental habitat, diet, developmental stage, and phylogeny. Gut bacterial diversity was significantly higher in omnivorous insects than in stenophagous (carnivorous and herbivorous) insects. This insect-order-spanning investigation of the gut microbiota provides insights into the relationships between insects and their gut bacterial communities. PMID:24928884

Gut microbiota-related complications in cirrhosis

PubMed Central

Gómez-Hurtado, Isabel; Such, José; Sanz, Yolanda; Francés, Rubén

2014-01-01

Gut microbiota plays an important role in cirrhosis. The liver is constantly challenged with commensal bacteria and their products arriving through the portal vein in the so-called gut-liver axis. Bacterial translocation from the intestinal lumen through the intestinal wall and to mesenteric lymph nodes is facilitated by intestinal bacterial overgrowth, impairment in the permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences. Deranged clearance of endogenous bacteria from portal and systemic circulation turns the gut into the major source of bacterial-related complications. Liver function may therefore be affected by alterations in the composition of the intestinal microbiota and a role for commensal flora has been evidenced in the pathogenesis of several complications arising in end-stage liver disease such as hepatic encephalopathy, splanchnic arterial vasodilatation and spontaneous bacterial peritonitis. The use of antibiotics is the main therapeutic pipeline in the management of these bacteria-related complications. However, other strategies aimed at preserving intestinal homeostasis through the use of pre-, pro- or symbiotic formulations are being studied in the last years. In this review, the role of intestinal microbiota in the development of the most frequent complications arising in cirrhosis and the different clinical and experimental studies conducted to prevent or improve these complications by modifying the gut microbiota composition are summarized. PMID:25400446

Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study

PubMed Central

2013-01-01

Background Elucidating gut microbiota among gallstone patients as well as the complex bacterial colonization of cholesterol gallstones may help in both the prediction and subsequent lowered risk of cholelithiasis. To this end, we studied the composition of bacterial communities of gut, bile, and gallstones from 29 gallstone patients as well as the gut of 38 normal individuals, examining and analyzing some 299, 217 bacterial 16S rRNA gene sequences from 120 samples. Results First, as compared with normal individuals, in gallstone patients there were significant (P < 0.001) increases of gut bacterial phylum Proteobacteria and decreases of three gut bacterial genera, Faecalibacterium, Lachnospira, and Roseburia. Second, about 70% of gut bacterial operational taxonomic units (OTUs) from gallstone patients were detectable in the biliary tract and bacteria diversity of biliary tract was significantly (P < 0.001) higher than that of gut. Third, analysis of the biliary tract core microbiome (represented by 106 bacteria OTUs) among gallstone patients showed that 33.96% (36/106) of constituents can be matched to known bacterial species (15 of which have publicly available genomes). A genome-wide search of MDR, BSH, bG, and phL genes purpotedly associated with the formation of cholesterol gallstones showed that all 15 species with known genomes (e.g., Propionibacterium acnes, Bacteroides vulgates, and Pseudomonas putida) contained at least contained one of the four genes. This finding could potentially provide underlying information needed to explain the association between biliary tract microbiota and the formation of cholesterol gallstones. Conclusions To the best of our knowledge, this is the first study to discover gut microbiota dysbiosis among gallstone patients, the presence of which may be a key contributor to the complex bacteria community assembly linked with the presence of cholesterol gallstones. Likewise, this study also provides the first large-scale glimpse of biliary tract microbiota potentially associated with cholesterol gallstones. Such a characterization of the biliary tract core microbiome has potentially important biological and medical implications regarding the role of bacteria in the formation cholesterol gallstones. PMID:24083370

Characterization of gut bacterial flora of Apis mellifera from north-west Pakistan.

PubMed

Anjum, Syed Ishtiaq; Shah, Abdul Haleem; Aurongzeb, Muhammad; Kori, Junaid; Azim, M Kamran; Ansari, Mohammad Javed; Bin, Li

2018-02-01

Gut microbiota has been recognized to play a beneficial role in honey bees ( Apis mellifera ). Present study was designed to characterize the gut bacterial flora of honey bees in north-west Pakistan. Total 150 aerobic and facultative anaerobic bacteria from guts of 45 worker bees were characterized using biochemical assays and 16S rDNA sequencing followed by bioinformatics analysis. The gut isolates were classified into three bacterial phyla of Firmicutes (60%), Proteobacteria (26%) and Actinobacteria (14%). Most of the isolates belonged to genera and families of Staphylococcus , Bacillus , Enterococcus , Ochrobactrum , Sphingomonas , Ralstonia , Enterobacteriaceae , Corynebacterium and Micrococcineae . Many of these bacteria were tolerant to acidic environments and fermented sugars, hence considered beneficial gut inhabitants and involved the maintenance of a healthy microbiota. However, several opportunistic commensals that proliferate in the hive environment including members Staphylococcus haemolyticus group and Sphingomonas paucimobilis were also identified. This is the first report on bee gut microbiota from north-west Pakistan geographically situated at the crossroads of Indian subcontinent and central Asia.

Intestinal microbiota composition in fishes is influenced by host ecology and environment.

PubMed

Wong, Sandi; Rawls, John F

2012-07-01

The digestive tracts of vertebrates are colonized by complex assemblages of micro-organisms, collectively called the gut microbiota. Recent studies have revealed important contributions of gut microbiota to vertebrate health and disease, stimulating intense interest in understanding how gut microbial communities are assembled and how they impact host fitness (Sekirov et al. 2010). Although all vertebrates harbour a gut microbiota, current information on microbiota composition and function has been derived primarily from mammals. Comparisons of different mammalian species have revealed intriguing associations between gut microbiota composition and host diet, anatomy and phylogeny (Ley et al. 2008b). However, mammals constitute <10% of all vertebrate species, and it remains unclear whether similar associations exist in more diverse and ancient vertebrate lineages such as fish. In this issue, Sullam et al. (2012) make an important contribution toward identifying factors determining gut microbiota composition in fishes. The authors conducted a detailed meta-analysis of 25 bacterial 16S rRNA gene sequence libraries derived from the intestines of different fish species. To provide a broader context for their analysis, they compared these data sets to a large collection of 16S rRNA gene sequence data sets from diverse free-living and host-associated bacterial communities. Their results suggest that variation in gut microbiota composition in fishes is strongly correlated with species habitat salinity, trophic level and possibly taxonomy. Comparison of data sets from fish intestines and other environments revealed that fish gut microbiota compositions are often similar to those of other animals and contain relatively few free-living environmental bacteria. These results suggest that the gut microbiota composition of fishes is not a simple reflection of the micro-organisms in their local habitat but may result from host-specific selective pressures within the gut (Bevins & Salzman 2011).

Gut microbiota imbalance and colorectal cancer

PubMed Central

Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde

2016-01-01

The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID:26811603

Nonalcoholic fatty liver disease: for better or worse, blame the gut microbiota?

PubMed

Li, Ding-You; Yang, Min; Edwards, Sarah; Ye, Shui-Qing

2013-11-01

Nonalcoholic fatty liver disease (NAFLD) is a major clinical consequence for people with obesity and metabolic syndrome and is also associated with enteral and parenteral nutrition. Early studies suggested that altered gut microbiota might contribute to obesity by affecting energy harvest from the diet and energy storage in the host. Recent evidence in humans as well as in animal models has linked gut microbiota to the development of NAFLD through the gut-liver axis. With bacterial overgrowth and increased intestinal permeability observed in patients with NAFLD and in animal models, gut-derived bacterial products such as endotoxin (lipopolysaccharide) and bacterial DNA are being delivered to the liver through the portal vein and then activate Toll-like receptors (TLRs), mainly TLR4 and TLR9, and their downstream cytokines and chemokines, leading to the development and progression of NAFLD. Given the limited data in humans, the role of gut microbiota in the pathogenesis of NAFLD is still open to discussion. Prebiotics and probiotics have been attempted to modify the microbiota as preventive or therapeutic strategies on this pathological condition. Their beneficial effects on NALFD have been demonstrated in animal models and limited human studies. However, prospective, appropriately powered, randomized, controlled clinical trials are needed to determine whether prebiotics and probiotics and other integrated strategies to modify intestinal microbiota are efficacious therapeutic modalities to treat NALFD.

Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg.

PubMed

Arab, Juan P; Martin-Mateos, Rosa M; Shah, Vijay H

2018-02-01

The term gut-liver axis is used to highlight the close anatomical and functional relationship between the intestine and the liver. The intestine has a highly specialized epithelial membrane which regulates transport across the mucosa. Due to dysbiosis, impairment of the intestinal barrier and altered immunity status, bacterial products can reach the liver through the portal vein, where they are recognized by specific receptors, activate the immune system and lead to a proinflammatory response. Gut microbiota and bacterial translocation play an important role in the pathogenesis of chronic liver diseases, including alcoholic and non-alcoholic fatty liver disease, cirrhosis, and its complications, such as portal hypertension, spontaneous bacterial peritonitis and hepatic encephalopaty. The gut microbiota also plays a critical role as a modulator of bile acid metabolism which can also influence intestinal permeability and portal hypertension through the farnesoid-X receptor. On the other hand, cirrhosis and portal hypertension affect the microbiota and increase translocation, leading to a "chicken and egg" situation, where translocation increases portal pressure, and vice versa. A myriad of therapies targeting gut microbiota have been evaluated specifically in patients with chronic liver disease. Further studies targeting intestinal microbiota and its possible hemodynamic and metabolic effects are needed. This review summarizes the current knowledge about the role of gut microbiota in the pathogenesis of chronic liver diseases and portal hypertension.

Engineering bacterial thiosulfate and tetrathionate sensors for detecting gut inflammation.

PubMed

Daeffler, Kristina N-M; Galley, Jeffrey D; Sheth, Ravi U; Ortiz-Velez, Laura C; Bibb, Christopher O; Shroyer, Noah F; Britton, Robert A; Tabor, Jeffrey J

2017-04-03

There is a groundswell of interest in using genetically engineered sensor bacteria to study gut microbiota pathways, and diagnose or treat associated diseases. Here, we computationally identify the first biological thiosulfate sensor and an improved tetrathionate sensor, both two-component systems from marine Shewanella species, and validate them in laboratory Escherichia coli Then, we port these sensors into a gut-adapted probiotic E. coli strain, and develop a method based upon oral gavage and flow cytometry of colon and fecal samples to demonstrate that colon inflammation (colitis) activates the thiosulfate sensor in mice harboring native gut microbiota. Our thiosulfate sensor may have applications in bacterial diagnostics or therapeutics. Finally, our approach can be replicated for a wide range of bacterial sensors and should thus enable a new class of minimally invasive studies of gut microbiota pathways. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

How gut transcriptional function of Drosophila melanogaster varies with the presence and composition of the gut microbiota.

PubMed

Bost, Alyssa; Franzenburg, Soeren; Adair, Karen L; Martinson, Vincent G; Loeb, Greg; Douglas, Angela E

2018-04-01

Despite evidence from laboratory experiments that perturbation of the gut microbiota affects many traits of the animal host, our understanding of the effect of variation in microbiota composition on animals in natural populations is very limited. The core purpose of this study on the fruit fly Drosophila melanogaster was to identify the impact of natural variation in the taxonomic composition of gut bacterial communities on host traits, with the gut transcriptome as a molecular index of microbiota-responsive host traits. Use of the gut transcriptome was validated by demonstrating significant transcriptional differences between the guts of laboratory flies colonized with bacteria and maintained under axenic conditions. Wild Drosophila from six field collections made over two years had gut bacterial communities of diverse composition, dominated to varying extents by Acetobacteraceae and Enterobacteriaceae. The gut transcriptomes also varied among collections and differed markedly from those of laboratory flies. However, no overall relationship between variation in the wild fly transcriptome and taxonomic composition of the gut microbiota was evident at all taxonomic scales of bacteria tested for both individual fly genes and functional categories in Gene Ontology. We conclude that the interaction between microbiota composition and host functional traits may be confounded by uncontrolled variation in both ecological circumstance and host traits (e.g., genotype, age physiological condition) under natural conditions, and that microbiota effects on host traits identified in the laboratory should, therefore, be extrapolated to field population with great caution. © 2017 John Wiley & Sons Ltd.

Gut microbial succession follows acute secretory diarrhea in humans.

PubMed

David, Lawrence A; Weil, Ana; Ryan, Edward T; Calderwood, Stephen B; Harris, Jason B; Chowdhury, Fahima; Begum, Yasmin; Qadri, Firdausi; LaRocque, Regina C; Turnbaugh, Peter J

2015-05-19

Disability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella. Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea. Disability after diarrhea is a major burden on public health in the developing world. Gut bacteria may affect this recovery, but it remains incompletely understood how resident microbes in the digestive tract respond to diarrheal illness. Here, we observed an orderly and reproducible succession of gut bacterial groups after cholera in humans. Genomic analyses associated the succession with bacterial dispersal in food, an altered microbial environment, and changing phage levels. Our findings suggest that it may one day be feasible to manage resident bacterial populations in the gut after infectious diarrhea. Copyright © 2015 David et al.

Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation.

PubMed

Ponziani, Francesca Romana; Zocco, Maria Assunta; D'Aversa, Francesca; Pompili, Maurizio; Gasbarrini, Antonio

2017-07-07

Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium , Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.

Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation

PubMed Central

Ponziani, Francesca Romana; Zocco, Maria Assunta; D’Aversa, Francesca; Pompili, Maurizio; Gasbarrini, Antonio

2017-01-01

Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings. PMID:28740337

Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy

USDA-ARS?s Scientific Manuscript database

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by immunoglobulin A (IgA) from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to sever...

The obese gut microbiome across the epidemiologic transition.

PubMed

Dugas, Lara R; Fuller, Miles; Gilbert, Jack; Layden, Brian T

2016-01-01

The obesity epidemic has emerged over the past few decades and is thought to be a result of both genetic and environmental factors. A newly identified factor, the gut microbiota, which is a bacterial ecosystem residing within the gastrointestinal tract of humans, has now been implicated in the obesity epidemic. Importantly, this bacterial community is impacted by external environmental factors through a variety of undefined mechanisms. We focus this review on how the external environment may impact the gut microbiota by considering, the host's geographic location 'human geography', and behavioral factors (diet and physical activity). Moreover, we explore the relationship between the gut microbiota and obesity with these external factors. And finally, we highlight here how an epidemiologic model can be utilized to elucidate causal relationships between the gut microbiota and external environment independently and collectively, and how this will help further define this important new factor in the obesity epidemic.

Chronic kidney disease, uremic milieu, and its effects on gut bacterial microbiota dysbiosis.

PubMed

Chaves, Lee D; McSkimming, Daniel I; Bryniarski, Mark A; Honan, Amanda M; Abyad, Sham; Thomas, Shruthi A; Wells, Steven; Buck, Michael J; Sun, Yijun; Genco, Robert J; Quigg, Richard J; Yacoub, Rabi

2018-04-25

Several lines of evidence suggest that gut bacterial microbiota is altered in patients with chronic kidney disease (CKD), though the mechanism of which this dysbiosis takes place is not well understood. Recent studies delineated changes in gut microbiota in both CKD patients and experimental animal models using microarray chips. We present 16S ribosomal RNA gene sequencing of both stool pellets and small bowel contents of C57Bl/6J mice that underwent a remnant kidney model, and establish that changes in microbiota take place in the early gastrointestinal track. Increased intestinal urea concertation has been hypothesized as a leading contributor for dysbiotic changes in CKD. We show that urea transporters UT-A and UT-B mRNA are both expressed throughout the whole gastrointestinal track. The noted increase in intestinal urea concentration appears to be independent of urea transporters' expression. Urea supplementation in drinking water resulted in alteration in bacterial gut microbiota that is quite different than that seen in CKD. This indicates that increased intestinal urea concentration might not fully explain the CKD associated dysbiosis.

Chemical communication in the gut: Effects of microbiota-generated metabolites on gastrointestinal bacterial pathogens.

PubMed

Vogt, Stefanie L; Peña-Díaz, Jorge; Finlay, B Brett

2015-08-01

Gastrointestinal pathogens must overcome many obstacles in order to successfully colonize a host, not the least of which is the presence of the gut microbiota, the trillions of commensal microorganisms inhabiting mammals' digestive tracts, and their products. It is well established that a healthy gut microbiota provides its host with protection from numerous pathogens, including Salmonella species, Clostridium difficile, diarrheagenic Escherichia coli, and Vibrio cholerae. Conversely, pathogenic bacteria have evolved mechanisms to establish an infection and thrive in the face of fierce competition from the microbiota for space and nutrients. Here, we review the evidence that gut microbiota-generated metabolites play a key role in determining the outcome of infection by bacterial pathogens. By consuming and transforming dietary and host-produced metabolites, as well as secreting primary and secondary metabolites of their own, the microbiota define the chemical environment of the gut and often determine specific host responses. Although most gut microbiota-produced metabolites are currently uncharacterized, several well-studied molecules made or modified by the microbiota are known to affect the growth and virulence of pathogens, including short-chain fatty acids, succinate, mucin O-glycans, molecular hydrogen, secondary bile acids, and the AI-2 quorum sensing autoinducer. We also discuss challenges and possible approaches to further study of the chemical interplay between microbiota and gastrointestinal pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diet-induced alterations of host cholesterol metabolism are likely to affect the gut microbiota composition in hamsters.

PubMed

Martínez, Inés; Perdicaro, Diahann J; Brown, Andrew W; Hammons, Susan; Carden, Trevor J; Carr, Timothy P; Eskridge, Kent M; Walter, Jens

2013-01-01

The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota.

Gut Microbial Succession Follows Acute Secretory Diarrhea in Humans

PubMed Central

David, Lawrence A.; Weil, Ana; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.; Chowdhury, Fahima; Begum, Yasmin; Qadri, Firdausi

2015-01-01

ABSTRACT Disability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella. Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea. PMID:25991682

Human Milk Glycomics and Gut Microbial Genomics in Infant Feces Show a Correlation between Human Milk Oligosaccharides and Gut Microbiota: A Proof-of-Concept Study

PubMed Central

2015-01-01

Human milk oligosaccharides (HMOs) play a key role in shaping and maintaining a healthy infant gut microbiota. This article demonstrates the potential of combining recent advances in glycomics and genomics to correlate abundances of fecal microbes and fecal HMOs. Serial fecal specimens from two healthy breast-fed infants were analyzed by bacterial DNA sequencing to characterize the microbiota and by mass spectrometry to determine abundances of specific HMOs that passed through the intestinal tract without being consumed by the luminal bacteria. In both infants, the fecal bacterial population shifted from non-HMO-consuming microbes to HMO-consuming bacteria during the first few weeks of life. An initial rise in fecal HMOs corresponded with bacterial populations composed primarily of non-HMO-consuming Enterobacteriaceae and Staphylococcaeae. This was followed by decreases in fecal HMOs as the proportion of HMO-consuming Bacteroidaceae and Bifidobacteriaceae increased. Analysis of HMO structures with isomer differentiation revealed that HMO consumption is highly structure-specific, with unique isomers being consumed and others passing through the gut unaltered. These results represent a proof-of-concept and are consistent with the highly selective, prebiotic effect of HMOs in shaping the gut microbiota in the first weeks of life. The analysis of selective fecal bacterial substrates as a measure of alterations in the gut microbiota may be a potential marker of dysbiosis. PMID:25300177

Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection.

PubMed

Midani, Firas S; Weil, Ana A; Chowdhury, Fahima; Begum, Yasmin A; Khan, Ashraful I; Debela, Meti D; Durand, Heather K; Reese, Aspen T; Nimmagadda, Sai N; Silverman, Justin D; Ellis, Crystal N; Ryan, Edward T; Calderwood, Stephen B; Harris, Jason B; Qadri, Firdausi; David, Lawrence A; LaRocque, Regina C

2018-04-12

Cholera is a public health problem worldwide and the risk factors for infection are only partially understood. We prospectively studied household contacts of cholera patients to compare those who were infected with those who were not. We constructed predictive machine learning models of susceptibility using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. We found that machine learning models based on gut microbiota predicted V. cholerae infection as well as models based on known clinical and epidemiological risk factors. A 'predictive gut microbiota' of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.

Carbohydrates and the human gut microbiota.

PubMed

Chassard, Christophe; Lacroix, Christophe

2013-07-01

Due to its scale and its important role in maintaining health, the gut microbiota can be considered as a 'new organ' inside the human body. Many complex carbohydrates are degraded and fermented by the human gut microbiota in the large intestine to both yield basic energy salvage and impact gut health through produced metabolites. This review will focus on the gut microbes and microbial mechanisms responsible for polysaccharides degradation and fermentation in the large intestine. Gut microbes and bacterial metabolites impact the host at many levels, including modulation of inflammation, and glucose and lipid metabolisms. A complex relationship occurs in the intestine between the human gut microbiota, diet and the host. Research on carbohydrates and gut microbiota composition and functionality is fast developing and will open opportunities for prevention and treatment of obesity, diabetes and other related metabolic disorders through manipulation of the gut ecosystem.

Starvation stress affects the interplay among shrimp gut microbiota, digestion and immune activities.

PubMed

Dai, Wen-Fang; Zhang, Jin-Jie; Qiu, Qiong-Fen; Chen, Jiong; Yang, Wen; Ni, Sui; Xiong, Jin-Bo

2018-05-24

Aquatic animals are frequently suffered from starvation due to restricted food availability or deprivation. It is currently known that gut microbiota assists host in nutrient acquisition. Thus, exploring the gut microbiota responses would improve our understanding on physiological adaptation to starvation. To achieve this, we investigated how the gut microbiota and shrimp digestion and immune activities were affected under starvation stress. The results showed that the measured digestion activities in starved shrimp were significantly lower than in normal cohorts; while the measured immune activities exhibited an opposite trend. A structural equation modeling (SEM) revealed that changes in the gut bacterial community were directly related to digestive and immune enzyme activities, which in turn markedly affected shrimp growth traits. Notably, several gut bacterial indicators that characterized the shrimp nutrient status were identified, with more abundant opportunistic pathogens in starved shrimp, although there were no statistical differences in the overall diversity and the structures of gut bacterial communities between starved and normal shrimp. Starved shrimp exhibited less connected and cooperative interspecies interaction as compared with normal cohorts. Additionally, the functional pathways involved in carbohydrate and protein digestion, glycan biosynthesis, lipid and enzyme metabolism remarkably decreased in starved shrimp. These attenuations could increase the susceptibility of starved shrimp to pathogens infection. In summary, this study provides novel insights into the interplay among shrimp digestion, immune activities and gut microbiota in response to starvation stress. Copyright © 2018 Elsevier Ltd. All rights reserved.

Recruitment and establishment of the gut microbiome in arctic shorebirds.

PubMed

Grond, Kirsten; Lanctot, Richard B; Jumpponen, Ari; Sandercock, Brett K

2017-12-01

Gut microbiota play a key role in host health. Mammals acquire gut microbiota during birth, but timing of gut microbial recruitment in birds is unknown. We evaluated whether precocial chicks from three species of arctic-breeding shorebirds acquire gut microbiota before or after hatching, and then documented the rate and compositional dynamics of accumulation of gut microbiota. Contrary to earlier reports of microbial recruitment before hatching in chickens, quantitative PCR and Illumina sequence data indicated negligible microbiota in the guts of shorebird embryos before hatching. Analyses of chick feces indicated an exponential increase in bacterial abundance of guts 0-2 days post-hatch, followed by stabilization. Gut communities were characterized by stochastic recruitment and convergence towards a community dominated by Clostridia and Gammaproteobacteria. We conclude that guts of shorebird chicks are likely void of microbiota prior to hatch, but that stable gut microbiome establishes as early as 3 days of age, probably from environmental inocula. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Functional characterization of IgA-targeted bacterial taxa from malnourished Malawian children that produce diet-dependent enteropathy

PubMed Central

Kau, Andrew L.; Planer, Joseph D.; Liu, Jie; Rao, Sindhuja; Yatsunenko, Tanya; Trehan, Indi; Manary, Mark J.; Liu, Ta-Chiang; Stappenbeck, Thaddeus S.; Maleta, Kenneth M.; Ashorn, Per; Dewey, Kathryn G.; Houpt, Eric R.; Hsieh, Chyi-Song; Gordon, Jeffrey I.

2015-01-01

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by IgA from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to several bacterial taxa, including Enterobacteriaceae, correlated with anthropometric measurements of nutritional status in longitudinal studies. The relationship between IgA responses and growth was further explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA+-bacterial consortium purified from the gut microbiota of undernourished children exhibited a diet-dependent enteropathy characterized by rapid disruption of the small intestinal and colonic epithelial barrier, weight loss and sepsis that could be prevented by administering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection of 11 IgA-targeted strains from an undernourished donor, sufficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted with other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses have etiologic, diagnostic, and therapeutic implications for childhood undernutrition. PMID:25717097

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.

Brain-gut-microbiota axis in Parkinson's disease.

PubMed

Mulak, Agata; Bonaz, Bruno

2015-10-07

Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.

The Mycobiome: A Neglected Component in the Microbiota-Gut-Brain Axis

PubMed Central

Enaud, Raphaël; Vandenborght, Louise-Eva; Coron, Noémie; Bazin, Thomas; Prevel, Renaud; Schaeverbeke, Thierry; Berger, Patrick; Fayon, Michael; Delhaes, Laurence

2018-01-01

In recent years, the gut microbiota has been considered as a full-fledged actor of the gut–brain axis, making it possible to take a new step in understanding the pathophysiology of both neurological and psychiatric diseases. However, most of the studies have been devoted to gut bacterial microbiota, forgetting the non-negligible fungal flora. In this review, we expose how the role of the fungal component in the microbiota-gut-brain axis is legitimate, through its interactions with both the host, especially with the immune system, and the gut bacteria. We also discuss published data that already attest to a role of the mycobiome in the microbiota-gut-brain axis, and the impact of fungi on clinical and therapeutic research. PMID:29522426

Composition of the gut microbiota modulates the severity of malaria

PubMed Central

Villarino, Nicolas F.; LeCleir, Gary R.; Denny, Joshua E.; Dearth, Stephen P.; Harding, Christopher L.; Sloan, Sarah S.; Gribble, Jennifer L.; Campagna, Shawn R.; Wilhelm, Steven W.; Schmidt, Nathan W.

2016-01-01

Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from “resistant” or “susceptible” mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden. PMID:26858424

The Role of the Gut Microbiota in Childhood Obesity.

PubMed

Pihl, Andreas Friis; Fonvig, Cilius Esmann; Stjernholm, Theresa; Hansen, Torben; Pedersen, Oluf; Holm, Jens-Christian

2016-08-01

Childhood and adolescent obesity has reached epidemic proportions worldwide. The pathogenesis of obesity is complex and multifactorial, in which genetic and environmental contributions seem important. The gut microbiota is increasingly documented to be involved in the dysmetabolism associated with obesity. We conducted a systematic search for literature available before October 2015 in the PubMed and Scopus databases, focusing on the interplay between the gut microbiota, childhood obesity, and metabolism. The review discusses the potential role of the bacterial component of the human gut microbiota in childhood and adolescent-onset obesity, with a special focus on the factors involved in the early development of the gut bacterial ecosystem, and how modulation of this microbial community might serve as a basis for new therapeutic strategies in combating childhood obesity. A vast number of variables are influencing the gut microbial ecology (e.g., the host genetics, delivery method, diet, age, environment, and the use of pre-, pro-, and antibiotics); but the exact physiological processes behind these relationships need to be clarified. Exploring the role of the gut microbiota in the development of childhood obesity may potentially reveal new strategies for obesity prevention and treatment.

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

Gut Microbiota in Cardiovascular Health and Disease

PubMed Central

Tang, W.H. Wilson; Kitai, Takeshi; Hazen, Stanley L

2017-01-01

Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through a number of pathways, including the trimethylamine (TMA)/ trimethylamine N-oxide (TMAO) pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addition to these “metabolism dependent” pathways, metabolism independent processes are suggested to also potentially contribute to CVD pathogenesis. For example, heart failure associated splanchnic circulation congestion, bowel wall edema and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are believed to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets. PMID:28360349

Gut Microbiota in Cardiovascular Health and Disease.

PubMed

Tang, W H Wilson; Kitai, Takeshi; Hazen, Stanley L

2017-03-31

Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through many pathways, including the trimethylamine/trimethylamine N -oxide pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addition to these metabolism-dependent pathways, metabolism-independent processes are suggested to also potentially contribute to cardiovascular disease pathogenesis. For example, heart failure-associated splanchnic circulation congestion, bowel wall edema, and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are thought to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites, and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets. © 2017 American Heart Association, Inc.

The influence of proton pump inhibitors and other commonly used medication on the gut microbiota.

PubMed

Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Lopez Manosalva, Ailine G; Koonen, Debby P Y; Fu, Jingyuan; Wijmenga, Cisca; Zhernakova, Alexandra; Weersma, Rinse K

2017-07-04

Proton pump inhibitors (PPIs), used to treat gastro-esophageal reflux and prevent gastric ulcers, are among the most widely used drugs in the world. The use of PPIs is associated with an increased risk of enteric infections. Since the gut microbiota can, depending on composition, increase or decrease the risk of enteric infections, we investigated the effect of PPI-use on the gut microbiota. We discovered profound differences in the gut microbiota of PPI users: 20% of their bacterial taxa were statistically significantly altered compared with those of non-users. Moreover, we found that it is not only PPIs, but also antibiotics, antidepressants, statins and other commonly used medication were associated with distinct gut microbiota signatures. As a consequence, commonly used medications could affect how the gut microbiota resist enteric infections, promote or ameliorate gut inflammation, or change the host's metabolism. More studies are clearly needed to understand the role of commonly used medication in altering the gut microbiota as well as the subsequent health consequences.

Gut DNA viromes of Malawian twins discordant for severe acute malnutrition

USDA-ARS?s Scientific Manuscript database

The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with...

Multi-Omics Analysis Reveals a Correlation between the Host Phylogeny, Gut Microbiota and Metabolite Profiles in Cyprinid Fishes

PubMed Central

Li, Tongtong; Long, Meng; Li, Huan; Gatesoupe, François-Joël; Zhang, Xujie; Zhang, Qianqian; Feng, Dongyue; Li, Aihua

2017-01-01

Gut microbiota play key roles in host nutrition and metabolism. However, little is known about the relationship between host genetics, gut microbiota and metabolic profiles. Here, we used high-throughput sequencing and gas chromatography/mass spectrometry approaches to characterize the microbiota composition and the metabolite profiles in the gut of five cyprinid fish species with three different feeding habits raised under identical husbandry conditions. Our results showed that host species and feeding habits significantly affect not only gut microbiota composition but also metabolite profiles (ANOSIM, p ≤ 0.05). Mantel test demonstrated that host phylogeny, gut microbiota, and metabolite profiles were significantly related to each other (p ≤ 0.05). Additionally, the carps with the same feeding habits had more similarity in gut microbiota composition and metabolite profiles. Various metabolites were correlated positively with bacterial taxa involved in food degradation. Our results shed new light on the microbiome and metabolite profiles in the gut content of cyprinid fishes, and highlighted the correlations between host genotype, fish gut microbiome and putative functions, and gut metabolite profiles. PMID:28367147

Host Genetic and Environmental Effects on Mouse Cecum Microbiota

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

Campbell, James H; Foster, Carmen M; Vishnivetskaya, Tatiana A

2012-01-01

The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived frommore » a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.« less

Deterministic Assembly of Complex Bacterial Communities in Guts of Germ-Free Cockroaches

PubMed Central

Mikaelyan, Aram; Thompson, Claire L.; Hofer, Markus J.

2015-01-01

The gut microbiota of termites plays important roles in the symbiotic digestion of lignocellulose. However, the factors shaping the microbial community structure remain poorly understood. Because termites cannot be raised under axenic conditions, we established the closely related cockroach Shelfordella lateralis as a germ-free model to study microbial community assembly and host-microbe interactions. In this study, we determined the composition of the bacterial assemblages in cockroaches inoculated with the gut microbiota of termites and mice using pyrosequencing analysis of their 16S rRNA genes. Although the composition of the xenobiotic communities was influenced by the lineages present in the foreign inocula, their structure resembled that of conventional cockroaches. Bacterial taxa abundant in conventional cockroaches but rare in the foreign inocula, such as Dysgonomonas and Parabacteroides spp., were selectively enriched in the xenobiotic communities. Donor-specific taxa, such as endomicrobia or spirochete lineages restricted to the gut microbiota of termites, however, either were unable to colonize germ-free cockroaches or formed only small populations. The exposure of xenobiotic cockroaches to conventional adults restored their normal microbiota, which indicated that autochthonous lineages outcompete foreign ones. Our results provide experimental proof that the assembly of a complex gut microbiota in insects is deterministic. PMID:26655763

Microbiota-inducible Innate Immune, Siderophore Binding Protein Lipocalin 2 is Critical for Intestinal Homeostasis.

PubMed

Singh, Vishal; Yeoh, Beng San; Chassaing, Benoit; Zhang, Benyue; Saha, Piu; Xiao, Xia; Awasthi, Deepika; Shashidharamurthy, Rangaiah; Dikshit, Madhu; Gewirtz, Andrew; Vijay-Kumar, Matam

2016-07-01

Lipocalin 2 (Lcn2) is a multifunctional innate immune protein whose expression closely correlates with extent of intestinal inflammation. However, whether Lcn2 plays a role in the pathogenesis of gut inflammation is unknown. Herein, we investigated the extent to which Lcn2 regulates inflammation and gut bacterial dysbiosis in mouse models of IBD. Lcn2 expression was monitored in murine colitis models and upon microbiota ablation/restoration. WT and Lcn2 knockout ( Lcn2 KO) mice were analyzed for gut bacterial load, composition by 16S rRNA gene pyrosequencing and, their colitogenic potential by co-housing with Il-10 KO mice. Acute (dextran sodium sulfate) and chronic (IL-10R neutralization and T-cell adoptive transfer) colitis was induced in WT and Lcn2 KO mice with or without antibiotics. Lcn2 expression was dramatically induced upon inflammation and was dependent upon presence of a gut microbiota and MyD88 signaling. Use of bone-marrow chimeric mice revealed non-immune cells are the major contributors of circulating Lcn2. Lcn2 KO mice exhibited elevated levels of entA -expressing gut bacteria burden and, moreover, a broadly distinct bacterial community relative to WT littermates. Lcn2 KO mice developed highly colitogenic T-cells and exhibited exacerbated colitis upon exposure to DSS or neutralization of IL-10. Such exacerbated colitis could be prevented by antibiotic treatment. Moreover, exposure to the microbiota of Lcn2 KO mice, via cohousing, resulted in severe colitis in Il-10 KO mice. Lcn2 is a bacterially-induced, MyD88-dependent, protein that play an important role in gut homeostasis and a pivotal role upon challenge. Hence, therapeutic manipulation of Lcn2 levels may provide a strategy to help manage diseases driven by alteration of the gut microbiota.

Microbiota regulation of the Mammalian gut-brain axis.

PubMed

Burokas, Aurelijus; Moloney, Rachel D; Dinan, Timothy G; Cryan, John F

2015-01-01

The realization that the microbiota-gut-brain axis plays a critical role in health and disease has emerged over the past decade. The brain-gut axis is a bidirectional communication system between the central nervous system (CNS) and the gastrointestinal tract. Regulation of the microbiota-brain-gut axis is essential for maintaining homeostasis, including that of the CNS. The routes of this communication are not fully elucidated but include neural, humoral, immune, and metabolic pathways. A number of approaches have been used to interrogate this axis including the use of germ-free animals, probiotic agents, antibiotics, or animals exposed to pathogenic bacterial infections. Together, it is clear that the gut microbiota can be a key regulator of mood, cognition, pain, and obesity. Understanding microbiota-brain interactions is an exciting area of research which may contribute new insights into individual variations in cognition, personality, mood, sleep, and eating behavior, and how they contribute to a range of neuropsychiatric diseases ranging from affective disorders to autism and schizophrenia. Finally, the concept of psychobiotics, bacterial-based interventions with mental health benefit, is also emerging. Copyright © 2015 Elsevier Inc. All rights reserved.

Helminth Colonization Is Associated with Increased Diversity of the Gut Microbiota

PubMed Central

Lee, Soo Ching; Tang, Mei San; Lim, Yvonne A. L.; Choy, Seow Huey; Kurtz, Zachary D.; Cox, Laura M.; Gundra, Uma Mahesh; Cho, Ilseung; Bonneau, Richard; Blaser, Martin J.; Chua, Kek Heng; Loke, P'ng

2014-01-01

Soil-transmitted helminths colonize more than 1.5 billion people worldwide, yet little is known about how they interact with bacterial communities in the gut microbiota. Differences in the gut microbiota between individuals living in developed and developing countries may be partly due to the presence of helminths, since they predominantly infect individuals from developing countries, such as the indigenous communities in Malaysia we examine in this work. We compared the composition and diversity of bacterial communities from the fecal microbiota of 51 people from two villages in Malaysia, of which 36 (70.6%) were infected by helminths. The 16S rRNA V4 region was sequenced at an average of nineteen thousand sequences per samples. Helminth-colonized individuals had greater species richness and number of observed OTUs with enrichment of Paraprevotellaceae, especially with Trichuris infection. We developed a new approach of combining centered log-ratio (clr) transformation for OTU relative abundances with sparse Partial Least Squares Discriminant Analysis (sPLS-DA) to enable more robust predictions of OTU interrelationships. These results suggest that helminths may have an impact on the diversity, bacterial community structure and function of the gut microbiota. PMID:24851867

Black Raspberries and Their Anthocyanin and Fiber Fractions Alter the Composition and Diversity of Gut Microbiota in F-344 Rats.

PubMed

Pan, Pan; Lam, Vy; Salzman, Nita; Huang, Yi-Wen; Yu, Jianhua; Zhang, Jianying; Wang, Li-Shu

2017-01-01

Natural compounds can alter the diversity and composition of the gut microbiome, potentially benefiting our health. We previously demonstrated chemopreventive effects of black raspberries (BRBs) in colorectal cancer, which is associated with gut dysbiosis. To investigate the effects of whole BRBs and their fractions on gut microbiota, we fed F-344 rats a control diet, 5% BRBs, the BRB anthocyanin fraction, or the BRB residue fraction for 6 weeks. Feces were collected at baseline and at weeks 3 and 6, and bacterial sequence counts were analyzed. We observed distinct patterns of microbiota from different diet groups. Beta diversity analysis suggested that all diet groups exerted time-dependent changes in the bacterial diversity. Hierarchical clustering analysis revealed that post-diet fecal microbiota was segregated from baseline fecal microbiota within each diet. It is interesting to note that fractions of BRBs induced different changes in gut bacteria compared to whole BRBs. The abundance of specific microbial species known to have anti-inflammatory effects, such as Akkermansia and Desulfovibrio, was increased by whole BRBs and their residue. Further, butyrate-producing bacteria, e.g., Anaerostipes, were increased by whole BRBs. Our results suggest that whole BRBs and their fractions alter the gut microbiota in ways that could significantly influence human health.

Toward Personalized Control of Human Gut Bacterial Communities.

PubMed

David, Lawrence A

2018-01-01

A key challenge in microbiology will be developing tools for manipulating human gut bacterial communities. Our ability to predict and control the dynamics of these communities is now in its infancy. To manage human gut microbiota, I am developing methods in three research domains. First, I am refining in vitro tools to experimentally study gut microbes at high throughput and in controlled settings. Second, I am adapting "big data" techniques to overcome statistical challenges confronting microbiota modeling. Third, I am testing study designs that can streamline human testing of microbiota manipulations. Assembling these methods creates new challenges, including training scientists who can work across disciplines such as engineering, ecology, and medicine. Nevertheless, I envision that overcoming these obstacles will enable my group to construct platforms that can personalize microbiota treatments, particularly ones based on diet. More broadly, I anticipate that such platforms will have applications across fields such as agriculture, biotechnology, and environmental management.

Spatiotemporal microbiota dynamics from quantitative in vitro and in silico models of the gut

NASA Astrophysics Data System (ADS)

Hwa, Terence

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth behaviors, which ultimately dictate the gut microbiota composition. Combining measurements of bacterial growth physiology with analysis of published data on human physiology into a quantitative modeling framework, we show how hydrodynamic forces in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla in the gut. Our model quantitatively explains the observed variation of microbiota composition among healthy adults, and predicts colonic water absorption (manifested as stool consistency) and nutrient intake to be two key factors determining this composition. The model further reveals that both factors, which have been identified in recent correlative studies, exert their effects through the same mechanism: changes in colonic pH that differentially affect the growth of different bacteria. Our findings show that a predictive and mechanistic understanding of microbial ecology in the human gut is possible, and offer the hope for the rational design of intervention strategies to actively control the microbiota. This work is supported by the Bill and Melinda Gates Foundation.

Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem?

PubMed Central

Mosca, Alexis; Leclerc, Marion; Hugot, Jean P.

2016-01-01

Most of the Human diseases affecting westernized countries are associated with dysbiosis and loss of microbial diversity in the gut microbiota. The Western way of life, with a wide use of antibiotics and other environmental triggers, may reduce the number of bacterial predators leading to a decrease in microbial diversity of the Human gut. We argue that this phenomenon is similar to the process of ecosystem impoverishment in macro ecology where human activity decreases ecological niches, the size of predator populations, and finally the biodiversity. Such pauperization is fundamental since it reverses the evolution processes, drives life backward into diminished complexity, stability, and adaptability. A simple therapeutic approach could thus be to reintroduce bacterial predators and restore a bacterial diversity of the host microbiota. PMID:27065999

Gut Microbiota in Human Systemic Lupus Erythematosus and a Mouse Model of Lupus.

PubMed

Luo, Xin M; Edwards, Michael R; Mu, Qinghui; Yu, Yang; Vieson, Miranda D; Reilly, Christopher M; Ahmed, S Ansar; Bankole, Adegbenga A

2018-02-15

Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of the gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis in a small group of SLE patients with active disease. The composition of the gut microbiota changed markedly before and after the onset of lupus disease in NZB/W F1 mice, with greater diversity and increased representation of several bacterial species as lupus progressed from the predisease stage to the diseased stage. However, we did not control for age and the cage effect. Using dexamethasone as an intervention to treat SLE-like signs, we also found that a greater abundance of a group of lactobacilli (for which a species assignment could not be made) in the gut microbiota might be correlated with more severe disease in NZB/W F1 mice. Results of the human study suggest that, compared to control subjects without immune-mediated diseases, SLE patients with active lupus disease possessed an altered gut microbiota that differed in several particular bacterial species (within the genera Odoribacter and Blautia and an unnamed genus in the family Rikenellaceae ) and was less diverse, with increased representation of Gram-negative bacteria. The Firmicutes / Bacteroidetes ratios did not differ between the SLE microbiota and the non-SLE microbiota in our human cohort. IMPORTANCE SLE is a complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota has been reported for both mice and humans with SLE. In this emerging field, however, more studies are required to delineate the roles of the gut microbiota in different lupus-prone mouse models and people with diverse manifestations of SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice and a group of SLE patients with active disease. Copyright © 2018 American Society for Microbiology.

Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy.

PubMed

Kau, Andrew L; Planer, Joseph D; Liu, Jie; Rao, Sindhuja; Yatsunenko, Tanya; Trehan, Indi; Manary, Mark J; Liu, Ta-Chiang; Stappenbeck, Thaddeus S; Maleta, Kenneth M; Ashorn, Per; Dewey, Kathryn G; Houpt, Eric R; Hsieh, Chyi-Song; Gordon, Jeffrey I

2015-02-25

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by immunoglobulin A (IgA) from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to several bacterial taxa, including Enterobacteriaceae, correlated with anthropometric measurements of nutritional status in longitudinal studies. The relationship between IgA responses and growth was further explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA(+) bacterial consortium purified from the gut microbiota of undernourished children exhibited a diet-dependent enteropathy characterized by rapid disruption of the small intestinal and colonic epithelial barrier, weight loss, and sepsis that could be prevented by administering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection of 11 IgA-targeted strains from an undernourished donor, sufficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted with other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses have etiologic, diagnostic, and therapeutic implications for childhood undernutrition. Copyright © 2015, American Association for the Advancement of Science.

Gut microbiota as an epigenetic regulator: pilot study based on whole-genome methylation analysis.

PubMed

Kumar, Himanshu; Lund, Riikka; Laiho, Asta; Lundelin, Krista; Ley, Ruth E; Isolauri, Erika; Salminen, Seppo

2014-12-16

The core human gut microbiota contributes to the developmental origin of diseases by modifying metabolic pathways. To evaluate the predominant microbiota as an epigenetic modifier, we classified 8 pregnant women into two groups based on their dominant microbiota, i.e., Bacteroidetes, Firmicutes, and Proteobacteria. Deep sequencing of DNA methylomes revealed a clear association between bacterial predominance and epigenetic profiles. The genes with differentially methylated promoters in the group in which Firmicutes was dominant were linked to risk of disease, predominantly to cardiovascular disease and specifically to lipid metabolism, obesity, and the inflammatory response. This is one of the first studies that highlights the association of the predominant bacterial phyla in the gut with methylation patterns. Further longitudinal and in-depth studies targeting individual microbial species or metabolites are recommended to give us a deeper insight into the molecular mechanism of such epigenetic modifications. Epigenetics encompasses genomic modifications that are due to environmental factors and do not affect the nucleotide sequence. The gut microbiota has an important role in human metabolism and could be a significant environmental factor affecting our epigenome. To investigate the association of gut microbiota with epigenetic changes, we assessed pregnant women and selected the participants based on their predominant gut microbiota for a study on their postpartum methylation profile. Intriguingly, we found that blood DNA methylation patterns were associated with gut microbiota profiles. The gut microbiota profiles, with either Firmicutes or Bacteroidetes as a dominant group, correlated with differential methylation status of gene promoters functionally associated with cardiovascular diseases. Furthermore, differential methylation of gene promoters linked to lipid metabolism and obesity was observed. For the first time, we report here a position of the predominant gut microbiota in epigenetic profiling, suggesting one potential mechanism in obesity with comorbidities, if proven in further in-depth studies. Copyright © 2014 Kumar et al.

Studies on Modulation of Gut Microbiota by Wine Polyphenols: From Isolated Cultures to Omic Approaches

PubMed Central

Dueñas, Montserrat; Cueva, Carolina; Muñoz-González, Irene; Jiménez-Girón, Ana; Sánchez-Patán, Fernando; Santos-Buelga, Celestino; Moreno-Arribas, M. Victoria; Bartolomé, Begoña

2015-01-01

Moderate consumption of wine seems to produce positive health effects derived from the occurrence of bioactive polyphenols. The gut microbiota is involved in the metabolism of phenolic compounds, and these compounds and/or their metabolites may modulate gut microbiota through the stimulation of the growth of beneficial bacteria and the inhibition of pathogenic bacteria. The characterization of bacterial metabolites derived from polyphenols is essential in order to understand their effects, including microbial modulation, and therefore to associate dietary intake with particular health effects. This review aims to summarize the current information about the two-way “wine polyphenols–gut microbiota” interaction, from a perspective based on the experimental and analytical designs used. The availability of advanced methods for monitoring bacterial communities, along with the combination of in vitro and in vivo models, could help to assess the metabolism of polyphenols in the human body and to monitor total bacterial communities, and, therefore, to elucidate the implications of diet on the modulation of microbiota for delivering health benefits. PMID:26785335

The role of gut microbiota in human obesity: recent findings and future perspectives.

PubMed

Tagliabue, A; Elli, M

2013-03-01

In recent years, gut microbiota have gained a growing interest as an environmental factor that may affect the predisposition toward adiposity. In this review, we describe and discuss the research that has focused on the involvement of gut microbiota in human obesity. We also summarize the current knowledge concerning the health effects of the composition of gut microbiota, acquired using the most recent methodological approaches, and the potential influence of gut microbiota on adiposity, as revealed by animal studies. Original research studies that were published in English or French until December 2011 were selected through a computer-assisted literature search. The studies conducted to date show that there are differences in the gut microbiota between obese and normal-weight experimental animals. There is also evidence that a high-fat diet may induce changes in gut microbiota in animal models regardless of the presence of obesity. In humans, obesity has been associated with reduced bacterial diversity and an altered representation of bacterial species, but the identified differences are not homogeneous among the studies. The question remains as to whether changes in the intestinal microbial community are one of the environmental causes of overweight and obesity or if they are a consequence of obesity, specifically of the unbalanced diet that often accompanies the development of excess weight gain. In the future, larger studies on the potential role of intestinal microbiota in human obesity should be conducted at the species level using standardized analytical techniques and taking all of the possible confounding variables into account. Copyright © 2012 Elsevier B.V. All rights reserved.

A possible link of gut microbiota alteration in type 2 diabetes and Alzheimer's disease pathogenicity: an update.

PubMed

Alam, Mohammad Z; Alam, Qamre; Kamal, Mohammad A; Abuzenadah, Adel M; Haque, Absarul

2014-04-01

Imbalances in gut microbiota are associated with metabolic disorder, which are a group of obesity-related metabolic abnormalities that increase an individual's risk of developing type 2 diabetes (T2D) and Alzheimer's disease (AD). Although a number of risk factors have been postulated that may trigger the development of AD, the root cause of this disease is still a matter of debate. This review further investigates the etiology of AD by accumulating the current role played by gut microbiota in human, and trying to establish an inter-link between T2D and AD pathogenesis. There is a growing body of evidence which suggests that obesity is associated with alteration in the normal gut flora, reduced bacterial diversity, metabolic pathways and altered representation of bacterial genes. Obesity and T2D are considered to be induced as a result of changes within the composition of gut microbiota. The evidence gathered so far clearly advocates the involvement of gut microbes in causing obesity, a state of chronic and low-grade inflammation. Hence, understanding the microbiota of the gut is significant in relation to inflammation, as it is a key contributor for diabetes which has a direct relation to the AD pathogenesis. Comparative analysis of gut microbiota may enable further novel insight into the complex biology of AD, which is very important in order to take preventive measure such as early diagnosis, identification of new therapeutic targets and development of novel drugs.

The influence of proton pump inhibitors and other commonly used medication on the gut microbiota

PubMed Central

Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Koonen, Debby P.Y.; Fu, Jingyuan; Zhernakova, Alexandra; Weersma, Rinse K.

2017-01-01

ABSTRACT Proton pump inhibitors (PPIs), used to treat gastro-esophageal reflux and prevent gastric ulcers, are among the most widely used drugs in the world. The use of PPIs is associated with an increased risk of enteric infections. Since the gut microbiota can, depending on composition, increase or decrease the risk of enteric infections, we investigated the effect of PPI-use on the gut microbiota. We discovered profound differences in the gut microbiota of PPI users: 20% of their bacterial taxa were statistically significantly altered compared with those of non-users. Moreover, we found that it is not only PPIs, but also antibiotics, antidepressants, statins and other commonly used medication were associated with distinct gut microbiota signatures. As a consequence, commonly used medications could affect how the gut microbiota resist enteric infections, promote or ameliorate gut inflammation, or change the host's metabolism. More studies are clearly needed to understand the role of commonly used medication in altering the gut microbiota as well as the subsequent health consequences. PMID:28118083

Structural shifts of fecal microbial communities in rats with acute rejection after liver transplantation.

PubMed

Xie, Yirui; Luo, Zhuanbo; Li, Zhengfeng; Deng, Min; Liu, Hao; Zhu, Biao; Ruan, Bing; Li, Lanjuan

2012-08-01

Bacterial translocation and the development of sepsis after orthotopic liver transplantation (OLT) may be promoted by immunological damage to the intestinal mucosa or by quantitative and qualitative changes in intestinal microbiota. This study monitored structural shifts of gut microbiota in rats with OLT using PCR-denaturing gradient gel electrophoresis (DGGE) and real-time quantitative PCR (RT-qPCR). RT-qPCR targets six major microorganisms (Domain Bacteria, Bacteroides, Bifidobacteria, Enterobacteriaceae, Lactobacillus and Clostridium leptum subgroup). Isograft, Allograft and Sham model were studied. Bacterial translocation to host organs and plasma endotoxin were determined. Alteration in gut microbiota was associated with the elevation of plasma endotoxin and a higher rate of bacterial translocation (BT) to liver in rats with acute rejection. Dynamic analysis of DGGE fingerprints showed that the gut microbiota structure of animals in the three groups was similar before the operation. But significant alterations in the composition of fecal microbiota in Allograft group were observed at 1 and 2 weeks after the OLT. The acute rejection was accompanied by the shifts of gut microbiota towards members of Bacteroides and Ruminococcus. Results from RT-qPCR indicated that Bacteroides significantly increased at 2 weeks after the OLT, whereas numbers of Bifidobacterium spp. decreased at 1 week and recovered at 2 weeks after the OLT. In summary, our data showed that rats with acute rejection after OLT exhibited significant structure shifts in the gut microbiota which dominant by overgrowth of Bacteroides and Ruminococcus, and these were associated with elevation of plasma endotoxin and higher rate of BT.

Microbiota-induced peritrophic matrix regulates midgut homeostasis and prevents systemic infection of malaria vector mosquitoes

PubMed Central

Rodgers, Faye H.

2017-01-01

Manipulation of the mosquito gut microbiota can lay the foundations for novel methods for disease transmission control. Mosquito blood feeding triggers a significant, transient increase of the gut microbiota, but little is known about the mechanisms by which the mosquito controls this bacterial growth whilst limiting inflammation of the gut epithelium. Here, we investigate the gut epithelial response to the changing microbiota load upon blood feeding in the malaria vector Anopheles coluzzii. We show that the synthesis and integrity of the peritrophic matrix, which physically separates the gut epithelium from its luminal contents, is microbiota dependent. We reveal that the peritrophic matrix limits the growth and persistence of Enterobacteriaceae within the gut, whilst preventing seeding of a systemic infection. Our results demonstrate that the peritrophic matrix is a key regulator of mosquito gut homeostasis and establish functional analogies between this and the mucus layers of the mammalian gastrointestinal tract. PMID:28545061

Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.

PubMed

Woodhouse, C A; Patel, V C; Singanayagam, A; Shawcross, D L

2018-01-01

Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target. To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver. We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', 'alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website. Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation. Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of "healthy" bacteria may ameliorate the dysbiosis and alter prognosis. © 2017 John Wiley & Sons Ltd.

The role of diet on gut microbiota composition.

PubMed

Bibbò, S; Ianiro, G; Giorgio, V; Scaldaferri, F; Masucci, L; Gasbarrini, A; Cammarota, G

2016-11-01

Gut microbiota is characterized by an inter-individual variability due to genetic and environmental factors. Among the environmental ones, dietary habits play a key role in the modulation of gut microbiota composition. There are main differences between the intestinal microbiota of subjects fed with prevalent Western diet and that of subjects with a diet rich in fibers. Specific changes in the composition of gut microbiota have been demonstrated among subjects according to a different dietary intake. A particular diet may promote the growth of specific bacterial strains, driving hosts to a consequent alteration of fermentative metabolism, with a direct effect on intestinal pH, which can be responsible for the development of a pathogenic flora. Moreover, a high-fat diet can promote the development of a pro-inflammatory gut microbiota, with a consequent increase of intestinal permeability and, consequently, of circulating levels of lipopolysaccharides. In this review, we discuss the direct role of the diet in the composition of gut microbiota and about the possible clinical consequences.

Gut Microbiota and Energy Expenditure in Health and Obesity.

PubMed

Bakker, Guido J; Zhao, Jing; Herrema, Hilde; Nieuwdorp, Max

2015-01-01

The contribution of intestinal bacterial strains (gut microbiota) to the development of obesity and obesity-related disorders is increasingly recognized as a potential diagnostic and pharmacologic target. Alterations in the intestinal bacterial composition have been associated with presence of chronic low-grade inflammation, a known feature of insulin resistance and type 2 diabetes mellitus. However, causality still needs to be proven. Fecal transplantation studies in germ-free mice have provided crucial insight into the causality of gut microbiota in development of obesity and obesity-related disorders. Moreover, fecal transplantation studies in conjunction with fecal sampling in prospectively followed cohorts will help identify causally involved intestinal bacterial strains in human obesity. Results from these studies will lead to characterization of novel diagnostic markers as well as therapeutic strategies that aim to treat obesity and obesity-related disorders.

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.

Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota

PubMed Central

Chung, Hachung; Pamp, Sünje J.; Hill, Jonathan A.; Surana, Neeraj K.; Edelman, Sanna M.; Troy, Erin B.; Reading, Nicola C.; Villablanca, Eduardo J.; Wang, Sen; Mora, Jorge R.; Umesaki, Yoshinori; Mathis, Diane; Benoist, Christophe; Relman, David A.; Kasper, Dennis L.

2012-01-01

SUMMARY Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4+ and CD8+ T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression–all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system. PMID:22726443

Microbiota-based treatments in alcoholic liver disease.

PubMed

Sung, Hotaik; Kim, Seung Woo; Hong, Meegun; Suk, Ki Tae

2016-08-07

Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD.

Review article: potential mechanisms of action of rifaximin in the management of hepatic encephalopathy and other complications of cirrhosis.

PubMed

Bajaj, J S

2016-01-01

Progressive gut milieu (microbiota) changes occur in patients with cirrhosis and are associated with complications [e.g. hepatic encephalopathy (HE)]. To examine the role of rifaximin in the management of HE and other complications of cirrhosis, including potential mechanisms of action and the need for future studies. A literature search was conducted using the keywords 'rifaximin', 'hepatic encephalopathy', 'ascites', 'variceal bleeding', 'peritonitis', 'portal hypertension', 'portopulmonary hypertension' and 'hepatorenal syndrome'. The nonsystemic agent rifaximin reduces the risk of HE recurrence and HE-related hospitalisations in cirrhosis. In patients with cirrhosis, rifaximin modulates the bacterial composition of the gut microbiota without a consistent effect on overall faecal microbiota composition. However, rifaximin can impact the function or activities of the gut microbiota. For example, rifaximin significantly increased serum levels of long-chain fatty acids and carbohydrate metabolism intermediates in patients with minimal HE. Rifaximin also favourably affects serum proinflammatory cytokine and faecal secondary bile acid levels. The gut microenvironment and associated microbiota play an important role in the pathogenesis of HE and other cirrhosis-related complications. Rifaximin's clinical activity may be attributed to effects on metabolic function of the gut microbiota, rather than a change in the relative bacterial abundance. © 2015 John Wiley & Sons Ltd.

Microbiota-based treatments in alcoholic liver disease

PubMed Central

Sung, Hotaik; Kim, Seung Woo; Hong, Meegun; Suk, Ki Tae

2016-01-01

Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD. PMID:27547010

Evolutionary, ecological and biotechnological perspectives on plasmids resident in the human gut mobile metagenome

PubMed Central

Ogilvie, Lesley A.; Firouzmand, Sepinoud; Jones, Brian V.

2012-01-01

Numerous mobile genetic elements (MGE) are associated with the human gut microbiota and collectively referred to as the gut mobile metagenome. The role of this flexible gene pool in development and functioning of the gut microbial community remains largely unexplored, yet recent evidence suggests that at least some MGE comprising this fraction of the gut microbiome reflect the co-evolution of host and microbe in the gastro-intestinal tract. In conjunction, the high level of novel gene content typical of MGE coupled with their predicted high diversity, suggests that the mobile metagenome constitutes an immense and largely unexplored gene-space likely to encode many novel activities with potential biotechnological or pharmaceutical value, as well as being important to the development and functioning of the gut microbiota. Of the various types of MGE that comprise the gut mobile metagenome, plasmids are of particular importance since these elements are often capable of autonomous transfer between disparate bacterial species, and are known to encode accessory functions that increase bacterial fitness in a given environment facilitating bacterial adaptation. In this article current knowledge regarding plasmids resident in the human gut mobile metagenome is reviewed, and available strategies to access and characterize this portion of the gut microbiome are described. The relative merits of these methods and their present as well as prospective impact on our understanding of the human gut microbiota is discussed. PMID:22126801

The human gut resistome.

PubMed

van Schaik, Willem

2015-06-05

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota ('the gut resistome'). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium.

The human gut resistome

PubMed Central

van Schaik, Willem

2015-01-01

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota (‘the gut resistome’). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium. PMID:25918444

How mass spectrometric approaches applied to bacterial identification have revolutionized the study of human gut microbiota.

PubMed

Grégory, Dubourg; Chaudet, Hervé; Lagier, Jean-Christophe; Raoult, Didier

2018-03-01

Describing the human hut gut microbiota is one the most exciting challenges of the 21 st century. Currently, high-throughput sequencing methods are considered as the gold standard for this purpose, however, they suffer from several drawbacks, including their inability to detect minority populations. The advent of mass-spectrometric (MS) approaches to identify cultured bacteria in clinical microbiology enabled the creation of the culturomics approach, which aims to establish a comprehensive repertoire of cultured prokaryotes from human specimens using extensive culture conditions. Areas covered: This review first underlines how mass spectrometric approaches have revolutionized clinical microbiology. It then highlights the contribution of MS-based methods to culturomics studies, paying particular attention to the extension of the human gut microbiota repertoire through the discovery of new bacterial species. Expert commentary: MS-based approaches have enabled cultivation methods to be resuscitated to study the human gut microbiota and thus to fill in the blanks left by high-throughput sequencing methods in terms of culturing minority populations. Continued efforts to recover new taxa using culture methods, combined with their rapid implementation in genomic databases, would allow for an exhaustive analysis of the gut microbiota through the use of a comprehensive approach.

Microbial community structure in the gut of the New Zealand insect Auckland tree weta (Hemideina thoracica).

PubMed

Waite, David W; Dsouza, Melissa; Biswas, Kristi; Ward, Darren F; Deines, Peter; Taylor, Michael W

2015-05-01

The endemic New Zealand weta is an enigmatic insect. Although the insect is well known by its distinctive name, considerable size, and morphology, many basic aspects of weta biology remain unknown. Here, we employed cultivation-independent enumeration techniques and rRNA gene sequencing to investigate the gut microbiota of the Auckland tree weta (Hemideina thoracica). Fluorescence in situ hybridisation performed on different sections of the gut revealed a bacterial community of fluctuating density, while rRNA gene-targeted amplicon pyrosequencing revealed the presence of a microbial community containing high bacterial diversity, but an apparent absence of archaea. Bacteria were further studied using full-length 16S rRNA gene sequences, with statistical testing of bacterial community membership against publicly available termite- and cockroach-derived sequences, revealing that the weta gut microbiota is similar to that of cockroaches. These data represent the first analysis of the weta microbiota and provide initial insights into the potential function of these microorganisms.

Gut microbial metabolites of polyunsaturated fatty acids correlate with specific fecal bacteria and serum markers of metabolic syndrome in obese women.

PubMed

Druart, Céline; Dewulf, Evelyne M; Cani, Patrice D; Neyrinck, Audrey M; Thissen, Jean-Paul; Delzenne, Nathalie M

2014-04-01

The aim of this human study was to assess the influence of prebiotic-induced gut microbiota modulation on PUFA-derived bacterial metabolites production. Therefore, we analyzed the circulating fatty acid profile including CLA/CLnA in obese women treated during 3 months with inulin-type fructan prebiotics. In these patients, we had already determined gut microbiota composition by phylogenetic microarray and qPCR analysis of 16S rDNA. Some PUFA-derived bacterial metabolites were detected in the serum of obese patients. Despite the prebiotic-induced modulation of gut microbiota, including changes in CLA/CLnA-producing bacteria, the treatment did not impact significantly on the circulating level of these metabolites. However, some PUFA-derived bacterial metabolites were positively correlated with specific fecal bacteria (Bifidobacterium spp., Eubacterium ventriosum and Lactobacillus spp.) and inversely correlated with serum cholesterol (total, LDL, HDL). These correlations suggest a potential beneficial effect of some of these metabolites but this remains to be confirmed by further investigation.

Marked seasonal variation in the wild mouse gut microbiota.

PubMed

Maurice, Corinne F; Knowles, Sarah C L; Ladau, Joshua; Pollard, Katherine S; Fenton, Andy; Pedersen, Amy B; Turnbaugh, Peter J

2015-11-01

Recent studies have provided an unprecedented view of the microbial communities colonizing captive mice; yet the host and environmental factors that shape the rodent gut microbiota in their natural habitat remain largely unexplored. Here, we present results from a 2-year 16 S ribosomal RNA gene sequencing-based survey of wild wood mice (Apodemus sylvaticus) in two nearby woodlands. Similar to other mammals, wild mice were colonized by 10 bacterial phyla and dominated by the Firmicutes, Bacteroidetes and Proteobacteria. Within the Firmicutes, the Lactobacillus genus was most abundant. Putative bacterial pathogens were widespread and often abundant members of the wild mouse gut microbiota. Among a suite of extrinsic (environmental) and intrinsic (host-related) factors examined, seasonal changes dominated in driving qualitative and quantitative differences in the gut microbiota. In both years examined, we observed a strong seasonal shift in gut microbial community structure, potentially due to the transition from an insect- to a seed-based diet. This involved decreased levels of Lactobacillus, and increased levels of Alistipes (Bacteroidetes phylum) and Helicobacter. We also detected more subtle but statistically significant associations between the gut microbiota and biogeography, sex, reproductive status and co-colonization with enteric nematodes. These results suggest that environmental factors have a major role in shaping temporal variations in microbial community structure within natural populations.

Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota.

PubMed

Malo, M S; Alam, S Nasrin; Mostafa, G; Zeller, S J; Johnson, P V; Mohammad, N; Chen, K T; Moss, A K; Ramasamy, S; Faruqui, A; Hodin, S; Malo, P S; Ebrahimi, F; Biswas, B; Narisawa, S; Millán, J L; Warren, H S; Kaplan, J B; Kitts, C L; Hohmann, E L; Hodin, R A

2010-11-01

The intestinal microbiota plays a critical role in maintaining human health; however, the mechanisms governing the normal homeostatic number and composition of these microbes are largely unknown. Previously it was shown that intestinal alkaline phosphatase (IAP), a small intestinal brush border enzyme, functions as a gut mucosal defence factor limiting the translocation of gut bacteria to mesenteric lymph nodes. In this study the role of IAP in the preservation of the normal homeostasis of the gut microbiota was investigated. Bacterial culture was performed in aerobic and anaerobic conditions to quantify the number of bacteria in the stools of wild-type (WT) and IAP knockout (IAP-KO) C57BL/6 mice. Terminal restriction fragment length polymorphism, phylogenetic analyses and quantitative real-time PCR of subphylum-specific bacterial 16S rRNA genes were used to determine the compositional profiles of microbiotas. Oral supplementation of calf IAP (cIAP) was used to determine its effects on the recovery of commensal gut microbiota after antibiotic treatment and also on the colonisation of pathogenic bacteria. IAP-KO mice had dramatically fewer and also different types of aerobic and anaerobic microbes in their stools compared with WT mice. Oral supplementation of IAP favoured the growth of commensal bacteria, enhanced restoration of gut microbiota lost due to antibiotic treatment and inhibited the growth of a pathogenic bacterium (Salmonella typhimurium). IAP is involved in the maintenance of normal gut microbial homeostasis and may have therapeutic potential against dysbiosis and pathogenic infections.

Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats.

PubMed

Úbeda, María; Lario, Margaret; Muñoz, Leticia; Borrero, María-José; Rodríguez-Serrano, Macarena; Sánchez-Díaz, Ana-María; Del Campo, Rosa; Lledó, Lourdes; Pastor, Óscar; García-Bermejo, Laura; Díaz, David; Álvarez-Mon, Melchor; Albillos, Agustín

2016-05-01

In advanced cirrhosis, gut bacterial translocation is the consequence of intestinal barrier disruption and leads to bacterial infection. Bile acid abnormalities in cirrhosis could play a role in the integrity of the intestinal barrier and the control of microbiota, mainly through the farnesoid X receptor. We investigated the long-term effects of the farnesoid X receptor agonist, obeticholic acid, on gut bacterial translocation, intestinal microbiota composition, barrier integrity and inflammation in rats with CCl4-induced cirrhosis with ascites. Cirrhotic rats received a 2-week course of obeticholic acid or vehicle starting once ascites developed. We then determined: bacterial translocation by mesenteric lymph node culture, ileum expression of antimicrobial peptides and tight junction proteins by qPCR, fecal albumin loss, enteric bacterial load and microbiota composition by qPCR and pyrosequencing of ileum mucosa-attached contents, and intestinal inflammation by cytometry of the inflammatory infiltrate. Obeticholic acid reduced bacterial translocation from 78.3% to 33.3% (p<0.01) and upregulated the expression of the farnesoid X receptor-associated gene small heterodimer partner. Treatment improved ileum expression of antimicrobial peptides, angiogenin-1 and alpha-5-defensin, tight junction proteins zonulin-1 and occludin, and reduced fecal albumin loss and liver fibrosis. Enteric bacterial load normalized, and the distinctive mucosal microbiota of cirrhosis was reduced. Gut immune cell infiltration was reduced and inflammatory cytokine and Toll-like receptor 4 expression normalized. In ascitic cirrhotic rats, obeticholic acid reduces gut bacterial translocation via several complementary mechanisms at the intestinal level. This agent could be used as an alternative to antibiotics to prevent bacterial infection in cirrhosis. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[Gut microbiota and digestion of polysaccharides].

PubMed

El Kaoutari, Abdessamad; Armougom, Fabrice; Raoult, Didier; Henrissat, Bernard

2014-03-01

The distal gut microbiota corresponds to all the microorganisms, essentially bacteria, that reside commonly in the colon. The microbial population is characterized by a large taxonomical diversity, counting approximately a thousand distinct bacterial species for a single individual. The pace of investigations of this microbial system has greatly accelerated these last few years, fuelled by the advent of metagenomics techniques, which do not rely on bacterial cultivation, but utilize high throughput DNA sequencing. In just a few years studies of the intestinal microbiota have become fashionable, albeit with often contradictory results when attempting to correlate changes in microbial composition to diverse pathologies. The article focuses on one of the essential functions of the distal gut microbiota: the digestion of the immense variety of polysaccharides from our diet that enzymes of the host cannot breakdown. © 2014 médecine/sciences – Inserm.

ZiBuPiYin recipe improves cognitive decline by regulating gut microbiota in Zucker diabetic fatty rats

PubMed Central

Wang, Wang; Xiang, Hong; Xu, Huiying; Liang, Lina; Sui, Hua; Zhan, Libin; Lu, Xiaoguang

2017-01-01

Numerous researches supported that microbiota can influence behavior and modulate cognitive function through “microbiota-gut-brain” axis. Our previous study has demonstrated that ZiBuPiYin recipe (ZBPYR) possesses excellent pharmacological effects against diabetes-associated cognitive decline. To elucidate the role of ZBPYR in regulating the balance of gut microbiota to improve psychological-stress-induced diabetes-associated cognitive decline (PSDACD), we compared blood glucose, behavioral and cognitive functions and diversity of the bacterial community among experimental groups. The Zucker diabetic fatty (ZDF) rats with PSDACD exhibited behavioral and cognitive anomalies showing as increased anxiety- and depression-like behaviors and decreased learning and memory abilities. High-throughput sequencing of the bacterial 16S rRNA gene revealed that Roseburia and Coprococcus were decreased in ZDF rats with PSDACD compared with control group. Notably, these changes were reversed by ZBPYR treatment. Our findings indicate that ZBPYR might prevent PSDACD by maintaining the compositions of gut microbiota, which could be developed as a new therapy for T2D with PSDACD. PMID:28099913

ZiBuPiYin recipe improves cognitive decline by regulating gut microbiota in Zucker diabetic fatty rats.

PubMed

Gu, Chunyan; Zhou, Wen; Wang, Wang; Xiang, Hong; Xu, Huiying; Liang, Lina; Sui, Hua; Zhan, Libin; Lu, Xiaoguang

2017-04-25

Numerous researches supported that microbiota can influence behavior and modulate cognitive function through "microbiota-gut-brain" axis. Our previous study has demonstrated that ZiBuPiYin recipe (ZBPYR) possesses excellent pharmacological effects against diabetes-associated cognitive decline. To elucidate the role of ZBPYR in regulating the balance of gut microbiota to improve psychological-stress-induced diabetes-associated cognitive decline (PSDACD), we compared blood glucose, behavioral and cognitive functions and diversity of the bacterial community among experimental groups. The Zucker diabetic fatty (ZDF) rats with PSDACD exhibited behavioral and cognitive anomalies showing as increased anxiety- and depression-like behaviors and decreased learning and memory abilities. High-throughput sequencing of the bacterial 16S rRNA gene revealed that Roseburia and Coprococcus were decreased in ZDF rats with PSDACD compared with control group. Notably, these changes were reversed by ZBPYR treatment. Our findings indicate that ZBPYR might prevent PSDACD by maintaining the compositions of gut microbiota, which could be developed as a new therapy for T2D with PSDACD.

Gut Microbiota Markers in Obese Adolescent and Adult Patients: Age-Dependent Differential Patterns.

PubMed

Del Chierico, Federica; Abbatini, Francesca; Russo, Alessandra; Quagliariello, Andrea; Reddel, Sofia; Capoccia, Danila; Caccamo, Romina; Ginanni Corradini, Stefano; Nobili, Valerio; De Peppo, Francesco; Dallapiccola, Bruno; Leonetti, Frida; Silecchia, Gianfranco; Putignani, Lorenza

2018-01-01

Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in the pathophysiology of obesity. We investigated the composition of gut microbiota in obese adolescents and adults compared to age-matched normal weight (NW) volunteers in order to assemble age- and obesity-related microbiota profiles. The composition of gut microbiota was analyzed by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed, and univariate, multivariate, and correlation analyses performed on bacterial profiles. The prediction of metagenome functional content from 16S rRNA gene surveys was carried out. Ecological analyses revealed a dissimilarity among the subgroups, and resultant microbiota profiles differed between obese adolescents and adults. Using statistical analyses, we assigned, as microbial markers, Faecalibacterium prausnitzii and Actinomyces to the microbiota of obese adolescents, and Parabacteroides , Rikenellaceae, Bacteroides caccae , Barnesiellaceae, and Oscillospira to the microbiota of NW adolescents. The predicted metabolic profiles resulted different in adolescent groups. Particularly, biosynthesis of primary bile acid and steroid acids, metabolism of fructose, mannose, galactose, butanoate, and pentose phosphate and glycolysis/gluconeogenesis were for the majority associated to obese, while biosynthesis and metabolism of glycan, biosynthesis of secondary bile acid, metabolism of steroid hormone and lipoic acid were associated to NW adolescents. Our study revealed unique features of gut microbiota in terms of ecological patterns, microbial composition and metabolism in obese patients. The assignment of novel obesity bacterial markers may open avenues for the development of patient-tailored treatments dependent on age-related microbiota profiles.

Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation.

PubMed

Broecker, Felix; Klumpp, Jochen; Schuppler, Markus; Russo, Giancarlo; Biedermann, Luc; Hombach, Michael; Rogler, Gerhard; Moelling, Karin

2016-01-01

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infections (RCDIs). However, long-term effects on the patients' gut microbiota and the role of viruses remain to be elucidated. Here, we characterized bacterial and viral microbiota in the feces of a cured RCDI patient at various time points until 4.5 yr post-FMT compared with the stool donor. Feces were subjected to DNA sequencing to characterize bacteria and double-stranded DNA (dsDNA) viruses including phages. The patient's microbial communities varied over time and showed little overall similarity to the donor until 7 mo post-FMT, indicating ongoing gut microbiota adaption in this time period. After 4.5 yr, the patient's bacteria attained donor-like compositions at phylum, class, and order levels with similar bacterial diversity. Differences in the bacterial communities between donor and patient after 4.5 yr were seen at lower taxonomic levels. C. difficile remained undetectable throughout the entire timespan. This demonstrated sustainable donor feces engraftment and verified long-term therapeutic success of FMT on the molecular level. Full engraftment apparently required longer than previously acknowledged, suggesting the implementation of year-long patient follow-up periods into clinical practice. The identified dsDNA viruses were mainly Caudovirales phages. Unexpectedly, sequences related to giant algae-infecting Chlorella viruses were also detected. Our findings indicate that intestinal viruses may be implicated in the establishment of gut microbiota. Therefore, virome analyses should be included in gut microbiota studies to determine the roles of phages and other viruses-such as Chlorella viruses-in human health and disease, particularly during RCDI.

A role for bacterial urease in gut dysbiosis and Crohn’s disease

PubMed Central

Ni, Josephine; Shen, Ting-Chin David; Chen, Eric Z.; Bittinger, Kyle; Bailey, Aubrey; Roggiani, Manuela; Sirota-Madi, Alexandra; Friedman, Elliot S.; Chau, Lillian; Lin, Andrew; Nissim, Ilana; Scott, Justin; Lauder, Abigail; Hoffmann, Christian; Rivas, Gloriany; Albenberg, Lindsey; Baldassano, Robert N.; Braun, Jonathan; Xavier, Ramnik J.; Clish, Clary B.; Yudkoff, Marc; Li, Hongzhe; Goulian, Mark; Bushman, Frederic D.; Lewis, James D.; Wu, Gary D.

2018-01-01

Gut dysbiosis during inflammatory bowel disease involves alterations in the gut microbiota associated with inflammation of the host gut. We used a combination of shotgun metagenomic sequencing and metabolomics to analyze fecal samples from pediatric patients with Crohn’s disease and found an association between disease severity, gut dysbiosis, and bacterial production of free amino acids. Nitrogen flux studies using 15N in mice showed that activity of bacterial urease, an enzyme that releases ammonia by hydrolysis of host urea, led to the transfer of murine host-derived nitrogen to the gutmicrobiota where it was used for amino acid synthesis. Inoculation of a conventional murine host (pretreated with antibiotics and polyethylene glycol) with commensal Escherichia coli engineered to express urease led to dysbiosis of the gut microbiota, resulting in a predominance of Proteobacteria species. This was associated with a worsening of immune-mediated colitis in these animals. A potential role for altered urease expression and nitrogen flux in the development of gut dysbiosis suggests that bacterial urease may be a potential therapeutic target for inflammatory bowel diseases. PMID:29141885

Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan.

PubMed

Bäuerl, C; Collado, M C; Diaz Cuevas, A; Viña, J; Pérez Martínez, G

2018-06-01

Alzheimer's disease (AD) is the most common form of dementia and one of the major causes of disability and dependency in older people. Accumulating evidences link gut microbiota with different diseases and its relationship with neurodegenerative diseases is becoming most intriguing. This study was aimed to compare the gut microbiota of transgenic APP/PS1 (TG) mice, a well-established deterministic mouse model of AD, with their C57BL/6 wild-type (WT) littermates. Faecal samples were collected from 3-, 6- and 24-month-old mice and analysed by pyrosequencing of the V1-V3 region of the bacterial 16S rRNA genes. Bacterial profiles were similar in all young mice (3 months old), and started to diverge so that 6-month-old WT and TG mice had different and more diverse microbiota. During ageing, Turicibacteriaceae (typical mice bacterial group) and Rikenellaceae increased in all groups, although total Bacteroidetes remained stable. TG mice were characterized by an increase in Proteobacteria after 6 months, particularly the genus Sutterella (Betaproteobacteria), interestingly also increased in autism disorder. Also, the inflammation related family Erysipelotrichaceae was more abundant in TG mice at 24 months compared to wild-type control. In summary, AD pathology in mice shifts the gut microbiota towards profiles that share features with autism and inflammatory disorders. Alzheimer's disease is a neurodegenerative disease and neuroinflammation in the central nervous system appears to have a pivotal role. Using the transgenic APP/PS1 (TG) mouse model, we successfully characterized how AD pathology shifted gut microbiota composition during ageing towards an inflammation related bacterial profile related to Proteobacteria and Erysipelotrichaceae and suggest that these changes could contribute to disease progression and severity. Microbiota-targeted interventions could therefore represent a strategy to postpone disease symptoms. © 2018 The Society for Applied Microbiology.

Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism.

PubMed

Zhang, Limin; Xie, Cen; Nichols, Robert G; Chan, Siu H J; Jiang, Changtao; Hao, Ruixin; Smith, Philip B; Cai, Jingwei; Simons, Margaret N; Hatzakis, Emmanuel; Maranas, Costas D; Gonzalez, Frank J; Patterson, Andrew D

2016-01-01

The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism. Predictions about the metabolic contribution of the gut microbiota to the host were made using 16S rRNA-based PICRUSt ( p hylogenetic i nvestigation of c ommunities by r econstruction of u nobserved st ates), then validated using 1 H nuclear magnetic resonance-based metabolomics, and results were summarized by using genome-scale metabolic models. Oral Gly-MCA administration altered the gut microbial community structure, notably reducing the ratio of Firmicutes to Bacteroidetes and its PICRUSt-predicted metabolic function, including reduced production of short-chain fatty acids (substrates for hepatic gluconeogenesis and de novo lipogenesis) in the ceca of HFD-fed mice. Metabolic improvement was intestinal FXR dependent, as revealed by the lack of changes in HFD-fed intestine-specific Fxr -null ( Fxr ΔIE ) mice treated with Gly-MCA. Integrative analyses based on genome-scale metabolic models demonstrated an important link between Lactobacillus and Clostridia bile salt hydrolase activity and bacterial fermentation. Hepatic metabolite levels after Gly-MCA treatment correlated with altered levels of gut bacterial species. In conclusion, modulation of the gut microbiota by inhibition of intestinal FXR signaling alters host liver lipid metabolism and improves obesity-related metabolic dysfunction. IMPORTANCE The farnesoid X receptor (FXR) plays an important role in mediating the dialog between the host and gut microbiota, particularly through modulation of enterohepatic circulation of bile acids. Mounting evidence suggests that genetic ablation of Fxr in the gut or gut-restricted chemical antagonism of the FXR promotes beneficial health effects, including the prevention of nonalcoholic fatty liver disease in rodent models. However, questions remain unanswered, including whether modulation of FXR activity plays a role in shaping the gut microbiota community structure and function and what metabolic pathways of the gut microbiota contribute in an FXR-dependent manner to the host phenotype. In this report, new insights are gained into the metabolic contribution of the gut microbiota to the metabolic phenotypes, including establishing a link between FXR antagonism, bacterial bile salt hydrolase activity, and fermentation. Multiple approaches, including unique mouse models as well as metabolomics and genome-scale metabolic models, were employed to confirm these results.

Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism

PubMed Central

Zhang, Limin; Xie, Cen; Nichols, Robert G.; Chan, Siu H. J.; Jiang, Changtao; Hao, Ruixin; Smith, Philip B.; Cai, Jingwei; Simons, Margaret N.; Hatzakis, Emmanuel; Maranas, Costas D.; Gonzalez, Frank J.

2016-01-01

ABSTRACT The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism. Predictions about the metabolic contribution of the gut microbiota to the host were made using 16S rRNA-based PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), then validated using 1H nuclear magnetic resonance-based metabolomics, and results were summarized by using genome-scale metabolic models. Oral Gly-MCA administration altered the gut microbial community structure, notably reducing the ratio of Firmicutes to Bacteroidetes and its PICRUSt-predicted metabolic function, including reduced production of short-chain fatty acids (substrates for hepatic gluconeogenesis and de novo lipogenesis) in the ceca of HFD-fed mice. Metabolic improvement was intestinal FXR dependent, as revealed by the lack of changes in HFD-fed intestine-specific Fxr-null (FxrΔIE) mice treated with Gly-MCA. Integrative analyses based on genome-scale metabolic models demonstrated an important link between Lactobacillus and Clostridia bile salt hydrolase activity and bacterial fermentation. Hepatic metabolite levels after Gly-MCA treatment correlated with altered levels of gut bacterial species. In conclusion, modulation of the gut microbiota by inhibition of intestinal FXR signaling alters host liver lipid metabolism and improves obesity-related metabolic dysfunction. IMPORTANCE The farnesoid X receptor (FXR) plays an important role in mediating the dialog between the host and gut microbiota, particularly through modulation of enterohepatic circulation of bile acids. Mounting evidence suggests that genetic ablation of Fxr in the gut or gut-restricted chemical antagonism of the FXR promotes beneficial health effects, including the prevention of nonalcoholic fatty liver disease in rodent models. However, questions remain unanswered, including whether modulation of FXR activity plays a role in shaping the gut microbiota community structure and function and what metabolic pathways of the gut microbiota contribute in an FXR-dependent manner to the host phenotype. In this report, new insights are gained into the metabolic contribution of the gut microbiota to the metabolic phenotypes, including establishing a link between FXR antagonism, bacterial bile salt hydrolase activity, and fermentation. Multiple approaches, including unique mouse models as well as metabolomics and genome-scale metabolic models, were employed to confirm these results. PMID:27822554

Engineering the gut microbiota to treat hyperammonemia.

PubMed

Shen, Ting-Chin David; Albenberg, Lindsey; Bittinger, Kyle; Chehoud, Christel; Chen, Ying-Yu; Judge, Colleen A; Chau, Lillian; Ni, Josephine; Sheng, Michael; Lin, Andrew; Wilkins, Benjamin J; Buza, Elizabeth L; Lewis, James D; Daikhin, Yevgeny; Nissim, Ilana; Yudkoff, Marc; Bushman, Frederic D; Wu, Gary D

2015-07-01

Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility.

Diet dominates host genotype in shaping the murine gut microbiota

PubMed Central

Carmody, Rachel N.; Gerber, Georg K.; Luevano, Jesus M.; Gatti, Daniel M.; Somes, Lisa; Svenson, Karen L.; Turnbaugh, Peter J.

2014-01-01

SUMMARY Mammals exhibit marked inter-individual variations in their gut microbiota, but it remains unclear if this is primarily driven by host genetics or by extrinsic factors like dietary intake. To address this, we examined the effect of dietary perturbations on the gut microbiota of five inbred mouse strains, mice deficient for genes relevant to host-microbial interactions (MyD88−/−, NOD2−/−, ob/ob, and Rag1−/−), and >200 outbred mice. In each experiment, consumption of a high-fat, high-sugar diet reproducibly altered the gut microbiota despite differences in host genotype. The gut microbiota exhibited a linear dose response to dietary perturbations, taking an average of 3.5 days for each diet-responsive bacterial groups to reach a new steady state. Repeated dietary shifts demonstrated that most changes to the gut microbiota are reversible, while also uncovering bacteria whose abundance depends on prior consumption. These results emphasize the dominant role that diet plays in shaping inter-individual variations in host-associated microbial communities. PMID:25532804

Microbiota and gut-liver axis: their influences on obesity and obesity-related liver disease.

PubMed

Vajro, Pietro; Paolella, Giulia; Fasano, Alessio

2013-05-01

A specific bacterial gut microbiota profile with increased extraction of energy has recently been associated with obesity, which has been shown to be a transmissible phenotype by microbiota transplantation. At the same time, there is now increasing evidence that gut microbiota plays a role in the development of hepatic steatosis and its progression to nonalcoholic steatohepatitis. This review summarizes well known and unexpected interacting factors leading to obesity and its related hepatic diseases, including intestinal mucosal permeability and its regulation, gut microbiota and translocation of its biological products, and gut-associated lymphoid tissue. These intestinal factors dictate also the balance between tolerance and immune response, which are critical for most of the complications in near and far organs or systems. We review novel mechanisms involving the development of gut permeability and adipose tissue plasticity, for example, the cross-talk between the gut microbiota, lipopolysaccharide, high-fat diet, and the endocannabinoid system tone, which have not been fully explored. Interactions between gut microbiota and other factors (eg, inflammasome deficiency) also are reviewed as emerging but far from being completely elucidated mechanisms influencing the onset of obesity and nonalcoholic fatty liver disease.

TFH-IgA responses keep microbiota in check.

PubMed

Honda, Kenya

2015-02-11

In this issue of Cell Host & Microbe, Kubinak et al. (2015) demonstrate that gut microbiota-mediated signaling through MyD88 in CD4+ T cells induces their differentiation into T follicular helper (TFH) cells that promote affinity-matured microbiota antigen-specific immunoglobulin A (IgA) responses. These TFH-driven IgA responses are essential for maintaining gut bacterial diversity and a healthy microbiota. Copyright © 2015 Elsevier Inc. All rights reserved.

Temporal analysis of the effect of extruded flaxseed on the swine gut microbiota.

PubMed

Holman, Devin B; Baurhoo, Bushansingh; Chénier, Martin R

2014-10-01

Flaxseed is a rich source of α-linolenic acid, an essential ω-3 fatty acid reported to have beneficial health effects in humans. Feeding swine a diet supplemented with flaxseed has been found to enrich pork products with ω-3 fatty acids. However, the effect of flaxseed supplementation on the swine gut microbiota has not been assessed to date. The purpose of this study was to investigate if extruded flaxseed has any impact on the bacterial and archaeal microbiota in the feces of growing-finishing pigs over a 51-day period, using denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Bacterial DGGE profile analysis revealed major temporal shifts in the bacterial microbiota with only minor ones related to diet. The archaeal microbiota was significantly less diverse than that of Bacteria. The majority of bacterial DGGE bands sequenced belonged to the Firmicutes phylum while the archaeal DGGE bands were found to consist of only 2 species, Methanobrevibacter smithii and Methanosphaera stadtmanae. The abundance of Bacteroidetes decreased significantly from day 0 to day 21 in all diet groups while the abundance of Firmicutes was relatively stable across all diet cohorts and sampling times. There was also no significant correlation between pig mass and the ratio of Firmicutes to Bacteroidetes. While the addition of extruded flaxseed to the feed of growing-finishing pigs was beneficial for improving ω-3 fatty acid content of pork, it had no detectable impact on the fecal bacterial and archaeal microbiota, suggesting that extruded flaxseed may be used to improve meat quality without adverse effect on the swine gut microbiota or animal performance.

Dietary supplementation with rice bran or navy bean alters gut bacterial metabolism in colorectal cancer survivors.

PubMed

Sheflin, Amy M; Borresen, Erica C; Kirkwood, Jay S; Boot, Claudia M; Whitney, Alyssa K; Lu, Shen; Brown, Regina J; Broeckling, Corey D; Ryan, Elizabeth P; Weir, Tiffany L

2017-01-01

Heat-stabilized rice bran (SRB) and cooked navy bean powder (NBP) contain a variety of phytochemicals that are fermented by colonic microbiota and may influence intestinal health. Dietary interventions with these foods should be explored for modulating colorectal cancer risk. A randomized-controlled pilot clinical trial investigated the effects of eating SRB (30 g/day) or cooked navy bean powder (35 g/day) on gut microbiota and metabolites (NCT01929122). Twenty-nine overweight/obese volunteers with a prior history of colorectal cancer consumed a study-provided meal and snack daily for 28 days. Volunteers receiving SRB or NBP showed increased gut bacterial diversity and altered gut microbial composition at 28 days compared to baseline. Supplementation with SRB or NBP increased total dietary fiber intake similarly, yet only rice bran intake led to a decreased Firmicutes:Bacteroidetes ratio and increased SCFA (propionate and acetate) in stool after 14 days but not at 28 days. These findings support modulation of gut microbiota and fermentation byproducts by SRB and suggest that foods with similar ability to increase dietary fiber intake may not have equal effects on gut microbiota and microbial metabolism. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Classifying the bacterial gut microbiota of termites and cockroaches: A curated phylogenetic reference database (DictDb).

PubMed

Mikaelyan, Aram; Köhler, Tim; Lampert, Niclas; Rohland, Jeffrey; Boga, Hamadi; Meuser, Katja; Brune, Andreas

2015-10-01

Recent developments in sequencing technology have given rise to a large number of studies that assess bacterial diversity and community structure in termite and cockroach guts based on large amplicon libraries of 16S rRNA genes. Although these studies have revealed important ecological and evolutionary patterns in the gut microbiota, classification of the short sequence reads is limited by the taxonomic depth and resolution of the reference databases used in the respective studies. Here, we present a curated reference database for accurate taxonomic analysis of the bacterial gut microbiota of dictyopteran insects. The Dictyopteran gut microbiota reference Database (DictDb) is based on the Silva database but was significantly expanded by the addition of clones from 11 mostly unexplored termite and cockroach groups, which increased the inventory of bacterial sequences from dictyopteran guts by 26%. The taxonomic depth and resolution of DictDb was significantly improved by a general revision of the taxonomic guide tree for all important lineages, including a detailed phylogenetic analysis of the Treponema and Alistipes complexes, the Fibrobacteres, and the TG3 phylum. The performance of this first documented version of DictDb (v. 3.0) using the revised taxonomic guide tree in the classification of short-read libraries obtained from termites and cockroaches was highly superior to that of the current Silva and RDP databases. DictDb uses an informative nomenclature that is consistent with the literature also for clades of uncultured bacteria and provides an invaluable tool for anyone exploring the gut community structure of termites and cockroaches. Copyright © 2015 Elsevier GmbH. All rights reserved.

Ménage à trois in the human gut: interactions between host, bacteria and phages.

PubMed

Mirzaei, Mohammadali Khan; Maurice, Corinne F

2017-07-01

The human gut is host to one of the densest microbial communities known, the gut microbiota, which contains bacteria, archaea, viruses, fungi and other microbial eukaryotes. Bacteriophages in the gut are largely unexplored, despite their potential to regulate bacterial communities and thus human health. In addition to helping us understand gut homeostasis, applying an ecological perspective to the study of bacterial and phage communities in the gut will help us to understand how this microbial system functions. For example, temporal studies of bacteria, phages and host immune cells in the gut during health and disease could provide key information about disease development and inform therapeutic treatments, whereas understanding the regulation of the replication cycles of phages could help harness the gut microbiota to improve disease outcomes. As the most abundant biological entities in our gut, we must consider bacteriophages in our pursuit of personalized medicine.

Comparison of the gut microbiota composition between wild and captive sika deer (Cervus nippon hortulorum) from feces by high-throughput sequencing.

PubMed

Guan, Yu; Yang, Haitao; Han, Siyu; Feng, Limin; Wang, Tianming; Ge, Jianping

2017-11-23

The gut microbiota is characterized as a complex ecosystem that has effects on health and diseases of host with the interactions of many other factors together. Sika deer is the national level for the protection of wild animals in China. The available sequencing data of gut microbiota from feces of wild sika deer, especially for Cervus nippon hortulorum in Northeast China, are limited. Here, we characterized the gastrointestinal bacterial communities of wild (7 samples) and captive (12 samples) sika deer from feces, and compared their gut microbiota by analyzing the V3-V4 region of 16S rRNA gene using high-throughput sequencing technology on the Illumina Hiseq platform. Firmicutes (77.624%), Bacteroidetes (18.288%) and Tenericutes (1.342%) were the most predominant phyla in wild sika deer. While in captive sika deer, Firmicutes (50.710%) was the dominant phylum, followed by Bacteroidetes (31.996%) and Proteobacteria (4.806%). A total of 9 major phyla, 22 families and 30 genera among gastrointestinal bacterial communities showed significant differences between wild and captive sika deer. The specific function and mechanism of Tenericutes in wild sika deer need further study. Our results indicated that captive sika deer in farm had higher fecal bacterial diversity than the wild. Abundance and quantity of diet source for sika deer played crucial role in shaping the composition and structure of gut microbiota.

Review article: the antimicrobial effects of rifaximin on the gut microbiota.

PubMed

DuPont, H L

2016-01-01

Disruption of the gut microbiota through use of systemic antimicrobials or activation of the mucosal inflammatory response by pathogens can cause dysregulation of the intestinal mucosa. To explore the mechanisms of action of rifaximin that may underlie its clinical benefits in travellers' diarrhoea (TD). A literature search was performed using the terms 'rifaximin' and 'L/105' in combination with the terms 'in vitro activity', 'diarrhea', 'microbiota' and 'gut flora'. Rifaximin has been traditionally identified as a nonsystemic, broad-spectrum, bactericidal antibiotic. Evidence shows that the activity of rifaximin against enteropathogens in this setting is likely enhanced by its increased solubility in the presence of bile acids in the small intestine. Results of clinical studies show that although rifaximin is efficacious in TD, a clinical cure often occurs without apparent bacterial eradication and with minimal effect on the gut microbiota, suggesting an effect of rifaximin other than direct antibiotic activity. Although definitive studies on the effect of rifaximin on the gut microbiota in large cohorts of healthy volunteers or patients have not been published, pre-clinical studies provide some insight. These studies have shown that rifaximin may have effects on both the pathogen and host, including direct effects on pathogenic bacteria (such as reducing the expression of bacterial virulence factors) and indirect effects on the host (such as inhibiting bacterial attachment and internalisation at the intestinal mucosa and reducing mucosal inflammation). © 2015 John Wiley & Sons Ltd.

Is the Gut Microbiota a New Factor Contributing to Obesity and Its Metabolic Disorders?

PubMed Central

Harris, Kristina; Kassis, Amira; Major, Geneviève; Chou, Chieh J.

2012-01-01

The gut microbiota refers to the trillions of microorganisms residing in the intestine and is integral in multiple physiological processes of the host. Recent research has shown that gut bacteria play a role in metabolic disorders such as obesity, diabetes, and cardiovascular diseases. The mechanisms by which the gut microbiota affects metabolic diseases are by two major routes: (1) the innate immune response to the structural components of bacteria (e.g., lipopolysaccharide) resulting in inflammation and (2) bacterial metabolites of dietary compounds (e.g., SCFA from fiber), which have biological activities that regulate host functions. Gut microbiota has evolved with humans as a mutualistic partner, but dysbiosis in a form of altered gut metagenome and collected microbial activities, in combination with classic genetic and environmental factors, may promote the development of metabolic disorders. This paper reviews the available literature about the gut microbiota and aforementioned metabolic disorders and reveals the gaps in knowledge for future study. PMID:22315672

Degradation of Marine Algae-Derived Carbohydrates by Bacteroidetes Isolated from Human Gut Microbiota.

PubMed

Li, Miaomiao; Shang, Qingsen; Li, Guangsheng; Wang, Xin; Yu, Guangli

2017-03-24

Carrageenan, agarose, and alginate are algae-derived undigested polysaccharides that have been used as food additives for hundreds of years. Fermentation of dietary carbohydrates of our food in the lower gut of humans is a critical process for the function and integrity of both the bacterial community and host cells. However, little is known about the fermentation of these three kinds of seaweed carbohydrates by human gut microbiota. Here, the degradation characteristics of carrageenan, agarose, alginate, and their oligosaccharides, by Bacteroides xylanisolvens , Bacteroides ovatus , and Bacteroides uniforms , isolated from human gut microbiota, are studied.

Degradation of Marine Algae-Derived Carbohydrates by Bacteroidetes Isolated from Human Gut Microbiota

PubMed Central

Li, Miaomiao; Shang, Qingsen; Li, Guangsheng; Wang, Xin; Yu, Guangli

2017-01-01

Carrageenan, agarose, and alginate are algae-derived undigested polysaccharides that have been used as food additives for hundreds of years. Fermentation of dietary carbohydrates of our food in the lower gut of humans is a critical process for the function and integrity of both the bacterial community and host cells. However, little is known about the fermentation of these three kinds of seaweed carbohydrates by human gut microbiota. Here, the degradation characteristics of carrageenan, agarose, alginate, and their oligosaccharides, by Bacteroides xylanisolvens, Bacteroides ovatus, and Bacteroides uniforms, isolated from human gut microbiota, are studied. PMID:28338633

Probiotics, gut microbiota and health.

PubMed

Butel, M-J

2014-01-01

The human gut is a huge complex ecosystem where microbiota, nutrients, and host cells interact extensively, a process crucial for the gut homeostasis and host development with a real partnership. The various bacterial communities that make up the gut microbiota have many functions including metabolic, barrier effect, and trophic functions. Hence, any dysbiosis could have negative consequences in terms of health and many diseases have been associated to impairment of the gut microbiota. These close relationships between gut microbiota, health, and disease, have led to great interest in using probiotics (i.e. live micro-organisms), or prebiotics (i.e. non-digestible substrates) to positively modulate the gut microbiota to prevent or treat some diseases. This review focuses on probiotics, their mechanisms of action, safety, and major health benefits. Health benefits remain to be proven in some indications, and further studies on the best strain(s), dose, and algorithm of administration to be used are needed. Nevertheless, probiotic administration seems to have a great potential in terms of health that justifies more research. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Conditionally Pathogenic Gut Microbes Promote Larval Growth by Increasing Redox-Dependent Fat Storage in High-Sugar Diet-Fed Drosophila.

PubMed

Whon, Tae Woong; Shin, Na-Ri; Jung, Mi-Ja; Hyun, Dong-Wook; Kim, Hyun Sik; Kim, Pil Soo; Bae, Jin-Woo

2017-12-01

Changes in the composition of the gut microbiota contribute to the development of obesity and subsequent complications that are associated with metabolic syndrome. However, the role of increased numbers of certain bacterial species during the progress of obesity and factor(s) controlling the community structure of gut microbiota remain unclear. Here, we demonstrate the inter-relationship between Drosophila melanogaster and their resident gut microbiota under chronic high-sugar diet (HSD) conditions. Chronic feeding of an HSD to Drosophila resulted in a predominance of resident uracil-secreting bacteria in the gut. Axenic insects mono-associated with uracil-secreting bacteria or supplemented with uracil under HSD conditions promoted larval development. Redox signaling induced by bacterial uracil promoted larval growth by regulating sugar and lipid metabolism via activation of p38a mitogen-activated protein kinase. The present study identified a new redox-dependent mechanism by which uracil-secreting bacteria (previously regarded as opportunistic pathobionts) protect the host from metabolic perturbation under chronic HSD conditions. These results illustrate how Drosophila and gut microbes form a symbiotic relationship under stress conditions, and changes in the gut microbiota play an important role in alleviating deleterious diet-derived effects such as hyperglycemia. Antioxid. Redox Signal. 27, 1361-1380.

Bacterial community composition in the gut content of Lampetra japonica revealed by 16S rRNA gene pyrosequencing.

PubMed

Zuo, Yu; Xie, Wenfang; Pang, Yue; Li, Tiesong; Li, Qingwei; Li, Yingying

2017-01-01

The composition of the bacterial communities in the hindgut contents of Lampetrs japonica was surveyed by Illumina MiSeq of the 16S rRNA gene. An average of 32385 optimized reads was obtained from three samples. The rarefaction curve based on the operational taxonomic units tended to approach the asymptote. The rank abundance curve representing the species richness and evenness was calculated. The composition of microbe in six classification levels was also analyzed. Top 20 members in genera level were displayed as the classification tree. The abundance of microorganisms in different individuals was displayed as the pie charts at the branch nodes in the classification tree. The differences of top 50 genera in abundance between individuals of lamprey are displayed as a heatmap. The pairwise comparison of bacterial taxa abundance revealed that there are no significant differences of gut microbiota between three individuals of lamprey at a given rarefied depth. Also, the gut microbiota derived from L. japonica displays little similarity with other aquatic organism of Vertebrata after UPGMA analysis. The metabolic function of the bacterial communities was predicted through KEGG analysis. This study represents the first analysis of the bacterial community composition in the gut content of L. japonica. The investigation of the gut microbiota associated with L. japonica will broaden our understanding of this unique organism.

Microbiome and bacterial translocation in cirrhosis.

PubMed

Gómez-Hurtado, Isabel; Such, José; Francés, Rubén

2016-12-01

Qualitative and quantitative changes in gut microbiota play a very important role in cirrhosis. Humans harbour around 100 quintillion gut bacteria, thus representing around 10 times more microbial cells than eukaryotic ones. The gastrointestinal tract is the largest surface area in the body and it is subject to constant exposure to these living microorganisms. The existing symbiosis, proven by the lack of proinflammatory response against commensal bacteria, implies the presence of clearly defined communication lines that contribute to the maintenance of homeostasis of the host. Therefore, alterations of gut flora seem to play a role in the pathogenesis and progress of multiple liver and gastrointestinal diseases. This has made its selective modification into an area of high therapeutic interest. Bacterial translocation is defined as the migration of bacteria or bacterial products from the intestines to the mesenteric lymph nodes. It follows that alteration in gut microbiota have shown importance, at least to some extent, in the pathogenesis of several complications arising from terminal liver disease, such as hepatic encephalopathy, portal hypertension and spontaneous bacterial peritonitis. This review sums up, firstly, how liver disease can alter the common composition of gut microbiota, and secondly, how this alteration contributes to the development of complications in cirrhosis. Copyright © 2015 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

Pathogen-mediated manipulation of arthropod microbiota to promote infection

PubMed Central

Abraham, Nabil M.; Liu, Lei; Jutras, Brandon Lyon; Yadav, Akhilesh K.; Narasimhan, Sukanya; Gopalakrishnan, Vissagan; Ansari, Juliana M.; Jefferson, Kimberly K.; Cava, Felipe; Jacobs-Wagner, Christine; Fikrig, Erol

2017-01-01

Arthropods transmit diverse infectious agents; however, the ways microbes influence their vector to enhance colonization are poorly understood. Ixodes scapularis ticks harbor numerous human pathogens, including Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. We now demonstrate that A. phagocytophilum modifies the I. scapularis microbiota to more efficiently infect the tick. A. phagocytophilum induces ticks to express Ixodes scapularis antifreeze glycoprotein (iafgp), which encodes a protein with several properties, including the ability to alter bacterial biofilm formation. IAFGP thereby perturbs the tick gut microbiota, which influences the integrity of the peritrophic matrix and gut barrier—critical obstacles for Anaplasma colonization. Mechanistically, IAFGP binds the terminal d-alanine residue of the pentapeptide chain of bacterial peptidoglycan, resulting in altered permeability and the capacity of bacteria to form biofilms. These data elucidate the molecular mechanisms by which a human pathogen appropriates an arthropod antibacterial protein to alter the gut microbiota and more effectively colonize the vector. PMID:28096373

The microbiota: an exercise immunology perspective.

PubMed

Bermon, Stéphane; Petriz, Bernardo; Kajėnienė, Alma; Prestes, Jonato; Castell, Lindy; Franco, Octavio L

2015-01-01

The gut microbiota consists of a cluster of microorganisms that produces several signaling molecules of a hormonal nature which are released into the blood stream and act at distal sites. There is a growing body of evidence indicating that microbiota may be modulated by several environmental conditions, including different exercise stimulus, as well some pathologies. Enriched bacterial diversity has also been associated with improved health status and alterations in immune system, making multiple connections between host and microbiota. Experimental evidence has shown that reduced levels and variations in the bacterial community are associated with health impairments, while increased microbiota diversity improves metabolic profile and immunological responses. So far, very few controlled studies have focused on the interactions between acute or chronic exercise and the gut microbiota. However, some preliminary experimental data obtained from animal studies or probiotics studies show some interesting results at the immune level, indicating that the microbiota also acts like an endocrine organ and is sensitive to the homeostatic and physiological changes associated with exercise. Thus, our review intends to shed some light on the interaction between gut microbiota, exercise and immunomodulation. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

Variation in the Gut Microbiota of Termites (Tsaitermes ampliceps) Against Different Diets.

PubMed

Su, Lijuan; Yang, Lele; Huang, Shi; Li, Yan; Su, Xiaoquan; Wang, Fengqin; Bo, Cunpei; Wang, En Tao; Song, Andong

2017-01-01

Termites are well recognized for their thriving on recalcitrant lignocellulosic diets through nutritional symbioses with gut-dwelling microbiota; however, the effects of diet changes on termite gut microbiota are poorly understood, especially for the lower termites. In this study, we employed high-throughput 454 pyrosequencing of 16S V1-V3 amplicons to compare gut microbiotas of Tsaitermes ampliceps fed with lignin-rich and lignin-poor cellulose diets after a 2-week-feeding period. As a result, the majority of bacterial taxa were shared across the treatments with different diets, but their relative abundances were modified. In particular, the relative abundance was reduced for Spirochaetes and it was increased for Proteobacteria and Bacteroides by feeding the lignin-poor diet. The evenness of gut microbiota exhibited a significant difference in response to the diet type (filter paper diets < corn stover diets < wood diets), while their richness was constant, which may be related to the lower recalcitrance of this biomass to degradation. These results have important implications for sampling and analysis strategies to probe the lignocellulose degradation features of termite gut microbiota and suggest that the dietary lignocellulose composition could cause shifting rapidly in the termite gut microbiota.

Cross-regulatory circuit between AHR and microbiota.

PubMed

Ji, Jian; Qu, Hao

2018-01-29

The gut microbes have a close symbiotic relationship with their host. Interactions between host and the microbiota affect the nutritional, immunological, and physiological status of the host. The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that mediates the toxicity of xenobiotics. Recently, the relationship between the gut microbiota and AHR has attracted the attention of many researchers. The AHR influences the intestinal microbiota population and mediates host-microbe homeostasis. Interestingly, the gut microbiota also produces ligands of AHR from bacterial metabolism and thereby activates the AHR signaling pathway. This review presents current knowledge of the cross-regulatory circuit between the AHR and intestinal microbiota. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Honeybee gut microbiota promotes host weight gain via bacterial metabolism and hormonal signaling

PubMed Central

Powell, J. Elijah; Steele, Margaret I.; Dietrich, Carsten; Moran, Nancy A.

2017-01-01

Social bees harbor a simple and specialized microbiota that is spatially organized into different gut compartments. Recent results on the potential involvement of bee gut communities in pathogen protection and nutritional function have drawn attention to the impact of the microbiota on bee health. However, the contributions of gut microbiota to host physiology have yet to be investigated. Here we show that the gut microbiota promotes weight gain of both whole body and the gut in individual honey bees. This effect is likely mediated by changes in host vitellogenin, insulin signaling, and gustatory response. We found that microbial metabolism markedly reduces gut pH and redox potential through the production of short-chain fatty acids and that the bacteria adjacent to the gut wall form an oxygen gradient within the intestine. The short-chain fatty acid profile contributed by dominant gut species was confirmed in vitro. Furthermore, metabolomic analyses revealed that the gut community has striking impacts on the metabolic profiles of the gut compartments and the hemolymph, suggesting that gut bacteria degrade plant polymers from pollen and that the resulting metabolites contribute to host nutrition. Our results demonstrate how microbial metabolism affects bee growth, hormonal signaling, behavior, and gut physicochemical conditions. These findings indicate that the bee gut microbiota has basic roles similar to those found in some other animals and thus provides a model in studies of host–microbe interactions. PMID:28420790

Sex differences in colonization of gut microbiota from a man with short-term vegetarian and inulin-supplemented diet in germ-free mice.

PubMed

Wang, Jing-Jing; Wang, Jing; Pang, Xiao-Yan; Zhao, Li-Ping; Tian, Ling; Wang, Xing-Peng

2016-10-31

Gnotobiotic mouse model is generally used to evaluate the efficacy of gut microbiota. Sex differences of gut microbiota are acknowledged, yet the effect of recipient's gender on the bacterial colonization remains unclear. Here we inoculated male and female germ-free C57BL/6J mice with fecal bacteria from a man with short-term vegetarian and inulin-supplemented diet. We sequenced bacterial 16S rRNA genes V3-V4 region from donor's feces and recipient's colonic content. Shannon diversity index showed female recipients have higher bacteria diversity than males. Weighted UniFrac principal coordinates analysis revealed the overall structures of male recipient's gut microbiota were significantly separated from those of females, and closer to the donor. Redundancy analysis identified 46 operational taxonomic units (OTUs) differed between the sexes. The relative abundance of 13 OTUs were higher in males, such as Parabacteroides distasonis and Blautia faecis, while 33 OTUs were overrepresented in females, including Clostridium groups and Escherichia fergusonii/Shigella sonnei. Moreover, the interactions of these differential OTUs were sexually distinct. These findings demonstrated that the intestine of male and female mice preferred to accommodate microbiota differently. Therefore, it is necessary to designate the gender of gnotobiotic mice for complete evaluation of modulatory effects of gut microbiota from human feces upon diseases.

Sex differences in colonization of gut microbiota from a man with short-term vegetarian and inulin-supplemented diet in germ-free mice

PubMed Central

Wang, Jing-jing; Wang, Jing; Pang, Xiao-yan; Zhao, Li-ping; Tian, Ling; Wang, Xing-peng

2016-01-01

Gnotobiotic mouse model is generally used to evaluate the efficacy of gut microbiota. Sex differences of gut microbiota are acknowledged, yet the effect of recipient’s gender on the bacterial colonization remains unclear. Here we inoculated male and female germ-free C57BL/6J mice with fecal bacteria from a man with short-term vegetarian and inulin-supplemented diet. We sequenced bacterial 16S rRNA genes V3-V4 region from donor’s feces and recipient’s colonic content. Shannon diversity index showed female recipients have higher bacteria diversity than males. Weighted UniFrac principal coordinates analysis revealed the overall structures of male recipient’s gut microbiota were significantly separated from those of females, and closer to the donor. Redundancy analysis identified 46 operational taxonomic units (OTUs) differed between the sexes. The relative abundance of 13 OTUs were higher in males, such as Parabacteroides distasonis and Blautia faecis, while 33 OTUs were overrepresented in females, including Clostridium groups and Escherichia fergusonii/Shigella sonnei. Moreover, the interactions of these differential OTUs were sexually distinct. These findings demonstrated that the intestine of male and female mice preferred to accommodate microbiota differently. Therefore, it is necessary to designate the gender of gnotobiotic mice for complete evaluation of modulatory effects of gut microbiota from human feces upon diseases. PMID:27796317

Convergence of gut microbiotas in the adaptive radiations of African cichlid fishes.

PubMed

Baldo, Laura; Pretus, Joan Lluís; Riera, Joan Lluís; Musilova, Zuzana; Bitja Nyom, Arnold Roger; Salzburger, Walter

2017-09-01

Ecoevolutionary dynamics of the gut microbiota at the macroscale level, that is, in across-species comparisons, are largely driven by ecological variables and host genotype. The repeated explosive radiations of African cichlid fishes in distinct lakes, following a dietary diversification in a context of reduced genetic diversity, provide a natural setup to explore convergence, divergence and repeatability in patterns of microbiota dynamics as a function of the host diet, phylogeny and environment. Here we characterized by 16S rRNA amplicon sequencing the gut microbiota of 29 cichlid species from two distinct lakes/radiations (Tanganyika and Barombi Mbo) and across a broad dietary and phylogenetic range. Within each lake, a significant deviation between a carnivorous and herbivorous lifestyle was found. Herbivore species were characterized by an increased bacterial taxonomic and functional diversity and converged in key compositional and functional community aspects. Despite a significant lake effect on the microbiota structure, this process has occurred with remarkable parallels in the two lakes. A metabolic signature most likely explains this trend, as indicated by a significant enrichment in herbivores/omnivores of bacterial taxa and functions associated with fiber degradation and detoxification of plant chemical compounds. Overall, compositional and functional aspects of the gut microbiota individually and altogether validate and predict main cichlid dietary habits, suggesting a fundamental role of gut bacteria in cichlid niche expansion and adaptation.

Convergence of gut microbiotas in the adaptive radiations of African cichlid fishes

PubMed Central

Baldo, Laura; Pretus, Joan Lluís; Riera, Joan Lluís; Musilova, Zuzana; Bitja Nyom, Arnold Roger; Salzburger, Walter

2017-01-01

Ecoevolutionary dynamics of the gut microbiota at the macroscale level, that is, in across-species comparisons, are largely driven by ecological variables and host genotype. The repeated explosive radiations of African cichlid fishes in distinct lakes, following a dietary diversification in a context of reduced genetic diversity, provide a natural setup to explore convergence, divergence and repeatability in patterns of microbiota dynamics as a function of the host diet, phylogeny and environment. Here we characterized by 16S rRNA amplicon sequencing the gut microbiota of 29 cichlid species from two distinct lakes/radiations (Tanganyika and Barombi Mbo) and across a broad dietary and phylogenetic range. Within each lake, a significant deviation between a carnivorous and herbivorous lifestyle was found. Herbivore species were characterized by an increased bacterial taxonomic and functional diversity and converged in key compositional and functional community aspects. Despite a significant lake effect on the microbiota structure, this process has occurred with remarkable parallels in the two lakes. A metabolic signature most likely explains this trend, as indicated by a significant enrichment in herbivores/omnivores of bacterial taxa and functions associated with fiber degradation and detoxification of plant chemical compounds. Overall, compositional and functional aspects of the gut microbiota individually and altogether validate and predict main cichlid dietary habits, suggesting a fundamental role of gut bacteria in cichlid niche expansion and adaptation. PMID:28509910

Gut Microbiota Patterns Associated with Colonization of Different Clostridium difficile Ribotypes

PubMed Central

Skraban, Jure; Dzeroski, Saso; Zenko, Bernard; Mongus, Domen; Gangl, Simon; Rupnik, Maja

2013-01-01

C. difficile infection is associated with disturbed gut microbiota and changes in relative frequencies and abundance of individual bacterial taxons have been described. In this study we have analysed bacterial, fungal and archaeal microbiota by denaturing high pressure liquid chromatography (DHPLC) and with machine learning methods in 208 faecal samples from healthy volunteers and in routine samples with requested C. difficile testing. The latter were further divided according to stool consistency, C. difficile presence or absence and C. difficile ribotype (027 or non-027). Lower microbiota diversity was a common trait of all routine samples and not necessarily connected only to C. difficile colonisation. Differences between the healthy donors and C. difficile positive routine samples were detected in bacterial, fungal and archaeal components. Bifidobacterium longum was the single most important species associated with C. difficile negative samples. However, by machine learning approaches we have identified patterns of microbiota composition predictive for C. difficile colonization. Those patterns also differed between samples with C. difficile ribotype 027 and other C. difficile ribotypes. The results indicate that not only the presence of a single species/group is important but that certain combinations of gut microbes are associated with C. difficile carriage and that some ribotypes (027) might be associated with more disturbed microbiota than the others. PMID:23469128

The impact of microbiota on brain and behavior: mechanisms & therapeutic potential.

PubMed

Borre, Yuliya E; Moloney, Rachel D; Clarke, Gerard; Dinan, Timothy G; Cryan, John F

2014-01-01

There is increasing evidence that host-microbe interactions play a key role in maintaining homeostasis. Alterations in gut microbial composition is associated with marked changes in behaviors relevant to mood, pain and cognition, establishing the critical importance of the bi-directional pathway of communication between the microbiota and the brain in health and disease. Dysfunction of the microbiome-brain-gut axis has been implicated in stress-related disorders such as depression, anxiety and irritable bowel syndrome and neurodevelopmental disorders such as autism. Bacterial colonization of the gut is central to postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Moreover, there is now expanding evidence for the view that enteric microbiota plays a role in early programming and later response to acute and chronic stress. This view is supported by studies in germ-free mice and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics. Although communication between gut microbiota and the CNS are not fully elucidated, neural, hormonal, immune and metabolic pathways have been suggested. Thus, the concept of a microbiome-brain-gut axis is emerging, suggesting microbiota-modulating strategies may be a tractable therapeutic approach for developing novel treatments for CNS disorders.

Impact of a 3-Months Vegetarian Diet on the Gut Microbiota and Immune Repertoire

PubMed Central

Zhang, Chenchen; Björkman, Andrea; Cai, Kaiye; Liu, Guilin; Wang, Chunlin; Li, Yin; Xia, Huihua; Sun, Lijun; Kristiansen, Karsten; Wang, Jun; Han, Jian; Hammarström, Lennart; Pan-Hammarström, Qiang

2018-01-01

The dietary pattern can influence the immune system directly, but may also modulate it indirectly by regulating the gut microbiota. Here, we investigated the effect of a 3-months lacto-ovo-vegetarian diet on the diversity of gut microbiota and the immune system in healthy omnivorous volunteers, using high-throughput sequencing technologies. The short-term vegetarian diet did not have any major effect on the diversity of the immune system and the overall composition of the metagenome. The prevalence of bacterial genera/species with known beneficial effects on the intestine, including butyrate-producers and probiotic species and the balance of autoimmune-related variable genes/families were, however, altered in the short-term vegetarians. A number of bacterial species that are associated with the expression level of IgA, a key immunoglobulin class that protects the gastrointestinal mucosal system, were also identified. Furthermore, a lower diversity of T-cell repertoire and expression level of IgE, as well as a reduced abundance of inflammation-related genes in the gut microbiota were potentially associated with a control group with long-term vegetarians. Thus, the composition and duration of the diet may have an impact on the balance of pro-/anti-inflammatory factors in the gut microbiota and immune system. PMID:29755475

Impact of a 3-Months Vegetarian Diet on the Gut Microbiota and Immune Repertoire.

PubMed

Zhang, Chenchen; Björkman, Andrea; Cai, Kaiye; Liu, Guilin; Wang, Chunlin; Li, Yin; Xia, Huihua; Sun, Lijun; Kristiansen, Karsten; Wang, Jun; Han, Jian; Hammarström, Lennart; Pan-Hammarström, Qiang

2018-01-01

The dietary pattern can influence the immune system directly, but may also modulate it indirectly by regulating the gut microbiota. Here, we investigated the effect of a 3-months lacto-ovo-vegetarian diet on the diversity of gut microbiota and the immune system in healthy omnivorous volunteers, using high-throughput sequencing technologies. The short-term vegetarian diet did not have any major effect on the diversity of the immune system and the overall composition of the metagenome. The prevalence of bacterial genera/species with known beneficial effects on the intestine, including butyrate-producers and probiotic species and the balance of autoimmune-related variable genes/families were, however, altered in the short-term vegetarians. A number of bacterial species that are associated with the expression level of IgA, a key immunoglobulin class that protects the gastrointestinal mucosal system, were also identified. Furthermore, a lower diversity of T-cell repertoire and expression level of IgE, as well as a reduced abundance of inflammation-related genes in the gut microbiota were potentially associated with a control group with long-term vegetarians. Thus, the composition and duration of the diet may have an impact on the balance of pro-/anti-inflammatory factors in the gut microbiota and immune system.

Alteration of the gastrointestinal microbiota of mice by edible blue-green algae.

PubMed

Rasmussen, H E; Martínez, I; Lee, J Y; Walter, J

2009-10-01

To characterize the effect of edible blue-green algae (cyanobacteria) on the gastrointestinal microbiota of mice. C57BL/6J mice were fed a diet supplemented with 0% or 5% dried Nostoc commune, Spirulina platensis or Afanizominon flos-aquae (w/w) for 4 weeks. Molecular fingerprinting of the colonic microbiota using denaturing gradient gel electrophoresis revealed that administration of N. commune induced major alterations in colonic microbiota composition, while administration of S. platensis or A. flos-aquae had a more subtle impact. Community profile analysis revealed that administration of N. commune did not reduce microbial diversity indices of the colonic microbiota. Despite its pronounced effects on the bacterial composition in the colon, total bacterial numbers in the gut of mice fed N. commune were not reduced as assessed by quantitative real-time PCR and bacteriological culture. The results presented here show that administration of blue-green algae, and especially N. commune, alters colonic microbiota composition in mice with limited effects on total bacterial numbers or microbial diversity. Blue-green algae are consumed in many countries as a source of nutrients and to promote health, and they are intensively studied for their pharmaceutical value. Given the importance of the gut microbiota for many host functions, the effects of blue-green algae on gut microbial ecology revealed during this study should be considered when using them as food supplements or when studying their pharmaceutical properties.

Aging Gut Microbiota at the Cross-Road between Nutrition, Physical Frailty, and Sarcopenia: Is There a Gut–Muscle Axis?

PubMed Central

Ticinesi, Andrea; Lauretani, Fulvio; Milani, Christian; Tana, Claudio; Maggio, Marcello; Ventura, Marco; Meschi, Tiziana

2017-01-01

Inadequate nutrition and physical inactivity are the mainstays of primary sarcopenia–physiopathology in older individuals. Gut microbiota composition is strongly dependent on both of these elements, and conversely, can also influence the host physiology by modulating systemic inflammation, anabolism, insulin sensitivity, and energy production. The bacterial metabolism of nutrients theoretically influences skeletal muscle cell functionality through producing mediators that drive all of these systemic effects. In this study, we review the scientific literature supporting the concept of the involvement of gut microbiota in primary sarcopenia physiopathology. First, we examine studies associating fecal microbiota alterations with physical frailty, i.e., the loss of muscle performance and normal muscle mass. Then, we consider studies exploring the effects of exercise on gut microbiota composition. Finally, we examine studies demonstrating the possible effects of mediators produced by gut microbiota on skeletal muscle, and intervention studies considering the effects of prebiotic or probiotic administration on muscle function. Even if there is no evidence of a distinct gut microbiota composition in older sarcopenic patients, we conclude that the literature supports the possible presence of a “gut–muscle axis”, whereby gut microbiota may act as the mediator of the effects of nutrition on muscle cells. PMID:29189738

The influence of Mediterranean, carbohydrate and high protein diets on gut microbiota composition in the treatment of obesity and associated inflammatory state.

PubMed

Lopez-Legarrea, Patricia; Fuller, Nicholas Robert; Zulet, María Angeles; Martinez, Jose Alfredo; Caterson, Ian Douglas

2014-01-01

The role of the gut microbiota in understanding the onset and development of obesity is gaining importance. Dietary strategies are the main tool employed to counteract obesity, and nowadays they are focused on a wide range of different aspects of diet and not only on calorie restriction. Additionally, diet is known to be a major factor influencing modification of the gut microbiota. Therefore the influence of both macronutrient and micronutrient content of any dietary strategy to treat obesity on gut bacterial composition should now be taken into consideration, in addition to energy restriction. This review aims to collect the available data regarding the influence of different dietary components on gut microbiota in relation to obesity and inflammatory states in humans. Although more work is needed, specific dietary factors (carbohydrate, protein and Mediterranean foods) have been shown to have an influence on the gut microbiome composition, meaning that there is an opportunity to prevent and treat obesity based on microbiota outcomes.

Influence of changing plant food sources on the gut microbiota of saltmarsh detritivores.

PubMed

Dittmer, Jessica; Lesobre, Jérôme; Raimond, Roland; Zimmer, Martin; Bouchon, Didier

2012-10-01

Changes in agricultural land-use of saltmarshes along the German North Sea coast have favoured the succession of the marsh grass Elytrigia atherica over the long-established Spartina anglica. Consequently, E. atherica represents a potential food source of increasing importance for plant-feeding soil detritivores. Considering the importance of this ecological guild for decomposition processes and nutrient cycling, we focussed on two sympatric saltmarsh soil macrodetritivores and their associated gut microbiota to investigate how the digestive processes of these species may be affected by changing plant food sources. Using genetic fingerprints of partial 16S rRNA gene sequences, we analysed composition and diversity of the bacterial gut community in a diplopod and an amphipod crustacean in relation to different feeding regimes representing the natural vegetation changes. Effects of syntopy on the host-specific gut microbiota were also taken into account by feeding the two detritivore species either independently or on the same plant sample. Bacterial community composition was influenced by both the host species and the available plant food sources, but the latter had a stronger effect on microbial community structure. Furthermore, bacterial diversity was highest after feeding on a mixture of both plant species, regardless of the host species. The gut microbiota of these two detritivores can thus be expected to change along with the on-going succession at the plant community level in this environment. Cloning and sequencing of bacterial 16S rRNA gene fragments further indicated a host-related effect since the two detritivores differed in terms of predominant bacterial taxa: diplopods harboured mainly representatives of the phyla Bacteroidetes and Gammaproteobacteria. In contrast, the genus Vibrio was found for the amphipod host across all feeding conditions.

Engineering Bacterial Thiosulfate and Tetrathionate Sensors for Detecting Gut Inflammation

DTIC Science & Technology

2017-04-03

Article Engineering bacterial thiosulfate and tetrathionate sensors for detecting gut inflammation Kristina N-M Daeffler1 , Jeffrey D Galley2, Ravi U...interest in using genetically engineered sensor bacteria to study gut microbiota pathways, and diagnose or treat associated diseases. Here, we...understood. Genetically engineered sensor bacteria have untapped potential as tools for analyzing gut pathways. Bacteria have evolved sensors of a large

Human gut microbiota community structures in urban and rural populations in Russia

PubMed Central

Tyakht, Alexander V.; Kostryukova, Elena S.; Popenko, Anna S.; Belenikin, Maxim S.; Pavlenko, Alexander V.; Larin, Andrey K.; Karpova, Irina Y.; Selezneva, Oksana V.; Semashko, Tatyana A.; Ospanova, Elena A.; Babenko, Vladislav V.; Maev, Igor V.; Cheremushkin, Sergey V.; Kucheryavyy, Yuriy A.; Shcherbakov, Petr L.; Grinevich, Vladimir B.; Efimov, Oleg I.; Sas, Evgenii I.; Abdulkhakov, Rustam A.; Abdulkhakov, Sayar R.; Lyalyukova, Elena A.; Livzan, Maria A.; Vlassov, Valentin V.; Sagdeev, Renad Z.; Tsukanov, Vladislav V.; Osipenko, Marina F.; Kozlova, Irina V.; Tkachev, Alexander V.; Sergienko, Valery I.; Alexeev, Dmitry G.; Govorun, Vadim M.

2013-01-01

The microbial community of the human gut has a crucial role in sustaining host homeostasis. High-throughput DNA sequencing has delineated the structural and functional configurations of gut metagenomes in world populations. The microbiota of the Russian population is of particular interest to researchers, because Russia encompasses a uniquely wide range of environmental conditions and ethnogeographical cohorts. Here we conduct a shotgun metagenomic analysis of gut microbiota samples from 96 healthy Russian adult subjects, which reveals novel microbial community structures. The communities from several rural regions display similarities within each region and are dominated by the bacterial taxa associated with the healthy gut. Functional analysis shows that the metabolic pathways exhibiting differential abundance in the novel types are primarily associated with the trade-off between the Bacteroidetes and Firmicutes phyla. The specific signatures of the Russian gut microbiota are likely linked to the host diet, cultural habits and socioeconomic status. PMID:24036685

Mining the Human Gut Microbiota for Immunomodulatory Organisms.

PubMed

Geva-Zatorsky, Naama; Sefik, Esen; Kua, Lindsay; Pasman, Lesley; Tan, Tze Guan; Ortiz-Lopez, Adriana; Yanortsang, Tsering Bakto; Yang, Liang; Jupp, Ray; Mathis, Diane; Benoist, Christophe; Kasper, Dennis L

2017-02-23

Within the human gut reside diverse microbes coexisting with the host in a mutually advantageous relationship. Evidence has revealed the pivotal role of the gut microbiota in shaping the immune system. To date, only a few of these microbes have been shown to modulate specific immune parameters. Herein, we broadly identify the immunomodulatory effects of phylogenetically diverse human gut microbes. We monocolonized mice with each of 53 individual bacterial species and systematically analyzed host immunologic adaptation to colonization. Most microbes exerted several specialized, complementary, and redundant transcriptional and immunomodulatory effects. Surprisingly, these were independent of microbial phylogeny. Microbial diversity in the gut ensures robustness of the microbiota's ability to generate a consistent immunomodulatory impact, serving as a highly important epigenetic system. This study provides a foundation for investigation of gut microbiota-host mutualism, highlighting key players that could identify important therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice

PubMed Central

Planer, Joseph D.; Peng, Yangqing; Kau, Andrew L.; Blanton, Laura V.; Ndao, I. Malick; Tarr, Phillip I.; Warner, Barbara B.; Gordon, Jeffrey I.

2016-01-01

Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function1–3. The repertoire of IgA bound to gut bacteria reflects both T cell-dependent and -independent pathways4,5, plus glycans present on the antibody’s secretory component6. Human gut bacterial taxa targeted by IgA in the setting of intestinal barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice7,8. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA9–11. How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (i) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly/maturation during the first 2 postnatal years that is shared across 40 healthy USA twin pairs; (ii) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (iii) assess the effects of zygosity, birth mode and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with fecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. The majority of these responses were robust to diet suggesting that ‘intrinsic’ properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and help discover ways for repairing or preventing perturbations in this facet of host immunity. PMID:27279225

Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice.

PubMed

Planer, Joseph D; Peng, Yangqing; Kau, Andrew L; Blanton, Laura V; Ndao, I Malick; Tarr, Phillip I; Warner, Barbara B; Gordon, Jeffrey I

2016-06-09

Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function. The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways, plus glycans present on the antibody's secretory component. Human gut bacterial taxa targeted by IgA in the setting of barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA. How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (1) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly and maturation during the first 2 postnatal years that is shared across 40 healthy twin pairs in the USA; (2) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (3) assess the effects of zygosity, birth mode, and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with faecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. Most of these responses were robust to diet, suggesting that 'intrinsic' properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and to help discover ways of repairing or preventing perturbations in this facet of host immunity.

Deciphering chicken gut microbial dynamics based on high-throughput 16S rRNA metagenomics analyses.

PubMed

Mohd Shaufi, Mohd Asrore; Sieo, Chin Chin; Chong, Chun Wie; Gan, Han Ming; Ho, Yin Wan

2015-01-01

Chicken gut microbiota has paramount roles in host performance, health and immunity. Understanding the topological difference in gut microbial community composition is crucial to provide knowledge on the functions of each members of microbiota to the physiological maintenance of the host. The gut microbiota profiling of the chicken was commonly performed previously using culture-dependent and early culture-independent methods which had limited coverage and accuracy. Advances in technology based on next-generation sequencing (NGS), offers unparalleled coverage and depth in determining microbial gut dynamics. Thus, the aim of this study was to investigate the ileal and caecal microbiota development as chicken aged, which is important for future effective gut modulation. Ileal and caecal contents of broiler chicken were extracted from 7, 14, 21 and 42-day old chicken. Genomic DNA was then extracted and amplified based on V3 hyper-variable region of 16S rRNA. Bioinformatics, ecological and statistical analyses such as Principal Coordinate Analysis (PCoA) was performed in mothur software and plotted using PRIMER 6. Additional analyses for predicted metagenomes were performed through PICRUSt and STAMP software package based on Greengenes databases. A distinctive difference in bacterial communities was observed between ilea and caeca as the chicken aged (P < 0.001). The microbial communities in the caeca were more diverse in comparison to the ilea communities. The potentially pathogenic bacteria such as Clostridium were elevated as the chicken aged and the population of beneficial microbe such as Lactobacillus was low at all intervals. On the other hand, based on predicted metagenomes analysed, clear distinction in functions and roles of gut microbiota such as gene pathways related to nutrient absorption (e.g. sugar and amino acid metabolism), and bacterial proliferation and colonization (e.g. bacterial motility proteins, two-component system and bacterial secretion system) were observed between ilea and caeca, respectively (P < 0.05). The caeca microbial communities were more diverse in comparison to ilea. The main functional differences between the two sites were found to be related to nutrient absorption and bacterial colonization. Based on the composition of the microbial community, future gut modulation with beneficial bacteria such as probiotics may benefit the host.

A core gut microbiome in obese and lean twins.

PubMed

Turnbaugh, Peter J; Hamady, Micah; Yatsunenko, Tanya; Cantarel, Brandi L; Duncan, Alexis; Ley, Ruth E; Sogin, Mitchell L; Jones, William J; Roe, Bruce A; Affourtit, Jason P; Egholm, Michael; Henrissat, Bernard; Heath, Andrew C; Knight, Rob; Gordon, Jeffrey I

2009-01-22

The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).

Having older siblings is associated with gut microbiota development during early childhood.

PubMed

Laursen, Martin Frederik; Zachariassen, Gitte; Bahl, Martin Iain; Bergström, Anders; Høst, Arne; Michaelsen, Kim F; Licht, Tine Rask

2015-08-01

Evidence suggests that early life infections, presence of older siblings and furred pets in the household affect the risk of developing allergic diseases through altered microbial exposure. Recently, low gut microbial diversity during infancy has also been linked with later development of allergies. We investigated whether presence of older siblings, furred pets and early life infections affected gut microbial communities at 9 and 18 months of age and whether these differences were associated with the cumulative prevalence of atopic symptoms of eczema and asthmatic bronchitis at 3 years of age. Bacterial compositions and diversity indices were determined in fecal samples collected from 114 infants in the SKOT I cohort at age 9 and 18 months by 16S rRNA gene sequencing. These were compared to the presence of older siblings, furred pets and early life infections and the cumulative prevalence of diagnosed asthmatic bronchitis and self-reported eczema at 3 years of age. The number of older siblings correlated positively with bacterial diversity (p = 0.030), diversity of the phyla Firmicutes (p = 0.013) and Bacteroidetes (p = 0.004) and bacterial richness (p = 0.006) at 18 months. Further, having older siblings was associated with increased relative abundance of several bacterial taxa at both 9 and 18 months of age. Compared to the effect of having siblings, presence of household furred pets and early life infections had less pronounced effects on the gut microbiota. Gut microbiota characteristics were not significantly associated with cumulative occurrence of eczema and asthmatic bronchitis during the first 3 years of life. Presence of older siblings is associated with increased gut microbial diversity and richness during early childhood, which could contribute to the substantiation of the hygiene hypothesis. However, no associations were found between gut microbiota and atopic symptoms of eczema and asthmatic bronchitis during early childhood and thus further studies are required to elucidate whether sibling-associated gut microbial changes influence development of allergies later in childhood.

Gut microbiomes of mobile predators vary with landscape context and species identity.

PubMed

Tiede, Julia; Scherber, Christoph; Mutschler, James; McMahon, Katherine D; Gratton, Claudio

2017-10-01

Landscape context affects predator-prey interactions and predator diet composition, yet little is known about landscape effects on insect gut microbiomes, a determinant of physiology and condition. Here, we combine laboratory and field experiments to examine the effects of landscape context on the gut bacterial community and body condition of predatory insects. Under laboratory conditions, we found that prey diversity increased bacterial richness in insect guts. In the field, we studied the performance and gut microbiota of six predatory insect species along a landscape complexity gradient in two local habitat types (soybean fields vs. prairie). Insects from soy fields had richer gut bacteria and lower fat content than those from prairies, suggesting better feeding conditions in prairies. Species origin mediated landscape context effects, suggesting differences in foraging of exotic and native predators on a landscape scale. Overall, our study highlights complex interactions among gut microbiota, predator identity, and landscape context.

The gut microbiota in larvae of the housefly Musca domestica and their horizontal transfer through feeding.

PubMed

Zhao, Yao; Wang, Wanqiang; Zhu, Fen; Wang, Xiaoyun; Wang, Xiaoping; Lei, Chaoliang

2017-12-01

House fly larvae provide a prolific and sustainable source of proteins used in poultry and fish feed. Wheat bran is a superior diet for house fly larvae and has been widely investigated to exploit its potential in the food and feed area. Using Illumina MiSeq 16S rDNA sequencing, this study investigated the gut microbiota of house fly larvae feeding on wheat bran and the bacterial community in the wheat bran. The bacterial communities in the house fly larvae were dominated by the phyla Proteobacteria and Firmicutes. Enterobacteriaceae and Providencia were the predominant bacteria at the family and genus levels, respectively. Some bacteria in the phyla Actinobacteria, Proteobacteria, Bacteroidetes and Firmicutes may be transferred from the gut of house flies to the wheat bran during feeding and may be involved in degrading and utilizing polysaccharides in the cell wall of wheat bran. The significance of the gut microbiota of house fly larvae, their transferring and roles in degradation of wheat bran is discussed. These findings regarding the gut microbiota of house fly larvae will provide opportunities for research on the impact of microbial communities on poultry and fish.

Changes in mouse gut bacterial community in response to different types of drinking water.

PubMed

Dias, Marcela F; Reis, Mariana P; Acurcio, Leonardo B; Carmo, Anderson O; Diamantino, Cristiane F; Motta, Amanda M; Kalapothakis, Evanguedes; Nicoli, Jacques R; Nascimento, Andréa M A

2018-04-01

Gut microbiota exerts a fundamental role on host physiology, and how extrinsic perturbations influence its composition has been increasingly examined. However, the effect of drinking water on gut microbiota is still poorly understood. In this study, we explored the response of mouse gut bacterial community (fecal and mucosa-adhered) to the ingestion of different types of drinking water. The experimental cohort was divided according to different water sources into four groups of mice that consumed autoclaved tap water (control group), water collected directly from a drinking water treatment plant, tap water, and commercial bottled mineral water. Differences among groups were observed, especially related to control group, which exhibited the smallest intra-group variation, and the largest distance from test groups on the last experimental day. Clinically important taxa, such as Acinetobacter and Staphylococcus, increased in feces of mice that drank tap water and in mucosa-adhered samples of animals from disinfected and tap water groups. Furthermore, statistical analyses showed that both time elapsed between samplings and water type significantly influenced the variation observed in the samples. Our results reveal that drinking water potentially affects gut microbiota composition. Additionally, the increase of typical drinking water clinically relevant and antibiotic resistance-associated bacteria in gut microbiota is a cause of concern. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dietary Supplementation with Rice Bran or Navy Bean Alters Gut Bacterial Metabolism in Colorectal Cancer Survivors

PubMed Central

Sheflin, Amy M.; Borresen, Erica C.; Kirkwood, Jay S.; Boot, Claudia M.; Whitney, Alyssa K.; Lu, Shen; Brown, Regina J.; Broeckling, Corey D.; Ryan, Elizabeth P.; Weir, Tiffany L.

2016-01-01

Scope Heat-stabilized rice bran and cooked navy bean powder contain a variety of phytochemicals that are fermented by colonic microbiota and may influence intestinal health. Dietary interventions with these foods should be explored for modulating colorectal cancer risk. Methods and results A randomized-controlled pilot clinical trial investigated the effects of eating heat-stabilized rice bran (30g/day) or cooked navy bean powder (35g/day) on gut microbiota and metabolites (NCT01929122). Twenty-nine overweight/obese volunteers with a prior history of colorectal cancer consumed a study-provided meal and snack daily for 28 days. Volunteers receiving rice bran or bean powder showed increased gut bacterial diversity and altered gut microbial composition at 28 days compared to baseline. Supplementation with rice bran or bean powder increased total dietary fiber intake similarly, yet only rice bran intake led to a decreased Firmicutes:Bacteroidetes ratio and increased short chain fatty acids (propionate and acetate) in stool after 14 days but not at 28 days. Conclusion These findings support modulation of gut microbiota and fermentation by-products by heat-stabilized rice bran and suggest that foods with similar ability to increase dietary fiber intake may not have equal effects on gut microbiota and microbial metabolism. PMID:27461523

Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children

PubMed Central

Subramanian, Sathish; Huq, Sayeeda; Yatsunenko, Tanya; Haque, Rashidul; Mahfuz, Mustafa; Alam, Mohammed A.; Benezra, Amber; DeStefano, Joseph; Meier, Martin F.; Muegge, Brian D.; Barratt, Michael J.; VanArendonk, Laura G.; Zhang, Qunyuan; Province, Michael A.; Petri, William A.; Ahmed, Tahmeed; Gordon, Jeffrey I.

2014-01-01

Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM) but incomplete restoration of healthy growth remains a major problem1,2. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S rRNA datasets generated from monthly fecal samples obtained from a birth-cohort of children, living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare development (defined here as maturation) of a child’s fecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors including diarrhea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes. PMID:24896187

Utilization of rye as energy source affects bacterial translocation, intestinal viscosity, microbiota composition, and bone mineralization in broiler chickens

USDA-ARS?s Scientific Manuscript database

Two independent trials were conducted to evaluate the effect of two different dietary cereal types, corn versus rye, on digesta viscosity, gut integrity, and gut microbiota composition in commercial broiler chickens. In each experiment, day-of-hatch, off-sex broiler chickens were randomly assigned ...

Gut microbiota and host metabolism in liver cirrhosis

PubMed Central

Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

2015-01-01

The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients. PMID:26556989

Gut microbiota and host metabolism in liver cirrhosis.

PubMed

Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

2015-11-07

The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients.

Gut microbiota and its implications in small bowel transplantation.

PubMed

Wang, Chenyang; Li, Qiurong; Li, Jieshou

2018-06-01

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBTand the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

Marine mammals harbor unique microbiotas shaped by and yet distinct from the sea.

PubMed

Bik, Elisabeth M; Costello, Elizabeth K; Switzer, Alexandra D; Callahan, Benjamin J; Holmes, Susan P; Wells, Randall S; Carlin, Kevin P; Jensen, Eric D; Venn-Watson, Stephanie; Relman, David A

2016-02-03

Marine mammals play crucial ecological roles in the oceans, but little is known about their microbiotas. Here we study the bacterial communities in 337 samples from 5 body sites in 48 healthy dolphins and 18 healthy sea lions, as well as those of adjacent seawater and other hosts. The bacterial taxonomic compositions are distinct from those of other mammals, dietary fish and seawater, are highly diverse and vary according to body site and host species. Dolphins harbour 30 bacterial phyla, with 25 of them in the mouth, several abundant but poorly characterized Tenericutes species in gastric fluid and a surprisingly paucity of Bacteroidetes in distal gut. About 70% of near-full length bacterial 16S ribosomal RNA sequences from dolphins are unique. Host habitat, diet and phylogeny all contribute to variation in marine mammal distal gut microbiota composition. Our findings help elucidate the factors structuring marine mammal microbiotas and may enhance monitoring of marine mammal health.

Marine mammals harbor unique microbiotas shaped by and yet distinct from the sea

PubMed Central

Bik, Elisabeth M.; Costello, Elizabeth K.; Switzer, Alexandra D.; Callahan, Benjamin J.; Holmes, Susan P.; Wells, Randall S.; Carlin, Kevin P.; Jensen, Eric D.; Venn-Watson, Stephanie; Relman, David A.

2016-01-01

Marine mammals play crucial ecological roles in the oceans, but little is known about their microbiotas. Here we study the bacterial communities in 337 samples from 5 body sites in 48 healthy dolphins and 18 healthy sea lions, as well as those of adjacent seawater and other hosts. The bacterial taxonomic compositions are distinct from those of other mammals, dietary fish and seawater, are highly diverse and vary according to body site and host species. Dolphins harbour 30 bacterial phyla, with 25 of them in the mouth, several abundant but poorly characterized Tenericutes species in gastric fluid and a surprisingly paucity of Bacteroidetes in distal gut. About 70% of near-full length bacterial 16S ribosomal RNA sequences from dolphins are unique. Host habitat, diet and phylogeny all contribute to variation in marine mammal distal gut microbiota composition. Our findings help elucidate the factors structuring marine mammal microbiotas and may enhance monitoring of marine mammal health. PMID:26839246

[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.

Potential for Monitoring Gut Microbiota for Diagnosing Infections and Graft-versus-Host Disease in Cancer and Stem Cell Transplant Patients.

PubMed

Koh, Andrew Y

2017-11-01

Gut microbiota, the collective community of microorganisms inhabiting the intestine, have been shown to provide many beneficial functions for the host. Recent advances in next-generation sequencing and advanced molecular biology approaches have allowed researchers to identify gut microbiota signatures associated with disease processes and, in some cases, establish causality and elucidate underlying mechanisms. This report reviews 3 commonly used methods for studying the gut microbiota and microbiome (the collective genomes of the gut microorganisms): 16S rRNA gene sequencing, bacterial group or species-specific quantitative polymerase chain reaction (qPCR), and metagenomic shotgun sequencing (MSS). The technical approaches and resources needed for each approach are outlined, and advantages and disadvantages for each approach are summarized. The findings regarding the role of the gut microbiota in the health of patients with cancer and stem cell transplant (SCT) patients (specifically in modulating the development of gut-derived bacterial infections and a posttransplant immune-mediated complication known as graft-vs-host-disease) are reviewed. Finally, there is discussion of the potential viability of these approaches in the actual clinical treatment of cancer and SCT patients. Advances in next-generation sequencing have revolutionized our understanding of the importance of the gut microbiome to human health. Both 16S rRNA gene sequencing and MSS are currently too labor-intensive or computationally burdensome to incorporate into real-time clinical monitoring of gut microbiomes. Yet, the lessons learned from these technologies could be adapted to currently used methods (e.g., qPCR) that could then be rigorously tested in the clinical care of these patients. © 2017 American Association for Clinical Chemistry.

Combination of Metagenomics and Culture-Based Methods to Study the Interaction Between Ochratoxin A and Gut Microbiota

PubMed Central

Guo, Mingzhang; Huang, Kunlun; Chen, Siyuan; Qi, Xiaozhe; He, Xiaoyun; Cheng, Wen-Hsing; Luo, Yunbo; Xia, Kai; Xu, Wentao

2014-01-01

Gut microbiota represent an important bridge between environmental substances and host metabolism. Here we reported a comprehensive study of gut microbiota interaction with ochratoxin A (OTA), a major food-contaminating mycotoxin, using the combination of metagenomics and culture-based methods. Rats were given OTA (0, 70, or 210 μg/kg body weight) by gavage and fecal samples were collected at day 0 and day 28. Bacterial genomic DNA was extracted from the fecal samples and both 16S rRNA and shotgun sequencing (two main methods of metagenomics) were performed. The results indicated OTA treatment decreased the within-subject diversity of the gut microbiota, and the relative abundance of Lactobacillus increased considerably. Changes in functional genes of gut microbiota including signal transduction, carbohydrate transport, transposase, amino acid transport system, and mismatch repair were observed. To further understand the biological sense of increased Lactobacillus, Lactobacillus selective medium was used to isolate Lactobacillus species from fecal samples, and a strain with 99.8% 16S rRNA similarity with Lactobacillus plantarum strain PFK2 was obtained. Thin-layer chromatography showed that this strain could absorb but not degrade OTA, which was in agreement with the result in metagenomics that no genes related to OTA degradation increased. In conclusion, combination of metagenomics and culture-based methods can be a new strategy to study intestinal toxicity of toxins and find applicable bacterial strains for detoxification. When it comes to OTA, this kind of mycotoxin can cause compositional and functional changes of gut microbiota, and Lactobacillus are key genus to detoxify OTA in vivo. PMID:24973096

Effects of antibiotic growth promoter and characterization of ecological succession in Swine gut microbiota.

PubMed

Unno, Tatsuya; Kim, Jung-Man; Guevarra, Robin B; Nguyen, Son G

2015-04-01

Ever since the ban on antibiotic growth promoters (AGPs), the livestock death rate has increased owing to pathogenic bacterial infections. There is a need of developing AGP alternatives; however, the mechanisms by which AGP enhances livestock growth performance are not clearly understood. In this study, we fed 3-week-old swine for 9 weeks with and without AGPs containing chlortetracycline, sulfathiazole, and penicillin to investigate the effects of AGPs on swine gut microbiota. Microbial community analysis was done based on bacterial 16S rRNA genes using MiSeq. The use of AGP showed no growth promoting effect, but inhibited the growth of potential pathogens during the early growth stage. Our results showed the significant increase in species richness after the stabilization of gut microbiota during the post-weaning period (4-week-old). Moreover, the swine gut microbiota was divided into four clusters based on the distribution of operational taxonomic units, which was significantly correlated to the swine weight regardless of AGP treatments. Taxonomic abundance analysis indicated a negative correlation between host weight and the abundance of the family Prevotellaceae species, but showed positive correlation to the abundance of the family Spirochaetaceae, Clostridiaceae_1, and Peptostreptococcaeae species. Although no growth performance enhancement was observed, the use of AGP inhibited the potential pathogens in the early growth stage of swine. In addition, our results indicated the ecological succession of swine gut microbiota according to swine weight. Here, we present a characterization of swine gut microbiota with respect to the effects of AGPs on growth performance.

Rapid Change of Microbiota Diversity in the Gut but Not the Hepatopancreas During Gonadal Development of the New Shrimp Model Neocaridina denticulata.

PubMed

Cheung, Man Kit; Yip, Ho Yin; Nong, Wenyan; Law, Patrick Tik Wan; Chu, Ka Hou; Kwan, Hoi Shan; Hui, Jerome Ho Lam

2015-12-01

During evolution of animals, their co-evolution with bacteria has generally been ignored. Recent studies have provided evidences that the symbiotic bacteria in the animal gut can either be essential or contributing to the plasticity of the host. The Crustacea includes crab, crayfish, lobster, and shrimp and represents the second largest subphylum on the planet. Although there are already studies investigating the intestinal bacterial communities in crustaceans, none of them has examined the microbiota in different parts of the digestive system during the gonad development of the host. Here, we utilized a new shrimp model Neocaridina denticulata and sequenced the 16S rRNA using the Ion Torrent platform to survey the bacterial populations colonizing the hepatopancreas, foregut, and intestine, including midgut and hindgut, of the early, mid, and late ovarian maturation stages of the shrimp. The predominant bacteria phylum was found to be Proteobacteria, with more than 80 % reads from the gut flora at the early gonad development belonged to a Coxiella-type bacterium. Distinct bacterial communities can be detected between the hepatopancreas and gut, although no significant difference could be revealed between the different regions of the gut investigated. Surprisingly, during the gonad development, bacterial diversity changed rapidly in the gut but not the hepatopancreas. This study provides the first evidence that microbiota modified differentially in specific regions of the digestive tract during gonadal development of crustaceans.

Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation.

PubMed

de La Serre, Claire Barbier; Ellis, Collin L; Lee, Jennifer; Hartman, Amber L; Rutledge, John C; Raybould, Helen E

2010-08-01

Consumption of diets high in fat and calories leads to hyperphagia and obesity, which is associated with chronic "low-grade" systemic inflammation. Ingestion of a high-fat diet alters the gut microbiota, pointing to a possible role in the development of obesity. The present study used Sprague-Dawley rats that, when fed a high-fat diet, exhibit either an obesity-prone (DIO-P) or obesity-resistant (DIO-R) phenotype, to determine whether changes in gut epithelial function and microbiota are diet or obese associated. Food intake and body weight were monitored daily in rats maintained on either low- or high-fat diets. After 8 or 12 wk, tissue was removed to determine adiposity and gut epithelial function and to analyze the gut microbiota using PCR. DIO-P but not DIO-R rats exhibit an increase in toll-like receptor (TLR4) activation associated with ileal inflammation and a decrease in intestinal alkaline phosphatase, a luminal enzyme that detoxifies lipopolysaccharide (LPS). Intestinal permeability and plasma LPS were increased together with phosphorylation of myosin light chain and localization of occludin in the cytoplasm of epithelial cells. Measurement of bacterial 16S rRNA showed a decrease in total bacterial density and an increase in the relative proportion of Bacteroidales and Clostridiales orders in high-fat-fed rats regardless of phenotype; an increase in Enterobacteriales was seen in the microbiota of DIO-P rats only. Consumption of a high-fat diet induces changes in the gut microbiota, but it is the development of inflammation that is associated with the appearance of hyperphagia and an obese phenotype.

Does the maternal vaginal microbiota play a role in seeding the microbiota of neonatal gut and nose?

PubMed

Sakwinska, O; Foata, F; Berger, B; Brüssow, H; Combremont, S; Mercenier, A; Dogra, S; Soh, S-E; Yen, J C K; Heong, G Y S; Lee, Y S; Yap, F; Meaney, M J; Chong, Y-S; Godfrey, K M; Holbrook, J D

2017-10-13

The acquisition and early maturation of infant microbiota is not well understood despite its likely influence on later health. We investigated the contribution of the maternal microbiota to the microbiota of infant gut and nose in the context of mode of delivery and feeding. Using 16S rRNA sequencing and specific qPCR, we profiled microbiota of 42 mother-infant pairs from the GUSTO birth cohort, at body sites including maternal vagina, rectum and skin; and infant stool and nose. In our study, overlap between maternal vaginal microbiota and infant faecal microbiota was minimal, while the similarity between maternal rectal microbiota and infant microbiota was more pronounced. However, an infant's nasal and gut microbiota were no more similar to that of its own mother, than to that of unrelated mothers. These findings were independent of delivery mode. We conclude that the transfer of maternal vaginal microbes play a minor role in seeding infant stool microbiota. Transfer of maternal rectal microbiota could play a larger role in seeding infant stool microbiota, but approaches other than the generally used analyses of community similarity measures are likely to be needed to quantify bacterial transmission. We confirmed the clear difference between microbiota of infants born by Caesarean section compared to vaginally delivered infants and the impact of feeding mode on infant gut microbiota. Only vaginally delivered, fully breastfed infants had gut microbiota dominated by Bifidobacteria. Our data suggest that reduced transfer of maternal vaginal microbial is not the main mechanism underlying the differential infant microbiota composition associated with Caesarean delivery. The sources of a large proportion of infant microbiota could not be identified in maternal microbiota, and the sources of seeding of infant gut and nasal microbiota remain to be elucidated.

Effect of ethnicity and socioeconomic variation to the gut microbiota composition among pre-adolescent in Malaysia

PubMed Central

Chong, Chun Wie; Ahmad, Arine Fadzlun; Lim, Yvonne Ai Lian; Teh, Cindy Shuan Ju; Yap, Ivan Kok Seng; Lee, Soo Ching; Chin, Yuee Teng; Loke, P’ng; Chua, Kek Heng

2015-01-01

Gut microbiota plays an important role in mammalian host metabolism and physiological functions. The functions are particularly important in young children where rapid mental and physical developments are taking place. Nevertheless, little is known about the gut microbiome and the factors that contribute to microbial variation in the gut of South East Asian children. Here, we compared the gut bacterial richness and composition of pre-adolescence in Northern Malaysia. Our subjects covered three distinct ethnic groups with relatively narrow range of socioeconomic discrepancy. These included the Malays (n = 24), Chinese (n = 17) and the Orang Asli (indigenous) (n = 20). Our results suggested a strong ethnicity and socioeconomic-linked bacterial diversity. Highest bacterial diversity was detected from the economically deprived indigenous children while the lowest diversity was recorded from the relatively wealthy Chinese children. In addition, predicted functional metagenome profiling suggested an over-representation of pathways pertinent to bacterial colonisation and chemotaxis in the former while the latter exhibited enriched gene pathways related to sugar metabolism. PMID:26290472

Gut-liver axis: gut microbiota in shaping hepatic innate immunity.

PubMed

Wu, Xunyao; Tian, Zhigang

2017-11-01

Gut microbiota play an essential role in shaping immune cell responses. The liver was continuously exposed to metabolic products of intestinal commensal bacterial through portal vein and alteration of gut commensal bateria was always associated with increased risk of liver inflammation and autoimmune disease. Considered as a unique immunological organ, the liver is enriched with a large number of innate immune cells. Herein, we summarize the available literature of gut microbiota in shaping the response of hepatic innate immune cells including NKT cells, NK cells, γδ T cells and Kupffer cells during health and disease. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of innate immune cell-related liver disease.

Gut microbiota and immunopathogenesis of diabetes mellitus type 1 and 2.

PubMed

Wang, Fei; Zhang, Chunfang; Zeng, Qiang

2016-06-01

Diabetes mellitus (DM) is a major increasing global health burden in the aging population. Understanding the etiology of DM is beneficial for its prevention as well as treatment. In light of the metagenome hypothesis, defined as the overall bacterial genome, gut microbes have attracted increasing attention in the pathogenesis of DM. Many studies have found that gut microbes are involved in the immunopathogenesis of DM. Probiotics strengthen the host's intestinal barrier and modulate the immune system, and have therefore been investigated in DM management. Recent epigenetic findings in context of genes associated with inflammation suggest a possible way in which gut microbiota participate in the immunopathogenesis of DM. In this review, we discuss the role of gut microbiota in the immunopathogenesis of DM.

Dysbiosis of the gut microbiota in disease

PubMed Central

Carding, Simon; Verbeke, Kristin; Vipond, Daniel T.; Corfe, Bernard M.; Owen, Lauren J.

2015-01-01

There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolic syndrome, cardiovascular disease, and obesity. In many of these conditions, the mechanisms leading to disease development involves the pivotal mutualistic relationship between the colonic microbiota, their metabolic products, and the host immune system. The establishment of a ‘healthy’ relationship early in life appears to be critical to maintaining intestinal homeostasis. Whilst we do not yet have a clear understanding of what constitutes a ‘healthy’ colonic microbiota, a picture is emerging from many recent studies identifying particular bacterial species associated with a healthy microbiota. In particular, the bacterial species residing within the mucus layer of the colon, either through direct contact with host cells, or through indirect communication via bacterial metabolites, may influence whether host cellular homeostasis is maintained or whether inflammatory mechanisms are triggered. In addition to inflammation, there is some evidence that perturbations in the gut microbiota is involved with the development of colorectal cancer. In this case, dysbiosis may not be the most important factor, rather the products of interaction between diet and the microbiome. High-protein diets are thought to result in the production of carcinogenic metabolites from the colonic microbiota that may result in the induction of neoplasia in the colonic epithelium. Ever more sensitive metabolomics methodologies reveal a suite of small molecules produced in the microbiome which mimic or act as neurosignallers or neurotransmitters. Coupled with evidence that probiotic interventions may alter psychological endpoints in both humans and in rodent models, these data suggest that CNS-related co-morbidities frequently associated with GI disease may originate in the intestine as a result of microbial dysbiosis. This review outlines the current evidence showing the extent to which the gut microbiota contributes to the development of disease. Based on evidence to date, we can assess the potential to positively modulate the composition of the colonic microbiota and ameliorate disease activity through bacterial intervention. PMID:25651997

Parasite-Microbiota Interactions With the Vertebrate Gut: Synthesis Through an Ecological Lens

PubMed Central

Leung, Jacqueline M.; Graham, Andrea L.; Knowles, Sarah C. L.

2018-01-01

The vertebrate gut teems with a large, diverse, and dynamic bacterial community that has pervasive effects on gut physiology, metabolism, and immunity. Under natural conditions, these microbes share their habitat with a similarly dynamic community of eukaryotes (helminths, protozoa, and fungi), many of which are well-known parasites. Both parasites and the prokaryotic microbiota can dramatically alter the physical and immune landscape of the gut, creating ample opportunities for them to interact. Such interactions may critically alter infection outcomes and affect overall host health and disease. For instance, parasite infection can change how a host interacts with its bacterial flora, either driving or protecting against dysbiosis and inflammatory disease. Conversely, the microbiota can alter a parasite's colonization success, replication, and virulence, shifting it along the parasitism-mutualism spectrum. The mechanisms and consequences of these interactions are just starting to be elucidated in an emergent transdisciplinary area at the boundary of microbiology and parasitology. However, heterogeneity in experimental designs, host and parasite species, and a largely phenomenological and taxonomic approach to synthesizing the literature have meant that common themes across studies remain elusive. Here, we use an ecological perspective to review the literature on interactions between the prokaryotic microbiota and eukaryotic parasites in the vertebrate gut. Using knowledge about parasite biology and ecology, we discuss mechanisms by which they may interact with gut microbes, the consequences of such interactions for host health, and how understanding parasite-microbiota interactions may lead to novel approaches in disease control. PMID:29867790

Parasite-Microbiota Interactions With the Vertebrate Gut: Synthesis Through an Ecological Lens.

PubMed

Leung, Jacqueline M; Graham, Andrea L; Knowles, Sarah C L

2018-01-01

The vertebrate gut teems with a large, diverse, and dynamic bacterial community that has pervasive effects on gut physiology, metabolism, and immunity. Under natural conditions, these microbes share their habitat with a similarly dynamic community of eukaryotes (helminths, protozoa, and fungi), many of which are well-known parasites. Both parasites and the prokaryotic microbiota can dramatically alter the physical and immune landscape of the gut, creating ample opportunities for them to interact. Such interactions may critically alter infection outcomes and affect overall host health and disease. For instance, parasite infection can change how a host interacts with its bacterial flora, either driving or protecting against dysbiosis and inflammatory disease. Conversely, the microbiota can alter a parasite's colonization success, replication, and virulence, shifting it along the parasitism-mutualism spectrum. The mechanisms and consequences of these interactions are just starting to be elucidated in an emergent transdisciplinary area at the boundary of microbiology and parasitology. However, heterogeneity in experimental designs, host and parasite species, and a largely phenomenological and taxonomic approach to synthesizing the literature have meant that common themes across studies remain elusive. Here, we use an ecological perspective to review the literature on interactions between the prokaryotic microbiota and eukaryotic parasites in the vertebrate gut. Using knowledge about parasite biology and ecology, we discuss mechanisms by which they may interact with gut microbes, the consequences of such interactions for host health, and how understanding parasite-microbiota interactions may lead to novel approaches in disease control.

Introduction: understanding mechanisms of the actions of rifaximin in selected gastrointestinal diseases.

PubMed

DuPont, H L

2016-01-01

Historically, the beneficial effects of the nonsystemic oral agent rifaximin on various gastrointestinal (GI) disorders have been attributed to direct antibiotic activity on gut microbiota. However, data are accumulating to suggest that other nonantibacterial effects may be involved in rifaximin efficacy. To explore the mechanisms of action of rifaximin that may underlie its clinical benefits in travellers' diarrhoea, hepatic encephalopathy and other cirrhosis complications, inflammatory bowel diseases, and irritable bowel syndrome with diarrhoea. Gastroenterology experts convened a round-table discussion to address clinical and pre-clinical rifaximin data pertaining to select GI diseases and the potential mechanisms of action that underlie rifaximin efficacy profiles. As preparation, the literature was searched for publications related to rifaximin, its mechanisms of action, and its efficacy in travellers' diarrhoea, hepatic encephalopathy and other cirrhosis-related complications, inflammatory bowel diseases and irritable bowel syndrome. Gut microbiota dysbiosis and proinflammatory activities are thought to significantly contribute to disease pathophysiology of these conditions. Rifaximin may resolve gut microbiota dysbiosis by promoting GI colonisation of beneficial bacterial species without drastic alterations in overall diversity. Rifaximin-induced changes in the production and metabolism of bacteria-produced agents (e.g. deoxycholic acid, lipopolysaccharides) also may help preserve normal gut microbiota. Rifaximin may suppress local and systemic inflammatory processes by preserving epithelial function (e.g. limiting bacterial translocation), modulating bacterial virulence and reducing proinflammatory cytokine production. The commonality of pathological mechanisms underlying multiple GI diseases and the ability of rifaximin to modulate the gut microenvironment (i.e. gut microenvironment modulator) may explain its diverse efficacy profile. © 2015 John Wiley & Sons Ltd.

Diversity in gut bacterial community of school-age children in Asia.

PubMed

Nakayama, Jiro; Watanabe, Koichi; Jiang, Jiahui; Matsuda, Kazunori; Chao, Shiou-Huei; Haryono, Pri; La-Ongkham, Orawan; Sarwoko, Martinus-Agus; Sujaya, I Nengah; Zhao, Liang; Chen, Kang-Ting; Chen, Yen-Po; Chiu, Hsueh-Hui; Hidaka, Tomoko; Huang, Ning-Xin; Kiyohara, Chikako; Kurakawa, Takashi; Sakamoto, Naoshige; Sonomoto, Kenji; Tashiro, Kousuke; Tsuji, Hirokazu; Chen, Ming-Ju; Leelavatcharamas, Vichai; Liao, Chii-Cherng; Nitisinprasert, Sunee; Rahayu, Endang S; Ren, Fa-Zheng; Tsai, Ying-Chieh; Lee, Yuan-Kun

2015-02-23

Asia differs substantially among and within its regions populated by diverse ethnic groups, which maintain their own respective cultures and dietary habits. To address the diversity in their gut microbiota, we characterized the bacterial community in fecal samples obtained from 303 school-age children living in urban or rural regions in five countries spanning temperate and tropical areas of Asia. The microbiota profiled for the 303 subjects were classified into two enterotype-like clusters, each driven by Prevotella (P-type) or Bifidobacterium/Bacteroides (BB-type), respectively. Majority in China, Japan and Taiwan harbored BB-type, whereas those from Indonesia and Khon Kaen in Thailand mainly harbored P-type. The P-type microbiota was characterized by a more conserved bacterial community sharing a greater number of type-specific phylotypes. Predictive metagenomics suggests higher and lower activity of carbohydrate digestion and bile acid biosynthesis, respectively, in P-type subjects, reflecting their high intake of diets rich in resistant starch. Random-forest analysis classified their fecal species community as mirroring location of resident country, suggesting eco-geographical factors shaping gut microbiota. In particular, children living in Japan harbored a less diversified microbiota with high abundance of Bifidobacterium and less number of potentially pathogenic bacteria, which may reflect their living environment and unique diet.

Gut microbiota may predict host divergence time during Glires evolution.

PubMed

Li, Huan; Qu, Jiapeng; Li, Tongtong; Yao, Minjie; Li, Jiaying; Li, Xiangzhen

2017-03-01

The gut microbial communities of animals play key roles in host evolution. However, the possible relationship between gut microbiota and host divergence time remains unknown. Here, we investigated the gut microbiota of eight Glires species (four lagomorph species and four rodent species) distributed throughout the Qinghai-Tibet plateau and Inner Mongolia grassland. Lagomorphs and rodents had distinct gut microbial compositions. Three out of four lagomorph species were dominated by Firmicutes, while rodents were dominated by Bacteroidetes in general. The alpha diversity values (Shannon diversity and evenness) exhibited significant differences between any two species within the lagomorphs, whereas there were no significant differences among rodents. The structure of the gut microbiota showed significant differences between lagomorphs and rodents. In addition, we calculated host phylogeny and divergence times, and used a phylogenetic approach to reconstruct how the animal gut microbiota has diverged from their ancestral species. Some core bacterial genera (e.g. Prevotella and Clostridium) shared by more than nine-tenths of all the Glires individuals associated with plant polysaccharide degradation showed marked changes within lagomorphs. Differences in Glires gut microbiota (based on weighted UniFrac and Bray-Curtis dissimilarity metrics) were positively correlated with host divergence time. Our results thus suggest the gut microbial composition is associated with host phylogeny, and further suggest that dissimilarity of animal gut microbiota may predict host divergence time. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Gut microbiota alterations and dietary modulation in childhood malnutrition - The role of short chain fatty acids.

PubMed

Pekmez, Ceyda Tugba; Dragsted, Lars Ove; Brahe, Lena Kirchner

2018-02-17

The gut microbiome affects the health status of the host through different mechanisms and is associated with a wide variety of diseases. Both childhood undernutrition and obesity are linked to alterations in composition and functionality of the gut microbiome. One of the possible mechanisms underlying the interplay between microbiota and host metabolism is through appetite-regulating hormones (including leptin, ghrelin, glucagon-like peptide-1). Short chain fatty acids, the end product of bacterial fermentation of non-digestible carbohydrates, might be able to alter energy harvest and metabolism through enteroendocrine cell signaling, adipogenesis and insulin-like growth factor-1 production. Elucidating these mechanisms may lead to development of new modulation practices of the gut microbiota as a potential prevention and treatment strategy for childhood malnutrition. The present overview will briefly outline the gut microbiota development in the early life, gut microbiota alterations in childhood undernutrition and obesity, and whether this relationship is causal. Further we will discuss possible underlying mechanisms in relation to the gut-brain axis and short chain fatty acids, and the potential of probiotics, prebiotics and synbiotics for modulating the gut microbiota during childhood as a prevention and treatment strategy against undernutrition and obesity. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Cospeciation of gut microbiota with hominids

PubMed Central

Moeller, Andrew H.; Caro-Quintero, Alejandro; Mjungu, Deus; Georgiev, Alexander V.; Lonsdorf, Elizabeth V.; Muller, Martin N.; Pusey, Anne E.; Peeters, Martine; Hahn, Beatrice H.; Ochman, Howard

2016-01-01

The evolutionary origins of the bacterial lineages that populate the human gut are unknown. Here we show that multiple lineages of the predominant bacterial taxa in the gut arose via cospeciation with humans, chimpanzees, bonobos, and gorillas over the past 15 million years. Analyses of strain-level bacterial diversity within hominid gut microbiomes revealed that clades of Bacteroidaceae and Bifidobacteriaceae have been maintained exclusively within host lineages across hundreds of thousands of host generations. Divergence times of these cospeciating gut bacteria are congruent with those of hominids, indicating that nuclear, mitochondrial, and gut bacterial genomes diversified in concert during hominid evolution. This study identifies human gut bacteria descended from ancient symbionts that speciated simultaneously with humans and the African apes. PMID:27463672

Gut microbiota composition modifies fecal metabolic profiles in mice.

PubMed

Zhao, Ying; Wu, Junfang; Li, Jia V; Zhou, Ning-Yi; Tang, Huiru; Wang, Yulan

2013-06-07

The gut microbiome is known to be extensively involved in human health and disease. In order to reveal the metabolic relationship between host and microbiome, we monitored recovery of the gut microbiota composition and fecal profiles of mice after gentamicin and/or ceftriaxone treatments. This was performed by employing (1)H nuclear magnetic resonance (NMR)-based metabonomics and denaturing gradient gel electrophoresis (DGGE) fingerprint of gut microbiota. The common features of fecal metabolites postantibiotic treatment include decreased levels of short chain fatty acids (SCFAs), amino acids and primary bile acids and increased oligosaccharides, d-pinitol, choline and secondary bile acids (deoxycholic acid). This suggests suppressed bacterial fermentation, protein degradation and enhanced gut microbial modification of bile acids. Barnesiella, Prevotella, and Alistipes levels were shown to decrease as a result of the antibiotic treatment, whereas levels of Bacteroides, Enterococcus and Erysipelotrichaceae incertae sedis, and Mycoplasma increased after gentamicin and ceftriaxone treatment. In addition, there was a strong correlation between fecal profiles and levels of Bacteroides, Barnesiella, Alistipes and Prevotella. The integration of metabonomics and gut microbiota profiling provides important information on the changes of gut microbiota and their impact on fecal profiles during the recovery after antibiotic treatment. The correlation between gut microbiota and fecal metabolites provides important information on the function of bacteria, which in turn could be important in optimizing therapeutic strategies, and developing potential microbiota-based disease preventions and therapeutic interventions.

Gut microbiota, epigenetic modification and colorectal cancer

PubMed Central

Rezasoltani, Sama; Asadzadeh-Aghdaei, Hamid; Nazemalhosseini-Mojarad, Ehsan; Dabiri, Hossein; Ghanbari, Reza; Zali, Mohammad Reza

2017-01-01

Micro-organisms contain 90% of cells in human body and trillions foreign genes versus less than 30 thousand of their own. The human colon host various species of microorganisms, appraised at more than 1014 microbiota and contained of over a thousand species. Although each one’s profile is separable, the relative abundance and distribution of bacterial species is the same between healthy ones, causing conservation of each person’s overall health. Germline DNA mutations have been attributed to the less than 5% of CRC occurrence while more than 90% is associated with the epigenetic regulation. The most ubiquitous environmental factor in epigenetic modification is gut microbiota. Disruptive changes in the gut microbiome strongly contributed to the improvement of colorectal cancer. Gut microbiota may play critical role in progression of CRC via their metabolite or their structural component interacting with host intestinal epithelial cell (IEC). Herein we discuss the mechanism of epigenetic modification and its implication in CRC development, progression even metastasis by gut microbiota induction. PMID:29213996

Gut Microbiota-Induced Immunoglobulin G Controls Systemic Infection by Symbiotic Bacteria and Pathogens

PubMed Central

Zeng, Melody Y.; Cisalpino, Daniel; Varadarajan, Saranyaraajan; Hellman, Judith; Warren, H. Shaw; Cascalho, Marilia; Inohara, Naohiro; Núñez, Gabriel

2016-01-01

The gut microbiota is compartmentalized in the intestinal lumen and induces local immune responses, but it remains unknown whether the gut microbiota can induce systemic response and contribute to systemic immunity. We report that selective gut symbiotic gram-negative bacteria were able to disseminate systemically to induce immunoglobulin G (IgG) response, which primarily targeted gram-negative bacterial antigens and conferred protection against systemic infections by E. coli and Salmonella by directly coating bacteria to promote killing by phagocytes. T cells and Toll-like receptor 4 on B cells were important in the generation of microbiota-specific IgG. We identified murein lipoprotein (MLP), a highly conserved gram-negative outer membrane protein, as a major antigen that induced systemic IgG homeostatically in both mice and humans. Administration of anti-MLP IgG conferred crucial protection against systemic Salmonella infection. Thus, our findings reveal an important function for the gut microbiota in combating systemic infection through the induction of protective IgG. PMID:26944199

Host and Symbiont Jointly Control Gut Microbiota during Complete Metamorphosis

PubMed Central

Johnston, Paul R.; Rolff, Jens

2015-01-01

Holometabolous insects undergo a radical anatomical re-organisation during metamorphosis. This poses a developmental challenge: the host must replace the larval gut but at the same time retain symbiotic gut microbes and avoid infection by opportunistic pathogens. By manipulating host immunity and bacterial competitive ability, we study how the host Galleria mellonella and the symbiotic bacterium Enterococcus mundtii interact to manage the composition of the microbiota during metamorphosis. Disenabling one or both symbiotic partners alters the composition of the gut microbiota, which incurs fitness costs: adult hosts with a gut microbiota dominated by pathogens such as Serratia and Staphylococcus die early. Our results reveal an interaction that guarantees the safe passage of the symbiont through metamorphosis and benefits the resulting adult host. Host-symbiont “conspiracies” as described here are almost certainly widespread in holometobolous insects including many disease vectors. PMID:26544881

Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats.

PubMed

Etxeberria, U; Arias, N; Boqué, N; Macarulla, M T; Portillo, M P; Martínez, J A; Milagro, F I

2015-06-01

Diet-induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability, and when they reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans-resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high-fat sucrose diet (HFS) and, in turn, improve gut health. Wistar rats were randomised into four groups fed an HFS diet supplemented or not with trans-resveratrol [15 mg/kg body weight (BW)/day], quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans-resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS-diet-induced gut microbiota dysbiosis. In contrast, trans-resveratrol supplementation alone or in combination with quercetin scarcely modified the profile of gut bacteria but acted at the intestinal level, altering the mRNA expression of tight-junction proteins and inflammation-associated genes. Copyright © 2015 Elsevier Inc. All rights reserved.

Gut microbiota role in irritable bowel syndrome: New therapeutic strategies

PubMed Central

Distrutti, Eleonora; Monaldi, Lorenzo; Ricci, Patrizia; Fiorucci, Stefano

2016-01-01

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required. PMID:26900286

How to Feed the Mammalian Gut Microbiota: Bacterial and Metabolic Modulation by Dietary Fibers

PubMed Central

Ferrario, Chiara; Statello, Rosario; Carnevali, Luca; Mancabelli, Leonardo; Milani, Christian; Mangifesta, Marta; Duranti, Sabrina; Lugli, Gabriele A.; Jimenez, Beatriz; Lodge, Samantha; Viappiani, Alice; Alessandri, Giulia; Dall’Asta, Margerita; Del Rio, Daniele; Sgoifo, Andrea; van Sinderen, Douwe; Ventura, Marco; Turroni, Francesca

2017-01-01

The composition of the gut microbiota of mammals is greatly influenced by diet. Therefore, evaluation of different food ingredients that may promote changes in the gut microbiota composition is an attractive approach to treat microbiota disturbances. In this study, three dietary fibers, such as inulin (I, 10%), resistant starch (RS, 10%), and citrus pectin (3%), were employed as supplements to normal chow diet of adult male rats for 2 weeks. Fecal microbiota composition and corresponding metabolite profiles were assessed before and after prebiotics supplementation. A general increase in the Bacteroidetes phylum was detected with a concurrent reduction in Firmicutes, in particular for I and RS experiments, while additional changes in the microbiota composition were evident at lower taxonomic levels for all the three substrates. Such modifications in the microbiota composition were correlated with changes in metabolic profiles of animals, in particular changes in acetate and succinate levels. This study represents a first attempt to modulate selectively the abundance and/or metabolic activity of various members of the gut microbiota by means of dietary fiber. PMID:28955319

Cultivation-independent methods reveal differences among bacterial gut microbiota in triatomine vectors of Chagas disease.

PubMed

da Mota, Fabio Faria; Marinho, Lourena Pinheiro; Moreira, Carlos José de Carvalho; Lima, Marli Maria; Mello, Cícero Brasileiro; Garcia, Eloi Souza; Carels, Nicolas; Azambuja, Patricia

2012-01-01

Chagas disease is a trypanosomiasis whose agent is the protozoan parasite Trypanosoma cruzi, which is transmitted to humans by hematophagous bugs known as triatomines. Even though insecticide treatments allow effective control of these bugs in most Latin American countries where Chagas disease is endemic, the disease still affects a large proportion of the population of South America. The features of the disease in humans have been extensively studied, and the genome of the parasite has been sequenced, but no effective drug is yet available to treat Chagas disease. The digestive tract of the insect vectors in which T. cruzi develops has been much less well investigated than blood from its human hosts and constitutes a dynamic environment with very different conditions. Thus, we investigated the composition of the predominant bacterial species of the microbiota in insect vectors from Rhodnius, Triatoma, Panstrongylus and Dipetalogaster genera. Microbiota of triatomine guts were investigated using cultivation-independent methods, i.e., phylogenetic analysis of 16s rDNA using denaturing gradient gel electrophoresis (DGGE) and cloned-based sequencing. The Chao index showed that the diversity of bacterial species in triatomine guts is low, comprising fewer than 20 predominant species, and that these species vary between insect species. The analyses showed that Serratia predominates in Rhodnius, Arsenophonus predominates in Triatoma and Panstrongylus, while Candidatus Rohrkolberia predominates in Dipetalogaster. The microbiota of triatomine guts represents one of the factors that may interfere with T. cruzi transmission and virulence in humans. The knowledge of its composition according to insect species is important for designing measures of biological control for T. cruzi. We found that the predominant species of the bacterial microbiota in triatomines form a group of low complexity whose structure differs according to the vector genus.

Characterization of fecal microbiota across seven Chinese ethnic groups by quantitative polymerase chain reaction.

PubMed

Kwok, Lai-yu; Zhang, Jiachao; Guo, Zhuang; Gesudu, Qimu; Zheng, Yi; Qiao, Jianmin; Huo, Dongxue; Zhang, Heping

2014-01-01

The human gut microbiota consists of complex microbial communities, which possibly play crucial roles in physiological functioning and health maintenance. China has evolved into a multicultural society consisting of the major ethnic group, Han, and 55 official ethnic minority groups. Nowadays, these minority groups inhabit in different Chinese provinces and some of them still keep their unique culture and lifestyle. Currently, only limited data are available on the gut microbiota of these Chinese ethnic groups. In this study, 10 major fecal bacterial groups of 314 healthy individuals from 7 Chinese ethnic origins were enumerated by quantitative polymerase chain reaction. Our data confirmed that the selected bacterial groups were common to all 7 surveyed ethnicities, but the amount of the individual bacterial groups varied to different degree. By principal component and canonical variate analyses of the 314 individuals or the 91 Han subjects, no distinct group clustering pattern was observed. Nevertheless, weak differences were noted between the Han and Zhuang from other ethnic minority groups, and between the Heilongjiang Hans from those of the other provinces. Thus, our results suggest that the ethnic origin may contribute to shaping the human gut microbiota.

Characterization of Fecal Microbiota across Seven Chinese Ethnic Groups by Quantitative Polymerase Chain Reaction

PubMed Central

Guo, Zhuang; Gesudu, Qimu; Zheng, Yi; Qiao, Jianmin; Huo, Dongxue; Zhang, Heping

2014-01-01

The human gut microbiota consists of complex microbial communities, which possibly play crucial roles in physiological functioning and health maintenance. China has evolved into a multicultural society consisting of the major ethnic group, Han, and 55 official ethnic minority groups. Nowadays, these minority groups inhabit in different Chinese provinces and some of them still keep their unique culture and lifestyle. Currently, only limited data are available on the gut microbiota of these Chinese ethnic groups. In this study, 10 major fecal bacterial groups of 314 healthy individuals from 7 Chinese ethnic origins were enumerated by quantitative polymerase chain reaction. Our data confirmed that the selected bacterial groups were common to all 7 surveyed ethnicities, but the amount of the individual bacterial groups varied to different degree. By principal component and canonical variate analyses of the 314 individuals or the 91 Han subjects, no distinct group clustering pattern was observed. Nevertheless, weak differences were noted between the Han and Zhuang from other ethnic minority groups, and between the Heilongjiang Hans from those of the other provinces. Thus, our results suggest that the ethnic origin may contribute to shaping the human gut microbiota. PMID:24699404

Host Age Affects the Development of Southern Catfish Gut Bacterial Community Divergent From That in the Food and Rearing Water.

PubMed

Zhang, Zhimin; Li, Dapeng; Refaey, Mohamed M; Xu, Weitong; Tang, Rong; Li, Li

2018-01-01

Host development influences gut microbial assemblies that may be confounded partly by dietary shifts and the changing environmental microbiota during ontogenesis. However, little is known about microbial colonization by excluding dietary effects and compositional differences in microbiota between the gut and environment at different ontogenetic stages. Herein, a developmental gut microbial experiment under controlled laboratory conditions was conducted with carnivorous southern catfish Silurus meridionalis fed on an identical prey with commensal and abundant microbiota. In this study, we provided a long-term analysis of gut microbiota associated with host age at 8, 18, 35, 65, and 125 day post-fertilization (dpf) and explored microbial relationships among host, food and water environment at 8, 35, and 125 dpf. The results showed that gut microbial diversity in southern catfish tended to increase linearly as host aged. Gut microbiota underwent significant temporal shifts despite similar microbial communities in food and rearing water during the host development and dramatically differed from the environmental microbiota. At the compositional abundance, Tenericute s and Fusobacteria were enriched in the gut and markedly varied with host age, whereas Spirochaetes and Bacteroidetes detected were persistently the most abundant phyla in food and water, respectively. In addition to alterations in individual microbial taxa, the individual differences in gut microbiota were at a lower level at the early stages than at the late stages and in which gut microbiota reached a stable status, suggesting the course of microbial successions. These results indicate that host development fundamentally shapes a key transition in microbial community structure, which is independent of dietary effects. In addition, the dominant taxa residing in the gut do not share their niche habitats with the abundant microbiota in the surrounding environment. It's inferred that complex gut microbiota could not be simple reflections of environmental microbiota. The knowledge enhances the understanding of gut microbial establishment in the developing fish and provides a useful resource for such studies of fish- or egg-associated microbiota in aquaculture.

Long-Term Green Tea Supplementation Does Not Change the Human Gut Microbiota

PubMed Central

Janssens, Pilou L. H. R.; Penders, John; Hursel, Rick; Budding, Andries E.; Savelkoul, Paul H. M.; Westerterp-Plantenga, Margriet S.

2016-01-01

Background Green tea catechins may play a role in body weight regulation through interactions with the gut microbiota. Aim We examined whether green tea supplementation for 12 weeks induces changes in composition of the human gut microbiota. Methods 58 Caucasian men and women were included in a randomized, placebo-controlled design. For 12 weeks, subjects consumed either green tea (>0.56 g/d epigallocatechin-gallate + 0.28 ∼ 0.45 g/d caffeine) or placebo capsules. Fecal samples were collected twice (baseline, vs. week 12) for analyses of total bacterial profiles by means of IS-profiling, a 16S-23S interspacer region-based profiling method. Results No significant changes between baseline and week 12 in subjects receiving green tea or placebo capsules, and no significant interactions between treatment (green tea or placebo) and time (baseline and week 12) were observed for body composition. Analysis of the fecal samples in subjects receiving green tea and placebo showed similar bacterial diversity and community structures, indicating there were no significant changes in bacterial diversity between baseline and week 12 in subjects receiving green tea capsules or in subjects receiving placebo capsules. No significant interactions were observed between treatment (green tea or placebo) and time (baseline and week 12) for the gut microbial diversity. Although, there were no significant differences between normal weight and overweight subjects in response to green tea, we did observe a reduced bacterial alpha diversity in overweight as compared to normal weight subjects (p = 0.002). Conclusion Green tea supplementation for 12 weeks did not have a significant effect on composition of the gut microbiota. Trial Registration ClinicalTrials.gov NCT01556321 PMID:27054321

Interplay between gut microbiota metabolism and inflammation in HIV infection.

PubMed

Vázquez-Castellanos, Jorge F; Serrano-Villar, Sergio; Jiménez-Hernández, Nuria; Soto Del Rio, María Dolores; Gayo, Sara; Rojo, David; Ferrer, Manuel; Barbas, Coral; Moreno, Santiago; Estrada, Vicente; Rattei, Tomas; Latorre, Amparo; Moya, Andrés; Gosalbes, María José

2018-05-23

HIV infection causes a disruption of gut-associated lymphoid tissue, driving a shift in the composition of gut microbiota. A deeper understanding of the metabolic changes and how they affect the interplay with the host is needed. Here, we assessed functional modifications of HIV-associated microbiota by combining metagenomic and metatranscriptomic analyses. The transcriptionally active microbiota was well-adapted to the inflamed environment, overexpressing pathways related to resistance to oxidative stress. Furthermore, gut inflammation was maintained by the Gram-negative nature of the HIV-associated microbiota and underexpression of anti-inflammatory processes, such as short chain fatty acid biosynthesis or indole production. We performed co-occurrence and metabolic network analyses that showed relevance in the microbiota structure of both taxonomic and metabolic HIV-associated biomarkers. The Bayesian network revealed the most determinant pathways for maintaining the structure stability of the bacterial community. In addition, we identified the taxa's contribution to metabolic activities and their interactions with host health.

Exploring the bacterial gut microbiota of supralittoral talitrid amphipods.

PubMed

Abdelrhman, Khaled F A; Bacci, Giovanni; Marras, Barbara; Nistri, Annamaria; Schintu, Marco; Ugolini, Alberto; Mengoni, Alessio

2017-01-01

Talitrid amphipods (sandhoppers and beach fleas) are typical of the supralittoral zone. They are known to thrive on stranded materials, including detrital marine angiosperms and macroalgae, as well as occasional dead animals. In this work, the gut microbiota of five species of talitrid amphipods (Talitrus saltator, Talorchestia ugolinii, Sardorchestia pelecaniformis, Orchestia montagui and Orchestia stephenseni) collected in Sardinia (Italy) has been investigated through: i) metabarcoding analysis of the amplified 16S rRNA V4 region; and ii) quantification of family 48 glycosyl hydrolase genes (GHF48), involved in cellulose degradation. Results indicate that, though talitrid gut biodiversity is not directly related to taxon or sampling locality, the animals' digestive tracts may host species-specific bacterial communities. In particular, gut microbiota of O. montagui, an inhabitant of Posidonia banquettes and macro-algae mat, showed the greatest differences in taxonomic composition and the highest proportion of GHF48 genes with respect to 16S rRNA genes. These results suggest that the different talitrid species may host species-specific bacterial communities whose function could partially reflect the different microhabitats and food preferences of their host. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

[Gut microbiota: Description, role and pathophysiologic implications].

PubMed

Landman, C; Quévrain, E

2016-06-01

The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis

PubMed Central

Montiel-Jarquín, Alvaro José; Pizano-Zárate, María Luisa

2017-01-01

Characterization and understanding of gut microbiota has recently increased representing a wide research field, especially in autoimmune diseases. Gut microbiota is the major source of microbes which might exert beneficial as well as pathogenic effects on human health. Intestinal microbiome's role as mediator of inflammation has only recently emerged. Microbiota has been observed to differ in subjects with early rheumatoid arthritis compared to controls, and this finding has commanded this study as a possible autoimmune process. Studies with intestinal microbiota have shown that rheumatoid arthritis is characterized by an expansion and/or decrease of bacterial groups as compared to controls. In this review, we present evidence linking intestinal dysbiosis with the autoimmune mechanisms involved in the development of rheumatoid arthritis. PMID:28948174

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.

Gut bacteria facilitate adaptation to crop rotation in the western corn rootworm

PubMed Central

Chu, Chia-Ching; Spencer, Joseph L.; Curzi, Matías J.; Zavala, Jorge A.; Seufferheld, Manfredo J.

2013-01-01

Insects are constantly adapting to human-driven landscape changes; however, the roles of their gut microbiota in these processes remain largely unknown. The western corn rootworm (WCR, Diabrotica virgifera virgifera LeConte) (Coleoptera: Chrysomelidae) is a major corn pest that has been controlled via annual rotation between corn (Zea mays) and nonhost soybean (Glycine max) in the United States. This practice selected for a “rotation-resistant” variant (RR-WCR) with reduced ovipositional fidelity to cornfields. When in soybean fields, RR-WCRs also exhibit an elevated tolerance of antiherbivory defenses (i.e., cysteine protease inhibitors) expressed in soybean foliage. Here we show that gut bacterial microbiota is an important factor facilitating this corn specialist’s (WCR's) physiological adaptation to brief soybean herbivory. Comparisons of gut microbiota between RR- and wild-type WCR (WT-WCR) revealed concomitant shifts in bacterial community structure with host adaptation to soybean diets. Antibiotic suppression of gut bacteria significantly reduced RR-WCR tolerance of soybean herbivory to the level of WT-WCR, whereas WT-WCR were unaffected. Our findings demonstrate that gut bacteria help to facilitate rapid adaptation of insects in managed ecosystems. PMID:23798396

A gut (microbiome) feeling about the brain.

PubMed

Sherwin, Eoin; Rea, Kieran; Dinan, Timothy G; Cryan, John F

2016-03-01

There is an increasing realization that the microorganisms which reside within our gut form part of a complex multidirectional communication network with the brain known as the microbiome-gut-brain axis. In this review, we focus on recent findings which support a role for this axis in modulating neurodevelopment and behavior. A growing body of research is uncovering that under homeostatic conditions and in response to internal and external stressors, the bacterial commensals of our gut can signal to the brain through a variety of mechanisms to influence processes such neurotransmission, neurogenesis, microglia activation, and modulate behavior. Moreover, the mechanisms underlying the ability of stress to modulate the microbiota and also for microbiota to change the set point for stress sensitivity are being unraveled. Dysregulation of the gut microbiota composition has been identified in a number of psychiatric disorders, including depression. This has led to the concept of bacteria that have a beneficial effect upon behavior and mood (psychobiotics) being proposed for potential therapeutic interventions. Understanding the mechanisms by which the bacterial commensals of our gut are involved in brain function may lead to the development of novel microbiome-based therapies for these mood and behavioral disorders.

Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome.

PubMed

Spychala, Monica S; Venna, Venugopal Reddy; Jandzinski, Michal; Doran, Sarah J; Durgan, David J; Ganesh, Bhanu Priya; Ajami, Nadim J; Putluri, Nagireddy; Graf, Joerg; Bryan, Robert M; McCullough, Louise D

2018-05-07

Objective Chronic systemic inflammation contributes to the pathogenesis of many age-related diseases. Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age-related inflammation. Methods Using stroke as a disease model, we tested the hypothesis that a youthful microbiota, when established in aged mice, produces positive outcomes following ischemic stroke. Conversely, an aged microbiota, when established in young mice, produces negative outcomes after stroke. Young and aged male mice had either a young or an aged microbiota established by fecal transplant gavage (FTG). Mice were subjected to ischemic stroke (MCAO) or sham surgery. During the subsequent weeks, mice underwent behavioral testing and fecal samples were collected for 16S rRNA analysis of bacterial content. Results We found that the microbiota is altered after experimental stroke in young mice, and resembles the biome of uninjured aged mice. In aged mice, the ratio of Firmicutes to Bacteroidetes (F:B), two main bacterial phyla in gut microbiota, increased ∼9-fold (P<0.001) compared to young. This increased F:B ratio in aged mice is indicative of dysbiosis. Altering the microbiota in young by fecal gavage to resemble that of aged mice (∼6-fold increase in F:B ratio, P<0.001) increased mortality following MCAO, decreased performance in behavioral testing, and increased cytokine levels. Conversely, altering the microbiota in aged to resemble that of young (∼9-fold decrease in F:B ratio, P<0.001) increased survival and improved recovery following MCAO. Interpretation Aged biome increased the levels of systemic pro-inflammatory cytokines. We conclude that the gut microbiota can be modified to positively impact outcomes from age-related diseases. This article is protected by copyright. All rights reserved. © 2018 American Neurological Association.

Influence of gut microbiota on the development and progression of nonalcoholic steatohepatitis.

PubMed

de Faria Ghetti, Fabiana; Oliveira, Daiane Gonçalves; de Oliveira, Juliano Machado; de Castro Ferreira, Lincoln Eduardo Villela Vieira; Cesar, Dionéia Evangelista; Moreira, Ana Paula Boroni

2018-04-01

Nonalcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation, and ballooning degeneration of hepatocytes, with or without fibrosis. The prevalence of NASH has increased with the obesity epidemic, but its etiology is multifactorial. The current studies suggest the role of gut microbiota in the development and progression of NASH. The aim is to review the studies that investigate the relationship between gut microbiota and NASH. These review also discusses the pathophysiological mechanisms and the influence of diet on the gut-liver axis. The available literature has proposed mechanisms for an association between gut microbiota and NASH, such as: modification energy homeostasis, lipopolysaccharides (LPS)-endotoxemia, increased endogenous production of ethanol, and alteration in the metabolism of bile acid and choline. There is evidence to suggest that NASH patients have a higher prevalence of bacterial overgrowth in the small intestine and changes in the composition of the gut microbiota. However, there is still a controversy regarding the microbiome profile in this population. The abundance of Bacteroidetes phylum may be increased, decreased, or unaltered in NASH patients. There is an increase in the Escherichia and Bacteroides genus. There is depletion of certain taxa, such as Prevotella and Faecalibacterium. Although few studies have evaluated the composition of the gut microbiota in patients with NASH, it is observed that these individuals have a distinct gut microbiota, compared to the control groups, which explains, at least in part, the genesis and progression of the disease through multiple mechanisms. Modulation of the gut microbiota through diet control offers new challenges for future studies.

Meta-analysis To Define a Core Microbiota in the Swine Gut

PubMed Central

Holman, Devin B.; Brunelle, Brian W.; Trachsel, Julian

2017-01-01

ABSTRACT The swine gut microbiota encompasses a large and diverse population of bacteria that play a significant role in pig health. As such, a number of recent studies have utilized high-throughput sequencing of the 16S rRNA gene to characterize the composition and structure of the swine gut microbiota, often in response to dietary feed additives. It is important to determine which factors shape the composition of the gut microbiota among multiple studies and if certain bacteria are always present in the gut microbiota of swine, independently of study variables such as country of origin and experimental design. Therefore, we performed a meta-analysis using 20 publically available data sets from high-throughput 16S rRNA gene sequence studies of the swine gut microbiota. Next to the “study” itself, the gastrointestinal (GI) tract section that was sampled had the greatest effect on the composition and structure of the swine gut microbiota (P = 0.0001). Technical variation among studies, particularly the 16S rRNA gene hypervariable region sequenced, also significantly affected the composition of the swine gut microbiota (P = 0.0001). Despite this, numerous commonalities were discovered. Among fecal samples, the genera Prevotella, Clostridium, Alloprevotella, and Ruminococcus and the RC9 gut group were found in 99% of all fecal samples. Additionally, Clostridium, Blautia, Lactobacillus, Prevotella, Ruminococcus, Roseburia, the RC9 gut group, and Subdoligranulum were shared by >90% of all GI samples, suggesting a so-called “core” microbiota for commercial swine worldwide. IMPORTANCE The results of this meta-analysis demonstrate that “study” and GI sample location are the most significant factors in shaping the swine gut microbiota. However, in comparisons of results from different studies, some biological factors may be obscured by technical variation among studies. Nonetheless, there are some bacterial taxa that appear to form a core microbiota within the swine GI tract regardless of country of origin, diet, age, or breed. Thus, these results provide the framework for future studies to manipulate the swine gut microbiota for potential health benefits. PMID:28567446

Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila.

PubMed

Lee, Kyung-Ah; Kim, Sung-Hee; Kim, Eun-Kyoung; Ha, Eun-Mi; You, Hyejin; Kim, Boram; Kim, Min-Ji; Kwon, Youngjoo; Ryu, Ji-Hwan; Lee, Won-Jae

2013-05-09

All metazoan guts are subjected to immunologically unique conditions in which an efficient antimicrobial system operates to eliminate pathogens while tolerating symbiotic commensal microbiota. However, the molecular mechanisms controlling this process are only partially understood. Here, we show that bacterial-derived uracil acts as a ligand for dual oxidase (DUOX)-dependent reactive oxygen species generation in Drosophila gut and that the uracil production in bacteria causes inflammation in the gut. The acute and controlled uracil-induced immune response is required for efficient elimination of bacteria, intestinal cell repair, and host survival during infection of nonresident species. Among resident gut microbiota, uracil production is absent in symbionts, allowing harmonious colonization without DUOX activation, whereas uracil release from opportunistic pathobionts provokes chronic inflammation. These results reveal that bacteria with distinct abilities to activate uracil-induced gut inflammation, in terms of intensity and duration, act as critical factors that determine homeostasis or pathogenesis in gut-microbe interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

Meta-Analysis of Fecal Microbiota and Metabolites in Experimental Colitic Mice during the Inflammatory and Healing Phases.

PubMed

Osaka, Toshifumi; Moriyama, Eri; Arai, Shunichi; Date, Yasuhiro; Yagi, Junji; Kikuchi, Jun; Tsuneda, Satoshi

2017-12-06

The imbalance of gut microbiota is known to be associated with inflammatory bowel disease, but it remains unknown whether dysbiosis is a cause or consequence of chronic gut inflammation. In order to investigate the effects of gut inflammation on microbiota and metabolome, the sequential changes in gut microbiota and metabolites from the onset of colitis to the recovery in dextran sulfate sodium-induced colitic mice were characterized by using meta 16S rRNA sequencing and proton nuclear magnetic resonance (¹H-NMR) analysis. Mice in the colitis progression phase showed the transient expansions of two bacterial families including Bacteroidaceae and Enterobacteriaceae and the depletion of major gut commensal bacteria belonging to the uncultured Bacteroidales family S24-7, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. After the initiation of the recovery, commensal Lactobacillus members promptly predominated in gut while other normally abundant bacteria excluding the Erysipelotrichaceae remained diminished. Furthermore, ¹H-NMR analysis revealed characteristic fluctuations in fecal levels of organic acids (lactate and succinate) associated with the disease states. In conclusion, acute intestinal inflammation is a perturbation factor of gut microbiota but alters the intestinal environments suitable for Lactobacillus members.

Gut Microbiota and the Liver: A Tale of 2 Cities: A Narrative View in 2 Acts.

PubMed

Koch, Maurizio

Microbes are mostly important for the digestion of food, the absorption of some micronutrients, and the production of vitamins. The microbiota stimulates lymphoid structures in the gastrointestinal mucosa and decrease pathogens by competing for nutrients and space. Bacterial translocation is defined as the escape of gut bacteria and their products through the intestinal mucosa to the outside of the intestine as portovenous or systemic circulation. This is induced by a leaky gut barrier. There is evidence for a role of intestinal permeability in the pathogenesis of nonalcoholic fatty liver disease. In the liver, bacterial products can bind to their specific pathogen recognition receptors on parenchymal and nonparenchymal cells, producing an inflammatory response and enhancing disease progression. When binding, bacterial products bind to their receptors, initiating intracellular signalling and inducing an inflammatory cascade, thus accelerating liver cell damage and fibrosis. However, the liver can also increase gut permeability, producing proinflammatory cytokines, and reversing them into the blood stream. Modification of the gut microbiota could lead to benefit in patients with liver disease. Nonabsorbable antibiotics (rifaximin) prevent and relieve overt encephalopathy. Probiotics alone are not capable of turning back overt encephalopathy, but could prevent its development. There is some evidence that probiotics could relent the progression of nonalcoholic liver disease, and possibly reverse steatosis. Antibiotics, such as fluoroquinolones, reduce the risk of development of the first episode of spontaneous bacterial peritonitis and mortality in cirrhotic patients.

Exposure to concentrated ambient PM2.5 alters the composition of gut microbiota in a murine model.

PubMed

Wang, Wanjun; Zhou, Ji; Chen, Minjie; Huang, Xingke; Xie, Xiaoyun; Li, Weihua; Cao, Qi; Kan, Haidong; Xu, Yanyi; Ying, Zhekang

2018-04-17

Exposure to ambient fine particulate matter (PM 2.5 ) correlates with abnormal glucose homeostasis, but the underlying biological mechanism has not been fully understood. The gut microbiota is an emerging crucial player in the homeostatic regulation of glucose metabolism. Few studies have investigated its role in the PM 2.5 exposure-induced abnormalities in glucose homeostasis. C57Bl/6J mice were exposed to filtered air (FA) or concentrated ambient PM 2.5 (CAP) for 12 months using a versatile aerosol concentration enrichment system (VACES) that was modified for long-term whole-body exposures. Their glucose homeostasis and gut microbiota were examined and analysed by correlation and mediation analysis. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) showed that CAP exposure markedly impaired their glucose and insulin tolerance. Faecal microbiota analysis demonstrated that the impairment in glucose homeostasis was coincided with decreased faecal bacterial ACE and Chao-1 estimators (the indexes of community richness), while there was no significant change in all faecal fungal alpha diversity estimators. The Pearson's correlation analyses showed that the bacterial richness estimators were correlated with glucose and insulin tolerance, and the mediation analyses displayed a significant mediation of CAP exposure-induced glucose intolerance by the alteration in the bacterial Chao-1 estimator. LEfSe analyses revealed 24 bacterial and 21 fungal taxa differential between CAP- and FA-exposed animals. Of these, 14 and 20 bacterial taxa were correlated with IPGTT AUC and ITT AUC, respectively, and 5 fungal taxa were correlated with abnormalities in glucose metabolism. Chronic exposure to PM 2.5 causes gut dysbiosis and may subsequently contribute to the development of abnormalities in glucose metabolism.

The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice

PubMed Central

Turnbaugh, Peter J.; Ridaura, Vanessa K.; Faith, Jeremiah J.; Rey, Federico E.; Knight, Rob; Gordon, Jeffrey I.

2010-01-01

Diet and nutritional status are among the most important, modifiable determinants of human health. The nutritional value of food is influenced in part by a person’s gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelationships between diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent, metagenomic analysis of the temporal, spatial and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized, and reproduced much of the bacterial diversity of the donor’s microbiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat/high-sugar “Western” diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community, but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle “clinical trials” that test the effects of environmental and genetic factors on the gut microbiota and host physiology. PMID:20368178

A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species.

PubMed

Martinson, Vincent G; Carpinteyro-Ponce, Javier; Moran, Nancy A; Markow, Therese A

2017-12-01

Almost all animals possess gut microbial communities, but the nature of these communities varies immensely. For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster , however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria. Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). We found that the D. nigrospiracula microbiota differs strikingly from that of the cactus tissue on which the flies feed. The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas , have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. Although the functions of these bacterial groups are mostly unexplored, Orbales species studied in bees are known to break down plant polysaccharides and use the resulting sugars. Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings. IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. This study highlights the importance of fieldwork-informed microbiota research. Copyright © 2017 American Society for Microbiology.

A Distinctive and Host-Restricted Gut Microbiota in Populations of a Cactophilic Drosophila Species

PubMed Central

Carpinteyro-Ponce, Javier

2017-01-01

ABSTRACT Almost all animals possess gut microbial communities, but the nature of these communities varies immensely. For example, in social bees and mammals, the composition is relatively constant within species and is dominated by specialist bacteria that do not live elsewhere; in laboratory studies and field surveys of Drosophila melanogaster, however, gut communities consist of bacteria that are ingested with food and that vary widely among individuals and localities. We addressed whether an ecological specialist in its natural habitat has a microbiota dominated by gut specialists or by environmental bacteria. Drosophila nigrospiracula is a species that is endemic to the Sonoran Desert and is restricted to decaying tissues of two giant columnar cacti, Pachycereus pringlei (cardón cactus) and Carnegiea gigantea (saguaro cactus). We found that the D. nigrospiracula microbiota differs strikingly from that of the cactus tissue on which the flies feed. The most abundant bacteria in the flies are rare or completely absent in the cactus tissue and are consistently abundant in flies from different cacti and localities. Several of these fly-associated bacterial groups, such as the bacterial order Orbales and the genera Serpens and Dysgonomonas, have been identified in prior surveys of insects from the orders Hymenoptera, Coleoptera, Lepidoptera, and Diptera, including several Drosophila species. Although the functions of these bacterial groups are mostly unexplored, Orbales species studied in bees are known to break down plant polysaccharides and use the resulting sugars. Thus, these bacterial groups appear to be specialized to the insect gut environment, where they may colonize through direct host-to-host transmission in natural settings. IMPORTANCE Flies in the genus Drosophila have become laboratory models for microbiota research, yet the bacteria commonly used in these experiments are rarely found in wild-caught flies and instead represent bacteria also present in the food. This study shows that an ecologically specialized Drosophila species possesses a distinctive microbiome, composed of bacterial types absent from the flies' natural food but widespread in other wild-caught insects. This study highlights the importance of fieldwork-informed microbiota research. PMID:28939605

The microbiota and microbiome in aging: potential implications in health and age-related diseases.

PubMed

Zapata, Heidi J; Quagliarello, Vincent J

2015-04-01

Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Effect of water flow and chemical environment on microbiota growth and composition in the human colon.

PubMed

Cremer, Jonas; Arnoldini, Markus; Hwa, Terence

2017-06-20

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota.

Effect of water flow and chemical environment on microbiota growth and composition in the human colon

PubMed Central

Cremer, Jonas; Arnoldini, Markus; Hwa, Terence

2017-01-01

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota. PMID:28588144

Impact of the gut microbiota on rodent models of human disease.

PubMed

Hansen, Axel Kornerup; Hansen, Camilla Hartmann Friis; Krych, Lukasz; Nielsen, Dennis Sandris

2014-12-21

Traditionally bacteria have been considered as either pathogens, commensals or symbionts. The mammal gut harbors 10(14) organisms dispersed on approximately 1000 different species. Today, diagnostics, in contrast to previous cultivation techniques, allow the identification of close to 100% of bacterial species. This has revealed that a range of animal models within different research areas, such as diabetes, obesity, cancer, allergy, behavior and colitis, are affected by their gut microbiota. Correlation studies may for some diseases show correlation between gut microbiota composition and disease parameters higher than 70%. Some disease phenotypes may be transferred when recolonizing germ free mice. The mechanistic aspects are not clear, but some examples on how gut bacteria stimulate receptors, metabolism, and immune responses are discussed. A more deeper understanding of the impact of microbiota has its origin in the overall composition of the microbiota and in some newly recognized species, such as Akkermansia muciniphila, Segmented filamentous bacteria and Faecalibacterium prausnitzii, which seem to have an impact on more or less severe disease in specific models. Thus, the impact of the microbiota on animal models is of a magnitude that cannot be ignored in future research. Therefore, either models with specific microbiota must be developed, or the microbiota must be characterized in individual studies and incorporated into data evaluation.

Comparative Analysis of Korean Human Gut Microbiota by Barcoded Pyrosequencing

PubMed Central

Nam, Young-Do; Jung, Mi-Ja; Roh, Seong Woon; Kim, Min-Soo; Bae, Jin-Woo

2011-01-01

Human gut microbiota plays important roles in harvesting energy from the diet, stimulating the proliferation of the intestinal epithelium, developing the immune system, and regulating fat storage in the host. Characterization of gut microbiota, however, has been limited to western people and is not sufficiently extensive to fully describe microbial communities. In this study, we investigated the overall composition of the gut microbiota and its host specificity and temporal stability in 20 Koreans using 454-pyrosequencing with barcoded primers targeting the V1 to V3 region of the bacterial 16S rRNA gene. A total of 303,402 high quality reads covered each sample and 8,427 reads were analyzed on average. The results were compared with those of individuals from the USA, China and Japan. In general, microbial communities were dominated by five previously identified phyla: Actinobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Proteobacteria. UPGMA cluster analysis showed that the species composition of gut microbiota was host-specific and stable over the duration of the test period, but the relative abundance of each member fluctuated. 43 core Korean gut microbiota were identified by comparison of sequences from each individual, of which 15 species level phylotypes were related to previously-reported butyrate-producing bacteria. UniFrac analysis revealed that human gut microbiota differed between countries: Korea, USA, Japan and China, but tended to vary less between individual Koreans, suggesting that gut microbial composition is related to internal and external characteristics of each country member such as host genetics and diet styles. PMID:21829445

The Gut Microbiota of Rural Papua New Guineans: Composition, Diversity Patterns, and Ecological Processes

DOE PAGES

Martínez, Inés; Stegen, James C.; Maldonado-Gómez, Maria X.; ...

2015-04-01

Comparisons between the fecal microbiota of humans from industrialized and non-industrialized communities indicate a pronounced impact of westernization on the diversity and composition of the human gut microbiota. However, the exact consequences of westernization on community characteristics are still insufficiently understood, and the ecological processes that drive differences have not been elucidated. Here we have compared the fecal microbiota of adults from two non-industrialized regions in Papua New Guinea (PNG) with that of United States (US) residents. Papua New Guineans harbor communities with greater bacterial diversity but lower inter-individual variation. Although the fecal microbiota in PNG and US was largelymore » dominated by shared bacterial lineages, the relative abundance of 25 families, 45 genera, and 230 species-level OTUs differed, and 47 core OTUs in PNG were undetectable in US residents. To gain insight into the ecological mechanisms that cause the observed differences, we quantified community assembly processes in PNG and US microbiomes using a null modeling approach. This analysis demonstrated a significant higher rate of bacterial dispersal in PNG and divergent selective environments in the US. Interestingly, equivalent findings were obtained for other datasets comparing industrialized and non-industrialized microbiomes. Overall, the findings demonstrate a dominant role for microbial dispersal in shaping the human gut microbiota in non-industrialized societies, and point to differential selection pressures across individuals as a major factor shaping microbiomes associated with modern lifestyle.« less

Amoxapine Demonstrates Incomplete Inhibition of β-Glucuronidase Activity from Human Gut Microbiota.

PubMed

Yang, Wei; Wei, Bin; Yan, Ru

2018-01-01

Amoxapine has been demonstrated to be a potent inhibitor of Escherichia coli β-glucuronidase. This study aims to explore the factors causing unsatisfactory efficacy of amoxapine in alleviating CPT-11-induced gastrointestinal toxicity in mice and to predict the outcomes in humans. Amoxapine (100 µM) exhibited poor and varied inhibition on β-glucuronidase activity in gut microbiota from 10 healthy individuals and their pool (pool, 11.9%; individuals, 3.6%-54.4%) with IC 50 >100 µM and potent inhibition toward E. coli β-glucuronidase (IC 50 = 0.34 µM). p-Nitrophenol formation from p-nitrophenyl-β-D-glucuronide by pooled and individual gut microbiota fitted classical Michaelis-Menten kinetics, showing similar affinity (K m = 113-189 µM) but varied catalytic capability (V max = 53-556 nmol/h/mg). Interestingly, amoxapine showed distinct inhibitory effects (8.7%-100%) toward β-glucuronidases of 13 bacterial isolates (including four Enterococcus, three Streptococcus, two Escherichia, and two Staphylococcus strains; gus genes belonging to OTU1, 2 or 21) regardless of their genetic similarity or bacterial origin. In addition, amoxapine inhibited the growth of pooled and individual gut microbiota at a high concentration (6.3%-30.8%, 200 µM). Taken together, these findings partly explain the unsatisfactory efficacy of amoxapine in alleviating CPT-11-induced toxicity and predict a poor outcome of β-glucuronidase inhibition in humans, highlighting the necessity of using a human gut microbiota community for drug screening.

MicroRNA-146a Deficiency Protects against Listeria monocytogenes Infection by Modulating the Gut Microbiota.

PubMed

Du, Chong-Tao; Gao, Wei; Ma, Ke; Yu, Shui-Xing; Li, Na; Yan, Shi-Qing; Zhou, Feng-Hua; Liu, Zhen-Zhen; Chen, Wei; Lei, Lian-Cheng; Yang, Yong-Jun; Han, Wen-Yu

2018-03-26

The gut microbiota and microRNAs play important roles in the defense against infection. However, the role of miR-146a in L. monocytogenes infection and gut microbiota remains unclear. We tried to determine whether miR-146a controlled L. monocytogenes infection by regulating the gut microbiota. Wild-type and miR-146a-deficient mice or macrophages were used to characterize the impact of miR-146a on animal survival, cell death, bacterial clearance, and gut microbiota following L. monocytogenes challenge. We found that L. monocytogenes infection induced miR-146a expression both in vitro and in vivo. When compared to wild-type mice, miR-146a-deficient mice were more resistant to L. monocytogenes infection. MiR-146a deficiency in macrophages resulted in reduced invasion and intracellular survival of L. monocytogenes . High-throughput sequencing of 16S rRNA revealed that the gut microbiota composition differed between miR-146a-deficient and wild-type mice. Relative to wild-type mice, miR-146a-deficient mice had decreased levels of the Proteobacteria phylum, Prevotellaceae family, and Parasutterella genus, and significantly increased short-chain fatty acid producing bacteria, including the genera Alistipes , Blautia , Coprococcus_1, and Ruminococcus_1 . Wild-type mice co-housed with miR-146a-deficient mice had increased resistance to L. monocytogenes , indicating that miR-146a deficiency guides the gut microbiota to alleviate infection. Together, these results suggest that miR-146a deficiency protects against L. monocytogenes infection by regulating the gut microbiota.

Mechanisms of inflammation-driven bacterial dysbiosis in the gut

PubMed Central

Zeng, MY; Inohara, N; Nuñez, G

2018-01-01

The gut microbiota has diverse and essential roles in host metabolism, development of the immune system and as resistance to pathogen colonization. Perturbations of the gut microbiota, termed gut dysbiosis, are commonly observed in diseases involving inflammation in the gut, including inflammatory bowel disease, infection, colorectal cancer and food allergies. Importantly, the inflamed microenvironment in the gut is particularly conducive to blooms of Enterobacteriaceae, which acquire fitness benefits while other families of symbiotic bacteria succumb to environmental changes inflicted by inflammation. Here we summarize studies that examined factors in the inflamed gut that contribute to blooms of Enterobacterieaceae, and highlight potential approaches to restrict Enterobacterial blooms in treating diseases that are otherwise complicated by overgrowth of virulent Enterobacterial species in the gut. PMID:27554295

The gut microbiome and degradation enzyme activity of wild freshwater fishes influenced by their trophic levels.

PubMed

Liu, Han; Guo, Xianwu; Gooneratne, Ravi; Lai, Ruifang; Zeng, Cong; Zhan, Fanbin; Wang, Weimin

2016-04-13

Vertebrate gut microbiome often underpins the metabolic capability and provides many beneficial effects on their hosts. However, little was known about how host trophic level influences fish gut microbiota and metabolic activity. In this study, more than 985,000 quality-filtered sequences from 24 16S rRNA libraries were obtained and the results revealed distinct compositions and diversities of gut microbiota in four trophic categories. PCoA test showed that gut bacterial communities of carnivorous and herbivorous fishes formed distinctly different clusters in PCoA space. Although fish in different trophic levels shared a large size of OTUs comprising a core microbiota community, at the genus level a strong distinction existed. Cellulose-degrading bacteria Clostridium, Citrobacter and Leptotrichia were dominant in the herbivorous, while Cetobacterium and protease-producing bacteria Halomonas were dominant in the carnivorous. PICRUSt predictions of metagenome function revealed that fishes in different trophic levels affected the metabolic capacity of their gut microbiota. Moreover, cellulase and amylase activities in herbivorous fishes were significantly higher than in the carnivorous, while trypsin activity in the carnivorous was much higher than in the herbivorous. These results indicated that host trophic level influenced the structure and composition of gut microbiota, metabolic capacity and gut content enzyme activity.

The gut microbiome and degradation enzyme activity of wild freshwater fishes influenced by their trophic levels

PubMed Central

Liu, Han; Guo, Xianwu; Gooneratne, Ravi; Lai, Ruifang; Zeng, Cong; Zhan, Fanbin; Wang, Weimin

2016-01-01

Vertebrate gut microbiome often underpins the metabolic capability and provides many beneficial effects on their hosts. However, little was known about how host trophic level influences fish gut microbiota and metabolic activity. In this study, more than 985,000 quality-filtered sequences from 24 16S rRNA libraries were obtained and the results revealed distinct compositions and diversities of gut microbiota in four trophic categories. PCoA test showed that gut bacterial communities of carnivorous and herbivorous fishes formed distinctly different clusters in PCoA space. Although fish in different trophic levels shared a large size of OTUs comprising a core microbiota community, at the genus level a strong distinction existed. Cellulose-degrading bacteria Clostridium, Citrobacter and Leptotrichia were dominant in the herbivorous, while Cetobacterium and protease-producing bacteria Halomonas were dominant in the carnivorous. PICRUSt predictions of metagenome function revealed that fishes in different trophic levels affected the metabolic capacity of their gut microbiota. Moreover, cellulase and amylase activities in herbivorous fishes were significantly higher than in the carnivorous, while trypsin activity in the carnivorous was much higher than in the herbivorous. These results indicated that host trophic level influenced the structure and composition of gut microbiota, metabolic capacity and gut content enzyme activity. PMID:27072196

The role of gut bacteria in Schmallenberg virus transmission by Culicoides biting midges

USDA-ARS?s Scientific Manuscript database

When an arbo-virus enters a vector it will first enter the gut system of this insect before entering cells of the insect body. Once in the gut-system, arbo-viruses and gut microbiota can interact with each other. We wondered if different gut bacterial communities could influence virus infection of b...

Acromyrmex Leaf-Cutting Ants Have Simple Gut Microbiota with Nitrogen-Fixing Potential

PubMed Central

Zhukova, Mariya; Hansen, Lars H.; Sørensen, Søren J.; Schiøtt, Morten

2015-01-01

Ants and termites have independently evolved obligate fungus-farming mutualisms, but their gardening procedures are fundamentally different, as the termites predigest their plant substrate whereas the ants deposit it directly on the fungus garden. Fungus-growing termites retained diverse gut microbiota, but bacterial gut communities in fungus-growing leaf-cutting ants have not been investigated, so it is unknown whether and how they are specialized on an exclusively fungal diet. Here we characterized the gut bacterial community of Panamanian Acromyrmex species, which are dominated by only four bacterial taxa: Wolbachia, Rhizobiales, and two Entomoplasmatales taxa. We show that the Entomoplasmatales can be both intracellular and extracellular across different gut tissues, Wolbachia is mainly but not exclusively intracellular, and the Rhizobiales species is strictly extracellular and confined to the gut lumen, where it forms biofilms along the hindgut cuticle supported by an adhesive matrix of polysaccharides. Tetracycline diets eliminated the Entomoplasmatales symbionts but hardly affected Wolbachia and only moderately reduced the Rhizobiales, suggesting that the latter are protected by the biofilm matrix. We show that the Rhizobiales symbiont produces bacterial NifH proteins that have been associated with the fixation of nitrogen, suggesting that these compartmentalized hindgut symbionts alleviate nutritional constraints emanating from an exclusive fungus garden diet reared on a substrate of leaves. PMID:26048932

Persistent Organic Pollutants Modify Gut Microbiota-Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation.

PubMed

Zhang, Limin; Nichols, Robert G; Correll, Jared; Murray, Iain A; Tanaka, Naoki; Smith, Philip B; Hubbard, Troy D; Sebastian, Aswathy; Albert, Istvan; Hatzakis, Emmanuel; Gonzalez, Frank J; Perdew, Gary H; Patterson, Andrew D

2015-07-01

Alteration of the gut microbiota through diet and environmental contaminants may disturb physiological homeostasis, leading to various diseases including obesity and type 2 diabetes. Because most exposure to environmentally persistent organic pollutants (POPs) occurs through the diet, the host gastrointestinal tract and commensal gut microbiota are likely to be exposed to POPs. We examined the effect of 2,3,7,8-tetrachlorodibenzofuran (TCDF), a persistent environmental contaminant, on gut microbiota and host metabolism, and we examined correlations between gut microbiota composition and signaling pathways. Six-week-old male wild-type and Ahr-/- mice on the C57BL/6J background were treated with 24 μg/kg TCDF in the diet for 5 days. We used 16S rRNA gene sequencing, 1H nuclear magnetic resonance (NMR) metabolomics, targeted ultra-performance liquid chromatography coupled with triplequadrupole mass spectrometry, and biochemical assays to determine the microbiota compositions and the physiological and metabolic effects of TCDF. Dietary TCDF altered the gut microbiota by shifting the ratio of Firmicutes to Bacteroidetes. TCDF-treated mouse cecal contents were enriched with Butyrivibrio spp. but depleted in Oscillobacter spp. compared with vehicle-treated mice. These changes in the gut microbiota were associated with altered bile acid metabolism. Further, dietary TCDF inhibited the farnesoid X receptor (FXR) signaling pathway, triggered significant inflammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered hepatic lipogenesis, gluconeogenesis, and glycogenolysis in an AHR-dependent manner. These findings provide new insights into the biochemical consequences of TCDF exposure involving the alteration of the gut microbiota, modulation of nuclear receptor signaling, and disruption of host metabolism.

Dietary fat and gut microbiota: mechanisms involved in obesity control.

PubMed

Coelho, Olívia Gonçalves Leão; Cândido, Flávia Galvão; Alfenas, Rita de Cássia Gonçalves

2018-05-31

Obesity is a serious global health problem that is directly related to various morbidities manifestation. Intestinal dysbiosis has been implicated on obesity pathogenesis. Diet composition can alter gut microbiota, regardless of energy intake. Dietary fatty acids quality may affect gut microbiota composition, which in turn may affect host metabolic health. The mechanisms by which the different type of FFA modulate gut microbiota is yet poor elucidate and there is a lack of studies regard to this. Fatty acids may act in cell membrane, interfere with energy production, inhibit enzymatic activities, impair nutrient absorption and generate toxic compounds to cells, leading to growth inhibition or even bacterial death. The beneficial effect of the consumption of n-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic acid (CLA) on microbiota, unlike n-6 PUFA and saturated fatty acids has been suggested. n-3 PUFA consumption promotes desirable changes on obese intestinal microbiota making it similar to that of normal weight individuals. More studies are needed to better understand the effect of CLA on microbiota and host health. Long term human controlled clinical trials must be conducted to allow us to understand the complex interaction between dietary fat, intestinal microbiota and obesity.

Gut microbiota and metabolic syndrome.

PubMed

Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

2014-11-21

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

Gut microbiota and metabolic syndrome

PubMed Central

Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

2014-01-01

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use. PMID:25473159

[Alteration of intestinal permeability: the missing link between gut microbiota modifications and inflammation in obesity?].

PubMed

Genser, Laurent; Poitou, Christine; Brot-Laroche, Édith; Rousset, Monique; Vaillant, Jean-Christophe; Clément, Karine; Thenet, Sophie; Leturque, Armelle

2016-05-01

The increasing incidence of obesity and associated metabolic complications is a worldwide public health issue. The role of the gut in the pathophysiology of obesity, with an important part for microbiota, is becoming obvious. In rodent models of diet-induced obesity, the modifications of gut microbiota are associated with an alteration of the intestinal permeability increasing the passage of food or bacterial antigens, which contribute to low-grade inflammation and insulin resistance. In human obesity, intestinal permeability modification, and its role in the crosstalk between gut microbiota changes and inflammation at systemic and tissular levels, are still poorly documented. Hence, further characterization of the triggering mechanisms of such inflammatory responses in obese subjects could enable the development of personalized intervention strategies that will help to reduce the risk of obesity-associated diseases. © 2016 médecine/sciences – Inserm.

Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis.

PubMed

Qin, Chenjie; Zhang, Huilu; Zhao, Linghao; Zeng, Min; Huang, Weijian; Fu, Gongbo; Zhou, Weiping; Wang, Hongyang; Yan, Hexin

2017-11-29

Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine (DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium (DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine, the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota.

Characterization of the gut microbiota in the red panda (Ailurus fulgens).

PubMed

Kong, Fanli; Zhao, Jiangchao; Han, Shushu; Zeng, Bo; Yang, Jiandong; Si, Xiaohui; Yang, Benqing; Yang, Mingyao; Xu, Huailiang; Li, Ying

2014-01-01

The red panda is the only living species of the genus Ailurus. Like giant pandas, red pandas are also highly specialized to feed mainly on highly fibrous bamboo. Although several studies have focused on the gut microbiota in the giant panda, little is known about the gut microbiota of the red panda. In this study, we characterized the fecal microbiota from both wild (n = 16) and captive (n = 6) red pandas using a pyrosequecing based approach targeting the V1-V3 hypervariable regions of the 16S rRNA gene. Distinct bacterial communities were observed between the two groups based on both membership and structure. Wild red pandas maintained significantly higher community diversity, richness and evenness than captive red pandas, the communities of which were skewed and dominated by taxa associated with Firmicutes. Phylogenetic analysis of the top 50 OTUs revealed that 10 of them were related to known cellulose degraders. To the best of our knowledge, this is the first study of the gut microbiota of the red panda. Our data suggest that, similar to the giant panda, the gut microbiota in the red panda might also play important roles in the digestion of bamboo.

Characterization of the Gut Microbiota in the Red Panda (Ailurus fulgens)

PubMed Central

Han, Shushu; Zeng, Bo; Yang, Jiandong; Si, Xiaohui; Yang, Benqing; Yang, Mingyao; Xu, Huailiang; Li, Ying

2014-01-01

The red panda is the only living species of the genus Ailurus. Like giant pandas, red pandas are also highly specialized to feed mainly on highly fibrous bamboo. Although several studies have focused on the gut microbiota in the giant panda, little is known about the gut microbiota of the red panda. In this study, we characterized the fecal microbiota from both wild (n = 16) and captive (n = 6) red pandas using a pyrosequecing based approach targeting the V1-V3 hypervariable regions of the 16S rRNA gene. Distinct bacterial communities were observed between the two groups based on both membership and structure. Wild red pandas maintained significantly higher community diversity, richness and evenness than captive red pandas, the communities of which were skewed and dominated by taxa associated with Firmicutes. Phylogenetic analysis of the top 50 OTUs revealed that 10 of them were related to known cellulose degraders. To the best of our knowledge, this is the first study of the gut microbiota of the red panda. Our data suggest that, similar to the giant panda, the gut microbiota in the red panda might also play important roles in the digestion of bamboo. PMID:24498390

The queen's gut refines with age: longevity phenotypes in a social insect model.

PubMed

Anderson, Kirk E; Ricigliano, Vincent A; Mott, Brendon M; Copeland, Duan C; Floyd, Amy S; Maes, Patrick

2018-06-18

In social insects, identical genotypes can show extreme lifespan variation providing a unique perspective on age-associated microbial succession. In honey bees, short- and long-lived host phenotypes are polarized by a suite of age-associated factors including hormones, nutrition, immune senescence, and oxidative stress. Similar to other model organisms, the aging gut microbiota of short-lived (worker) honey bees accrue Proteobacteria and are depleted of Lactobacillus and Bifidobacterium, consistent with a suite of host senescence markers. In contrast, long-lived (queen) honey bees maintain youthful cellular function with much lower expression of oxidative stress genes, suggesting a very different host environment for age-associated microbial succession. We sequenced the microbiota of 63 honey bee queens exploring two chronological ages and four alimentary tract niches. To control for genetic and environmental variation, we quantified carbonyl accumulation in queen fat body tissue as a proxy for biological aging. We compared our results to the age-specific microbial succession of worker guts. Accounting for queen source variation, two or more bacterial species per niche differed significantly by queen age. Biological aging in queens was correlated with microbiota composition highlighting the relationship of microbiota with oxidative stress. Queens and workers shared many major gut bacterial species, but differ markedly in community structure and age succession. In stark contrast to aging workers, carbonyl accumulation in queens was significantly associated with increased Lactobacillus and Bifidobacterium and depletion of various Proteobacteria. We present a model system linking changes in gut microbiota to diet and longevity, two of the most confounding variables in human microbiota research. The pattern of age-associated succession in the queen microbiota is largely the reverse of that demonstrated for workers. The guts of short-lived worker phenotypes are progressively dominated by three major Proteobacteria, but these same species were sparse or significantly depleted in long-lived queen phenotypes. More broadly, age-related changes in the honey bee microbiota reflect the regulatory anatomy of reproductive host metabolism. Our synthesis suggests that the evolution of colony-level reproductive physiology formed the context for host-microbial interactions and age-related succession of honey bee microbiota.

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.

The Gut Microbiome, Its Metabolome, and Their Relationship to Health and Disease.

PubMed

Wu, Gary D

2016-01-01

Despite its importance in maintaining the health of the host, growing evidence suggests that gut microbiota may also be an important factor in the pathogenesis of various diseases. The composition of the microbiota can be influenced by many factors, including age, genetics, host environment, and diet. There are epidemiologic data associating diet with the development of inflammatory bowel disease as well as evidence that diet can influence both the form and the function of the microbiome. Based on this evidence, studies are now underway to examine the effect of defined formula diets, an effective therapeutic modality in Crohn's disease, on both the gut microbiome and its metabolome as a therapeutic probe. Diet has an impact upon both the composition and the function of the microbiota in part through small-molecule production that may influence the development of both immune-mediated and metabolic diseases. By comparing dietary intake, the gut microbiota, and the plasma metabolome in omnivores versus vegans, we provide evidence that the production of certain bacterial metabolites is constrained by the composition of the gut microbiota. In total, these results demonstrate the potential promise of dietary manipulation of the gut microbiota and its metabolome as a modality to both maintain health and treat disease. © 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.

Lotus Seed Resistant Starch Regulates Gut Microbiota and Increases Short-Chain Fatty Acids Production and Mineral Absorption in Mice.

PubMed

Zeng, Hongliang; Huang, Cancan; Lin, Shan; Zheng, Mingjing; Chen, Chuanjie; Zheng, Baodong; Zhang, Yi

2017-10-25

Lotus seed resistant starch, known as resistant starch type 3 (LRS3), was orally administered to mice to investigate its effects on the gut microbiota, short-chain fatty acids (SCFAs) production, and mineral absorption. The results showed that mice fed LRS3 displayed a lower level of gut bacterial diversity than other groups. The numbers of starch-utilizing and butyrate-producing bacteria, such as Lactobacillus and Bifidobacterium and Lachnospiraceae, Ruminococcaceae, and Clostridium, respectively, in mice increased after the administration of medium and high doses of LRS3, while those of Rikenellaceae and Porphyromonadaceae decreased. Furthermore, SCFAs and lactic acid in mice feces were affected by LRS3, and lactate was fermented to butyrate by gut microbiota. LRS3 enhanced the intestinal absorption of calcium, magnesium, and iron, and this was dependent on the type and concentration of SCFAs, especially butyrate. Thus, LRS3 promoted the production of SCFAs and mineral absorption by regulating gut microbiota in mice.

Impact of stressor exposure on the interplay between commensal microbiota and host inflammation.

PubMed

Galley, Jeffrey D; Bailey, Michael T

2014-01-01

Exposure to stressful stimuli results in the activation of multiple physiological processes aimed at maintaining homeostasis within the body. These physiological processes also have the capacity to influence the composition of microbial communities, and research now indicates that exposure to stressful stimuli leads to gut microbiota dysbiosis. While the relative abundance of many different bacterial types can be altered during stressor exposure, findings in nonhuman primates and laboratory rodents, as well as humans, indicate that bacteria in the genus Lactobacillus are consistently reduced in the gut during stress. The gut microbiota, including the lactobacilli, have many functions that enhance the health of the host. This review presents studies involving germfree and antibiotic treated mice, as well as mice given Lactobacillus spp. to prevent stressor-induced reductions in lactobacilli, to provide evidence that the microbiota contribute to stressor-induced immunomodulation, both in gut mucosa as well as in systemic compartments. This review will also discuss the evidence that commensal gut microbes have bidirectional effects on gastrointestinal physiology during stressor exposure.

The gut microbiota of rural papua new guineans: composition, diversity patterns, and ecological processes.

PubMed

Martínez, Inés; Stegen, James C; Maldonado-Gómez, Maria X; Eren, A Murat; Siba, Peter M; Greenhill, Andrew R; Walter, Jens

2015-04-28

Although recent research revealed an impact of westernization on diversity and composition of the human gut microbiota, the exact consequences on metacommunity characteristics are insufficiently understood, and the underlying ecological mechanisms have not been elucidated. Here, we have compared the fecal microbiota of adults from two non-industrialized regions in Papua New Guinea (PNG) with that of United States (US) residents. Papua New Guineans harbor communities with greater bacterial diversity, lower inter-individual variation, vastly different abundance profiles, and bacterial lineages undetectable in US residents. A quantification of the ecological processes that govern community assembly identified bacterial dispersal as the dominant process that shapes the microbiome in PNG but not in the US. These findings suggest that the microbiome alterations detected in industrialized societies might arise from modern lifestyle factors limiting bacterial dispersal, which has implications for human health and the development of strategies aimed to redress the impact of westernization. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The role of gut microbiota in fetal methylmercury exposure: Insights from a pilot study

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

Rothenberg, Sarah E.; Keiser, Sharon; Ajami, Nadim J.

The mechanisms by which gut microbiota contribute to methylmercury metabolism remain unclear. Among a cohort of pregnant mothers, the main objectives of our pilot study were to determine 1) associations between gut microbiota and mercury concentrations in biomarkers (stool, hair and cord blood) and 2) the contributions of gut microbial mercury methylation/demethylation to stool methylmercury. Moreover, for pregnant women (36-39 weeks gestation, n=17) donated hair and stool specimens, and cord blood was collected for a subset (n=7). The diversity of gut microbiota was determined using 16S rRNA gene profiling (n=17). For 6 stool samples with highest/lowest methylmercury concentrations, metagenomic wholemore » genome shotgun sequencing was employed to search for one mercury methylation gene (hgcA), and two mer operon genes involved in methylmercury detoxification (merA and merB). There were seventeen bacterial genera that were significantly correlated (increasing or decreasing) with stool methylmercury, stool inorganic mercury, or hair total mercury; however, aside from one genus, there was no overlap between biomarkers. No definitive matches for hgcA or merB, while merA were detected at low concentrations in all six samples. Proportional differences in stool methylmercury were not likely attributed to gut microbiota through methylation/demethylation. Gut microbiota potentially altered methylmercury metabolism using indirect pathways.« less

The role of gut microbiota in fetal methylmercury exposure: Insights from a pilot study

DOE PAGES

Rothenberg, Sarah E.; Keiser, Sharon; Ajami, Nadim J.; ...

2016-02-01

The mechanisms by which gut microbiota contribute to methylmercury metabolism remain unclear. Among a cohort of pregnant mothers, the main objectives of our pilot study were to determine 1) associations between gut microbiota and mercury concentrations in biomarkers (stool, hair and cord blood) and 2) the contributions of gut microbial mercury methylation/demethylation to stool methylmercury. Moreover, for pregnant women (36-39 weeks gestation, n=17) donated hair and stool specimens, and cord blood was collected for a subset (n=7). The diversity of gut microbiota was determined using 16S rRNA gene profiling (n=17). For 6 stool samples with highest/lowest methylmercury concentrations, metagenomic wholemore » genome shotgun sequencing was employed to search for one mercury methylation gene (hgcA), and two mer operon genes involved in methylmercury detoxification (merA and merB). There were seventeen bacterial genera that were significantly correlated (increasing or decreasing) with stool methylmercury, stool inorganic mercury, or hair total mercury; however, aside from one genus, there was no overlap between biomarkers. No definitive matches for hgcA or merB, while merA were detected at low concentrations in all six samples. Proportional differences in stool methylmercury were not likely attributed to gut microbiota through methylation/demethylation. Gut microbiota potentially altered methylmercury metabolism using indirect pathways.« less

Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile.

PubMed

Bakker, Guido J; Nieuwdorp, Max

2017-08-01

The human intestinal tract contains trillions of bacteria, collectively called the gut microbiota. Recent insights have linked the gut microbiota to a plethora of diseases, including Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), and metabolic diseases such as obesity, type 2 diabetes (T2D), and nonalcoholic steatohepatitis (NASH). Fecal microbiota transplantation (FMT) is currently tested as a therapeutic option in various diseases and can also help to dissect association from causality with respect to gut microbiota and disease. In CDI, FMT has been shown to be superior to antibiotic treatment. For IBD, T2D, and NASH, several placebo-controlled randomized controlled trials are under way. Moreover, techniques and standardization are developing. With the extension of FMT as a treatment modality in diseases other than CDI, a whole new treatment option may be emerging. Moreover, correlating alterations in specific strains to disease outcome may prove pivotal in finding new bacterial targets. Thus, although causality of the gut microbiota in various diseases still needs to be proven, FMT may prove to be a powerful tool providing us with diagnostic and therapeutic leads.

Allometry and Ecology of the Bilaterian Gut Microbiome

PubMed Central

Sherrill-Mix, Scott; McCormick, Kevin; Lauder, Abigail; Bailey, Aubrey; Zimmerman, Laurie; Li, Yingying; Django, Jean-Bosco N.; Bertolani, Paco; Colin, Christelle; Hart, John A.; Hart, Terese B.; Georgiev, Alexander V.; Sanz, Crickette M.; Morgan, David B.; Atencia, Rebeca; Cox, Debby; Muller, Martin N.; Sommer, Volker; Piel, Alexander K.; Stewart, Fiona A.; Speede, Sheri; Roman, Joe; Wu, Gary; Taylor, Josh; Bohm, Rudolf; Rose, Heather M.; Carlson, John; Mjungu, Deus; Schmidt, Paul; Gaughan, Celeste; Bushman, Joyslin I.; Schmidt, Ella; Bittinger, Kyle; Collman, Ronald G.; Hahn, Beatrice H.

2018-01-01

ABSTRACT Classical ecology provides principles for construction and function of biological communities, but to what extent these apply to the animal-associated microbiota is just beginning to be assessed. Here, we investigated the influence of several well-known ecological principles on animal-associated microbiota by characterizing gut microbial specimens from bilaterally symmetrical animals (Bilateria) ranging from flies to whales. A rigorously vetted sample set containing 265 specimens from 64 species was assembled. Bacterial lineages were characterized by 16S rRNA gene sequencing. Previously published samples were also compared, allowing analysis of over 1,098 samples in total. A restricted number of bacterial phyla was found to account for the great majority of gut colonists. Gut microbial composition was associated with host phylogeny and diet. We identified numerous gut bacterial 16S rRNA gene sequences that diverged deeply from previously studied taxa, identifying opportunities to discover new bacterial types. The number of bacterial lineages per gut sample was positively associated with animal mass, paralleling known species-area relationships from island biogeography and implicating body size as a determinant of community stability and niche complexity. Samples from larger animals harbored greater numbers of anaerobic communities, specifying a mechanism for generating more-complex microbial environments. Predictions for species/abundance relationships from models of neutral colonization did not match the data set, pointing to alternative mechanisms such as selection of specific colonists by environmental niche. Taken together, the data suggest that niche complexity increases with gut size and that niche selection forces dominate gut community construction. PMID:29588401

Early gut colonizers shape parasite susceptibility and microbiota composition in honey bee workers

USDA-ARS?s Scientific Manuscript database

Microbial symbionts living within animal guts are largely composed of resident bacterial species, forming communities that often provide benefits to the host. Gut microbiomes of adult honey bees (Apis mel- lifera) include core residents such as the betaproteobacterium Snod- grassella alvi, alongside...

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.

Influences of graphene on microbial community and antibiotic resistance genes in mouse gut as determined by high-throughput sequencing.

PubMed

Xie, Yongchao; Wu, Bing; Zhang, Xu-Xiang; Yin, Jinbao; Mao, Liang; Hu, Maojie

2016-02-01

Graphene is a promising candidate as an antibacterial material owning to its bacterial toxicity. However, little information on influence of graphene on gut microbiota is available. In this study, mice were exposed to graphene for 4 weeks, and high-throughput sequencing was applied to characterize the changes in microbial community and antibiotic resistance genes (ARGs) in mouse gut. The results showed that graphene exposure increased biodiversity of gut microbiota, and changed their community. The 1 μg/d graphene exposure had higher influences on the gut microbiota than 10 μg/d and 100 μg/d graphene exposures, which might be due to higher aggregation of high-level graphene. The influence of graphene on gut microbiota might attribute to that graphene could induce oxidative stress and damage of cell membrane integrity. The results were verified by the increase of ratio of Gram-negative bacteria. Outer membrane of Gram-negative bacteria could reduce the membrane damage induced by graphene and make them more tolerance to graphene. Further, we found that graphene exposure significantly increased the abundance and types of ARGs, indicating a potential health risk of graphene. This study firstly provides new insight to the health effects of graphene on gut microbiota. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.

PubMed

Chassaing, Benoit; Koren, Omry; Goodrich, Julia K; Poole, Angela C; Srinivasan, Shanthi; Ley, Ruth E; Gewirtz, Andrew T

2015-03-05

The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.

Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome

PubMed Central

Chassaing, Benoit; Koren, Omry; Goodrich, Julia; Poole, Angela; Srinivasan, Shanthi; Ley, Ruth E.; Gewirtz, Andrew T.

2015-01-01

Summary The intestinal tract is inhabited by a large diverse community of microbes collectively referred to as gut microbiota. While gut microbiota provide important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease (IBD) and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multilayered mucus structures that cover the intestinal surface thus allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine 1. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro 2, might be promoting the post-mid 20th century increase in IBD 3. Herein, we observed that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in WT hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition, and increased pro-inflammatory potential. Use of germ-free mice and fecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that broad use of emulsifying agents might be contributing to increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases. PMID:25731162

Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88.

PubMed

Larsson, Erik; Tremaroli, Valentina; Lee, Ying Shiuan; Koren, Omry; Nookaew, Intawat; Fricker, Ashwana; Nielsen, Jens; Ley, Ruth E; Bäckhed, Fredrik

2012-08-01

The gut microbiota has profound effects on host physiology but local host-microbial interactions in the gut are only poorly characterised and are likely to vary from the sparsely colonised duodenum to the densely colonised colon. Microorganisms are recognised by pattern recognition receptors such as Toll-like receptors, which signal through the adaptor molecule MyD88. To identify host responses induced by gut microbiota along the length of the gut and whether these required MyD88, transcriptional profiles of duodenum, jejunum, ileum and colon were compared from germ-free and conventionally raised wild-type and Myd88-/- mice. The gut microbial ecology was assessed by 454-based pyrosequencing and viruses were analysed by PCR. The gut microbiota modulated the expression of a large set of genes in the small intestine and fewer genes in the colon but surprisingly few microbiota-regulated genes required MyD88 signalling. However, MyD88 was essential for microbiota-induced colonic expression of the antimicrobial genes Reg3β and Reg3γ in the epithelium, and Myd88 deficiency was associated with both a shift in bacterial diversity and a greater proportion of segmented filamentous bacteria in the small intestine. In addition, conventionally raised Myd88-/- mice had increased expression of antiviral genes in the colon, which correlated with norovirus infection in the colonic epithelium. This study provides a detailed description of tissue-specific host transcriptional responses to the normal gut microbiota along the length of the gut and demonstrates that the absence of MyD88 alters gut microbial ecology.

Characterization of the human gut microbiome during travelers' diarrhea

PubMed Central

Youmans, Bonnie P; Ajami, Nadim J; Jiang, Zhi-Dong; Campbell, Frederick; Wadsworth, W Duncan; Petrosino, Joseph F; DuPont, Herbert L; Highlander, Sarah K

2015-01-01

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel. PMID:25695334

Characterization of the human gut microbiome during travelers' diarrhea.

PubMed

Youmans, Bonnie P; Ajami, Nadim J; Jiang, Zhi-Dong; Campbell, Frederick; Wadsworth, W Duncan; Petrosino, Joseph F; DuPont, Herbert L; Highlander, Sarah K

2015-01-01

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.

Bacteria, phages and pigs: the effects of in-feed antibiotics on the microbiome at different gut locations.

PubMed

Looft, Torey; Allen, Heather K; Cantarel, Brandi L; Levine, Uri Y; Bayles, Darrell O; Alt, David P; Henrissat, Bernard; Stanton, Thaddeus B

2014-08-01

Disturbance of the beneficial gut microbial community is a potential collateral effect of antibiotics, which have many uses in animal agriculture (disease treatment or prevention and feed efficiency improvement). Understanding antibiotic effects on bacterial communities at different intestinal locations is essential to realize the full benefits and consequences of in-feed antibiotics. In this study, we defined the lumenal and mucosal bacterial communities from the small intestine (ileum) and large intestine (cecum and colon) plus feces, and characterized the effects of in-feed antibiotics (chlortetracycline, sulfamethazine and penicillin (ASP250)) on these communities. 16S rRNA gene sequence and metagenomic analyses of bacterial membership and functions revealed dramatic differences between small and large intestinal locations, including enrichment of Firmicutes and phage-encoding genes in the ileum. The large intestinal microbiota encoded numerous genes to degrade plant cell wall components, and these genes were lacking in the ileum. The mucosa-associated ileal microbiota harbored greater bacterial diversity than the lumen but similar membership to the mucosa of the large intestine, suggesting that most gut microbes can associate with the mucosa and might serve as an inoculum for the lumen. The collateral effects on the microbiota of antibiotic-fed animals caused divergence from that of control animals, with notable changes being increases in Escherichia coli populations in the ileum, Lachnobacterium spp. in all gut locations, and resistance genes to antibiotics not administered. Characterizing the differential metabolic capacities and response to perturbation at distinct intestinal locations will inform strategies to improve gut health and food safety.

Challenges in fecal donor selection and screening for fecal microbiota transplantation: A review.

PubMed

Woodworth, Michael H; Carpentieri, Cynthia; Sitchenko, Kaitlin L; Kraft, Colleen S

2017-05-04

Fecal microbiota transplantation is best understood as an effective and inexpensive therapy for recurrent Clostridium difficile infection but fecal donor selection and screening should be periodically revised. Here, we review current recommendations for selection and screening of fecal donors for fecal microbiota transplantation. We recommend considering diabetes mellitus, prior cardiovascular events, and clinical healthcare exposure as fecal donor exclusion criteria until more is known about the association of these conditions with the human gut microbiome. We review the non-bacterial members of the human gut microbiome, associations of the gut microbiome with colorectal malignancies, the human gut resistome and how these may impact future donor screening recommendations. Collaboration between clinicians, clinical laboratory scientists, industry and regulatory agencies will be critically important for continued improvement in donor selection and screening.

Variation in Rural African Gut Microbiota Is Strongly Correlated with Colonization by Entamoeba and Subsistence

PubMed Central

Morton, Elise R.; Lynch, Joshua; Froment, Alain; Lafosse, Sophie; Heyer, Evelyne; Przeworski, Molly; Blekhman, Ran; Ségurel, Laure

2015-01-01

The human gut microbiota is impacted by host nutrition and health status and therefore represents a potentially adaptive phenotype influenced by metabolic and immune constraints. Previous studies contrasting rural populations in developing countries to urban industrialized ones have shown that industrialization is strongly correlated with patterns in human gut microbiota; however, we know little about the relative contribution of factors such as climate, diet, medicine, hygiene practices, host genetics, and parasitism. Here, we focus on fine-scale comparisons of African rural populations in order to (i) contrast the gut microbiota of populations inhabiting similar environments but having different traditional subsistence modes and either shared or distinct genetic ancestry, and (ii) examine the relationship between gut parasites and bacterial communities. Characterizing the fecal microbiota of Pygmy hunter-gatherers as well as Bantu individuals from both farming and fishing populations in Southwest Cameroon, we found that the gut parasite Entamoeba is significantly correlated with microbiome composition and diversity. We show that across populations, colonization by this protozoa can be predicted with 79% accuracy based on the composition of an individual's gut microbiota, and that several of the taxa most important for distinguishing Entamoeba absence or presence are signature taxa for autoimmune disorders. We also found gut communities to vary significantly with subsistence mode, notably with some taxa previously shown to be enriched in other hunter-gatherers groups (in Tanzania and Peru) also discriminating hunter-gatherers from neighboring farming or fishing populations in Cameroon. PMID:26619199

Mining the human gut microbiota for effector strains that shape the immune system

PubMed Central

Ahern, Philip P.; Faith, Jeremiah J.; Gordon, Jeffrey I.

2014-01-01

Summary The gut microbiota co-develops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community-immune system co-regulation, and in order to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally-arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually-housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed. PMID:24950201

Characterization of gut microbiota profiles in coronary artery disease patients using data mining analysis of terminal restriction fragment length polymorphism: gut microbiota could be a diagnostic marker of coronary artery disease.

PubMed

Emoto, Takuo; Yamashita, Tomoya; Kobayashi, Toshio; Sasaki, Naoto; Hirota, Yushi; Hayashi, Tomohiro; So, Anna; Kasahara, Kazuyuki; Yodoi, Keiko; Matsumoto, Takuya; Mizoguchi, Taiji; Ogawa, Wataru; Hirata, Ken-Ichi

2017-01-01

The association between atherosclerosis and gut microbiota has been attracting increased attention. We previously demonstrated a possible link between gut microbiota and coronary artery disease. Our aim of this study was to clarify the gut microbiota profiles in coronary artery disease patients using data mining analysis of terminal restriction fragment length polymorphism (T-RFLP). This study included 39 coronary artery disease (CAD) patients and 30 age- and sex- matched no-CAD controls (Ctrls) with coronary risk factors. Bacterial DNA was extracted from their fecal samples and analyzed by T-RFLP and data mining analysis using the classification and regression algorithm. Five additional CAD patients were newly recruited to confirm the reliability of this analysis. Data mining analysis could divide the composition of gut microbiota into 2 characteristic nodes. The CAD group was classified into 4 CAD pattern nodes (35/39 = 90 %), while the Ctrl group was classified into 3 Ctrl pattern nodes (28/30 = 93 %). Five additional CAD samples were applied to the same dividing model, which could validate the accuracy to predict the risk of CAD by data mining analysis. We could demonstrate that operational taxonomic unit 853 (OTU853), OTU657, and OTU990 were determined important both by the data mining method and by the usual statistical comparison. We classified the gut microbiota profiles in coronary artery disease patients using data mining analysis of T-RFLP data and demonstrated the possibility that gut microbiota is a diagnostic marker of suffering from CAD.

Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study.

PubMed

Healey, Genelle; Murphy, Rinki; Butts, Christine; Brough, Louise; Whelan, Kevin; Coad, Jane

2018-01-01

Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-type fructan prebiotic. In this randomised, double-blind, placebo-controlled, cross-over study, thirty-four healthy participants were classified as LDF or HDF consumers. Gut microbiota composition (16S rRNA bacterial gene sequencing) and SCFA concentrations were assessed following 3 weeks of daily prebiotic supplementation (Orafti® Synergy 1; 16 g/d) or placebo (Glucidex® 29 Premium; 16 g/d), as well as after 3 weeks of the alternative intervention, following a 3-week washout period. In the LDF group, the prebiotic intervention led to an increase in Bifidobacterium (P=0·001). In the HDF group, the prebiotic intervention led to an increase in Bifidobacterium (P<0·001) and Faecalibacterium (P=0·010) and decreases in Coprococcus (P=0·010), Dorea (P=0·043) and Ruminococcus (Lachnospiraceae family) (P=0·032). This study demonstrates that those with HDF intakes have a greater gut microbiota response and are therefore more likely to benefit from an inulin-type fructan prebiotic than those with LDF intakes. Future studies aiming to modulate the gut microbiota and improve host health, using an inulin-type fructan prebiotic, should take habitual dietary fibre intake into account.

Effects of dietary supplementation of Ulva pertusa and non-starch polysaccharide enzymes on gut microbiota of Siganus canaliculatus

NASA Astrophysics Data System (ADS)

Zhang, Xinxu; Wu, Huijuan; Li, Zhongzhen; Li, Yuanyou; Wang, Shuqi; Zhu, Dashi; Wen, Xiaobo; Li, Shengkang

2018-03-01

Fishes represent the highest diversity of vertebrates; however, our understanding of the compositions and functions of their gut microbiota is limited. In this study, we provided the first insight into the gut microbiota of the herbivorous fish Siganus canaliculatus by using three molecular ecology techniques based on the 16S rRNA genes (denaturing gradient gel electrophoresis, clone library construction, and highthroughput Illumina sequencing), and the Illumina sequencing technique is suggested here due to its higher overall coverage of the total 16S rRNA genes. A core gut microbiota of 29 bacterial groups, covering >99.9% of the total bacterial community, was found to be dominated by Proteobacteria and Firmicutes in fish fed three different diets with/without the supplementation of Ulva pertusa and non-starch polysaccharide (NSP) enzymes (cellulase, xylanase, and β-glucanase). Diverse potential NSP-degrading bacteria and probiotics (e.g., Ruminococcus, Clostridium and Lachnospiraceae) were detected in the intestine of the fish fed U. pertusa, suggesting that these microorganisms likely participated in the degradation of NSPs derived from U. pertusa. This study supports our previous conclusion that U. pertusa-based diets are suitable for the production of S. canaliculatus with lower costs without compromising quality.

The protective effect of Lactobacillus and Bifidobacterium as the gut microbiota members against chronic urticaria.

PubMed

Rezazadeh, Akram; Shahabi, Shahram; Bagheri, Morteza; Nabizadeh, Edris; Jazani, Nima Hosseini

2018-06-01

Chronic Urticaria is a common disorder which is defined by recurrent occurrence of wheals and sometimes angioedema. It has a notable influence on the patients' quality of life. Regulation of the immune system is one of the important roles of the gut microbiota. The effect of dysbiosis considering some members of gut microbiota in patients with chronic urticaria has been demonstrated in our previous study. Comparing the frequency and bacterial load of Lactobacillus, Bifidobacterium, and Bacteroides between patients with chronic urticaria and healthy controls. 20 patients with chronic urticaria and 20 age and sex matched healthy individuals were included in the present study. Stool samples were analyzed for determining the frequency and bacterial load of Lactobacillus, Bifidobacterium, and Bacteroides genera. There were no significant differences among the frequencies of detectable Lactobacillus, Bifidobacterium, or Bacteroides in stool samples of patients with chronic urticaria and healthy controls. The relative amounts of Lactobacillus and Bifidobacterium were significantly higher in fecal samples from controls compared to patients with chronic urticaria (P = 0.038 and 0.039, respectively). It is the first study on the implication of Lactobacillus, Bifidobacterium, and Bacteroides genera as gut microbiota members in patients with chronic urticaria. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of dietary supplementation of Ulva pertusa and non-starch polysaccharide enzymes on gut microbiota of Siganus canaliculatus

NASA Astrophysics Data System (ADS)

Zhang, Xinxu; Wu, Huijuan; Li, Zhongzhen; Li, Yuanyou; Wang, Shuqi; Zhu, Dashi; Wen, Xiaobo; Li, Shengkang

2017-05-01

Fishes represent the highest diversity of vertebrates; however, our understanding of the compositions and functions of their gut microbiota is limited. In this study, we provided the first insight into the gut microbiota of the herbivorous fish Siganus canaliculatus (S. canaliculatus) by using three molecular ecology techniques based on the 16S rRNA genes (denaturing gradient gel electrophoresis, clone library construction, and high-throughput Illumina sequencing), and the Illumina sequencing technique is suggested here due to its higher overall coverage of the total 16S rRNA genes. A core gut microbiota of 29 bacterial groups, covering >99.9% of the total bacterial community, was found to be dominated by Proteobacteria and Firmicutes in fish fed three different diets with/without the supplementation of Ulva pertusa (U. pertusa) and non-starch polysaccharide (NSP) enzymes (cellulase, xylanase, and β-glucanase). Diverse potential NSP-degrading bacteria and probiotics (e.g., Ruminococcus, Clostridium and Lachnospiraceae) were detected in the intestine of the fish fed U. pertusa, suggesting that these microorganisms likely participated in the degradation of NSPs derived from U. pertusa. This study supports our previous conclusion that U. pertusa-based diets are suitable for the production of S. canaliculatus with lower costs without compromising quality.

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.

Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.

PubMed

Zhang, Chenhong; Yin, Aihua; Li, Hongde; Wang, Ruirui; Wu, Guojun; Shen, Jian; Zhang, Menghui; Wang, Linghua; Hou, Yaping; Ouyang, Haimei; Zhang, Yan; Zheng, Yinan; Wang, Jicheng; Lv, Xiaofei; Wang, Yulan; Zhang, Feng; Zeng, Benhua; Li, Wenxia; Yan, Feiyan; Zhao, Yufeng; Pang, Xiaoyan; Zhang, Xiaojun; Fu, Huaqing; Chen, Feng; Zhao, Naisi; Hamaker, Bruce R; Bridgewater, Laura C; Weinkove, David; Clement, Karine; Dore, Joel; Holmes, Elaine; Xiao, Huasheng; Zhao, Guoping; Yang, Shengli; Bork, Peer; Nicholson, Jeremy K; Wei, Hong; Tang, Huiru; Zhang, Xiaozhuang; Zhao, Liping

2015-08-01

Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader-Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

Microbiome structure influences infection by the parasite Crithidia bombi in bumble bees.

PubMed

Mockler, Blair K; Kwong, Waldan K; Moran, Nancy A; Koch, Hauke

2018-01-26

Recent declines in bumble bee populations are of great concern, and have prompted critical evaluations of the role of pathogen introductions and host resistance in bee health. One factor that may influence host resilience when facing infection is the gut microbiota. Previous experiments with Bombus terrestris , a European bumble bee, showed that the gut microbiota can protect against Crithidia bombi , a widespread trypanosomatid parasite of bumble bees. However, the particular characteristics of the microbiome responsible for this protective effect have thus far eluded identification. Using wild and commercially-sourced Bombus impatiens , an important North American pollinator, we conducted cross-wise microbiota transplants to naïve hosts of both backgrounds, and challenged them with Crithidia As with B. terrestris , we find that microbiota-dependent protection against Crithidia operates in B. impatiens Lower Crithidia infection loads were experimentally associated with high microbiome diversity, large gut bacterial populations, and the presence of Apibacter , Lactobacillus Firm-5, and Gilliamella in the gut community. These results indicate that even subtle differences between gut community structures can have a significant impact on the microbiome's ability to defend against parasite infections. Importance Many wild bumble bee populations are under threat by human activity, including through introductions of pathogens via commercially-raised bees. Recently, it was found that the bumble bee gut microbiota can help defend against a common parasite, Crithidia bombi , but the particular factors contributing to this protection are unknown. Using both wild and commercially-raised bees, we conduct microbiota transplants to show that microbiome diversity, total gut bacterial load, and the presence of certain core members of the microbiota may all impact bee susceptibility to Crithidia infection. Bee origin (genetic background) was also a factor. Finally, by examining this phenomenon in a previously uninvestigated bee species, our study demonstrates that microbiome-mediated resistance to Crithidia is conserved across multiple bumble bee species. These findings highlight how intricate interactions between hosts, microbiomes, and parasites can have wide-ranging consequences for the health of ecologically important species. Copyright © 2018 American Society for Microbiology.

Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children☆

PubMed Central

Zhang, Chenhong; Yin, Aihua; Li, Hongde; Wang, Ruirui; Wu, Guojun; Shen, Jian; Zhang, Menghui; Wang, Linghua; Hou, Yaping; Ouyang, Haimei; Zhang, Yan; Zheng, Yinan; Wang, Jicheng; Lv, Xiaofei; Wang, Yulan; Zhang, Feng; Zeng, Benhua; Li, Wenxia; Yan, Feiyan; Zhao, Yufeng; Pang, Xiaoyan; Zhang, Xiaojun; Fu, Huaqing; Chen, Feng; Zhao, Naisi; Hamaker, Bruce R.; Bridgewater, Laura C.; Weinkove, David; Clement, Karine; Dore, Joel; Holmes, Elaine; Xiao, Huasheng; Zhao, Guoping; Yang, Shengli; Bork, Peer; Nicholson, Jeremy K.; Wei, Hong; Tang, Huiru; Zhang, Xiaozhuang; Zhao, Liping

2015-01-01

Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader–Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. Research in context Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader–Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces. PMID:26425705

The link between inflammation, bugs, the intestine and the brain in alcohol dependence.

PubMed

Leclercq, S; de Timary, P; Delzenne, N M; Stärkel, P

2017-02-28

In recent years, some new processes have been proposed to explain how alcohol may influence behavior, psychological symptoms and alcohol seeking in alcohol-dependent subjects. In addition to its important effect on brain and neurotransmitters equilibrium, alcohol abuse also affects peripheral organs including the gut. By yet incompletely understood mechanisms, chronic alcohol abuse increases intestinal permeability and alters the composition of the gut microbiota, allowing bacterial components from the gut lumen to reach the systemic circulation. These gut-derived bacterial products are recognized by immune cells circulating in the blood or residing in target organs, which consequently synthesize and release pro-inflammatory cytokines. Circulating cytokines are considered important mediators of the gut-brain communication, as they can reach the central nervous system and induce neuroinflammation that is associated with change in mood, cognition and drinking behavior. These observations support the possibility that targeting the gut microbiota, by the use of probiotics or prebiotics, could restore the gut barrier function, reduce systemic inflammation and may have beneficial effect in treating alcohol dependence and in reducing alcohol relapse.

Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates.

PubMed

Vandeputte, Doris; Falony, Gwen; Vieira-Silva, Sara; Tito, Raul Y; Joossens, Marie; Raes, Jeroen

2016-01-01

The assessment of potentially confounding factors affecting colon microbiota composition is essential to the identification of robust microbiome based disease markers. Here, we investigate the link between gut microbiota variation and stool consistency using Bristol Stool Scale classification, which reflects faecal water content and activity, and is considered a proxy for intestinal colon transit time. Through 16S rDNA Illumina profiling of faecal samples of 53 healthy women, we evaluated associations between microbiome richness, Bacteroidetes:Firmicutes ratio, enterotypes, and genus abundance with self-reported, Bristol Stool Scale-based stool consistency. Each sample's microbiota growth potential was calculated to test whether transit time acts as a selective force on gut bacterial growth rates. Stool consistency strongly correlates with all known major microbiome markers. It is negatively correlated with species richness, positively associated to the Bacteroidetes:Firmicutes ratio, and linked to Akkermansia and Methanobrevibacter abundance. Enterotypes are distinctly distributed over the BSS-scores. Based on the correlations between microbiota growth potential and stool consistency scores within both enterotypes, we hypothesise that accelerated transit contributes to colon ecosystem differentiation. While shorter transit times can be linked to increased abundance of fast growing species in Ruminococcaceae-Bacteroides samples, hinting to a washout avoidance strategy of faster replication, this trend is absent in Prevotella-enterotyped individuals. Within this enterotype adherence to host tissue therefore appears to be a more likely bacterial strategy to cope with washout. The strength of the associations between stool consistency and species richness, enterotypes and community composition emphasises the crucial importance of stool consistency assessment in gut metagenome-wide association studies. 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 gut microbiota metabolite indole alleviates liver inflammation in mice.

PubMed

Beaumont, Martin; Neyrinck, Audrey M; Olivares, Marta; Rodriguez, Julie; de Rocca Serra, Audrey; Roumain, Martin; Bindels, Laure B; Cani, Patrice D; Evenepoel, Pieter; Muccioli, Giulio G; Demoulin, Jean-Baptiste; Delzenne, Nathalie M

2018-06-15

The gut microbiota regulates key hepatic functions, notably through the production of bacterial metabolites that are transported via the portal circulation. We evaluated the effects of metabolites produced by the gut microbiota from aromatic amino acids (phenylacetate, benzoate, p-cresol, and indole) on liver inflammation induced by bacterial endotoxin. Precision-cut liver slices prepared from control mice, Kupffer cell (KC)-depleted mice, and obese mice ( ob/ ob) were treated with or without LPS and bacterial metabolites. We observed beneficial effects of indole that dose-dependently reduced the LPS-induced up-regulation of proinflammatory mediators at both mRNA and protein levels in precision-cut liver slices prepared from control or ob/ ob mice. KC depletion partly prevented the antiinflammatory effects of indole, notably through a reduction of nucleotide-binding domain and leucine-rich repeat containing (NLR) family pyrin domain-containing 3 (NLRP3) pathway activation. In vivo, the oral administration of indole before an LPS injection reduced the expression of key proteins of the NF-κB pathway and downstream proinflammatory gene up-regulation. Indole also prevented LPS-induced alterations of cholesterol metabolism through a transcriptional regulation associated with increased 4β-hydroxycholesterol hepatic levels. In summary, indole appears as a bacterial metabolite produced from tryptophan that is able to counteract the detrimental effects of LPS in the liver. Indole could be a new target to develop innovative strategies to decrease hepatic inflammation.-Beaumont, M., Neyrinck, A. M., Olivares, M., Rodriguez, J., de Rocca Serra, A., Roumain, M., Bindels, L. B., Cani, P. D., Evenepoel, P., Muccioli, G. G., Demoulin, J.-B., Delzenne, N. M. The gut microbiota metabolite indole alleviates liver inflammation in mice.

Food restriction followed by refeeding with a casein- or whey-based diet differentially affects the gut microbiota of pre-pubertal male rats.

PubMed

Masarwi, Majdi; Solnik, Hadas Isaac; Phillip, Moshe; Yaron, Sima; Shamir, Raanan; Pasmanic-Chor, Metsada; Gat-Yablonski, Galia

2018-01-01

Researchers are gaining an increasing understanding of host-gut microbiota interactions, but studies of the role of gut microbiota in linear growth are scarce. The aim of this study was to investigate the effect of food restriction and refeeding with different diets on gut microbiota composition in fast-growing rats. Young male Sprague-Dawley rats were fed regular rat chow ad libitum (control group) or subjected to 40% food restriction for 36 days followed by continued restriction or ad libitum refeeding for 24 days. Three different diets were used for refeeding: regular vegetarian protein chow or chow in which the sole source of protein was casein or whey. In the control group, the composition of the microbiota remained stable. Food restriction for 60 days led to a significant change in the gut microbiota at the phylum level, with a reduction in the abundance of Firmicutes and an increase in Bacteroidetes and Proteobacteria. Rats refed with the vegetarian protein diet had a different microbiota composition than rats refed the casein- or whey-based diet. Similarities in the bacterial population were found between rats refed vegetarian protein or a whey-based diet and control rats, and between rats refed a casein-based diet and rats on continued restriction. There was a significant strong correlation between the gut microbiota and growth parameters: humerus length, epiphyseal growth plate height, and levels of insulin-like growth factor 1 and leptin. In conclusion, the type of protein in the diet significantly affects the gut microbiota and, thereby, may affect animal's health. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria.

PubMed

Martínez-del Campo, Ana; Bodea, Smaranda; Hamer, Hilary A; Marks, Jonathan A; Haiser, Henry J; Turnbaugh, Peter J; Balskus, Emily P

2015-04-14

Elucidation of the molecular mechanisms underlying the human gut microbiota's effects on health and disease has been complicated by difficulties in linking metabolic functions associated with the gut community as a whole to individual microorganisms and activities. Anaerobic microbial choline metabolism, a disease-associated metabolic pathway, exemplifies this challenge, as the specific human gut microorganisms responsible for this transformation have not yet been clearly identified. In this study, we established the link between a bacterial gene cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism in human gut isolates by combining transcriptional, biochemical, bioinformatic, and cultivation-based approaches. Quantitative reverse transcription-PCR analysis and in vitro biochemical characterization of two cut gene products linked the entire cluster to growth on choline and supported a model for this pathway. Analyses of sequenced bacterial genomes revealed that the cut cluster is present in many human gut bacteria, is predictive of choline utilization in sequenced isolates, and is widely but discontinuously distributed across multiple bacterial phyla. Given that bacterial phylogeny is a poor marker for choline utilization, we were prompted to develop a degenerate PCR-based method for detecting the key functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA. Using this tool, we found that new choline-metabolizing gut isolates universally possessed cutC. We also demonstrated that this gene is widespread in stool metagenomic data sets. Overall, this work represents a crucial step toward understanding anaerobic choline metabolism in the human gut microbiota and underscores the importance of examining this microbial community from a function-oriented perspective. Anaerobic choline utilization is a bacterial metabolic activity that occurs in the human gut and is linked to multiple diseases. While bacterial genes responsible for choline fermentation (the cut gene cluster) have been recently identified, there has been no characterization of these genes in human gut isolates and microbial communities. In this work, we use multiple approaches to demonstrate that the pathway encoded by the cut genes is present and functional in a diverse range of human gut bacteria and is also widespread in stool metagenomes. We also developed a PCR-based strategy to detect a key functional gene (cutC) involved in this pathway and applied it to characterize newly isolated choline-utilizing strains. Both our analyses of the cut gene cluster and this molecular tool will aid efforts to further understand the role of choline metabolism in the human gut microbiota and its link to disease. Copyright © 2015 Martínez-del Campo et al.

Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach.

PubMed

Soldi, Sara; Vasileiadis, Sotirios; Uggeri, Francesca; Campanale, Mariachiara; Morelli, Lorenzo; Fogli, Maria Vittoria; Calanni, Fiorella; Grimaldi, Maria; Gasbarrini, Antonio

2015-01-01

Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali-/quantitative modification of upper gastrointestinal microbiota and clinical response.

Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach

PubMed Central

Soldi, Sara; Vasileiadis, Sotirios; Uggeri, Francesca; Campanale, Mariachiara; Morelli, Lorenzo; Fogli, Maria Vittoria; Calanni, Fiorella; Grimaldi, Maria; Gasbarrini, Antonio

2015-01-01

Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali-/quantitative modification of upper gastrointestinal microbiota and clinical response. PMID:26673000

Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver

PubMed Central

Nakajima, Mayuka; Arimatsu, Kei; Kato, Tamotsu; Matsuda, Yumi; Minagawa, Takayoshi; Takahashi, Naoki; Ohno, Hiroshi; Yamazaki, Kazuhisa

2015-01-01

Although periodontitis has been implicated as a risk factor for various systemic diseases, the precise mechanisms by which periodontitis induces systemic disease remain to be elucidated. We have previously revealed that repeated oral administration of Porphyromonas gingivalis elicits endotoxemia via changes in the gut microbiota of the ileum, and thereby induces systemic inflammation and insulin resistance. However, it is not clear to what extent a single administration of P. gingivalis could affect gut microbiota composition, gut barrier function, and subsequent influx of gut microbiota into the liver. Therefore, in the present study, C57BL/6 mice were orally administered P. gingivalis (strain W83) once and compared to sham-inoculated mice. The phylogenetic structure and diversity of microbial communities in the gut and liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined by a Limulus amebocyte lysate test. Gene expression in the intestine and expression of 16S rRNA genes in the blood and liver were examined by quantitative polymerase chain reaction. Administration of P. gingivalis significantly altered gut microbiota, with an increased proportion of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and increased serum endotoxin levels. In the intestinal tissues, gene expression of tjp-1 and occludin, which are involved in intestinal permeability, were downregulated. Higher amounts of bacterial DNA were detected in the liver of infected mice. Importantly, changes in gut microbiota preceded systemic inflammatory changes. These results further support the idea that disturbance of the gut microbiota composition by orally derived periodontopathic bacteria may be a causal mechanism linking periodontitis and systemic disease. PMID:26218067

Gut microbiota in autoimmunity: potential for clinical applications.

PubMed

Kim, Donghyun; Yoo, Seung-Ah; Kim, Wan-Uk

2016-11-01

Microbial habitation in the human body begins immediately after birth, and adults are colonized by microbes outnumbering human cells by a factor of ten. Especially, intestinal track is a living space for diverse microbial species that have coevolved symbiotically. A principal function of the gut microbiota is to protect the host from harmful bacteria and to provide benefits for the host through several mechanisms, including direct competition for limited nutrients, training of host immune systems to recognize specifically foreign materials and conversion of otherwise indigestible food into energy and absorbable nutrients. Therefore, gut dysbiosis, a bacterial imbalance state, is related with the pathogenesis of various host diseases including autoimmune diseases. In the current review, we highlight the importance of gut microbiota in the normal health and autoimmune diseases. We also discuss regulation of gut dysbiosis and future direction for potential clinical applications, including treatment and diagnostics of autoimmune diseases.

Prior Dietary Practices and Connections to a Human Gut Microbial Metacommunity Alter Responses to Diet Interventions.

PubMed

Griffin, Nicholas W; Ahern, Philip P; Cheng, Jiye; Heath, Andrew C; Ilkayeva, Olga; Newgard, Christopher B; Fontana, Luigi; Gordon, Jeffrey I

2017-01-11

Ensuring that gut microbiota respond consistently to prescribed dietary interventions, irrespective of prior dietary practices (DPs), is critical for effective nutritional therapy. To address this, we identified DP-associated gut bacterial taxa in individuals either practicing chronic calorie restriction with adequate nutrition (CRON) or without dietary restrictions (AMER). When transplanted into gnotobiotic mice, AMER and CRON microbiota responded predictably to CRON and AMER diets but with variable response strengths. An individual's microbiota is connected to other individuals' communities ("metacommunity") by microbial exchange. Sequentially cohousing AMER-colonized mice with two different groups of CRON-colonized mice simulated metacommunity effects, resulting in enhanced responses to a CRON diet intervention and changes in several metabolic features in AMER animals. This response was driven by an influx of CRON DP-associated taxa. Certain DPs may impair responses to dietary interventions, necessitating the introduction of diet-responsive bacterial lineages present in other individuals and identified using the strategies described. Copyright © 2017 Elsevier Inc. All rights reserved.

Gut dysbiosis impairs recovery after spinal cord injury

PubMed Central

Wang, Lingling; Mo, Xiaokui

2016-01-01

The trillions of microbes that exist in the gastrointestinal tract have emerged as pivotal regulators of mammalian development and physiology. Disruption of this gut microbiome, a process known as dysbiosis, causes or exacerbates various diseases, but whether gut dysbiosis affects recovery of neurological function or lesion pathology after traumatic spinal cord injury (SCI) is unknown. Data in this study show that SCI increases intestinal permeability and bacterial translocation from the gut. These changes are associated with immune cell activation in gut-associated lymphoid tissues (GALTs) and significant changes in the composition of both major and minor gut bacterial taxa. Postinjury changes in gut microbiota persist for at least one month and predict the magnitude of locomotor impairment. Experimental induction of gut dysbiosis in naive mice before SCI (e.g., via oral delivery of broad-spectrum antibiotics) exacerbates neurological impairment and spinal cord pathology after SCI. Conversely, feeding SCI mice commercial probiotics (VSL#3) enriched with lactic acid–producing bacteria triggers a protective immune response in GALTs and confers neuroprotection with improved locomotor recovery. Our data reveal a previously unknown role for the gut microbiota in influencing recovery of neurological function and neuropathology after SCI. PMID:27810921

Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans.

PubMed

Beaumont, Martin; Portune, Kevin Joseph; Steuer, Nils; Lan, Annaïg; Cerrudo, Victor; Audebert, Marc; Dumont, Florent; Mancano, Giulia; Khodorova, Nadezda; Andriamihaja, Mireille; Airinei, Gheorghe; Tomé, Daniel; Benamouzig, Robert; Davila, Anne-Marie; Claus, Sandrine Paule; Sanz, Yolanda; Blachier, François

2017-10-01

Background: Although high-protein diets (HPDs) are frequently consumed for body-weight control, little is known about the consequences for gut microbiota composition and metabolic activity and for large intestine mucosal homeostasis. Moreover, the effects of HPDs according to the source of protein need to be considered in this context. Objective: The objective of this study was to evaluate the effects of the quantity and source of dietary protein on microbiota composition, bacterial metabolite production, and consequences for the large intestinal mucosa in humans. Design: A randomized, double-blind, parallel-design trial was conducted in 38 overweight individuals who received a 3-wk isocaloric supplementation with casein, soy protein, or maltodextrin as a control. Fecal and rectal biopsy-associated microbiota composition was analyzed by 16S ribosomal DNA sequencing. Fecal, urinary, and plasma metabolomes were assessed by 1 H-nuclear magnetic resonance. Mucosal transcriptome in rectal biopsies was determined with the use of microarrays. Results: HPDs did not alter the microbiota composition, but induced a shift in bacterial metabolism toward amino acid degradation with different metabolite profiles according to the protein source. Correlation analysis identified new potential bacterial taxa involved in amino acid degradation. Fecal water cytotoxicity was not modified by HPDs, but was associated with a specific microbiota and bacterial metabolite profile. Casein and soy protein HPDs did not induce inflammation, but differentially modified the expression of genes playing key roles in homeostatic processes in rectal mucosa, such as cell cycle or cell death. Conclusions: This human intervention study shows that the quantity and source of dietary proteins act as regulators of gut microbiota metabolite production and host gene expression in the rectal mucosa, raising new questions on the impact of HPDs on the large intestine mucosa homeostasis. This trial was registered at clinicaltrials.gov as NCT02351297. © 2017 American Society for Nutrition.

Manipulation of the microbiota of mass-reared Mediterranean fruit flies Ceratitis capitata (Diptera: Tephritidae) improves sterile male sexual performance.

PubMed

Ben Ami, Eyal; Yuval, Boaz; Jurkevitch, Edouard

2010-01-01

The sterile insect technique (SIT) is a method of biological control whereby millions of factory reared sterile male insects are released into the field. This technique is commonly used to combat the Mediterranean fruit fly (Ceratitis capitata, Diptera: Tephritidae). Sterile medfly males are less competent in attracting and mating with wild females, a property commonly linked to the irradiation process responsible for the sterilization. As bacteria are important partners in the fly's life cycle, we used molecular analytical methods to study the community structure of the gut microbiota in irradiated male medflies. We find that the sterilizing irradiation procedure affects the gut bacterial community structure of the Mediterranean fruit fly. Although the Enterobacteriaceae family remains the dominant bacterial group present in the gut, the levels of Klebsiella species decreases significantly in the days after sterilization. In addition, we detected substantial differences in some bacterial species between the mass rearing strain Vienna 8 and the wild strain. Most notable among these are the increased levels of the potentially pathogenic species Pseudomonas in the industrial strain. Testing the hypothesis that regenerating the original microbiota community could result in enhanced competitiveness of the sterile flies, we found that the addition of the bacterial species Klebsiella oxytoca to the postirradiation diet enables colonization of these bacteria in the gut while resulting in decreased levels of the Pseudomonas sp. Feeding on diets containing bacteria significantly improved sterile male performance in copulatory tests. Further studies will determine the feasibility of bacterial amelioration in SIT operations.

The gut microbiota, obesity and insulin resistance.

PubMed

Shen, Jian; Obin, Martin S; Zhao, Liping

2013-02-01

The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate fundamental discoveries in energy metabolism, molecular endocrinology and immunobiology and may lead to new strategies for prevention of obesity and its complications. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fumonisin-Exposure Impairs Age-Related Ecological Succession of Bacterial Species in Weaned Pig Gut Microbiota.

PubMed

Mateos, Ivan; Combes, Sylvie; Pascal, Géraldine; Cauquil, Laurent; Barilly, Céline; Cossalter, Anne-Marie; Laffitte, Joëlle; Botti, Sara; Pinton, Philippe; Oswald, Isabelle P

2018-06-05

Pigs are highly affected by dietary mycotoxin contamination and particularly by fumonisin. The effects of fumonisin on pig intestinal health are well documented, but little is known regarding its impact on gut microbiota. We investigate the effects of the fumonisin (FB1, 12 mg/kg feed) on the fecal microbiota of piglets ( n = 6) after 0, 8, 15, 22, and 29 days of exposure. A control group of six piglets received a diet free of FB1. Bacterial community diversity, structure and taxonomic composition were carried out by V3⁻V4 16S rRNA gene sequencing. Exposure to FB1 decreases the diversity index, and shifts and constrains the structure and the composition of the bacterial community. This takes place as early as after 15 days of exposure and is at a maximum after 22 days of exposure. Compared to control, FB1 alters the ecological succession of fecal microbiota species toward higher levels of Lactobacillus and lower levels of the Lachnospiraceae and Veillonellaceae families, and particularly OTUs (Operational Taxonomic Units) of the genera Mitsuokella , Faecalibacterium and Roseburia . In conclusion, FB1 shifts and constrains age-related evolution of microbiota. The direct or indirect contribution of FB1 microbiota alteration in the global host response to FB1 toxicity remains to be investigated.

Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

PubMed

Martin, Rocio; Makino, Hiroshi; Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

2016-01-01

Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the developing infant gut microbiome.

Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota

PubMed Central

Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

2016-01-01

Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the developing infant gut microbiome. PMID:27362264

Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.

PubMed

Desbonnet, Lieve; Clarke, Gerard; Traplin, Alexander; O'Sullivan, Orla; Crispie, Fiona; Moloney, Rachel D; Cotter, Paul D; Dinan, Timothy G; Cryan, John F

2015-08-01

There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may contribute to the pathogenesis of disorders associated with altered anxiety and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection

PubMed Central

Vincent, Caroline; Manges, Amee R.

2015-01-01

Clostridium difficile infection (CDI) is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT) is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material. PMID:27025623

Small Bowel Transit and Altered Gut Microbiota in Patients With Liver Cirrhosis.

PubMed

Liu, Yang; Jin, Ye; Li, Jun; Zhao, Lei; Li, Zhengtian; Xu, Jun; Zhao, Fuya; Feng, Jing; Chen, Huinan; Fang, Chengyuan; Shilpakar, Rojina; Wei, Yunwei

2018-01-01

Disturbance of the gut microbiota is common in liver cirrhosis (LC) patients, the underlying mechanisms of which are yet to be unfolded. This study aims to explore the relationship between small bowel transit (SBT) and gut microbiota in LC patients. Cross-sectional design was applied with 36 LC patients and 20 healthy controls (HCs). The gut microbiota was characterized by 16S rRNA gene sequencing. The Firmicutes/Bacteroidetes (F/B) ratio and the Microbial Dysbiosis index (MDI) were used to evaluate the severity of microbiota dysbiosis. The scintigraphy method was performed in patients to describe the objective values of SBT. Patients were then subdivided according to the Child-Pugh score (threshold = 5) or SBT value (threshold = 0.6) for microbiota analysis. LC patients were characterized by an altered gut microbiota; F/B ratios and MDI were higher than HC in both Child_5 (14.00 ± 14.69 vs. 2.86 ± 0.99, p < 0.01; 0.49 ± 0.80 vs. -0.47 ± 0.69, p < 0.01) and Child_5+ (15.81 ± 15.11 vs. 2.86±0.99, p < 0.01; 1.11 ± 1.05 vs. -0.47 ± 0.69, p < 0.01) sub-groups in patients. Difference in the gut microbiota between Child_ 5 and Child_5+ patients was inappreciable, but the SBT was relatively slower in Child_5+ patients (43 ± 26% vs. 80 ± 15%, p < 0.05). Compared with the Child-Pugh score indicators, SBT showed stronger associations with bacterial genera. A clear difference in the gut microbiota was observed between SBT_0.6- and SBT_0.6+ patients [Pr(> F ) = 0.0068, pMANOVA], with higher F/B ratios and MDI in SBT_0.6- patients (19.71 ± 16.62 vs. 7.33 ± 6.65, p < 0.01; 1.02 ± 0.97 vs. 0.20 ± 0.58, p < 0.01). Similar results were observed between the SBT_0.6- and SBT_0.6+ sub-groups of patients with normal liver function and a Child-Pugh score of 5. SBT was negatively correlated with both the F/B ratio and MDI ( r = -0.34, p < 0.05; r = -0.38, p < 0.05). Interestingly, an increased capacity for the inferred pathway "bacterial invasion of epithelial cells" in patients, was highly negatively correlated with SBT ( r = -0.57, p < 0.01). The severity of microbiota dysbiosis in LC patients depends on SBT rather than Child-Pugh score. SBT per se might be significantly related to the gut microbiota abnormalities observed in patients with LC.

Fecal concentrations of bacterially-derived vitamin K forms are associated with gut microbiota composition but not plasma or fecal cytokine concentrations in healthy adults

USDA-ARS?s Scientific Manuscript database

Background: Emerging evidence suggests novel roles for bacterially-derived vitamin K forms known as menaquinones (MKn) in health and disease which may be attributable in part to anti-inflammatory effects. However, the relevance of MKn produced by gut bacteria to vitamin K requirements and inflammati...

Role of Gut Microbiota in Liver Disease.

PubMed

Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

2015-01-01

Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.

Alteration in the Gut Microbiota Provokes Susceptibility to Tuberculosis.

PubMed

Khan, Nargis; Vidyarthi, Aurobind; Nadeem, Sajid; Negi, Shikha; Nair, Girish; Agrewala, Javed N

2016-01-01

The microbiota that resides in the gastrointestinal tract provides essential health benefits to the host. In particular, they regulate immune homeostasis. Recently, several evidences indicate that alteration in the gut microbial community can cause infectious and non-infectious diseases. Tuberculosis (TB) is the most devastating disease, inflicting mortality and morbidity. It remains unexplored, whether changes in the gut microbiota can provoke or prevent TB. In the current study, we have demonstrated the antibiotics driven changes in the gut microbial composition and their impact on the survival of Mycobacterium tuberculosis ( Mtb ) in the lungs, liver, and spleen of infected mice, compared to those with intact microbiota. Interestingly, dysbiosis of microbes showed significant increase in the bacterial burden in lungs and dissemination of Mtb to spleen and liver. Furthermore, elevation in the number of Tregs and decline in the pool of IFN-γ- and TNF-α-releasing CD4 T cells was noticed. Interestingly, fecal transplantation in the gut microbiota disrupted animals exhibited improved Th1 immunity and lesser Tregs population. Importantly, these animals displayed reduced severity to Mtb infection. This study for the first time demonstrated the novel role of gut microbes in the susceptibility to TB and its prevention by microbial implants. In future, microbial therapies may help in treating patients suffering from TB.

Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice.

PubMed

Uebanso, Takashi; Kano, Saki; Yoshimoto, Ayumi; Naito, Chisato; Shimohata, Takaaki; Mawatari, Kazuaki; Takahashi, Akira

2017-07-14

The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans . It is used as a food additive to prevent caries. We previously showed that 1.5-4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella , whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism.

Human gut microbiota: does diet matter?

PubMed

Maukonen, Johanna; Saarela, Maria

2015-02-01

The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated.

Gut microbiota and bacterial translocation in digestive surgery: the impact of probiotics.

PubMed

Komatsu, Shunichiro; Yokoyama, Yukihiro; Nagino, Masato

2017-05-01

It is conceivable that manipulation of the gut microbiota could reduce the incidence or magnitude of surgical complications in digestive surgery. However, the evidence remains inconclusive, although much effort has been devoted to randomized controlled trials (RCTs) and meta-analyses on probiotics. Furthermore, the mechanism behind the protective effects of probiotics appears elusive, our understanding of probiotic actions being fragmentary. The objective of this review is to assess the clinical relevance of the perioperative use of probiotics in major digestive surgery, based on a comprehensive view of the gut microbiota, bacterial translocation (BT), and host defense system. The first part of this article describes the pathophysiological events associated with the gut microbiota. Results of RCTs for the perioperative use of probiotics in major digestive surgery are reviewed in the latter part. The development of the structural and functional barrier to protect against BT primarily results from the generally cooperative interactions between the host and resident microbiota. There is a large body of evidence indicating that probiotics, by enhancing beneficial interactions, reinforce the host defense system to limit BT. The perioperative use of probiotics in patients undergoing hepatobiliary and pancreatic surgery is a promising approach for the prevention of postoperative infectious complications, while the effectiveness in colorectal surgery remains controversial due to substantial heterogeneity among the RCTs with small sample populations. Further studies, such as multi-center RCTs with a larger sample size, are necessary to confirm the clinical relevance of probiotic agents in major digestive surgery.

Early-Life Diet Affects Host Microbiota and Later-Life Defenses Against Parasites in Frogs.

PubMed

Knutie, Sarah A; Shea, Lauren A; Kupselaitis, Marinna; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

2017-10-01

Food resources can affect the health of organisms by altering their symbiotic microbiota and affecting energy reserves for host defenses against parasites. Different diets can vary in their macronutrient content and therefore they might favor certain bacterial communities of the host and affect the development and maintenance of the immune system, such as the inflammatory or antibody responses. Thus, testing the effect of diet, especially for animals with wide diet breadths, on host-associated microbiota and defenses against parasites might be important in determining infection and disease risk. Here, we test whether the early-life diet of Cuban tree frogs (Osteopilus septentrionalis) affects early- and later-life microbiota as well as later-life defenses against skin-penetrating, gut worms (Aplectana hamatospicula). We fed tadpoles two ecologically common diets: a diet of conspecifics or a diet of algae (Arthrospira sp.). We then: (1) characterized the gut microbiota of tadpoles and adults; and (2) challenged adult frogs with parasitic worms and measured host resistance (including the antibody-mediated immune response) and tolerance of infections. Tadpole diet affected bacterial communities in the guts of tadpoles but did not have enduring effects on the bacterial communities of adults. In contrast, tadpole diet had enduring effects on host resistance and tolerance of infections in adult frogs. Frogs that were fed a conspecific-based diet as tadpoles were more resistant to worm penetration compared with frogs that were fed an alga-based diet as tadpoles, but less resistant to worm establishment, which may be related to their suppressed antibody response during worm establishment. Furthermore, frogs that were fed a conspecific-based diet as tadpoles were more tolerant to the effect of parasite abundance on host mass during worm establishment. Overall, our study demonstrates that the diet of Cuban tree frog tadpoles affects the gut microbiota and defenses against parasitic gut worms of frogs, but these effects depend on the stage of the host and infection, respectively. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Differential effects of antibiotic therapy on the structure and function of human gut microbiota.

PubMed

Pérez-Cobas, Ana Elena; Artacho, Alejandro; Knecht, Henrik; Ferrús, María Loreto; Friedrichs, Anette; Ott, Stephan J; Moya, Andrés; Latorre, Amparo; Gosalbes, María José

2013-01-01

The human intestinal microbiota performs many essential functions for the host. Antimicrobial agents, such as antibiotics (AB), are also known to disturb microbial community equilibrium, thereby having an impact on human physiology. While an increasing number of studies investigate the effects of AB usage on changes in human gut microbiota biodiversity, its functional effects are still poorly understood. We performed a follow-up study to explore the effect of ABs with different modes of action on human gut microbiota composition and function. Four individuals were treated with different antibiotics and samples were taken before, during and after the AB course for all of them. Changes in the total and in the active (growing) microbiota as well as the functional changes were addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. We have found that the class of antibiotic, particularly its antimicrobial effect and mode of action, played an important role in modulating the gut microbiota composition and function. Furthermore, analysis of the resistome suggested that oscillatory dynamics are not only due to antibiotic-target resistance, but also to fluctuations in the surviving bacterial community. Our results indicated that the effect of AB on the human gut microbiota relates to the interaction of several factors, principally the properties of the antimicrobial agent, and the structure, functions and resistance genes of the microbial community.

The influence of Staphylococcus aureus on gut microbial ecology in an in vitro continuous culture human colonic model system.

PubMed

Sannasiddappa, Thippeswamy H; Costabile, Adele; Gibson, Glenn R; Clarke, Simon R

2011-01-01

An anaerobic three-stage continuous culture model of the human colon (gut model), which represent different anatomical areas of the large intestine, was used to study the effect of S. aureus infection of the gut on the resident faecal microbiota. Studies on the development of the microbiota in the three vessels were performed and bacteria identified by culture independent fluorescence in situ hybridization (FISH). Furthermore, short chain fatty acids (SCFA), as principal end products of gut bacterial metabolism, were measured along with a quantitative assessment of the predominant microbiota. During steady state conditions, numbers of S. aureus cells stabilised until they were washed out, but populations of indigenous bacteria were transiently altered; thus S. aureus was able to compromise colonisation resistance by the colonic microbiota. Furthermore, the concentration of butyric acid in the vessel representing the proximal colon was significantly decreased by infection. Thus infection by S. aureus appears to be able to alter the overall structure of the human colonic microbiota and the microbial metabolic profiles. This work provides an initial in vitro model to analyse interactions with pathogens.

Intestinal microbiota in primary sclerosing cholangitis.

PubMed

Hov, Johannes R; Kummen, Martin

2017-03-01

Alterations of the gut-liver axis have been linked to the pathogenesis of primary sclerosing cholangitis (PSC) since the disease was first described. The purpose of this review is to discuss multiple recent studies on the intestinal microbiota in human PSC and experimental models of this disease. Data are available from eight cross-sectional studies of human PSC, which include a variable number of patients (n = 11-85), material (mucosal or fecal), and microbiota profiling methodology. Despite the heterogeneity of the studies, a pattern of differences is observed that could represent a theme or signature of the PSC gut microbiota, characterized by low diversity and with alterations in multiple bacterial taxa. In experimental models of PSC, re-derivation of animals into germ-free facilities may either aggravate or attenuate the disease, depending on host genetics and putative disease mechanisms (e.g., fibrotic or immune-driven processes, respectively). The present data provide a strong rationale to explore the functional consequences of the observed gut microbial alterations and their influence on the pathogenesis in PSC. Studies of gut microbiota as biomarker and treatment target may potentially also lead to early translation into clinical practice.

The role of gut microbiota in nutritional status.

PubMed

O'Connor, Eibhlís M

2013-09-01

The objective of this review is to outline the contribution of the gut microbiota to nutritional status and to highlight the mechanisms by which this can occur. Historically, research linking intestinal bacteria with nutritional status focused on the degradation of indigestible food components by bacterial enzymes and metabolites. Of late, emerging evidence suggests an independent role of the gut microbiota in the regulation of glucose and energy homeostasis via complex interactions between microbially derived metabolites and specific target tissue cells. In addition, novel findings highlight specific microbial species involved in the production of a number of micronutrient components, which could potentially improve nutritional status in certain population groups, if available to the host at sufficiently abundant levels. New insights into the role of the gut microbiota and its holistic effects on the host are now emerging. High-throughput technologies allow for a greater insight into the role of the intestinal microbiota and the mechanisms by which it can contribute to overall nutritional status. Further, exploration of this evolving field of research will advance our understanding of how this complex ecosystem could advance the area of personalized nutrition in the future.

Lifestyle and geographic insights into the distinct gut microbiota in elderly women from two different geographic locations.

PubMed

Shin, Ji-Hee; Sim, Minju; Lee, Joo-Young; Shin, Dong-Mi

2016-12-12

A large number of microorganisms reside within the gastrointestinal tract, especially in the colon, and play important roles in human health and disease. The composition of the human gut microbiota is determined by intrinsic host factors and environmental factors. While investigating environmental factors to promote human health is of great interest, few studies have focused on their effect on the gut microbiota. This study aimed to investigate differences in gut microbiota composition according to lifestyle and geographical area, even in people with similar genetic background. We enrolled ten and nine elderly women in their seventies from island and inland areas, respectively. Fecal samples were obtained from individuals, and bacterial 16S ribosomal RNA genes were analyzed by next-generation sequencing to define the gut microbiota composition. We assessed their diet, which can influence the gut microbial community. We also conducted physical examination and determined the physical activity levels of the subjects. The inland subjects had a significantly higher rectal temperature, systolic blood pressure, and heart rate and a significantly lower physical activity score than the island subjects. Fecal samples from the island group showed a tendency to have greater microbial diversity than those from the inland group. Interestingly, the microbial community composition differed significantly between the two groups. Catenibacterium was enriched in subjects from the island area. Catenibacterium showed a negative correlation with rectal temperature and a positive correlation with the dietary level of animal fat. In contrast, Butyricimonas was enriched in the inland subjects. A positive correlation was found between Butyricimonas and mean arterial pressure. This study identified differences in the gut microbiota composition between elderly women from different parts of South Korea, and our findings suggest that further studies of the human gut microbiota should evaluate aspects of the living environment.

Alternation of Gut Microbiota in Patients with Pulmonary Tuberculosis.

PubMed

Luo, Mei; Liu, Yong; Wu, Pengfei; Luo, Dong-Xia; Sun, Qun; Zheng, Han; Hu, Richard; Pandol, Stephen J; Li, Qing-Feng; Han, Yuan-Ping; Zeng, Yilan

2017-01-01

One-third of the world's population has been infected with Mycobacterium tuberculosis ( M. tuberculosis ), a primary pathogen of the mammalian respiratory system, while about 10% of latent infections progress to active tuberculosis (TB), indicating that host and environmental factors may determine the outcomes such as infection clearance/persistence and treatment prognosis. The gut microbiota is essential for development of host immunity, defense, nutrition and metabolic homeostasis. Thus, the pattern of gut microbiota may contribute to M. tuberculosis infection and prognosis. In current study we characterized the differences in gut bacterial communities in new tuberculosis patients (NTB), recurrent tuberculosis patients (RTB), and healthy control. The abundance-based coverage estimator (ACE) showed the diversity index of the gut microbiota in the patients with recurrent tuberculosis was increased significantly compared with healthy controls ( p < 0.05). At the phyla level, Actinobacteria and Proteobacteria, which contain many pathogenic species, were significantly enriched in the feces RTB patients. Conversely, phylum Bacteroidetes, containing a variety of beneficial commensal organisms, was reduced in the patients with the recurrent tuberculosis compared to healthy controls. The Gram-negative genus Prevotella of oral origin from phylum of Bacteroidetes and genus Lachnospira from phylum of Firmicutes were significantly decreased in both the new and recurrent TB patient groups, compared with the healthy control group ( p < 0.05). We also found that there was a positive correlation between the gut microbiota and peripheral CD4+ T cell counts in the patients. This study, for the first time, showed associations between gut microbiota with tuberculosis and its clinical outcomes. Maintaining eubiosis, namely homeostasis of gut microbiota, may be beneficial for host recovery and prevention of recurrence of M. tuberculosis infection.

Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension.

PubMed

Durgan, David J; Ganesh, Bhanu P; Cope, Julia L; Ajami, Nadim J; Phillips, Sharon C; Petrosino, Joseph F; Hollister, Emily B; Bryan, Robert M

2016-02-01

Individuals suffering from obstructive sleep apnea (OSA) are at increased risk for systemic hypertension. The importance of a healthy gut microbiota, and detriment of a dysbiotic microbiota, on host physiology is becoming increasingly evident. We tested the hypothesis that gut dysbiosis contributes to hypertension observed with OSA. OSA was modeled in rats by inflating a tracheal balloon during the sleep cycle (10-s inflations, 60 per hour). On normal chow diet, OSA had no effect on blood pressure; however, in rats fed a high-fat diet, blood pressure increased 24 and 29 mm Hg after 7 and 14 days of OSA, respectively (P<0.05 each). Bacterial community characterization was performed on fecal pellets isolated before and after 14 days of OSA in chow and high-fat fed rats. High-fat diet and OSA led to significant alterations of the gut microbiota, including decreases in bacterial taxa known to produce the short chain fatty acid butyrate (P<0.05). Finally, transplant of dysbiotic cecal contents from hypertensive OSA rats on high-fat diet into OSA recipient rats on normal chow diet (shown to be normotensive) resulted in hypertension similar to that of the donor (increased 14 and 32 mm Hg after 7 and 14 days of OSA, respectively; P<0.05). These studies demonstrate a causal relationship between gut dysbiosis and hypertension, and suggest that manipulation of the microbiota may be a viable treatment for OSA-induced, and possibly other forms of, hypertension. © 2015 American Heart Association, Inc.

Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice.

PubMed

Krych, Ł; Nielsen, D S; Hansen, A K; Hansen, C H F

2015-01-01

Gut microbiota regulated imbalances in the host's immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3(+) regulatory T cells, CD11b(+) dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24-7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.

Graphene oxide as an anaerobic membrane scaffold for the enhancement of B. adolescentis proliferation and antagonistic effects against pathogens E. coli and S. aureus

NASA Astrophysics Data System (ADS)

Chen, Han-qing; Gao, Di; Wang, Bing; Zhao, Rui-fang; Guan, Ming; Zheng, Ling-na; Zhou, Xiao-yan; Chai, Zhi-fang; Feng, Wei-yue

2014-04-01

The impact of the gut microbiota on human health is widely perceived as the most exciting advancement in biomedicine. The gut microbiota has been known to play a crucial role in defining states of human health and diseases, and thus becomes a potential new territory for drug targeting. Herein, graphene oxide (GO) interaction with five common human gut bacteria, B. adolescentis, L. acidophilus, E. coli, E. faecalis, and S. aureus, was studied. It was shown that, in bacterial media, GO sheets were able to form effective, anaerobic membrane scaffolds that enhanced the antagonistic activity of B. adolescentis against the pathogens E. coli andS. aureus. Data obtained using bacterial growth measurements, colony counting and 16S rRNA gene sequencing consistently indicated that GO sheets promoted proliferation of gut bacteria, particularly for B. adolescentis. Scanning electron microscopy, atomic force microscopy images, and membrane potential measurements showed that cell membranes maintained their integrity and that no observable variations in cell morphology were induced after interaction with GO sheets, indicating good biocompatibility of GO. These results suggest the possibility of using GO sheets as efficient drug carriers in therapeutic applications to treat diseases related to the gut microbiota.

The link between inflammation, bugs, the intestine and the brain in alcohol dependence

PubMed Central

Leclercq, S; de Timary, P; Delzenne, N M; Stärkel, P

2017-01-01

In recent years, some new processes have been proposed to explain how alcohol may influence behavior, psychological symptoms and alcohol seeking in alcohol-dependent subjects. In addition to its important effect on brain and neurotransmitters equilibrium, alcohol abuse also affects peripheral organs including the gut. By yet incompletely understood mechanisms, chronic alcohol abuse increases intestinal permeability and alters the composition of the gut microbiota, allowing bacterial components from the gut lumen to reach the systemic circulation. These gut-derived bacterial products are recognized by immune cells circulating in the blood or residing in target organs, which consequently synthesize and release pro-inflammatory cytokines. Circulating cytokines are considered important mediators of the gut–brain communication, as they can reach the central nervous system and induce neuroinflammation that is associated with change in mood, cognition and drinking behavior. These observations support the possibility that targeting the gut microbiota, by the use of probiotics or prebiotics, could restore the gut barrier function, reduce systemic inflammation and may have beneficial effect in treating alcohol dependence and in reducing alcohol relapse. PMID:28244981

Gut microbiota in alcoholic liver disease: pathogenetic role and therapeutic perspectives.

PubMed

Malaguarnera, Giulia; Giordano, Maria; Nunnari, Giuseppe; Bertino, Gaetano; Malaguarnera, Michele

2014-11-28

Alcoholic liver disease (ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.

Gut microbiota in alcoholic liver disease: Pathogenetic role and therapeutic perspectives

PubMed Central

Malaguarnera, Giulia; Giordano, Maria; Nunnari, Giuseppe; Bertino, Gaetano; Malaguarnera, Michele

2014-01-01

Alcoholic liver disease (ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics. PMID:25469033

Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 attenuate D-galactosamine-induced liver injury by modifying the gut microbiota.

PubMed

Fang, Daiqiong; Shi, Ding; Lv, Longxian; Gu, Silan; Wu, Wenrui; Chen, Yanfei; Guo, Jing; Li, Ang; Hu, Xinjun; Guo, Feifei; Ye, Jianzhong; Li, Yating; Li, Lanjian

2017-08-18

The gut microbiota is altered in liver diseases, and several probiotics have been shown to reduce the degree of liver damage. We hypothesized that oral administration of specific Bifidobacterium strains isolated from healthy guts could attenuate liver injury. Five strains were tested in this study. Acute liver injury was induced by D-galactosamine after pretreating Sprague-Dawley rats with the Bifidobacterium strains, and liver function, liver and ileum histology, plasma cytokines, bacterial translocation and the gut microbiome were assessed. Two strains, Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10, conferred liver protection, as well as alleviated the increase in plasma M-CSF, MIP-1α and MCP-1 and bacterial translocation. They also ameliorated ileal mucosal injury and gut flora dysbiosis, especially the enrichment of the opportunistic pathogen Parasutterella and the depletion of the SCFA-producing bacteria Anaerostipes, Coprococcus and Clostridium XI. Negative correlations were found between MIP-1α / MCP-1 and Odoribacter (LI09 group) and MIP-1α / M-CSF and Flavonifractor (LI10 group). Our results indicate that the liver protection effects might be mediated through gut microbiota modification, which thus affect the host immune profile. The desirable characteristics of these two strains may enable them to serve as potential probiotics for the prevention or adjuvant treatment of liver injury.

The microbiome: stress, health and disease.

PubMed

Moloney, Rachel D; Desbonnet, Lieve; Clarke, Gerard; Dinan, Timothy G; Cryan, John F

2014-02-01

Bacterial colonisation of the gut plays a major role in postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Individually, these systems have been implicated in the neuropathology of many CNS disorders and collectively they form an important bidirectional pathway of communication between the microbiota and the brain in health and disease. Regulation of the microbiome-brain-gut axis is essential for maintaining homeostasis, including that of the CNS. Moreover, there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. Research has focused on how the microbiota communicates with the CNS and thereby influences brain function. The routes of this communication are not fully elucidated but include neural, humoral, immune and metabolic pathways. This view is underpinned by studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics which indicate a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus, the concept of a microbiome-brain-gut axis is emerging which suggests that modulation of the gut microflora may be a tractable strategy for developing novel therapeutics for complex stress-related CNS disorders where there is a huge unmet medical need.

Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.

PubMed

Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Fu, Jingyuan; Gevers, Dirk; Visschedijk, Marijn C; Spekhorst, Lieke M; Alberts, Rudi; Franke, Lude; van Dullemen, Hendrik M; Ter Steege, Rinze W F; Huttenhower, Curtis; Dijkstra, Gerard; Xavier, Ramnik J; Festen, Eleonora A M; Wijmenga, Cisca; Zhernakova, Alexandra; Weersma, Rinse K

2018-01-01

Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2 , CARD9 , ATG16L1 , IRGM and FUT2 . Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10 -13 ). We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD. 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/.

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.

Impact of ethnicity, geography, and disease on the microbiota in health and inflammatory bowel disease.

PubMed

Prideaux, Lani; Kang, Seungha; Wagner, Josef; Buckley, Michael; Mahar, Jackie E; De Cruz, Peter; Wen, Zhonghui; Chen, Liping; Xia, Bing; van Langenberg, Daniel R; Lockett, Trevor; Ng, Siew C; Sung, Joseph J Y; Desmond, Paul; McSweeney, Chris; Morrison, Mark; Kirkwood, Carl D; Kamm, Michael A

2013-12-01

The gut microbiota is central to health and disorders such as inflammatory bowel disease. Differences in microbiota related to geography and ethnicity may hold the key to recent changes in the incidence of microbiota-related disorders. Gut mucosal microbiota was analyzed in 190 samples from 87 Caucasian and Chinese subjects, from Australia and Hong Kong, comprising 22 patients with Crohn's disease, 30 patients with ulcerative colitis, 29 healthy controls, and 6 healthy relatives of patients with Crohn's disease. Bacterial 16S rRNA microarray and 454 pyrosequencing were performed. The microbiota was diverse in health, regardless of ethnicity or geography (operational taxonomic unit number and Shannon diversity index). Ethnicity and geography, however, did affect microbial composition. Crohn's disease resulted in reduced bacterial diversity, regardless of ethnicity or geography, and was the strongest determinant of composition. In ulcerative colitis, diversity was reduced in Chinese subjects only, suggesting that ethnicity is a determinant of bacterial diversity, whereas composition was determined by disease and ethnicity. Specific phylotypes were different between health and disease. Chinese patients with inflammatory bowel disease more often than healthy Chinese tended to have had a Western diet in childhood, in the East and West. The healthy microbiota is diverse but compositionally affected by geographical and ethnic factors. The microbiota is substantially altered in inflammatory bowel disease, but ethnicity may also play an important role. This may be key to the changing epidemiology in developing countries, and emigrants to the West.

Gut Microorganisms Found Necessary for Successful Cancer Therapy | Poster

Cancer.gov

By Nancy Parrish, Staff Writer Humans play host to trillions of microorganisms that help our bodies perform basic functions, like digestion, growth, and fighting disease. In fact, bacterial cells outnumber the human cells in our bodies by 10 to 1.1 The tens of trillions of microorganisms thriving in our intestines are known as gut microbiota, and those that are not harmful to us are referred to as commensal microbiota. In a recent paper in Science, NCI scientists described their discovery that, in mice, the presence of commensal microbiota is needed for successful response to cancer therapy.

Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth.

PubMed

Grier, Alex; Qiu, Xing; Bandyopadhyay, Sanjukta; Holden-Wiltse, Jeanne; Kessler, Haeja A; Gill, Ann L; Hamilton, Brooke; Huyck, Heidie; Misra, Sara; Mariani, Thomas J; Ryan, Rita M; Scholer, Lori; Scheible, Kristin M; Lee, Yi-Horng; Caserta, Mary T; Pryhuber, Gloria S; Gill, Steven R

2017-12-11

Identification of factors that influence the neonatal gut microbiome is urgently needed to guide clinical practices that support growth of healthy preterm infants. Here, we examined the influence of nutrition and common practices on the gut microbiota and growth in a cohort of preterm infants. With weekly gut microbiota samples spanning postmenstrual age (PMA) 24 to 46 weeks, we developed two models to test associations between the microbiota, nutrition and growth: a categorical model with three successive microbiota phases (P1, P2, and P3) and a model with two periods (early and late PMA) defined by microbiota composition and PMA, respectively. The more significant associations with phase led us to use a phase-based framework for the majority of our analyses. Phase transitions were characterized by rapid shifts in the microbiota, with transition out of P1 occurring nearly simultaneously with the change from meconium to normal stool. The rate of phase progression was positively associated with gestational age at birth, and delayed transition to a P3 microbiota was associated with growth failure. We found distinct bacterial metabolic functions in P1-3 and significant associations between nutrition, microbiota phase, and infant growth. The phase-dependent impact of nutrition on infant growth along with phase-specific metabolic functions suggests a pioneering potential for improving growth outcomes by tailoring nutrient intake to microbiota phase.

Low-abundant bacteria drive compositional changes in the gut microbiota after dietary alteration.

PubMed

Benjamino, Jacquelynn; Lincoln, Stephen; Srivastava, Ranjan; Graf, Joerg

2018-05-10

As the importance of beneficial bacteria is better recognized, understanding the dynamics of symbioses becomes increasingly crucial. In many gut symbioses, it is essential to understand whether changes in host diet play a role in the persistence of the bacterial gut community. In this study, termites were fed six dietary sources and the microbial community was monitored over a 49-day period using 16S rRNA gene sequencing. A deep backpropagation artificial neural network (ANN) was used to learn how the six different lignocellulose food sources affected the temporal composition of the hindgut microbiota of the termite as well as taxon-taxon and taxon-substrate interactions. Shifts in the termite gut microbiota after diet change in each colony were observed using 16S rRNA gene sequencing and beta diversity analyses. The artificial neural network accurately predicted the relative abundances of taxa at random points in the temporal study and showed that low-abundant taxa maintain community driving correlations in the hindgut. This combinatorial approach utilizing 16S rRNA gene sequencing and deep learning revealed that low-abundant bacteria that often do not belong to the core community are drivers of the termite hindgut bacterial community composition.

The effect of high-fat diet on the composition of the gut microbiota in cloned and non-cloned pigs of lean and obese phenotype

PubMed Central

Pedersen, Rebecca; Andersen, Anders Daniel; Hermann-Bank, Marie Louise; Stagsted, Jan; Boye, Mette

2013-01-01

The aim of this study was to investigate the effect of high-far-high-energy diet on cloned and non-cloned domestic pigs of both lean and obese phenotype and to evaluate if the lean cloned pigs had a lower inter-individual variation as compared with non-cloned pigs. The microbiota of colon and terminal ileum was investigated in cloned and non-cloned pigs that received a high-far-high-energy diet with either restricted or ad libitum access to feed, resulting in lean and obese phenotypes, respectively. The fecal microbiota of lean pigs was investigated by terminal restriction fragment length polymorphism (T-RFLP). The intestinal microbiota of lean and obese cloned and non-cloned pigs was analyzed by quantitative real time PCR and a novel high-throughput qPCR platform (Fluidigm). Principal component analysis (PCA) of the T-RFLP profiles revealed that lean cloned and non-cloned pigs had a different overall composition of their gut microbiota. The colon of lean cloned pigs contained relatively more bacteria belonging to the phylum Firmicutes and less from the phylum Bacteroidetes than obese cloned pigs as estimated by qPCR. Fluidigm qPCR results revealed differences in specific bacterial groups in the gut microbiota of both lean and obese pigs. Our results suggest that high-far-high-energy diet is associated with changes in the gut microbiota even in the absence of obesity. Overall, the cloned pigs had a different gut microbiota from that of non-cloned pigs. To our knowledge this is the first study to investigate the gut microbiota of cloned domestic pigs of lean and obese phenotype. PMID:23974297

The effect of high-fat diet on the composition of the gut microbiota in cloned and non-cloned pigs of lean and obese phenotype.

PubMed

Pedersen, Rebecca; Andersen, Anders Daniel; Hermann-Bank, Marie Louise; Stagsted, Jan; Boye, Mette

2013-01-01

The aim of this study was to investigate the effect of high-far-high-energy diet on cloned and non-cloned domestic pigs of both lean and obese phenotype and to evaluate if the lean cloned pigs had a lower inter-individual variation as compared with non-cloned pigs. The microbiota of colon and terminal ileum was investigated in cloned and non-cloned pigs that received a high-far-high-energy diet with either restricted or ad libitum access to feed, resulting in lean and obese phenotypes, respectively. The fecal microbiota of lean pigs was investigated by terminal restriction fragment length polymorphism (T-RFLP). The intestinal microbiota of lean and obese cloned and non-cloned pigs was analyzed by quantitative real time PCR and a novel high-throughput qPCR platform (Fluidigm). Principal component analysis (PCA) of the T-RFLP profiles revealed that lean cloned and non-cloned pigs had a different overall composition of their gut microbiota. The colon of lean cloned pigs contained relatively more bacteria belonging to the phylum Firmicutes and less from the phylum Bacteroidetes than obese cloned pigs as estimated by qPCR. Fluidigm qPCR results revealed differences in specific bacterial groups in the gut microbiota of both lean and obese pigs. Our results suggest that high-far-high-energy diet is associated with changes in the gut microbiota even in the absence of obesity. Overall, the cloned pigs had a different gut microbiota from that of non-cloned pigs. To our knowledge this is the first study to investigate the gut microbiota of cloned domestic pigs of lean and obese phenotype.

Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.

PubMed

Kang, Dae-Wook; Adams, James B; Gregory, Ann C; Borody, Thomas; Chittick, Lauren; Fasano, Alessio; Khoruts, Alexander; Geis, Elizabeth; Maldonado, Juan; McDonough-Means, Sharon; Pollard, Elena L; Roux, Simon; Sadowsky, Michael J; Lipson, Karen Schwarzberg; Sullivan, Matthew B; Caporaso, J Gregory; Krajmalnik-Brown, Rosa

2017-01-23

Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10 13 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. This trial was registered on the ClinicalTrials.gov, with the registration number  NCT02504554.

Influence of functional food components on gut health.

PubMed

Wan, Murphy L Y; Ling, K H; El-Nezami, Hani; Wang, M F

2018-01-30

Intestinal epithelial cells (IECs) lining the gastrointestinal tract establish a barrier between external environments and the internal milieu. An intact intestinal barrier maintains gut health and overall good health of the body by preventing from tissue injury, pathogen infection and disease development. When the intestinal barrier function is compromised, bacterial translocation can occur. Our gut microbiota also plays a fundamentally important role in health, for example, by maintaining intestinal barrier integrity, metabolism and modulating the immune system, etc. Any disruption of gut microbiota composition (also termed dysbiosis) can lead to various pathological conditions. In short, intestinal barrier and gut microbiota are two crucial factors affecting gut health. The gastrointestinal tract is a complex environment exposed to many dietary components and commensal bacteria. Dietary components are increasingly recognized to play various beneficial roles beyond basic nutrition, resulting in the development of the functional food concepts. Various dietary modifiers, including the consumption of live bacteria (probiotics) and ingestible food constituents such as prebiotics, as well as polyphenols or synbiotics (combinations of probiotics and prebiotics) are the most well characterized dietary bioactive compounds and have been demonstrated to beneficially impact the gut health and the overall well-being of the host. In this review we depict the roles of intestinal epithelium and gut microbiota in mucosal defence responses and the influence of certain functional food components on the modulation of gut health, with a particular focus on probiotics, prebiotics and polyphenols.

Exploring the bovine rumen bacterial community from birth to adulthood.

PubMed

Jami, Elie; Israel, Adi; Kotser, Assaf; Mizrahi, Itzhak

2013-06-01

The mammalian gut microbiota is essential in shaping many of its host's functional attributes. One such microbiota resides in the bovine digestive tract in a compartment termed as the rumen. The rumen microbiota is necessary for the proper physiological development of the rumen and for the animal's ability to digest and convert plant mass into food products, making it highly significant to humans. The establishment of this microbial population and the changes occurring with the host's age are important for understanding this key microbial community. Despite its importance, little information about colonization of the microbial populations in newborn animals, and the gradual changes occurring thereafter, exists. Here, we characterized the overall bovine ruminal bacterial populations of five age groups, from 1-day-old calves to 2-year-old cows. We describe the changes occurring in the rumen ecosystem after birth, reflected by a decline in aerobic and facultative anaerobic taxa and an increase in anaerobic ones. Some rumen bacteria that are essential for mature rumen function could be detected as early as 1 day after birth, long before the rumen is active or even before ingestion of plant material occurs. The diversity and within-group similarity increased with age, suggesting a more diverse but homogeneous and specific mature community, compared with the more heterogeneous and less diverse primary community. In addition, a convergence toward a mature bacterial arrangement with age was observed. These findings have also been reported for human gut microbiota, suggesting that similar forces drive the establishment of gut microbiotas in these two distinct mammalian digestive systems.

Exploring the bovine rumen bacterial community from birth to adulthood

PubMed Central

Jami, Elie; Israel, Adi; Kotser, Assaf; Mizrahi, Itzhak

2013-01-01

The mammalian gut microbiota is essential in shaping many of its host's functional attributes. One such microbiota resides in the bovine digestive tract in a compartment termed as the rumen. The rumen microbiota is necessary for the proper physiological development of the rumen and for the animal's ability to digest and convert plant mass into food products, making it highly significant to humans. The establishment of this microbial population and the changes occurring with the host's age are important for understanding this key microbial community. Despite its importance, little information about colonization of the microbial populations in newborn animals, and the gradual changes occurring thereafter, exists. Here, we characterized the overall bovine ruminal bacterial populations of five age groups, from 1-day-old calves to 2-year-old cows. We describe the changes occurring in the rumen ecosystem after birth, reflected by a decline in aerobic and facultative anaerobic taxa and an increase in anaerobic ones. Some rumen bacteria that are essential for mature rumen function could be detected as early as 1 day after birth, long before the rumen is active or even before ingestion of plant material occurs. The diversity and within-group similarity increased with age, suggesting a more diverse but homogeneous and specific mature community, compared with the more heterogeneous and less diverse primary community. In addition, a convergence toward a mature bacterial arrangement with age was observed. These findings have also been reported for human gut microbiota, suggesting that similar forces drive the establishment of gut microbiotas in these two distinct mammalian digestive systems. PMID:23426008

Oral supplementation of Bifidobacterium longum strain BR-108 alters cecal microbiota by stimulating gut immune system in mice irrespectively of viability.

PubMed

Makioka, Yuko; Tsukahara, Takamitsu; Ijichi, Tetsuo; Inoue, Ryo

2018-03-20

Effect on cecal microbiota and gene expression of various cytokines in ileal Peyer's patches and cecal tissues were compared between viable and heat-killed Bifidobacterium longum strain BR-108 (BR-108) using a mouse model. Irrespectively of viability, oral supplementation of BR-108 altered the cecal microbiota and stimulated gene expression of cytokines such as IL-6 and IL-10 in ileal Peyer's patches and cecal tissue of mice. In addition, BR-108 supplementation significantly affected the relative abundance of bacterial genera and family, Oscillospira, Bacteroides and S24-7. The abundance of these bacterial genera and family strongly correlated with gene expression induced by BR-108. This study demonstrated that the effect of heat-killed BR-108 on the mouse cecal microbiota is similar to that of viable BR-108, most likely due to stimulation of the gut immune system by both heat-killed and viable BR-108 is also similar.

The Intestinal Microbiota of Tadpoles Differs from Those of Syntopic Aquatic Invertebrates.

PubMed

Lyra, Mariana L; Bletz, Molly C; Haddad, Célio F B; Vences, Miguel

2017-11-20

Bacterial communities associated to eukaryotes play important roles in the physiology, development, and health of their hosts. Here, we examine the intestinal microbiota in tadpoles and aquatic invertebrates (insects and gastropods) to better understand the degree of specialization in the tadpole microbiotas. Samples were collected at the same time in one pond, and the V4 region of the bacterial 16S rRNA gene was sequenced with Illumina amplicon sequencing. We found that bacterial richness and diversity were highest in two studied snail individuals, intermediate in tadpoles, and lowest in the four groups of aquatic insects. All groups had substantial numbers of exclusive bacterial operational taxonomic units (OTUs) in their guts, but also shared a high proportion of OTUs, probably corresponding to transient environmental bacteria. Significant differences were found for all pairwise comparisons of tadpoles and snails with the major groups of insects, but not among insect groups or between snails and tadpoles. The similarity between tadpoles and snails may be related to similar feeding mode as both snails and tadpoles scratch biofilms and algae from surfaces; however, this requires confirmation due to low sample sizes. Overall, the gut microbiota differences found among syntopic aquatic animals are likely shaped by both food preferences and host identity.

Gut microbiota from twins discordant for obesity modulate metabolism in mice.

PubMed

Ridaura, Vanessa K; Faith, Jeremiah J; Rey, Federico E; Cheng, Jiye; Duncan, Alexis E; Kau, Andrew L; Griffin, Nicholas W; Lombard, Vincent; Henrissat, Bernard; Bain, James R; Muehlbauer, Michael J; Ilkayeva, Olga; Semenkovich, Clay F; Funai, Katsuhiko; Hayashi, David K; Lyle, Barbara J; Martini, Margaret C; Ursell, Luke K; Clemente, Jose C; Van Treuren, William; Walters, William A; Knight, Rob; Newgard, Christopher B; Heath, Andrew C; Gordon, Jeffrey I

2013-09-06

The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.

Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development.

PubMed

Wopereis, Harm; Sim, Kathleen; Shaw, Alexander; Warner, John O; Knol, Jan; Kroll, J Simon

2018-04-01

Development of the gut microbiota in infancy is important in maturation of the immune system. Deviations in colonization patterns have been associated with allergic manifestations such as eczema, but exact microbiome dysfunctions underlying allergies remain unclear. We studied the gut microbiota of 138 infants at increased risk of allergy, participating in a clinical trial investigating the effectiveness of a partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides on the prevention of eczema. The effects of interventions and breast-feeding on fecal microbiota were investigated. Additionally, we aimed to identify microbial patterns associated with the onset of eczema. Bacterial taxonomic compositions in the first 26 weeks of life were analyzed by using 16S rRNA gene sequencing. Additionally, fecal pH and microbial metabolite levels were measured. Fecal microbial composition, metabolites, and pH of infants receiving partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides was closer to that of breast-fed infants than that of infants receiving standard cow's milk formula. Infants with eczema by 18 months showed discordant development of bacterial genera of Enterobacteriaceae and Parabacteroides species in the first 26 weeks, as well as decreased acquisition of lactate-utilizing bacteria producing butyrate, namely Eubacterium and Anaerostipes species, supported by increased lactate and decreased butyrate levels. We showed that a partially hydrolyzed protein infant formula with specific prebiotics modulated the gut microbiota closer to that of breast-fed infants. Additionally, we identified a potential link between microbial activity and onset of eczema, which might reflect a suboptimal implementation of gut microbiota at specific developmental stages in infants at high risk for allergy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC/MS-based metabolomics.

PubMed

Yu, Meng; Jia, Hongmei; Zhou, Chao; Yang, Yong; Zhao, Yang; Yang, Maohua; Zou, Zhongmei

2017-05-10

As a prevalent, life-threatening and highly recurrent psychiatric illness, depression is characterized by a wide range of pathological changes; however, its etiology remains incompletely understood. Accumulating evidence supports that gut microbiota affects not only gastrointestinal physiology but also central nervous system (CNS) function and behavior through the microbiota-gut-brain axis. To assess the impact of gut microbiota on fecal metabolic phenotype in depressive conditions, an integrated approach of 16S rRNA gene sequencing combined with ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) based metabolomics was performed in chronic variable stress (CVS)-induced depression rat model. Interestingly, depression led to significant gut microbiota changes, at the phylum and genus levels in rats treated with CVS compared to controls. The relative abundances of the bacterial genera Marvinbryantia, Corynebacterium, Psychrobacter, Christensenella, Lactobacillus, Peptostreptococcaceae incertae sedis, Anaerovorax, Clostridiales incertae sedis and Coprococcus were significantly decreased, whereas Candidatus Arthromitus and Oscillibacter were markedly increased in model rats compared with normal controls. Meanwhile, distinct changes in fecal metabolic phenotype of depressive rats were also found, including lower levels of amino acids, and fatty acids, and higher amounts of bile acids, hypoxanthine and stercobilins. Moreover, there were substantial associations of perturbed gut microbiota genera with the altered fecal metabolites, especially compounds involved in the metabolism of tryptophan and bile acids. These results showed that the gut microbiota was altered in association with fecal metabolism in depressive conditions. These findings suggest that the 16S rRNA gene sequencing and LC-MS based metabolomics approach can be further applied to assess pathogenesis of depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Diet is the primary determinant of bacterial community structure in the guts of higher termites.

PubMed

Mikaelyan, Aram; Dietrich, Carsten; Köhler, Tim; Poulsen, Michael; Sillam-Dussès, David; Brune, Andreas

2015-10-01

The gut microbiota of termites plays critical roles in the symbiotic digestion of lignocellulose. While phylogenetically 'lower termites' are characterized by a unique association with cellulolytic flagellates, higher termites (family Termitidae) harbour exclusively prokaryotic communities in their dilated hindguts. Unlike the more primitive termite families, which primarily feed on wood, they have adapted to a variety of lignocellulosic food sources in different stages of humification, ranging from sound wood to soil organic matter. In this study, we comparatively analysed representatives of different taxonomic lineages and feeding groups of higher termites to identify the major drivers of bacterial community structure in the termite gut, using amplicon libraries of 16S rRNA genes from 18 species of higher termites. In all analyses, the wood-feeding species were clearly separated from humus and soil feeders, irrespective of their taxonomic affiliation, offering compelling evidence that diet is the primary determinant of bacterial community structure. Within each diet group, however, gut communities of termites from the same subfamily were more similar than those of distantly related species. A highly resolved classification using a curated reference database revealed only few genus-level taxa whose distribution patterns indicated specificity for certain host lineages, limiting any possible cospeciation between the gut microbiota and host to short evolutionary timescales. Rather, the observed patterns in the host-specific distribution of the bacterial lineages in termite guts are best explained by diet-related differences in the availability of microhabitats and functional niches. © 2015 John Wiley & Sons Ltd.

Analysis of gut microbiota revealed Lactococcus garviaeae could be an indicative of skin ulceration syndrome in farmed sea cucumber Apostichopus japonicus.

PubMed

Zhang, Zhen; Xing, Ronglian; Lv, Zhimeng; Shao, Yina; Zhang, Weiwei; Zhao, Xuelin; Li, Chenghua

2018-06-02

Accumulative evidence has supported the pivotal roles of gut microbiota in shaping host health in a wide range of animals. However, the relationship between gut microbiota and sea cucumber disease is poorly understood. Using the Illumina sequencing of bacterial 16 S rRNA gene, we investigated the divergence of gut bacterial communities between healthy and skin ulceration syndrome (SUS) diseased Apostichopus japonicus. The results showed that bacterial phylotypes in both groups were closely related at phylum level with predominant component of Proteobacteria (>90%). However, Firmicutes and Verrucomicrobia displayed opposite trends in two groups with higher abundance of Firmicutes and lower of Verrucomicrobia in diseased group. Further KEGG enrichment revealed that bacterial-mediated infectious diseases and signal transduction pathways were significantly induced in the SUS group. We also identified one OTU of Lactococcus garvieae from Firmicutes exhibited significantly different abundances in diseased sea cucumber as compared to healthy subjects. The relative abundance of the species was 27.67% ± 10.52% in diseased group compared to 2.78% ± 2.59% in healthy sea cucumber. Three virulence genes of hlyⅢ, fbp and pva encoded by L. garvieae were investigated by qPCR, and were found to be significantly induced (P < 0.05) in diseased sea cucumbers as compared to healthy ones. All our results supported that L. garvieae might be a potential pathogen for SUS outbreak and could be served as a bio-indicator for this disease monitoring. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gut Microbiota in a Rat Oral Sensitization Model: Effect of a Cocoa-Enriched Diet

PubMed Central

Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J.; Franch, Àngels

2017-01-01

Increasing evidence is emerging suggesting a relation between dietary compounds, microbiota, and the susceptibility to allergic diseases, particularly food allergy. Cocoa, a source of antioxidant polyphenols, has shown effects on gut microbiota and the ability to promote tolerance in an oral sensitization model. Taking these facts into consideration, the aim of the present study was to establish the influence of an oral sensitization model, both alone and together with a cocoa-enriched diet, on gut microbiota. Lewis rats were orally sensitized and fed with either a standard or 10% cocoa diet. Faecal microbiota was analysed through metagenomics study. Intestinal IgA concentration was also determined. Oral sensitization produced few changes in intestinal microbiota, but in those rats fed a cocoa diet significant modifications appeared. Decreased bacteria from the Firmicutes and Proteobacteria phyla and a higher percentage of bacteria belonging to the Tenericutes and Cyanobacteria phyla were observed. In conclusion, a cocoa diet is able to modify the microbiota bacterial pattern in orally sensitized animals. As cocoa inhibits the synthesis of specific antibodies and also intestinal IgA, those changes in microbiota pattern, particularly those of the Proteobacteria phylum, might be partially responsible for the tolerogenic effect of cocoa. PMID:28239436

Gut Microbiota in a Rat Oral Sensitization Model: Effect of a Cocoa-Enriched Diet.

PubMed

Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J; Franch, Àngels; Castell, Margarida

2017-01-01

Increasing evidence is emerging suggesting a relation between dietary compounds, microbiota, and the susceptibility to allergic diseases, particularly food allergy. Cocoa, a source of antioxidant polyphenols, has shown effects on gut microbiota and the ability to promote tolerance in an oral sensitization model. Taking these facts into consideration, the aim of the present study was to establish the influence of an oral sensitization model, both alone and together with a cocoa-enriched diet, on gut microbiota. Lewis rats were orally sensitized and fed with either a standard or 10% cocoa diet. Faecal microbiota was analysed through metagenomics study. Intestinal IgA concentration was also determined. Oral sensitization produced few changes in intestinal microbiota, but in those rats fed a cocoa diet significant modifications appeared. Decreased bacteria from the Firmicutes and Proteobacteria phyla and a higher percentage of bacteria belonging to the Tenericutes and Cyanobacteria phyla were observed. In conclusion, a cocoa diet is able to modify the microbiota bacterial pattern in orally sensitized animals. As cocoa inhibits the synthesis of specific antibodies and also intestinal IgA, those changes in microbiota pattern, particularly those of the Proteobacteria phylum, might be partially responsible for the tolerogenic effect of cocoa.

Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans.

PubMed

Allen, Jacob M; Mailing, Lucy J; Niemiro, Grace M; Moore, Rachel; Cook, Marc D; White, Bryan A; Holscher, Hannah D; Woods, Jeffrey A

2018-04-01

Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of 6 wk of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls before outcome variable collection. Thirty-two lean (n = 18 [9 female]) and obese (n = 14 [11 female]), previously sedentary subjects participated in 6 wk of supervised, endurance-based exercise training (3 d·wk) that progressed from 30 to 60 min·d and from moderate (60% of HR reserve) to vigorous intensity (75% HR reserve). Subsequently, participants returned to a sedentary lifestyle activity for a 6-wk washout period. Fecal samples were collected before and after 6 wk of exercise, as well as after the sedentary washout period, with 3-d dietary controls in place before each collection. β-diversity analysis revealed that exercise-induced alterations of the gut microbiota were dependent on obesity status. Exercise increased fecal concentrations of short-chain fatty acids in lean, but not obese, participants. Exercise-induced shifts in metabolic output of the microbiota paralleled changes in bacterial genes and taxa capable of short-chain fatty acid production. Lastly, exercise-induced changes in the microbiota were largely reversed once exercise training ceased. These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet and contingent on the sustainment of exercise.

Changes in the Functional Potential of the Gut Microbiome Following Probiotic Supplementation during Helicobacter Pylori Treatment.

PubMed

Oh, Bumjo; Kim, Ji Won; Kim, Bong-Soo

2016-12-01

Probiotic supplementation is utilized to alleviate the side effects associated with antibiotic therapy for Helicobacter pylori infection. Several studies have described the effects of administration of probiotics on the gut microbiota during antibiotic therapy. However, most of these studies have focused on specific bacteria, thereby providing limited information on the functional roles of the altered microbiota. Therefore, we examined the impact of probiotic supplementation on the structure and functional dynamics of the gut microbiota during H. pylori eradication, using whole-metagenomic sequence analysis. Subjects were divided into two groups: the antibiotics group, which received only antibiotics, and the probiotics group, which received antibiotics with probiotic supplementation. The structural and functional profiles of gut microbiota was analyzed using metagenomic DNA extracted from the feces during treatment by Illumina MiSeq system. The overall alterations in microbiota, as revealed by whole metagenome sequencing, were similar with results from our previous 16S rRNA gene-based analysis. The proportional shift in functional gene families was greater in the antibiotics group than in the probiotics group. In particular, the proportion of genes related to selenocompound metabolism was reduced in the probiotics group, whereas genes associated with the metabolism of nucleotide sugars were increased. The functional alterations of gut microbiota may link to the reduction in intestinal irritation and maintenance of bacterial diversity observed following probiotic supplementation with antibiotic therapy. The potential beneficial roles of altered gut microbiota following probiotic supplementation are expected a reduction in side effects such as intestinal irritation and antibiotics resistance. © 2016 John Wiley & Sons Ltd.

The gut microbiota appears to compensate for seasonal diet variation in the wild black howler monkey (Alouatta pigra).

PubMed

Amato, Katherine R; Leigh, Steven R; Kent, Angela; Mackie, Roderick I; Yeoman, Carl J; Stumpf, Rebecca M; Wilson, Brenda A; Nelson, Karen E; White, Bryan A; Garber, Paul A

2015-02-01

For most mammals, including nonhuman primates, diet composition varies temporally in response to differences in food availability. Because diet influences gut microbiota composition, it is likely that the gut microbiota of wild mammals varies in response to seasonal changes in feeding patterns. Such variation may affect host digestive efficiency and, ultimately, host nutrition. In this study, we investigate the temporal variation in diet and gut microbiota composition and function in two groups (N = 13 individuals) of wild Mexican black howler monkeys (Alouatta pigra) over a 10-month period in Palenque National Park, Mexico. Temporal changes in the relative abundances of individual bacterial taxa were strongly correlated with changes in host diet. For example, the relative abundance of Ruminococcaceae was highest during periods when energy intake was lowest, and the relative abundance of Butyricicoccus was highest when young leaves and unripe fruit accounted for 68 % of the diet. Additionally, the howlers exhibited increased microbial production of energy during periods of reduced energy intake from food sources. Because we observed few changes in howler activity and ranging patterns during the course of our study, we propose that shifts in the composition and activity of the gut microbiota provided additional energy and nutrients to compensate for changes in diet. Energy and nutrient production by the gut microbiota appears to provide an effective buffer against seasonal fluctuations in energy and nutrient intake for these primates and is likely to have a similar function in other mammal species.

Design and Investigation of PolyFermS In Vitro Continuous Fermentation Models Inoculated with Immobilized Fecal Microbiota Mimicking the Elderly Colon

PubMed Central

Fehlbaum, Sophie; Chassard, Christophe; Haug, Martina C.; Fourmestraux, Candice; Derrien, Muriel; Lacroix, Christophe

2015-01-01

In vitro gut modeling is a useful approach to investigate some factors and mechanisms of the gut microbiota independent of the effects of the host. This study tested the use of immobilized fecal microbiota to develop different designs of continuous colonic fermentation models mimicking elderly gut fermentation. Model 1 was a three-stage fermentation mimicking the proximal, transverse and distal colon. Models 2 and 3 were based on the new PolyFermS platform composed of an inoculum reactor seeded with immobilized fecal microbiota and used to continuously inoculate with the same microbiota different second-stage reactors mounted in parallel. The main gut bacterial groups, microbial diversity and metabolite production were monitored in effluents of all reactors using quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC, respectively. In all models, a diverse microbiota resembling the one tested in donor’s fecal sample was established. Metabolic stability in inoculum reactors seeded with immobilized fecal microbiota was shown for operation times of up to 80 days. A high microbial and metabolic reproducibility was demonstrated for downstream control and experimental reactors of a PolyFermS model. The PolyFermS models tested here are particularly suited to investigate the effects of environmental factors, such as diet and drugs, in a controlled setting with the same microbiota source. PMID:26559530

Design and Investigation of PolyFermS In Vitro Continuous Fermentation Models Inoculated with Immobilized Fecal Microbiota Mimicking the Elderly Colon.

PubMed

Fehlbaum, Sophie; Chassard, Christophe; Haug, Martina C; Fourmestraux, Candice; Derrien, Muriel; Lacroix, Christophe

2015-01-01

In vitro gut modeling is a useful approach to investigate some factors and mechanisms of the gut microbiota independent of the effects of the host. This study tested the use of immobilized fecal microbiota to develop different designs of continuous colonic fermentation models mimicking elderly gut fermentation. Model 1 was a three-stage fermentation mimicking the proximal, transverse and distal colon. Models 2 and 3 were based on the new PolyFermS platform composed of an inoculum reactor seeded with immobilized fecal microbiota and used to continuously inoculate with the same microbiota different second-stage reactors mounted in parallel. The main gut bacterial groups, microbial diversity and metabolite production were monitored in effluents of all reactors using quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC, respectively. In all models, a diverse microbiota resembling the one tested in donor's fecal sample was established. Metabolic stability in inoculum reactors seeded with immobilized fecal microbiota was shown for operation times of up to 80 days. A high microbial and metabolic reproducibility was demonstrated for downstream control and experimental reactors of a PolyFermS model. The PolyFermS models tested here are particularly suited to investigate the effects of environmental factors, such as diet and drugs, in a controlled setting with the same microbiota source.

In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota.

PubMed

Martin, Glynn; Kolida, Sofia; Marchesi, Julian R; Want, Elizabeth; Sidaway, James E; Swann, Jonathan R

2018-01-01

Bile acids, the products of concerted host and gut bacterial metabolism, have important signaling functions within the mammalian metabolic system and a key role in digestion. Given the complexity of the mega-variate bacterial community residing in the gastrointestinal tract, studying associations between individual bacterial genera and bile acid processing remains a challenge. Here, we present a novel in vitro approach to determine the bacterial genera associated with the metabolism of different primary bile acids and their potential to contribute to inter-individual variation in this processing. Anaerobic, pH-controlled batch cultures were inoculated with human fecal microbiota and treated with individual conjugated primary bile acids (500 μg/ml) to serve as the sole substrate for 24 h. Samples were collected throughout the experiment (0, 5, 10, and 24 h) and the bacterial composition was determined by 16S rRNA gene sequencing and the bile acid signatures were characterized using a targeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) approach. Data fusion techniques were used to identify statistical bacterial-metabolic linkages. An increase in gut bacteria associated bile acids was observed over 24 h with variation in the rate of bile acid metabolism across the volunteers ( n = 7). Correlation analysis identified a significant association between the Gemmiger genus and the deconjugation of glycine conjugated bile acids while the deconjugation of taurocholic acid was associated with bacteria from the Eubacterium and Ruminococcus genera. A positive correlation between Dorea and deoxycholic acid production suggest a potential role for this genus in cholic acid dehydroxylation. A slower deconjugation of taurocholic acid was observed in individuals with a greater abundance of Parasutterella and Akkermansia . This work demonstrates the utility of integrating compositional (metataxonomics) and functional (metabonomics) systems biology approaches, coupled to in vitro model systems, to study the biochemical capabilities of bacteria within complex ecosystems. Characterizing the dynamic interactions between the gut microbiota and the bile acid pool enables a greater understanding of how variation in the gut microbiota influences host bile acid signatures, their associated functions and their implications for health.

A cross-sectional comparative study of gut bacterial community of Indian and Finnish children.

PubMed

Kumbhare, Shreyas V; Kumar, Himanshu; Chowdhury, Somak P; Dhotre, Dhiraj P; Endo, Akihito; Mättö, Jaana; Ouwehand, Arthur C; Rautava, Samuli; Joshi, Ruchi; Patil, Nitinkumar P; Patil, Ravindra H; Isolauri, Erika; Bavdekar, Ashish R; Salminen, Seppo; Shouche, Yogesh S

2017-09-05

The human gut microbiome plays a crucial role in the compositional development of gut microbiota. Though well documented in western pediatrics population, little is known about how various host conditions affect populations in different geographic locations such as the Indian subcontinent. Given the impact of distinct environmental conditions, our study assess the gut bacterial diversity of a small cohort of Indian and Finnish children and investigated the influence of FUT2 secretor status and birth mode on the gut microbiome of these populations. Using multiple profiling techniques, we show that the gut bacterial community structure in 13-14-year-old Indian (n = 47) and Finnish (n = 52) children differs significantly. Specifically, Finnish children possessed higher Blautia and Bifidobacterium, while genera Prevotella and Megasphaera were predominant in Indian children. Our study also demonstrates a strong influence of FUT2 and birth mode variants on specific gut bacterial taxa, influence of which was noticed to differ between the two populations under study.

Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet

PubMed Central

Kang, Chao; Wang, Bin; Kaliannan, Kanakaraju; Wang, Xiaolan; Lang, Hedong; Hui, Suocheng; Huang, Li; Zhang, Yong; Zhou, Ming; Chen, Mengting

2017-01-01

ABSTRACT Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI) responsible for the development of obesity. Capsaicin (CAP) is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD) supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA) measurements, and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS)-producing family S24_7. Predicted function analysis (PICRUSt) showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1) by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation. PMID:28536285

Associations between micronutrient intakes and gut microbiota in a group of adults with cystic fibrosis.

PubMed

Li, Li; Krause, Lutz; Somerset, Shawn

2017-08-01

Cystic fibrosis (CF) involves chronic inflammation and oxidative stress affecting mainly the respiratory and digestive systems. Survival rates for CF have improved with advances in treatment including nutritional interventions such as micronutrient supplementation. Diet can modulate gut microbiota in the general population with consequences on local and systemic immunity, and inflammation. The gut microbiota appears disrupted and may associate with pulmonary status in CF. This study investigated associations between micronutrient intakes and gut microbiota variations in a group of adults with CF. Faecal microbiota of sixteen free-living adults with CF was profiled by 16ss rDNA sequencing on the GS-FLX platform. Associations were tested between UniFrac distances of faecal microbiota and time-corresponding micronutrient intakes. Associations between relative abundances of bacterial taxa and micronutrient intakes (those showing significant associations with UniFrac distances) were examined by Spearman correlation. Unweighted UniFrac distances were associated with intakes of potassium and antioxidant vitamins C, E and beta-carotene equivalents, whereas weighted UniFrac distances were associated with antioxidant vitamins riboflavin, niacin equivalents, beta-carotene equivalents and vitamin A equivalents. Intakes of beta-carotene equivalents, vitamin C, vitamin E, niacin equivalents and riboflavin correlated negatively with Bacteroides and/or its corresponding higher level taxa. Intakes of beta-carotene equivalents and vitamin E also positively correlated with Firmicutes and specific taxa belonging to Firmicutes. Some micronutrients, particularly antioxidant vitamins, correlated with gut microbiota variations in the studied cohort. Further research is required to clarify whether antioxidant vitamin intakes can influence CF gut microbiota and potential clinical/therapeutic implications in CF. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Composition of gut microbiota in obese and normal-weight Mexican school-age children and its association with metabolic traits.

PubMed

López-Contreras, B E; Morán-Ramos, S; Villarruel-Vázquez, R; Macías-Kauffer, L; Villamil-Ramírez, H; León-Mimila, P; Vega-Badillo, J; Sánchez-Muñoz, F; Llanos-Moreno, L E; Canizalez-Román, A; Del Río-Navarro, B; Ibarra-González, I; Vela-Amieva, M; Villarreal-Molina, T; Ochoa-Leyva, A; Aguilar-Salinas, C A; Canizales-Quinteros, S

2018-06-01

Childhood obesity is a serious public health problem in Mexico. Adult gut microbiota composition has been linked to obesity, but few studies have addressed the role of gut microbiota in childhood obesity. The aim of this study is to compare gut microbiota composition in obese and normal-weight children and to associate gut microbiota profiles with amino acid serum levels and obesity-related metabolic traits. Microbial taxa relative abundance was determined by 16S rRNA sequencing in 67 normal-weight and 71 obese children aged 6-12 years. Serum amino acid levels were measured by mass spectrometry. Associations between microbiota composition, metabolic parameters and amino acid serum levels were tested. No significant differences in phyla abundances or Firmicutes/Bacteroidetes ratios were observed between normal-weight and obese children. However, Bacteroides eggerthii abundance was significantly higher in obese children and correlated positively with body fat percentage and negatively with insoluble fibre intake. Additionally, Bacteroides plebeius and unclassified Christensenellaceae abundances were significantly higher in normal-weight children. Abundance of both these species correlated negatively with phenylalanine serum levels, a metabolite also found to be associated with obesity in Mexican children. The study identified bacterial species associated with obesity, metabolic complications and amino acid serum levels in Mexican children. © 2017 World Obesity Federation.

Intestinal crosstalk between microbiota and serotonin and its impact on gut motility.

PubMed

Ge, Xiaolong; Pan, Junhai; Liu, Yichang; Wang, Hongkan; Zhou, Wei; Wang, Xianfa

2018-05-27

The gastrointestinal tract harbours a diverse bacterial community that contributes to health and disease. A number of studies have demonstrated that the gut microbiota plays a critical role in the metabolism of serotonin. Microbial-derived metabolites, such as bile acids and short-chain fatty acids, are reported to affect the production of serotonin which, in turn, directly or indirectly regulates gut motility. Enterochromaffin cells are important specialized endocrine cells found in the intestine, which is the major location of serotonin biosynthesis. The relationship between microbiota and gut motility are studied depended on microbial-derived metabolites and serotonin. Both bile acids and short-chain fatty acids can modulate serotonin metabolism in hosts by affecting key intermediates of the serotonin pathway. Thus, gut motility may be regulated through microbial modifications of host serotonin biosynthesis, which continues to be evaluated as a target for functional gastrointestinal disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex.

PubMed

Rizzetto, Lisa; Fava, Francesca; Tuohy, Kieran M; Selmi, Carlo

2018-05-31

Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in preventing or ameliorating AID. Finally, we suggest that, given consistent observations of microbiota dysbiosis associated with AID and the ability of SCFA and BA to regulate intestinal permeability and inflammation, further mechanistic studies, examining how dietary microbiota modulation can protect against AID, hold considerable potential to tackle increased incidence of AID at the population level. Copyright © 2018 Elsevier Ltd. All rights reserved.

Yeast culture dietary supplementation modulates gut microbiota, growth and biochemical parameters of grass carp.

PubMed

Liu, Han; Li, Juntao; Guo, Xianwu; Liang, Yunxiang; Wang, Weimin

2018-05-01

Gut microbiota contributes positively to the physiology of their host. Some feed additives have been suggested to improve livestock health and stimulate growth performance by modulating gut bacteria species. Here, we fed grass carp with 0 (control), 8% (Treat1), 10% (Treat2), 12% (Treat3) and 16% (Treat4) of yeast culture (YC) for 10 weeks. The gut microbiota was analysed by 16S rRNA gene V3-4 region via an Illumina MiSeq platform. PCoA test showed that gut bacterial communities in the control and Treat3 formed distinctly separate clusters. Although all the groups shared a large size of OTUs as a core microbiota community, a strong distinction existed at genus level. Treat3 contained the highest proportion of the beneficial bacteria and obviously enhanced the capacity of amino acid, lipid metabolism and digestive system. In addition, Treat3 significantly improved the fish growth and increased the liver and serum T-SOD activities while dramatically decreased the liver GPT and GOT. Collectively, these findings demonstrate the beneficial effects of YC feeding on gut microbiota, growth and biochemical parameters and Treat3 might be the optimal supplementation amount for grass carp, which opens up the possibility that a new feed additive can be developed for healthy aquaculture. © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Human gut microbiota plays a role in the metabolism of drugs.

PubMed

Jourova, Lenka; Anzenbacher, Pavel; Anzenbacherova, Eva

2016-09-01

The gut microbiome, an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract, is now known to play a critical role in human health and predisposition to disease. It is also involved in the biotransformation of xenobiotics and several recent studies have shown that the gut microbiota can affect the pharmacokinetics of orally taken drugs with implications for their oral bioavailability. Review of Pubmed, Web of Science and Science Direct databases for the years 1957-2016. Recent studies make it clear that the human gut microbiota can play a major role in the metabolism of xenobiotics and, the stability and oral bioavailability of drugs. Over the past 50 years, more than 30 drugs have been identified as a substrate for intestinal bacteria. Questions concerning the impact of the gut microbiota on drug metabolism, remain unanswered or only partially answered, namely (i) what are the molecular mechanisms and which bacterial species are involved? (ii) What is the impact of host genotype and environmental factors on the composition and function of the gut microbiota, (iii) To what extent is the composition of the intestinal microbiome stable, transmissible, and resilient to perturbation? (iv) Has past exposure to a given drug any impact on future microbial response, and, if so, for how long? Answering such questions should be an integral part of pharmaceutical research and personalised health care.

Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota.

PubMed

Cai, Jingwei; Zhang, Limin; Jones, Richard A; Correll, Jared B; Hatzakis, Emmanuel; Smith, Philip B; Gonzalez, Frank J; Patterson, Andrew D

2016-02-05

Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver (1)H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum (1)H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles was observed in germ-free mice, thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function, resulting in reduced host energy availability and a significant shift in liver metabolism toward a more catabolic state.

Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice

PubMed Central

Uebanso, Takashi; Kano, Saki; Yoshimoto, Ayumi; Naito, Chisato; Shimohata, Takaaki; Takahashi, Akira

2017-01-01

The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans. It is used as a food additive to prevent caries. We previously showed that 1.5–4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella, whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism. PMID:28708089

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.

Assessing the Influence of Vegan, Vegetarian and Omnivore Oriented Westernized Dietary Styles on Human Gut Microbiota: A Cross Sectional Study.

PubMed

Losasso, Carmen; Eckert, Ester M; Mastrorilli, Eleonora; Villiger, Jorg; Mancin, Marzia; Patuzzi, Ilaria; Di Cesare, Andrea; Cibin, Veronica; Barrucci, Federica; Pernthaler, Jakob; Corno, Gianluca; Ricci, Antonia

2018-01-01

Diet and lifestyle have a strong influence on gut microbiota, which in turn has important implications on a variety of health-related aspects. Despite great advances in the field, it remains unclear to which extent the composition of the gut microbiota is modulated by the intake of animal derived products, compared to a vegetable based diet. Here the specific impact of vegan, vegetarian, and omnivore feeding type on the composition of gut microbiota of 101 adults was investigated among groups homogeneous for variables known to have a role in modulating gut microbial composition such as age, anthropometric variables, ethnicity, and geographic area. The results displayed a picture where the three different dietetic profiles could be well distinguished on the basis of participant's dietetic regimen. Regarding the gut microbiota; vegetarians had a significantly greater richness compared to omnivorous. Moreover, counts of Bacteroidetes related operational taxonomic units (OTUs) were greater in vegans and vegetarians compared to omnivores. Interestingly considering the whole bacterial community composition the three cohorts were unexpectedly similar, which is probably due to their common intake in terms of nutrients rather than food, e.g., high fat content and reduced protein and carbohydrate intake. This finding suggests that fundamental nutritional choices such as vegan, vegetarian, or omnivore do influence the microbiota but do not allow to infer conclusions on gut microbial composition, and suggested the possibility for a preferential impact of other variables, probably related to the general life style on shaping human gut microbial community in spite of dietary influence. Consequently, research were individuals are categorized on the basis of their claimed feeding types is of limited use for scientific studies, since it appears to be oversimplified.

Assessing the Influence of Vegan, Vegetarian and Omnivore Oriented Westernized Dietary Styles on Human Gut Microbiota: A Cross Sectional Study

PubMed Central

Losasso, Carmen; Eckert, Ester M.; Mastrorilli, Eleonora; Villiger, Jorg; Mancin, Marzia; Patuzzi, Ilaria; Di Cesare, Andrea; Cibin, Veronica; Barrucci, Federica; Pernthaler, Jakob; Corno, Gianluca; Ricci, Antonia

2018-01-01

Diet and lifestyle have a strong influence on gut microbiota, which in turn has important implications on a variety of health-related aspects. Despite great advances in the field, it remains unclear to which extent the composition of the gut microbiota is modulated by the intake of animal derived products, compared to a vegetable based diet. Here the specific impact of vegan, vegetarian, and omnivore feeding type on the composition of gut microbiota of 101 adults was investigated among groups homogeneous for variables known to have a role in modulating gut microbial composition such as age, anthropometric variables, ethnicity, and geographic area. The results displayed a picture where the three different dietetic profiles could be well distinguished on the basis of participant’s dietetic regimen. Regarding the gut microbiota; vegetarians had a significantly greater richness compared to omnivorous. Moreover, counts of Bacteroidetes related operational taxonomic units (OTUs) were greater in vegans and vegetarians compared to omnivores. Interestingly considering the whole bacterial community composition the three cohorts were unexpectedly similar, which is probably due to their common intake in terms of nutrients rather than food, e.g., high fat content and reduced protein and carbohydrate intake. This finding suggests that fundamental nutritional choices such as vegan, vegetarian, or omnivore do influence the microbiota but do not allow to infer conclusions on gut microbial composition, and suggested the possibility for a preferential impact of other variables, probably related to the general life style on shaping human gut microbial community in spite of dietary influence. Consequently, research were individuals are categorized on the basis of their claimed feeding types is of limited use for scientific studies, since it appears to be oversimplified. PMID:29556222

Perinatal factors and type 1 diabetes-associated dysbiosis in Mexican infants.

PubMed

Mejía-León, María Esther; Calderón de la Barca, Ana María

Type 1 diabetes (T1D) is currently an autoimmune disease occurring more frequently and early in life. T1D development requires genetic predisposition and environmental factors, which influence the gut microbiota in early infancy and could increase the risk for T1D-associated autoimmunity. In Mexico there are no published microbiota studies in children <6 years old with T1D. We report two contrasting Mexican T1D cases of children <6 years of age and a third case of a healthy child prior to autoimmunity and T1D onset. Perinatal factors, feeding regimes in the first year of life and gut microbiota composition are discussed and related to the T1D onset. The three cases show a particular microbiota profile with decreased bacterial diversity as compared with healthy children, which could be related to environmental factors prior to the development of T1D and disease control. T1D infant cases presented a decreased bacterial diversity, which appeared before autoimmunity and T1D onset. Glycemic control could tend to correct the gut dysbiosis in T1D children. Prospective studies are needed to follow-up healthy children at high genetic risk to assess factors related to the microbiota structure. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Functional metagenomic profiling of intestinal microbiome in extreme ageing.

PubMed

Rampelli, Simone; Candela, Marco; Turroni, Silvia; Biagi, Elena; Collino, Sebastiano; Franceschi, Claudio; O'Toole, Paul W; Brigidi, Patrizia

2013-12-01

Age-related alterations in human gut microbiota composition have been thoroughly described, but a detailed functional description of the intestinal bacterial coding capacity is still missing. In order to elucidate the contribution of the gut metagenome to the complex mosaic of human longevity, we applied shotgun sequencing to total fecal bacterial DNA in a selection of samples belonging to a well-characterized human ageing cohort. The age-related trajectory of the human gut microbiome was characterized by loss of genes for shortchain fatty acid production and an overall decrease in the saccharolytic potential, while proteolytic functions were more abundant than in the intestinal metagenome of younger adults. This altered functional profile was associated with a relevant enrichment in "pathobionts", i.e. opportunistic pro-inflammatory bacteria generally present in the adult gut ecosystem in low numbers. Finally, as a signature for long life we identified 116 microbial genes that significantly correlated with ageing. Collectively, our data emphasize the relationship between intestinal bacteria and human metabolism, by detailing the modifications in the gut microbiota as a consequence of and/or promoter of the physiological changes occurring in the human host upon ageing.

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.

Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels

PubMed Central

Xu, Jian Hui; Liu, Xing Zhen; Pan, Wei; Zou, Da Jin

2017-01-01

Systemic inflammation, which can be induced by metabolic endotoxemia, and corresponding high-fat diet-mediated metabolic disorders are associated with gut microbiota. In the present study reverse transcription-polymerase chain reaction, immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed to assess whether berberine can protect against diet-induced obesity, through modulating the gut microbiota and consequently improving metabolic endotoxemia and gastrointestinal hormone levels. Alterations in the gut microbiota induced by berberine resulted in a significant reduction in bacterial lipopolysaccharide levels in portal plasma. Levels of inflammatory and oxidative stress markers, as well as the mRNA expression levels of macrophage infiltration markers in visceral adipose tissue, were also reduced by berberine. Inhibition of the inflammatory response was associated with a reduction in intestinal permeability and an increase in the expression of tight junction proteins. In addition, berberine was reported to restore aberrant levels of gut hormones in the portal plasma, such as glucagon-like peptide-1 and −2, peptide YY, glucose-dependent insulinotropic polypeptide and pancreatic polypeptide. The present findings indicated that berberine, through modulating gut microbiota, restored the gut barrier, reduced metabolic endotoxemia and systemic inflammation, and improved gut peptide levels in high-fat diet-fed rats. The present study suggests that berberine may be an effective therapeutic strategy for the treatment of obesity and insulin resistance. PMID:28447763

Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels.

PubMed

Xu, Jian Hui; Liu, Xing Zhen; Pan, Wei; Zou, Da Jin

2017-05-01

Systemic inflammation, which can be induced by metabolic endotoxemia, and corresponding high‑fat diet‑mediated metabolic disorders are associated with gut microbiota. In the present study reverse transcription-polymerase chain reaction, immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed to assess whether berberine can protect against diet-induced obesity, through modulating the gut microbiota and consequently improving metabolic endotoxemia and gastrointestinal hormone levels. Alterations in the gut microbiota induced by berberine resulted in a significant reduction in bacterial lipopolysaccharide levels in portal plasma. Levels of inflammatory and oxidative stress markers, as well as the mRNA expression levels of macrophage infiltration markers in visceral adipose tissue, were also reduced by berberine. Inhibition of the inflammatory response was associated with a reduction in intestinal permeability and an increase in the expression of tight junction proteins. In addition, berberine was reported to restore aberrant levels of gut hormones in the portal plasma, such as glucagon‑like peptide‑1 and ‑2, peptide YY, glucose‑dependent insulinotropic polypeptide and pancreatic polypeptide. The present findings indicated that berberine, through modulating gut microbiota, restored the gut barrier, reduced metabolic endotoxemia and systemic inflammation, and improved gut peptide levels in high‑fat diet‑fed rats. The present study suggests that berberine may be an effective therapeutic strategy for the treatment of obesity and insulin resistance.

Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against Clostridium difficile

PubMed Central

Schubert, Alyxandria M.; Sinani, Hamide

2015-01-01

ABSTRACT Perturbations to the gut microbiota can result in a loss of colonization resistance against gastrointestinal pathogens such as Clostridium difficile. Although C. difficile infection is commonly associated with antibiotic use, the precise alterations to the microbiota associated with this loss in function are unknown. We used a variety of antibiotic perturbations to generate a diverse array of gut microbiota structures, which were then challenged with C. difficile spores. Across these treatments we observed that C. difficile resistance was never attributable to a single organism, but rather it was the result of multiple microbiota members interacting in a context-dependent manner. Using relative abundance data, we built a machine learning regression model to predict the levels of C. difficile that were found 24 h after challenging the perturbed communities. This model was able to explain 77.2% of the variation in the observed number of C. difficile per gram of feces. This model revealed important bacterial populations within the microbiota, which correlation analysis alone did not detect. Specifically, we observed that populations associated with the Porphyromonadaceae, Lachnospiraceae, Lactobacillus, and Alistipes were protective and populations associated with Escherichia and Streptococcus were associated with high levels of colonization. In addition, a population affiliated with the Akkermansia indicated a strong context dependency on other members of the microbiota. Together, these results indicate that individual bacterial populations do not drive colonization resistance to C. difficile. Rather, multiple diverse assemblages act in concert to mediate colonization resistance. PMID:26173701

Postprandial remodeling of the gut microbiota in Burmese pythons

PubMed Central

Costello, Elizabeth K.; Gordon, Jeffrey I.; Secor, Stephen M.; Knight, Rob

2014-01-01

The vertebrate gut microbiota evolved in an environment typified by periodic fluctuations in nutrient availability, yet little is known about its responses to host feeding and fasting. Because many model species (e.g., mice) are adapted to lifestyles of frequent small meals, we turned to the Burmese python, a sit-and-wait foraging snake that consumes large prey at long intervals (>1 month), to examine the effects of a dynamic nutrient milieu on the gut microbiota. We employed multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities harvested from the intestines of fasted and digesting snakes, and from their rodent meal. In this unprecedented survey of a reptilian host, we found that Bacteroidetes and Firmicutes numerically dominated the python gut. In the large intestine, fasting was associated with increased abundances of the genera Bacteroides, Rikenella, Synergistes, and Akkermansia, and reduced overall diversity. A marked postprandial shift in bacterial community configuration occurred. Between 12 hours and 3 days after feeding, Firmicutes, including the taxa Clostridium, Lactobacillus, and Peptostreptococcaceae, gradually outnumbered the fasting-dominant Bacteroidetes, and overall ‘species’-level diversity increased significantly. Most lineages appeared to be indigenous to the python rather than ingested with the meal, but a dietary source of Lactobacillus could not be ruled out. Thus, the observed large-scale alterations of the gut microbiota that accompany the Burmese python's own dramatic physiological and morphological changes during feeding and fasting emphasize the need to consider both microbial and host cellular responses to nutrient flux. The Burmese python may provide a unique model for dissecting these interrelationships. PMID:20520652

Gut Microbiota Composition Before and After Use of Proton Pump Inhibitors.

PubMed

Hojo, Mariko; Asahara, Takashi; Nagahara, Akihito; Takeda, Tsutomu; Matsumoto, Kohei; Ueyama, Hiroya; Matsumoto, Kenshi; Asaoka, Daisuke; Takahashi, Takuya; Nomoto, Koji; Yamashiro, Yuichiro; Watanabe, Sumio

2018-05-24

Recently, problems associated with proton pump inhibitor (PPI) use have begun to surface. PPIs influence the gut microbiota; therefore, PPI use may increase the risk of enteric infections and cause bacterial translocation. In this study, we investigated fecal microbiota composition, fecal organic acid concentrations and pH, and gut bacteria in the blood of the same patients before and after PPI use. Twenty patients with reflux esophagitis based on endoscopic examination received 8 weeks of treatment with PPIs. To analyze fecal microbiota composition and gut bacteria in blood and organic acid concentrations, 16S and 23S rRNA-targeted quantitative RT-PCR and high-performance liquid chromatography were conducted. Lactobacillus species were significantly increased at both 4 and 8 weeks after PPI treatment compared with bacterial counts before treatment (P = 0.011 and P = 0.002, respectively). Among Lactobacillus spp., counts of the L. gasseri subgroup, L. fermentum, the L. reuteri subgroup, and the L. ruminis subgroup were significantly increased at 4 and 8 weeks after treatment compared with counts before treatment. Streptococcus species were also significantly increased at 4 and 8 weeks after PPI treatment compared with counts before treatment (P < 0.01 and P < 0.001, respectively). There was no significant difference in the total organic acid concentrations before and after PPI treatment. Detection rates of bacteria in blood before and after PPI treatment were 22 and 28%, respectively, with no significant differences. Our quantitative RT-PCR results showed that gut dysbiosis was caused by PPI use, corroborating previous results obtained by metagenomic analysis.

Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

PubMed Central

Darzi, Youssef; Mongodin, Emmanuel F.; Pan, Chongle; Shah, Manesh; Halfvarson, Jonas; Tysk, Curt; Henrissat, Bernard; Raes, Jeroen; Verberkmoes, Nathan C.; Jansson, Janet K.

2012-01-01

Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers. PMID:23209564

Dietary Fiber and the Human Gut Microbiota: Application of Evidence Mapping Methodology.

PubMed

Sawicki, Caleigh M; Livingston, Kara A; Obin, Martin; Roberts, Susan B; Chung, Mei; McKeown, Nicola M

2017-02-10

Interest is rapidly growing around the role of the human gut microbiota in facilitating beneficial health effects associated with consumption of dietary fiber. An evidence map of current research activity in this area was created using a newly developed database of dietary fiber intervention studies in humans to identify studies with the following broad outcomes: (1) modulation of colonic microflora; and/or (2) colonic fermentation/short-chain fatty acid concentration. Study design characteristics, fiber exposures, and outcome categories were summarized. A sub-analysis described oligosaccharides and bacterial composition in greater detail. One hundred eighty-eight relevant studies were identified. The fiber categories represented by the most studies were oligosaccharides (20%), resistant starch (16%), and chemically synthesized fibers (15%). Short-chain fatty acid concentration (47%) and bacterial composition (88%) were the most frequently studied outcomes. Whole-diet interventions, measures of bacterial activity, and studies in metabolically at-risk subjects were identified as potential gaps in the evidence. This evidence map efficiently captured the variability in characteristics of expanding research on dietary fiber, gut microbiota, and physiological health benefits, and identified areas that may benefit from further research. We hope that this evidence map will provide a resource for researchers to direct new intervention studies and meta-analyses.

Dietary Fiber and the Human Gut Microbiota: Application of Evidence Mapping Methodology

PubMed Central

Sawicki, Caleigh M.; Livingston, Kara A.; Obin, Martin; Roberts, Susan B.; Chung, Mei; McKeown, Nicola M.

2017-01-01

Interest is rapidly growing around the role of the human gut microbiota in facilitating beneficial health effects associated with consumption of dietary fiber. An evidence map of current research activity in this area was created using a newly developed database of dietary fiber intervention studies in humans to identify studies with the following broad outcomes: (1) modulation of colonic microflora; and/or (2) colonic fermentation/short-chain fatty acid concentration. Study design characteristics, fiber exposures, and outcome categories were summarized. A sub-analysis described oligosaccharides and bacterial composition in greater detail. One hundred eighty-eight relevant studies were identified. The fiber categories represented by the most studies were oligosaccharides (20%), resistant starch (16%), and chemically synthesized fibers (15%). Short-chain fatty acid concentration (47%) and bacterial composition (88%) were the most frequently studied outcomes. Whole-diet interventions, measures of bacterial activity, and studies in metabolically at-risk subjects were identified as potential gaps in the evidence. This evidence map efficiently captured the variability in characteristics of expanding research on dietary fiber, gut microbiota, and physiological health benefits, and identified areas that may benefit from further research. We hope that this evidence map will provide a resource for researchers to direct new intervention studies and meta-analyses. PMID:28208609

Disruption of bacterial balance in the gut of Portunus trituberculatus induced by Vibrio alginolyticus infection

NASA Astrophysics Data System (ADS)

Xia, Mengjie; Pei, Feng; Mu, Changkao; Ye, Yangfang; Wang, Chunlin

2018-04-01

Gut microbiota impacts the health of crustaceans. Vibrio alginolyticus is a main causative pathogen that induces the vibriosis in farmed swimming crabs, Portunus trituberculatus. However, it remains unknown whether gut bacteria perform functions during the progression of vibriosis. In this study, 16S rRNA gene amplicon sequencing was used to investigate temporal alteration of gut bacterial community in swimming crabs in response to 72-h V. alginolyticus challenge. Our results show that V. alginolyticus infection resulted in dynamic changes of bacterial community composition in swimming crabs. Such changes were highlighted by the overwhelming overabundance of Vibrio and a signifi cant fluctuation in the gut bacteria including the bacteria with high relative abundance and especially those with low relative abundance. These findings reveal that crab vibriosis gradually develops with the infection time of V. alginolyticus and tightly relates to the dysbiosis of gut bacterial community structure. This work contributes to our appreciation of the importance of the balance of gut bacterial community structure in maintaining the health of crustaceans.

Changes in Composition of the Gut Bacterial Microbiome after Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in a Pediatric Heart Transplant Patient.

PubMed

Flannigan, Kyle L; Rajbar, Taylor; Moffat, Andrew; McKenzie, Leanna S; Dicke, Frank; Rioux, Kevin; Workentine, Matthew L; Louie, Thomas J; Hirota, Simon A; Greenway, Steven C

2017-01-01

The microbiome is increasingly recognized as an important influence on human health and many of the comorbidities that affect patients after solid organ transplantation (SOT) have been shown to involve changes in gut bacterial populations. Thus, microbiome changes in an individual patient may have important health implications after SOT but this area remains understudied. We describe changes in the composition of the fecal microbiome from a pediatric heart transplant recipient before and >2.5 years after he underwent repeated fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI). With both documented episodes of CDI, there was marked loss of bacterial diversity with overgrowth of Proteobacteria (>98.9% of phyla identified) associated with symptomatic colitis that was corrected after FMT. We hypothesize that a second CDI occurring after FMT was related to incomplete restoration of normal bowel flora post-FMT with relative deficiencies of the phyla Firmicutes and Bacteroidetes and the families Lachnospiraceae and Ruminococcaceae . Following the second FMT, there was a gradual shift in gut bacterial composition coincident with the recipient developing lymphonodular hyperplasia of the colon and painless hematochezia that resolved with discontinuation of mycophenolate mofetil (MMF). This case documents dynamic changes in the bacterial microbiome after FMT and suggests that MMF may influence the gut microbiome with consequences for the patient.

Measuring the gut microbiome in birds: Comparison of faecal and cloacal sampling.

PubMed

Videvall, Elin; Strandh, Maria; Engelbrecht, Anel; Cloete, Schalk; Cornwallis, Charlie K

2018-05-01

The gut microbiomes of birds and other animals are increasingly being studied in ecological and evolutionary contexts. Numerous studies on birds and reptiles have made inferences about gut microbiota using cloacal sampling; however, it is not known whether the bacterial community of the cloaca provides an accurate representation of the gut microbiome. We examined the accuracy with which cloacal swabs and faecal samples measure the microbiota in three different parts of the gastrointestinal tract (ileum, caecum, and colon) using a case study on juvenile ostriches, Struthio camelus, and high-throughput 16S rRNA sequencing. We found that faeces were significantly better than cloacal swabs in representing the bacterial community of the colon. Cloacal samples had a higher abundance of Gammaproteobacteria and fewer Clostridia relative to the gut and faecal samples. However, both faecal and cloacal samples were poor representatives of the microbial communities in the caecum and ileum. Furthermore, the accuracy of each sampling method in measuring the abundance of different bacterial taxa was highly variable: Bacteroidetes was the most highly correlated phylum between all three gut sections and both methods, whereas Actinobacteria, for example, was only strongly correlated between faecal and colon samples. Based on our results, we recommend sampling faeces, whenever possible, as this sample type provides the most accurate assessment of the colon microbiome. The fact that neither sampling technique accurately portrayed the bacterial community of the ileum nor the caecum illustrates the difficulty in noninvasively monitoring gut bacteria located further up in the gastrointestinal tract. These results have important implications for the interpretation of avian gut microbiome studies. © 2017 John Wiley & Sons Ltd.

Bacterial adaptation to the gut environment favors successful colonization: microbial and metabonomic characterization of a simplified microbiota mouse model.

PubMed

Rezzonico, Enea; Mestdagh, Renaud; Delley, Michèle; Combremont, Séverine; Dumas, Marc-Emmanuel; Holmes, Elaine; Nicholson, Jeremy; Bibiloni, Rodrigo

2011-01-01

Rodent models harboring a simple yet functional human intestinal microbiota provide a valuable tool to study the relationships between mammals and their bacterial inhabitants. In this study, we aimed to develop a simplified gnotobiotic mouse model containing 10 easy-to-grow bacteria, readily available from culture repositories, and of known genome sequence, that overall reflect the dominant commensal bacterial makeup found in adult human feces. We observed that merely inoculating a mix of fresh bacterial cultures into ex-germ free mice did not guarantee a successful intestinal colonization of the entire bacterial set, as mice inoculated simultaneously with all strains only harbored 3 after 21 d. Therefore, several inoculation procedures were tested and levels of individual strains were quantified using molecular tools. Best results were obtained by inoculating single bacterial strains into individual animals followed by an interval of two weeks before allowing the animals to socialize to exchange their commensal microbes. Through this procedure, animals were colonized with almost the complete bacterial set (9/10). Differences in the intestinal composition were also reflected in the urine and plasma metabolic profiles, where changes in lipids, SCFA, and amino acids were observed. We conclude that adaptation of bacterial strains to the host's gut environment (mono-colonization) may predict a successful establishment of a more complex microbiota in rodents.

Microbial shifts of the silkworm larval gut in response to lettuce leaf feeding.

PubMed

Liang, Xue; Fu, Yuming; Tong, Ling; Liu, Hong

2014-04-01

Silkworm (Bombyx mori L.) larvae were used as an ideal animal protein source for astronauts in the bioregenerative life support system (BLSS). Here, we compared the difference in bacterial communities of the silkworm larval gut between the BLSS rearing way (BRW) and the traditional rearing way (TRW) through culture-dependent approach, 16S rRNA gene analysis, and denaturing gradient gel electrophoresis (DGGE). The culture-dependent approach revealed that the numbers of gut bacteria of silkworm in the BRW significantly decreased compared with that of the TRW. The analysis of clone libraries showed that the gut microbiota in the BRW was significantly less diverse than that in the TRW. Acinetobacter and Bacteroides were dominant populations in the BRW, and Bacillus and Arcobacter dominated in the TRW. DGGE profiles confirmed the difference of silkworm gut bacterial community between two rearing ways. These results demonstrate that gut bacteria change from the BRW contributes to the decrease of silkworm physiological activity. This study increases our understanding of the change of silkworm gut microbiota in response to lettuce leaf feeding in the BRW. We could use the dominant populations to make probiotic products for nutrient absorption and disease prevention in the BLSS to improve gut microecology, as well as the yield and quality of animal protein.

Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders

PubMed Central

Saviano, A.; Newton, E. E.; Serricchio, M. L.; Dal Lago, A. A.

2018-01-01

Gut microbiota is key to the development and modulation of the mucosal immune system. It plays a central role in several physiological functions, in the modulation of inflammatory signaling and in the protection against infections. In healthy states, there is a perfect balance between commensal and pathogens, and microbiota and the immune system interact to maintain gut homeostasis. The alteration of such balance, called dysbiosis, determines an intestinal bacterial overgrowth which leads to the disruption of the intestinal barrier with systemic translocation of pathogens. The pancreas does not possess its own microbiota, and it is believed that inflammatory and neoplastic processes affecting the gland may be linked to intestinal dysbiosis. Increasing research evidence testifies a correlation between intestinal dysbiosis and various pancreatic disorders, but it remains unclear whether dysbiosis is the cause or an effect. The analysis of specific alterations in the microbiome profile may permit to develop novel tools for the early detection of several pancreatic disorders, utilizing samples, such as blood, saliva, and stools. Future studies will have to elucidate the mechanisms by which gut microbiota is modulated and how it tunes the immune system, in order to be able to develop innovative treatment strategies for pancreatic disorders. PMID:29563853

Gut-Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease.

PubMed

Poeta, Marco; Pierri, Luca; Vajro, Pietro

2017-08-02

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A "multiple-hit" hypothesis has been invoked to explain its pathogenesis. The "first hit" is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as "second hits" implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut-liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

Comparative Analysis of Drosophila melanogaster Gut Microbiota with Respect to Host Strain, Sex, and Age.

PubMed

Han, Gangsik; Lee, Hyo Jung; Jeong, Sang Eun; Jeon, Che Ok; Hyun, Seogang

2017-07-01

Microbiota has a significant impact on the health of the host individual. The complexity of the interactions between mammalian hosts and their microbiota highlights the value of using Drosophila melanogaster as a model organism, because of its relatively simple microbial community and ease of physiological and genetic manipulation. However, highly variable and sometimes inconsistent results regarding the microbiota of D. melanogaster have been reported for host samples collected from different geographical locations; discrepancies that may be because of the inherent physiological conditions of the D. melanogaster host. Here, we conducted a comparative analysis of the gut microbiota of two D. melanogaster laboratory strains, w 1118 and Canton S, with respect to the sex and age of the host, by pyrosequencing of the 16S rRNA gene. In addition to the widespread and abundant commensal bacterial genera Lactobacillus and Acetobacter, we identified Enterococcus and Leuconostoc as major host-strain-specific bacterial genera. The relative proportions of these bacterial genera, and those of the species within each, were found to differ markedly with respect to strain, sex, and age of the host, even though host individuals were reared under the same nutritional conditions. By using various bioinformatic tools, we uncovered several characteristic features of microbiota corresponding to specific categories of the flies: host-sex-bias association of specific bacteria, age-dependent alteration of microbiota across host species and sex, and uniqueness of the microbiota of female w 1118 flies. Our results, thus, help to further our understanding of host-microbe interactions in the D. melanogaster model.

The Fecal Microbial Community of Breast-fed Infants from Armenia and Georgia

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

Lewis, Zachery T.; Sidamonidze, Ketevan; Tsaturyan, Vardan

Multiple factors help shape the infant intestinal microbiota early in life. Environmental conditions such as the presence of bioactive molecules from breast milk dictate gut microbial growth and survival. Infants also receive distinct, personalized, bacterial exposures leading to differential colonization. Microbial exposures and gut environmental conditions differ between infants in different locations, as does the typical microbial community structure in an infant’s gut. Here we evaluate potential influences on the infant gut microbiota through a longitudinal study on cohorts of breast-fed infants from the neighboring countries of Armenia and Georgia, an area of the world for which the infant microbiomemore » has not been previously investigated. Marker gene sequencing of 16S ribosomal genes revealed that the gut microbial communities of infants from these countries were dominated by bifidobacteria, were different from each other, and were marginally influenced by their mother’s secretor status. Species-level differences in the bifidobacterial communities of each country and birth method were also observed. These community differences suggest that environmental variation between individuals in different locations may influence the gut microbiota of infants.« less

The Fecal Microbial Community of Breast-fed Infants from Armenia and Georgia

PubMed Central

Lewis, Zachery T; Sidamonidze, Ketevan; Tsaturyan, Vardan; Tsereteli, David; Khachidze, Nika; Pepoyan, Astghik; Zhgenti, Ekaterine; Tevzadze, Liana; Manvelyan, Anahit; Balayan, Marine; Imnadze, Paata; Torok, Tamas; Lemay, Danielle G.; Mills, David A.

2017-01-01

Multiple factors help shape the infant intestinal microbiota early in life. Environmental conditions such as the presence of bioactive molecules from breast milk dictate gut microbial growth and survival. Infants also receive distinct, personalized, bacterial exposures leading to differential colonization. Microbial exposures and gut environmental conditions differ between infants in different locations, as does the typical microbial community structure in an infant’s gut. Here we evaluate potential influences on the infant gut microbiota through a longitudinal study on cohorts of breast-fed infants from the neighboring countries of Armenia and Georgia, an area of the world for which the infant microbiome has not been previously investigated. Marker gene sequencing of 16S ribosomal genes revealed that the gut microbial communities of infants from these countries were dominated by bifidobacteria, were different from each other, and were marginally influenced by their mother’s secretor status. Species-level differences in the bifidobacterial communities of each country and birth method were also observed. These community differences suggest that environmental variation between individuals in different locations may influence the gut microbiota of infants. PMID:28150690

The Fecal Microbial Community of Breast-fed Infants from Armenia and Georgia

DOE PAGES

Lewis, Zachery T.; Sidamonidze, Ketevan; Tsaturyan, Vardan; ...

2017-02-02

Multiple factors help shape the infant intestinal microbiota early in life. Environmental conditions such as the presence of bioactive molecules from breast milk dictate gut microbial growth and survival. Infants also receive distinct, personalized, bacterial exposures leading to differential colonization. Microbial exposures and gut environmental conditions differ between infants in different locations, as does the typical microbial community structure in an infant’s gut. Here we evaluate potential influences on the infant gut microbiota through a longitudinal study on cohorts of breast-fed infants from the neighboring countries of Armenia and Georgia, an area of the world for which the infant microbiomemore » has not been previously investigated. Marker gene sequencing of 16S ribosomal genes revealed that the gut microbial communities of infants from these countries were dominated by bifidobacteria, were different from each other, and were marginally influenced by their mother’s secretor status. Species-level differences in the bifidobacterial communities of each country and birth method were also observed. These community differences suggest that environmental variation between individuals in different locations may influence the gut microbiota of infants.« less

The role of gut microbiota in the regulation of standard metabolic rate in female Periplaneta americana.

PubMed

Ayayee, Paul A; Ondrejech, Andrew; Keeney, George; Muñoz-Garcia, Agustí

2018-01-01

Insect gut microbiota contribute significantly to host nutritional ecology. Disrupting insect gut microbial assemblages impacts nutrient provisioning functions, and can potentially affect host standard metabolic rate (SMR), a measure of host energy balance. In this study, we evaluated the effect of disrupting gut microbial assemblages on the SMR of female Periplaneta americana cockroaches fed dog food (DF, high protein/carbohydrate (p/c) ratio), and cellulose-amended dog food (CADF, 30% dog food, 70% cellulose, low p/c ratio) diets, supplemented with none, low, or high antibiotic doses. Bacterial loads decreased significantly between diet types ( P = 0.04) and across antibiotic doses ( P = 0.04). There was a significant diet type x antibiotic dose interaction on SMR of females on both diets ( P = 0.05) by the end of the seven-day experimental period. In CADF-fed females, SMR decreased linearly with decreasing bacterial load. However, SMR of DF-fed females on the low dose was significantly higher than those in the control and high dose groups. This is interpreted as a diet-dependent response by low dose DF-fed females to the loss of nutritional services provided by gut bacteria. Severe reductions in bacterial load at high doses reduced SMR of females on both diet types. This study provides insights into the potential role of gut bacteria as modulators of host energy expenditure under varying dietary conditions.

Effects of One-Week Empirical Antibiotic Therapy on the Early Development of Gut Microbiota and Metabolites in Preterm Infants.

PubMed

Zhu, Danping; Xiao, Sa; Yu, Jialin; Ai, Qing; He, Yu; Cheng, Chen; Zhang, Yunhui; Pan, Yun

2017-08-14

The early postnatal period is the most dynamic and vulnerable stage in the assembly of intestinal microbiota. Antibiotics are commonly prescribed to newborn preterm babies and are frequently used for a prolonged duration in China. We hypothesized that the prolonged antibiotic therapy would affect the early development of intestinal microbiota and their metabolites. To test this hypothesis, we analyzed the stool microbiota and metabolites in 36 preterm babies with or without antibiotic treatment. These babies were divided into three groups, including two groups treated with the combination of penicillin and moxalactam or piperacillin-tazobactam for 7 days, and the other group was free of antibiotics. Compared to the antibiotic-free group, both antibiotic-treated groups had distinct gut microbial communities and metabolites, including a reduction of bacterial diversity and an enrichment of harmful bacteria such as Streptococcus and Pseudomonas. In addition, there was a significant difference in the composition of gut microbiota and their metabolites between the two antibiotic-treated groups, where the piperacillin-tazobactam treatment group showed an overgrowth of Enterococcus. These findings suggest that prolonged antibiotic therapy affects the early development of gut microbiota in preterm infants, which should be considered when prescribing antibiotics for this population.

Circadian Rhythm Shapes the Gut Microbiota Affecting Host Radiosensitivity.

PubMed

Cui, Ming; Xiao, Huiwen; Luo, Dan; Zhang, Xin; Zhao, Shuyi; Zheng, Qisheng; Li, Yuan; Zhao, Yu; Dong, Jiali; Li, Hang; Wang, Haichao; Fan, Saijun

2016-10-26

Modern lifestyles, such as shift work, nocturnal social activities, and jet lag, disturb the circadian rhythm. The interaction between mammals and the co-evolved intestinal microbiota modulates host physiopathological processes. Radiotherapy is a cornerstone of modern management of malignancies; however, it was previously unknown whether circadian rhythm disorder impairs prognosis after radiotherapy. To investigate the effect of circadian rhythm on radiotherapy, C57BL/6 mice were housed in different dark/light cycles, and their intestinal bacterial compositions were compared using high throughput sequencing. The survival rate, body weight, and food intake of mice in diverse cohorts were measured following irradiation exposure. Finally, the enteric bacterial composition of irradiated mice that experienced different dark/light cycles was assessed using 16S RNA sequencing. Intriguingly, mice housed in aberrant light cycles harbored a reduction of observed intestinal bacterial species and shifts of gut bacterial composition compared with those of the mice kept under 12 h dark/12 h light cycles, resulting in a decrease of host radioresistance. Moreover, the alteration of enteric bacterial composition of mice in different groups was dissimilar. Our findings provide novel insights into the effects of biological clocks on the gut bacterial composition, and underpin that the circadian rhythm influences the prognosis of patients after radiotherapy in a preclinical setting.

Gut Microbiota Linked to Sexual Preference and HIV Infection.

PubMed

Noguera-Julian, Marc; Rocafort, Muntsa; Guillén, Yolanda; Rivera, Javier; Casadellà, Maria; Nowak, Piotr; Hildebrand, Falk; Zeller, Georg; Parera, Mariona; Bellido, Rocío; Rodríguez, Cristina; Carrillo, Jorge; Mothe, Beatriz; Coll, Josep; Bravo, Isabel; Estany, Carla; Herrero, Cristina; Saz, Jorge; Sirera, Guillem; Torrela, Ariadna; Navarro, Jordi; Crespo, Manel; Brander, Christian; Negredo, Eugènia; Blanco, Julià; Guarner, Francisco; Calle, Maria Luz; Bork, Peer; Sönnerborg, Anders; Clotet, Bonaventura; Paredes, Roger

2016-03-01

The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction.

Comparative Gut Microbiomes of Four Species Representing the Higher and the Lower Termites.

PubMed

Su, LiJuan; Yang, LeLe; Huang, Shi; Su, XiaoQuan; Li, Yan; Wang, FengQin; Wang, EnTao; Kang, Ning; Xu, Jian; Song, AnDong

2016-01-01

Aiming at learning the association between the gut microbiota and termites with different diet habits and phylogenetic positions, the gut bacteria of three populations for each of the two higher termites (wood-feeding Mironasutitermes shangchengensis and fungus-feeding Odontotermes formosanus) and two wood-feeding lower termites (Tsaitermes ampliceps and Reticulitermes flaviceps) were analyzed by high-throughput 454 pyrosequencing of 16S V1-V3 amplicons. As results, 132 bacterial genera and some unidentified operational taxonomic units within 29 phyla in the gut bacteria were detected, with Spirochaetes (11-55%), Firmicutes (7-18%), Bacteroidetes (7-31%), and Proteobacteria (8-14%) as the main phyla, and Treponema, TG5, Dysgonomonas, Tannerella, za29, Lactococcus, Pseudomonas, and SJA-88 as the common genera in all the four termites. The diversity of gut bacterial communities in the higher termite guts was significantly greater than that in the lower termites; while the gut microbiota in M. shangchengensis (wood-feeding higher termite) was more similar to those of the wood-feeding lower termites rather than that of O. formosanus (fungus-feeding higher termite), and phylum Spirochaetes and nitrogen-fixing bacteria were super-dominant in the wood-feeding termites, despite of their phylogenetic relations. This study reported for the first time the gut bacterial communities for the termites of M. shangchengensis and T. ampliceps and the comparative analyses showed that the gut microbial communities varied according to the phylogeny and the diet habits of termites. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America.

Comparative analysis of the intestinal bacterial communities in different species of carp by pyrosequencing.

PubMed

Li, Tongtong; Long, Meng; Gatesoupe, François-Joël; Zhang, Qianqian; Li, Aihua; Gong, Xiaoning

2015-01-01

Gut microbiota is increasingly regarded as an integral component of the host, due to important roles in the modulation of the immune system, the proliferation of the intestinal epithelium and the regulation of the dietary energy intake. Understanding the factors that influence the composition of these microbial communities is essential to health management, and the application to aquatic animals still requires basic investigation. In this study, we compared the bacterial communities harboured in the intestines and in the rearing water of grass carp (Ctenopharyngodon idellus), crucian carp (Carassius cuvieri), and bighead carp (Hypophthalmichthys nobilis), by using 454-pyrosequencing with barcoded primers targeting the V4 to V5 regions of the bacterial 16S rRNA gene. The specimens of the three species were cohabiting in the same pond. Between 6,218 and 10,220 effective sequences were read from each sample, resulting in a total of 110,398 sequences for 13 samples from gut microbiota and pond water. In general, the microbial communities of the three carps were dominated by Fusobacteria, Firmicutes, Proteobacteria and Bacteroidetes, but the abundance of each phylum was significantly different between species. At the genus level, the overwhelming group was Cetobacterium (97.29 ± 0.46 %) in crucian carp, while its abundance averaged c. 40 and 60 % of the sequences read in the other two species. There was higher microbial diversity in the gut of filter-feeding bighead carp than the gut of the two other species, with grazing feeding habits. The composition of intestine microbiota of grass carp and crucian carp shared higher similarity when compared with bighead carp. The principal coordinates analysis (PCoA) with the weighted UniFrac distance and the heatmap analysis suggested that gut microbiota was not a simple reflection of the microbial community in the local habitat but resulted from species-specific selective pressures, possibly dependent on behavioural, immune and metabolic characteristics.

Characterizing the gut (Gallus gallus) microbiota following the consumption of an iron biofortified Rwandan cream seeded carioca (Phaseolus Vulgaris L.) bean-based diet.

PubMed

Reed, Spenser; Neuman, Hadar; Glahn, Raymond P; Koren, Omry; Tako, Elad

2017-01-01

Biofortification is a plant breeding method that introduces increased concentrations of minerals in staple food crops (e.g., legumes, cereal grains), and has shown success in alleviating insufficient Fe intake in various human populations. Unlike other strategies utilized to alleviate Fe deficiency, studies of the gut microbiota in the context of Fe biofortification have not yet been reported, although the consumption of Fe biofortified staple food crops has increased significantly over time. Hence, in this study, we performed a 6-week feeding trial in Gallus gallus (n = 14), aimed to investigate the alterations in the gut microbiome following administration of an Fe biofortified bean-based diet (biofortified, BFe) versus a bean based diet with poorly-bioavailable Fe (standard, SFe). Cream seeded carioca bean based diets were designed in an identical fashion to those used in a recent human clinical trial of Fe biofortified beans in Rwanda. We hypothesized that the different dietary Fe contents in the beans based diets will alter the composition and function of the intestinal microbiome. The primary outcomes were changes in the gut microbiome composition and function analyzed by 16S rRNA gene sequencing. We observed no significant changes in phylogenetic diversity between groups. There were significant differences in the composition of the microbiota between groups, with the BFe group harboring fewer taxa participating in bacterial Fe uptake, increased abundance of bacteria involved in phenolic catabolism, and increased abundance of beneficial butyrate-producing bacteria. Additionally, depletion of key bacterial pathways responsible for bacterial viability and Fe uptake suggest that improvements in Fe bioavailability, in addition to increases in Fe-polyphenol and Fe-phytate complexes due to biofortification, led to decreased concentrations of cecal Fe available for bacterial utilization. Our findings demonstrate that Fe biofortification may improve Fe status without negatively altering the structure and function of the gut microbiota, as is observed with other nutritional methods of Fe supplementation. These results may be used to further improve the efficacy and safety of future biofortification efforts in eradicating global Fe deficiency.

Spatial organization of the gastrointestinal microbiota in urban Canada geese

USGS Publications Warehouse

Drovetski, Sergei V.; O'Mahoney, Michael; Ransome, Emma J.; Matterson, Kenan O.; Lim, Haw Chuan; Chesser, Terry; Graves, Gary R.

2018-01-01

Recent reviews identified the reliance on fecal or cloacal samples as a significant limitation hindering our understanding of the avian gastrointestinal (gut) microbiota and its function. We investigated the microbiota of the esophagus, duodenum, cecum, and colon of a wild urban population of Canada goose (Branta canadensis). From a population sample of 30 individuals, we sequenced the V4 region of the 16S SSU rRNA on an Illumina MiSeq and obtained 8,628,751 sequences with a median of 76,529 per sample. These sequences were assigned to 420 bacterial OTUs and a single archaeon. Firmicutes, Proteobacteria, and Bacteroidetes accounted for 90% of all sequences. Microbiotas from the four gut regions differed significantly in their richness, composition, and variability among individuals. Microbial communities of the esophagus were the most distinctive whereas those of the colon were the least distinctive, reflecting the physical downstream mixing of regional microbiotas. The downstream mixing of regional microbiotas was also responsible for the majority of observed co-occurrence patterns among microbial families. Our results indicate that fecal and cloacal samples inadequately represent the complex patterns of richness, composition, and variability of the gut microbiota and obscure patterns of co-occurrence of microbial lineages.

An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

PubMed

Antharam, Vijay C; McEwen, Daniel C; Garrett, Timothy J; Dossey, Aaron T; Li, Eric C; Kozlov, Andrew N; Mesbah, Zhubene; Wang, Gary P

2016-01-01

Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

Overweight and the feline gut microbiome - a pilot study.

PubMed

Kieler, I N; Mølbak, L; Hansen, L L; Hermann-Bank, M L; Bjornvad, C R

2016-06-01

Compared with lean humans, the gut microbiota is altered in the obese. Whether these changes are due to an obesogenic diet, and whether the microbiota contributes to adiposity is currently discussed. In the cat population, where obesity is also prevalent, gut microbiome changes associated with obesity have not been studied. Consequently, the aim of this study was to compare the gut microbiota of lean cats, with that of overweight and obese cats. Seventy-seven rescue-shelter cats housed for ≥3 consecutive days were included in the study. Faecal samples were obtained by rectal swab and, when available, by a paired litter box sample. Body condition was assessed using a 9-point scoring system. DNA was extracted, and the 16S rRNA gene was amplified with a high-throughput quantitative real-time PCR chip. Overweight and obese cats had a significantly different gut microbiota compared to lean cats (p < 0.05), but this finding could not be linked to differences in specific bacterial groups. The rectal samples obtained higher DNA concentration than litter box samples (p < 0.0001). In conclusion, overweight and obese cats seem to have an altered gut microbiome as compared to lean cats. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet.

PubMed

Olson, Christine A; Vuong, Helen E; Yano, Jessica M; Liang, Qingxing Y; Nusbaum, David J; Hsiao, Elaine Y

2018-06-14

The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota and treatment with Akkermansia and Parabacteroides each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum, and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA/glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity, and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice. Copyright © 2018 Elsevier Inc. All rights reserved.

Methodology challenges in studying human gut microbiota - effects of collection, storage, DNA extraction and next generation sequencing technologies.

PubMed

Panek, Marina; Čipčić Paljetak, Hana; Barešić, Anja; Perić, Mihaela; Matijašić, Mario; Lojkić, Ivana; Vranešić Bender, Darija; Krznarić, Željko; Verbanac, Donatella

2018-03-23

The information on microbiota composition in the human gastrointestinal tract predominantly originates from the analyses of human faeces by application of next generation sequencing (NGS). However, the detected composition of the faecal bacterial community can be affected by various factors including experimental design and procedures. This study evaluated the performance of different protocols for collection and storage of faecal samples (native and OMNIgene.GUT system) and bacterial DNA extraction (MP Biomedicals, QIAGEN and MO BIO kits), using two NGS platforms for 16S rRNA gene sequencing (Ilumina MiSeq and Ion Torrent PGM). OMNIgene.GUT proved as a reliable and convenient system for collection and storage of faecal samples although favouring Sutterella genus. MP provided superior DNA yield and quality, MO BIO depleted Gram positive organisms while using QIAGEN with OMNIgene.GUT resulted in greatest variability compared to other two kits. MiSeq and IT platforms in their supplier recommended setups provided comparable reproducibility of donor faecal microbiota. The differences included higher diversity observed with MiSeq and increased capacity of MiSeq to detect Akkermansia muciniphila, [Odoribacteraceae], Erysipelotrichaceae and Ruminococcaceae (primarily Faecalibacterium prausnitzii). The results of our study could assist the investigators using NGS technologies to make informed decisions on appropriate tools for their experimental pipelines.

The Roles of Inflammation, Nutrient Availability and the Commensal Microbiota in Enteric Pathogen Infection.

PubMed

Stecher, Bärbel

2015-06-01

The healthy human intestine is colonized by as many as 1014 bacteria belonging to more than 500 different species forming a microbial ecosystem of unsurpassed diversity, termed the microbiota. The microbiota's various bacterial members engage in a physiological network of cooperation and competition within several layers of complexity. Within the last 10 years, technological progress in the field of next-generation sequencing technologies has tremendously advanced our understanding of the wide variety of physiological and pathological processes that are influenced by the commensal microbiota (1, 2). An increasing number of human disease conditions, such as inflammatory bowel diseases (IBD), type 2 diabetes, obesity, allergies and colorectal cancer are linked with altered microbiota composition (3). Moreover, a clearer picture is emerging of the composition of the human microbiota in healthy individuals, its variability over time and between different persons and how the microbiota is shaped by environmental factors (i.e., diet) and the host's genetic background (4). A general feature of a normal, healthy gut microbiota can generate conditions in the gut that disfavor colonization of enteric pathogens. This is termed colonization-resistance (CR). Upon disturbance of the microbiota, CR can be transiently disrupted, and pathogens can gain the opportunity to grow to high levels. This disruption can be caused by exposure to antibiotics (5, 6), changes in diet (7, 8), application of probiotics and drugs (9), and a variety of diseases (3). Breakdown of CR can boost colonization by intrinsic pathogens or increase susceptibility to infections (10). One consequence of pathogen expansion is the triggering of inflammatory host responses and pathogen-mediated disease. Interestingly, human enteric pathogens are part of a small group of bacterial families that belong to the Proteobacteria: the Enterobacteriaceae (E. coli, Yersinia spp., Salmonella spp., Shigella spp.), the Vibrionaceae (Vibrio cholerae) and the Campylobacteriaceae (Campylobacter spp.). In general, members of these families (be it commensals or pathogens) only constitute a minority of the intestinal microbiota. However, proteobacterial "blooms" are a characteristic trait of an abnormal microbiota such as in the course of antibiotic therapy, dietary changes or inflammation (11). It has become clear that the gut microbiota not only plays a major role in priming and regulating mucosal and systemic immunity, but that the immune system also contributes to host control over microbiota composition. These two ways of mutual communication between the microbiota and the immune system were coined as "outside-in" and "inside-out," respectively (12). The significance of those interactions for human health is particularly evident in Crohn's disease (CD) and Ulcerative Colitis (UC). The symptoms of these recurrent, chronic types of gut inflammation are caused by an excessive immune response against one's own commensal microbiota (13). It is assumed that deregulated immune responses can be caused by a genetic predisposition, leading to, for example, the impairment of intestinal barrier function or disruption of mucosal T-cell homeostasis. In CD or UC patients, an abnormally composed microbiota, referred to as "dysbiosis," is commonly observed (discussed later). This is often characterized by an increased relative abundance of facultative anaerobic bacteria (e.g., Enterobacteriaeceae, Bacilli) and, at the same time, depletion of obligate anaerobic bacteria of the classes Bacteroidia and Clostridia. So far, it is unclear whether dysbiosis is a cause or a consequence of inflammatory bowel disease (IBD). In fact, both scenarios are equally conceivable. Recent work suggests that inflammatory immune responses in the gut (both IBD and pathogen-induced) can alter the gut luminal milieu in a way that favors dysbiosis (14). In this chapter, I present a survey on our current state of understanding of the characteristics and mechanisms underlying gut inflammation-associated dysbiosis. The role of dysbiosis in enteric infections and human IBD is discussed. In addition, I will focus on competition of enteric pathogens and the gut microbiota in the inflamed gut and the role of dysbiotic microbiota alterations (e.g., "Enterobacterial blooms" (11)) for the evolution of pathogenicity.

Human gut microbiome: the second genome of human body.

PubMed

Zhu, Baoli; Wang, Xin; Li, Lanjuan

2010-08-01

The human body is actually a super-organism that is composed of 10 times more microbial cells than our body cells. Metagenomic study of the human microbiome has demonstrated that there are 3.3 million unique genes in human gut, 150 times more genes than our own genome, and the bacterial diversity analysis showed that about 1000 bacterial species are living in our gut and a majority of them belongs to the divisions of Firmicutes and Bacteriodetes. In addition, most people share a core microbiota that comprises 50-100 bacterial species when the frequency of abundance at phylotype level is not considered, and a core microbiome harboring more than 6000 functional gene groups is present in the majority of human gut surveyed till now. Gut bacteria are not only critical for regulating gut metabolism, but also important for host immune system as revealed by animal studies.

Persistent Organic Pollutants Modify Gut Microbiota–Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation

PubMed Central

Zhang, Limin; Nichols, Robert G.; Correll, Jared; Murray, Iain A.; Tanaka, Naoki; Smith, Philip B.; Hubbard, Troy D.; Sebastian, Aswathy; Albert, Istvan; Hatzakis, Emmanuel; Gonzalez, Frank J.; Perdew, Gary H.

2015-01-01

Background Alteration of the gut microbiota through diet and environmental contaminants may disturb physiological homeostasis, leading to various diseases including obesity and type 2 diabetes. Because most exposure to environmentally persistent organic pollutants (POPs) occurs through the diet, the host gastrointestinal tract and commensal gut microbiota are likely to be exposed to POPs. Objectives We examined the effect of 2,3,7,8-tetrachlorodibenzofuran (TCDF), a persistent environmental contaminant, on gut microbiota and host metabolism, and we examined correlations between gut microbiota composition and signaling pathways. Methods Six-week-old male wild-type and Ahr–/– mice on the C57BL/6J background were treated with 24 μg/kg TCDF in the diet for 5 days. We used 16S rRNA gene sequencing, 1H nuclear magnetic resonance (NMR) metabolomics, targeted ultra-performance liquid chromatography coupled with triplequadrupole mass spectrometry, and biochemical assays to determine the microbiota compositions and the physiological and metabolic effects of TCDF. Results Dietary TCDF altered the gut microbiota by shifting the ratio of Firmicutes to Bacteroidetes. TCDF-treated mouse cecal contents were enriched with Butyrivibrio spp. but depleted in Oscillobacter spp. compared with vehicle-treated mice. These changes in the gut microbiota were associated with altered bile acid metabolism. Further, dietary TCDF inhibited the farnesoid X receptor (FXR) signaling pathway, triggered significant inflammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered hepatic lipogenesis, gluconeogenesis, and glycogenolysis in an AHR-dependent manner. Conclusion These findings provide new insights into the biochemical consequences of TCDF exposure involving the alteration of the gut microbiota, modulation of nuclear receptor signaling, and disruption of host metabolism. Citation Zhang L, Nichols RG, Correll J, Murray IA, Tanaka N, Smith PB, Hubbard TD, Sebastian A, Albert I, Hatzakis E, Gonzalez FJ, Perdew GH, Patterson AD. 2015. Persistent organic pollutants modify gut microbiota–host metabolic homeostasis in mice through aryl hydrocarbon receptor activation. Environ Health Perspect 123:679–688; http://dx.doi.org/10.1289/ehp.1409055 PMID:25768209

Ontogenetic Characterization of the Intestinal Microbiota of Channel Catfish through 16S rRNA Gene Sequencing Reveals Insights on Temporal Shifts and the Influence of Environmental Microbes

PubMed Central

Bledsoe, Jacob W.; Peterson, Brian C.; Swanson, Kelly S.; Small, Brian C.

2016-01-01

Aquaculture recently overtook capture fisheries as the largest producer of food fish, but to continue increasing fish production the industry is in search of better methods of improving fish health and growth. Pre- and probiotic supplementation has gained attention as a means of solving these issues, however, for such approaches to be successful, we must first gain a more holistic understanding of the factors influencing the microbial communities present in the intestines of fish. In this study, we characterize the bacterial communities associated with the digestive tract of a highly valuable U.S. aquaculture species, channel catfish Ictalurus punctatus, over the first 193 days of life to evaluate temporal changes that may occur throughout ontogenetic development of the host. Intestinal microbiota were surveyed with high-throughput DNA sequencing of 16S rRNA V4 gene amplicons derived from fish at 3, 65, 125, and 193 days post hatch (dph), while also characterizing the environmental microbes derived from the water supply and the administered diets. Microbial communities inhabiting the intestines of catfish early in life were dynamic, with significant shifts occurring up to 125 dph when the microbiota somewhat stabilized, as shifts were less apparent between 125 to 193 dph. Bacterial phyla present in the gut of catfish throughout ontogeny include Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria; with the species Cetobacterium somerae and Plesiomonas shigelloides showing the highest abundance in the catfish microbiota after 3 dph. Comparisons of the gut microbiota to the environmental microbes reveals that the fish gut is maintained as a niche habitat, separate from the overall microbial communities present in diets and water-supply. Although, there is also evidence that the environmental microbiota serves as an inoculum to the fish gut. Our results have implications for future research related to channel catfish biology and culture, and increase our understanding of ontogenetic effects on the microbiota of teleost fish. PMID:27846300

Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice.

PubMed

De Minicis, Samuele; Rychlicki, Chiara; Agostinelli, Laura; Saccomanno, Stefania; Candelaresi, Cinzia; Trozzi, Luciano; Mingarelli, Eleonora; Facinelli, Bruna; Magi, Gloria; Palmieri, Claudio; Marzioni, Marco; Benedetti, Antonio; Svegliati-Baroni, Gianluca

2014-05-01

Nonalcoholic fatty liver disease (NAFLD) may lead to hepatic fibrosis. Dietary habits affect gut microbiota composition, whereas endotoxins produced by Gram-negative bacteria stimulate hepatic fibrogenesis. However, the mechanisms of action and the potential effect of microbiota in the liver are still unknown. Thus, we sought to analyze whether microbiota may interfere with liver fibrogenesis. Mice fed control (CTRL) or high-fat diet (HFD) were subjected to either bile duct ligation (BDL) or CCl4 treatment. Previously gut-sterilized mice were subjected to microbiota transplantation by oral gavage of cecum content obtained from donor CTRL- or HFD-treated mice. Fibrosis, intestinal permeability, bacterial translocation, and serum endotoxemia were measured. Inflammasome components were evaluated in gut and liver. Microbiota composition (dysbiosis) was evaluated by Pyrosequencing. Fibrosis degree was increased in HFD+BDL versus CTRL+BDL mice, whereas no differences were observed between CTRL+CCl4 and HFD+CCl4 mice. Culture of mesenteric lymph nodes showed higher density of infection in HFD+BDL mice versus CTRL+BDL mice, suggesting higher bacterial translocation rate. Pyrosequencing revealed an increase in percentage of Gram-negative versus Gram-postive bacteria, a reduced ratio between Bacteroidetes and Firmicutes, as well as a dramatic increase of Gram-negative Proteobacteria in HFD+BDL versus CTRL+BDL mice. Inflammasome expression was increased in liver of fibrotic mice, but significantly reduced in gut. Furthermore, microbiota transplantation revealed more liver damage in chimeric mice fed CTRL diet, but receiving the microbiota of HFD-treated mice; liver damage was further enhanced by transplantation of selected Gram-negative bacteria obtained from cecum content of HFD+BDL-treated mice. Dietary habits, by increasing the percentage of intestinal Gram-negative endotoxin producers, may accelerate liver fibrogenesis, introducing dysbiosis as a cofactor contributing to chronic liver injury in NAFLD. © 2014 by the American Association for the Study of Liver Diseases.

Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson's Disease.

PubMed

Caputi, Valentina; Giron, Maria Cecilia

2018-06-06

Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. The highly bidirectional communication between the brain and the gut is markedly influenced by the microbiome through integrated immunological, neuroendocrine and neurological processes. The gut microbiota and its relevant metabolites interact with the host via a series of biochemical and functional inputs, thereby affecting host homeostasis and health. Indeed, a dysregulated microbiota-gut-brain axis in PD might lie at the basis of gastrointestinal dysfunctions which predominantly emerge many years prior to the diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs primarily found in microorganisms and a dysregulation in their signaling may be implicated in α-synucleinopathy, such as PD. An overstimulation of the innate immune system due to gut dysbiosis and/or small intestinal bacterial overgrowth, together with higher intestinal barrier permeability, may provoke local and systemic inflammation as well as enteric neuroglial activation, ultimately triggering the development of alpha-synuclein pathology. In this review, we provide the current knowledge regarding the relationship between the microbiota-gut⁻brain axis and TLRs in PD. A better understanding of the dialogue sustained by the microbiota-gut-brain axis and innate immunity via TLR signaling should bring interesting insights in the pathophysiology of PD and provide novel dietary and/or therapeutic measures aimed at shaping the gut microbiota composition, improving the intestinal epithelial barrier function and balancing the innate immune response in PD patients, in order to influence the early phases of the following neurodegenerative cascade.

The Monoclonal Antitoxin Antibodies (Actoxumab-Bezlotoxumab) Treatment Facilitates Normalization of the Gut Microbiota of Mice with Clostridium difficile Infection.

PubMed

Džunková, Mária; D'Auria, Giuseppe; Xu, Hua; Huang, Jun; Duan, Yinghua; Moya, Andrés; Kelly, Ciarán P; Chen, Xinhua

2016-01-01

Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab-bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials. Although the main mechanism of protection is through direct neutralization of the toxins, the impact of MK-3415A on gut microbiota and its restoration has not been examined. Using a CDI murine model, we compared the bacterial diversity of the gut microbiome of mice under different treatments including MK-3415A, vancomycin, or vancomycin combined with MK-3415A, sampled longitudinally. Here, we showed that C. difficile infection resulted in the prevalence of Enterobacter species. Sixty percent of mice in the vehicle group died after 2 days and their microbiome was almost exclusively formed by Enterobacter . MK-3415A treatment resulted in lower Enterobacter levels and restoration of Blautia, Akkermansia , and Lactobacillus which were the core components of the original microbiota. Vancomycin treatment led to significantly lower survival rate than the combo treatment of MK-3415A and vancomycin. Vancomycin treatment decreased bacterial diversity with predominant Enterobacter and Akkermansia , while Staphylococcus expanded after vancomycin treatment was terminated. In contrast, mice treated by vancomycin combined with MK-3415A also experienced decreased bacterial diversity during vancomycin treatment. However, these animals were able to recover their initial Blautia and Lactobacillus proportions, even though episodes of Staphylococcus overgrowth were detected by the end of the experiments. In conclusion, MK-3415A (actoxumab-bezlotoxumab) treatment facilitates normalization of the gut microbiota in CDI mice. It remains to be examined whether or not the prevention of recurrent CDI by the antitoxin antibodies observed in clinical trials occurs through modulation of microbiota.

Structural modulation of gut microbiota in Bama minipigs in response to treatment with a "growth-promoting agent", salbutamol.

PubMed

Lu, Chenyang; Zhou, Jun; Li, Yanyan; Zhang, Dijun; Wang, Zuzhong; Li, Ye; Cheong, Lingzhi; Zhang, Chundan; Su, Xiurong

2017-07-01

Even though salbutamol (SAL) had remarkable effects on the enhancement of growth rate and carcass composition in different livestock species such as cattle, pigs, sheep and poultry, it was banned as a growth promoter because of its adverse effects on health. However, the specific mechanism by which salbutamol enhances growth efficiency remains unknown. In this study, Bama pigs were randomly allocated to receive salbutamol (5 mg/kg) for 30 or 60 days and were compared with untreated pigs. Pigs treated with salbutamol demonstrated enhanced growth rates and carcass composition; however, they showed deterioration in blood biochemical indices and organ development. We hypothesized that salbutamol exerts its effects by modulating the composition of the gut microbiota population. The faecal microbiome of pigs was characterized via pyrosequencing of the bacterial 16S rRNA gene. The gut microbiota population analysis showed that salbutamol caused shifts in the microbial composition of less abundant species. Redundancy analysis indicated an increase in abundance of the phylum Bacteroidetes, class Betaproteobacteria, family Christensenellaceae and genus Lactobacillus, and a decreased ratio of the phylum Firmicutes, class Clostridia and genera Ruminococcus, Blautia and Subdoligranulum. In conclusion, our study provided circumstantial evidence that the various effects of salbutamol are caused by gut microbiota modulation, and several potential candidates were identified for SAL detection via the gut microbiota. Our findings provided new insights into the roles of the gut microbiota during salbutamol treatment, and these findings will aid in the screening of alternative strategies for animal health improvement and production enhancement.

An exclusive metabolic niche enables strain engraftment in the gut microbiota.

PubMed

Shepherd, Elizabeth Stanley; DeLoache, William C; Pruss, Kali M; Whitaker, Weston R; Sonnenburg, Justin L

2018-05-01

The dense microbial ecosystem in the gut is intimately connected to numerous facets of human biology, and manipulation of the gut microbiota has broad implications for human health. In the absence of profound perturbation, the bacterial strains that reside within an individual are mostly stable over time 1 . By contrast, the fate of exogenous commensal and probiotic strains applied to an established microbiota is variable, generally unpredictable and greatly influenced by the background microbiota 2,3 . Therefore, analysis of the factors that govern strain engraftment and abundance is of critical importance to the emerging field of microbiome reprogramming. Here we generate an exclusive metabolic niche in mice via administration of a marine polysaccharide, porphyran, and an exogenous Bacteroides strain harbouring a rare gene cluster for porphyran utilization. Privileged nutrient access enables reliable engraftment of the exogenous strain at predictable abundances in mice harbouring diverse communities of gut microbes. This targeted dietary support is sufficient to overcome priority exclusion by an isogenic strain 4 , and enables strain replacement. We demonstrate transfer of the 60-kb porphyran utilization locus into a naive strain of Bacteroides, and show finely tuned control of strain abundance in the mouse gut across multiple orders of magnitude by varying porphyran dosage. Finally, we show that this system enables the introduction of a new strain into the colonic crypt ecosystem. These data highlight the influence of nutrient availability in shaping microbiota membership, expand the ability to perform a broad spectrum of investigations in the context of a complex microbiota, and have implications for cell-based therapeutic strategies in the gut.

Gut bacterial microbiota and obesity.

PubMed

Million, M; Lagier, J-C; Yahav, D; Paul, M

2013-04-01

Although probiotics and antibiotics have been used for decades as growth promoters in animals, attention has only recently been drawn to the association between the gut microbiota composition, its manipulation, and obesity. Studies in mice have associated the phylum Firmicutes with obesity and the phylum Bacteroidetes with weight loss. Proposed mechanisms linking the microbiota to fat content and weight include differential effects of bacteria on the efficiency of energy extraction from the diet, and changes in host metabolism of absorbed calories. The independent effect of the microbiota on fat accumulation has been demonstrated in mice, where transplantation of microbiota from obese mice or mice fed western diets to lean or germ-free mice produced fat accumulation among recipients. The microbiota can be manipulated by prebiotics, probiotics, and antibiotics. Probiotics affect the microbiota directly by modulating its bacterial content, and indirectly through bacteriocins produced by the probiotic bacteria. Interestingly, certain probiotics are associated with weight gain both in animals and in humans. The effects are dependent on the probiotic strain, the host, and specific host characteristics, such as age and baseline nutritional status. Attention has recently been drawn to the association between antibiotic use and weight gain in children and adults. We herein review the studies describing the associations between the microbiota composition, its manipulation, and obesity. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Association between Yogurt Consumption and Intestinal Microbiota in Healthy Young Adults Differs by Host Gender

PubMed Central

Suzuki, Yoshio; Ikeda, Keiichi; Sakuma, Kazuhiko; Kawai, Sachio; Sawaki, Keisuke; Asahara, Takashi; Takahashi, Takuya; Tsuji, Hirokazu; Nomoto, Koji; Nagpal, Ravinder; Wang, Chongxin; Nagata, Satoru; Yamashiro, Yuichiro

2017-01-01

Human intestinal microbiota are influenced by various factors viz. diet, environment, age, gender, geographical, and socioeconomic situation, etc. among which diet has the most profound impact. However, studies investigating this impact have mostly included subjects from diverse geographic/socioeconomic backgrounds and hence the precise effects of dietary factors on gut microbiota composition remain largely confounded. Herein, with an aim to evaluate the association between dietary habits, specifically yogurt consumption, and the gut microbiota in healthy young adults sharing similar age, lifestyle routine, geographical setting, etc., we conducted a cross-sectional study wherein 293 collegiate freshmen answered a questionnaire about their frequency of yogurt consumption over the last 2 months and provided stool specimens for microbiota analysis. Fecal microbiota were analyzed by highly sensitive reverse-transcription-quantitative-PCR assays targeting bacterial 16S rRNA molecules. Fecal organic acids were measured by HPLC. Overall, the gut microbiota were predominated (97.1 ± 8.6%) by Clostridium coccoides group, Clostridium leptum subgroup, Bacteroides fragilis group, Bifidobacterium and Atopobium cluster. Interestingly, after adjusting the data for yogurt consumption, females were found to have higher total bacterial (P = 0.013) and Bifidobacterium (P = 0.046) count and fecal pH (P = 0.007) and lower fecal concentration of total organic acids (P = 0.030), succinic acid (P = 0.007) and formic acid (P = 0.046) as compared to males. Altogether, yogurt consumption showed positive linear association with Lactobacillus and Lactobacillus gasseri subgroup in both male and female subjects; however, several gender-specific disparities were also detected in this yogurt-microbiota association. Yogurt consumption demonstrated a negative association with L. sakei subgroup, Enterobacteriaceae and Staphylococcus in males but shared a positive association with L. casei subgroup and succinic acid in female subjects. The study manifests the association between yogurt consumption and gut microbiota in a healthy homogeneous cohort and show how this association can differ by host gender. The findings should be helpful for prospective studies investigating the diet–microbiome interaction in human health and disease. PMID:28553274

Human Catestatin Alters Gut Microbiota Composition in Mice

PubMed Central

Rabbi, Mohammad F.; Munyaka, Peris M.; Eissa, Nour; Metz-Boutigue, Marie-Hélène; Khafipour, Ehsan; Ghia, Jean Eric

2017-01-01

The mammalian intestinal tract is heavily colonized with a dense, complex, and diversified microbial populations. In healthy individuals, an array of epithelial antimicrobial agents is secreted in the gut to aid intestinal homeostasis. Enterochromaffin cells (EC) in the intestinal epithelium are a major source of chromogranin A (CgA), which is a pro-hormone and can be cleaved into many bioactive peptides that include catestatin (CST). This study was carried out to evaluate the possible impact of CST on gut microbiota in vivo using a mouse model. The CST (Human CgA352−372) or normal saline was intrarectally administered in C57BL/6 male mice for 6 days and then sacrificed. Feces and colonic mucosa tissue samples were collected, DNA was extracted, the V4 region of bacterial 16S rRNA gene was amplified and subjected to MiSeq Illumina sequencing. The α-diversity was calculated using Chao 1 and β-diversity was determined using QIIME. Differences at the genus level were determined using partial least square discriminant analysis (PLS-DA). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict functional capacity of bacterial community. CST treatment did not modify bacterial richness in fecal and colonic mucosa-associated microbiota; however, treatment significantly modified bacterial community composition between the groups. Also, CST-treated mice had a significantly lower relative abundance of Firmicutes and higher abundance of Bacteroidetes, observed only in fecal samples. However, at lower phylogenetic levels, PLS-DA analysis revealed that some bacterial taxa were significantly associated with the CST-treated mice in both fecal and colonic mucosa samples. In addition, differences in predicted microbial functional pathways in both fecal and colonic mucosa samples were detected. The results support the hypothesis that CST treatment modulates gut microbiota composition under non-pathophysiological conditions, however, the result of this study needs to be further validated in a larger experiment. The data may open new avenues for the development of a potential new line of antimicrobial peptides and their use as therapeutic agents to treat several inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), or other health conditions. PMID:28144234

Social status shapes the bacterial and fungal gut communities of the honey bee.

PubMed

Yun, Ji-Hyun; Jung, Mi-Ja; Kim, Pil Soo; Bae, Jin-Woo

2018-01-31

Despite the fungal abundance in honey and bee bread, little is known about the fungal gut community of the honey bee and its effect on host fitness. Using pyrosequencing of the 16S rRNA gene and ITS2 region amplicons, we analysed the bacterial and fungal gut communities of the honey bee as affected by the host social status. Both communities were significantly affected by the host social status. The bacterial gut community was similar to those characterised in previous studies. The fungal gut communities of most worker bees were highly dominated by Saccharomyces but foraging bees and queens were colonised by diverse fungal species and Zygosaccharomyces, respectively. The high fungal density and positive correlation between Saccharomyces species and Lactobacillus species, known yeast antagonists, were only observed in the nurse bee; this suggested that the conflict between Saccharomyces and Lactobacillus was compromised by the metabolism of the host and/or other gut microbes. PICRUSt analysis revealed significant differences in enriched gene clusters of the bacterial gut communities of the nurse and foraging bees, suggesting that different host social status might induce changes in the gut microbiota, and, that consequently, gut microbial community shifts to adapt to the gut environment.

Acute exposure to PBDEs at an environmentally realistic concentration causes abrupt changes in the gut microbiota and host health of zebrafish.

PubMed

Chen, Lianguo; Hu, Chenyan; Lok-Shun Lai, Nelson; Zhang, Weipeng; Hua, Jianghuan; Lam, Paul K S; Lam, James C W; Zhou, Bingsheng

2018-05-02

Contamination from lower brominated PBDEs is ubiquitous in the environments. However, their effects on gut microbiota and intestinal health have not yet been investigated. This study exposed adult zebrafish to an environmentally realistic concentration of pentaBDE mixture (DE-71) at 5.0 ng/L for 7 days, after which metagenomic sequencing of the intestinal microbiome was conducted and host physiological activities in the intestine and liver were also examined. The results showed that acute exposure to DE-71 significantly shifted the gut microbial community in a sex-specific manner. Certain genera (e.g., Mycoplasma, Ruminiclostridium, unclassified Firmicutes sensu stricto, and Fusobacterium) disappeared from the DE-71-exposed intestines, resulting in decreased bacterial diversity. Bacterial metabolic functions in guts were also affected by DE-71, namely those covering energy metabolism, virulence, respiration, cell division, cell signaling, and stress response. In addition, measurement of diverse sensitive biomarkers showed that the health of male intestines was remarkably compromised by the DE-71 exposure, as indicated by the disruption to its neural signaling (serotonin), epithelial barrier integrity (tight junction protein 2), inflammatory response (interleukin 1β), oxidative stress and antioxidant capacity, as well as detoxifying potential (ethoxyresorufin-O-deethylase activity). However, female intestines maintained intact physiological activities. Compared to the direct impact on intestines, a latent effect of DE-71 was observed in livers. Co-occurrence network analysis demonstrated that the gut bacteria vigorously interacted to establish the fittest community under DE-71 stress by promoting the reproduction of favorable genera, while diminishing the survival of unfavorable ones. Significant correlations between the zebrafish gut microbiota and physiological activities (e.g., oxidative stress, detoxification, neurotransmission, and epithelial integrity) were also observed. Overall, this study has demonstrated, for the first time, the high susceptibility of gut microbiota and intestinal health of zebrafish to DE-71, thus warranting more work to reveal its mode of toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Changes in the composition of the human fecal microbiome following bacteriotherapy for recurrent Clostridium difficile-associated diarrhea

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

Khoruts, A.; Dicksved, J.; Jansson, J.K.

CDAD is the major known cause of antibiotic-induced diarrhea and colitis, and the disease is thought to result from persistent disruption of commensal gut microbiota. Bacteriotherapy by way of fecal transplantation can be used to treat recurrent CDAD and is thought to re-establish the normal colonic microflora. However, limitations of conventional microbiologic techniques have until recently precluded testing of this idea. In this study we used T-RFLP and 16S rRNA gene sequencing approaches to characterize the bacterial composition of the colonic microflora in a patient suffering from recurrent CDAD, before and after treatment by fecal transplantation from a healthy donor.more » While the patient's residual colonic microbiota, prior to therapy, was deficient in members of the bacterial divisions-Firmicutes and Bacteriodetes, transplantation had a dramatic impact on the composition of the patient's gut microbiota. By 14 days post transplantation, the fecal bacterial composition of the recipient was highly similar to the donor and was dominated by Bacteroides spp. strains and an uncharacterized butyrate producing bacterium. The change in bacterial composition was accompanied by resolution of the patient's symptoms. The striking similarity of the recipient's and donor's intestinal microbiota following bacteriotherapy suggests that the donor's bacteria quickly occupied their requisite niches, resulting in restoration of both the structure and function of the microbial communities present.« less

Bacterial infection causes stress-induced memory dysfunction in mice.

PubMed

Gareau, Mélanie G; Wine, Eytan; Rodrigues, David M; Cho, Joon Ho; Whary, Mark T; Philpott, Dana J; Macqueen, Glenda; Sherman, Philip M

2011-03-01

The brain-gut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established. To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation. Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated. No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota. The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.

Identifying the core microbial community in the gut of fungus-growing termites.

PubMed

Otani, Saria; Mikaelyan, Aram; Nobre, Tânia; Hansen, Lars H; Koné, N'Golo A; Sørensen, Søren J; Aanen, Duur K; Boomsma, Jacobus J; Brune, Andreas; Poulsen, Michael

2014-09-01

Gut microbes play a crucial role in decomposing lignocellulose to fuel termite societies, with protists in the lower termites and prokaryotes in the higher termites providing these services. However, a single basal subfamily of the higher termites, the Macrotermitinae, also domesticated a plant biomass-degrading fungus (Termitomyces), and how this symbiont acquisition has affected the fungus-growing termite gut microbiota has remained unclear. The objective of our study was to compare the intestinal bacterial communities of five genera (nine species) of fungus-growing termites to establish whether or not an ancestral core microbiota has been maintained and characterizes extant lineages. Using 454-pyrosequencing of the 16S rRNA gene, we show that gut communities have representatives of 26 bacterial phyla and are dominated by Firmicutes, Bacteroidetes, Spirochaetes, Proteobacteria and Synergistetes. A set of 42 genus-level taxa was present in all termite species and accounted for 56-68% of the species-specific reads. Gut communities of termites from the same genus were more similar than distantly related species, suggesting that phylogenetic ancestry matters, possibly in connection with specific termite genus-level ecological niches. Finally, we show that gut communities of fungus-growing termites are similar to cockroaches, both at the bacterial phylum level and in a comparison of the core Macrotermitinae taxa abundances with representative cockroach, lower termite and higher nonfungus-growing termites. These results suggest that the obligate association with Termitomyces has forced the bacterial gut communities of the fungus-growing termites towards a relatively uniform composition with higher similarity to their omnivorous relatives than to more closely related termites. © 2014 John Wiley & Sons Ltd.

Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study

PubMed Central

2013-01-01

Background A recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1 diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level. Methods A case-control study was carried out with 16 children with type 1 diabetes and 16 healthy children. The fecal bacteria composition was investigated by polymerase chain reaction-denaturing gradient gel electrophoresis and real-time quantitative polymerase chain reaction. Results The mean similarity index was 47.39% for the healthy children and 37.56% for the children with diabetes, whereas the intergroup similarity index was 26.69%. In the children with diabetes, the bacterial number of Actinobacteria and Firmicutes, and the Firmicutes to Bacteroidetes ratio were all significantly decreased, with the quantity of Bacteroidetes significantly increased with respect to healthy children. At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes. We also found that the number of Bifidobacterium and Lactobacillus, and the Firmicutes to Bacteroidetes ratio correlated negatively and significantly with the plasma glucose level while the quantity of Clostridium correlated positively and significantly with the plasma glucose level in the diabetes group. Conclusions This is the first study showing that type 1 diabetes is associated with compositional changes in gut microbiota. The significant differences in the number of Bifidobacterium, Lactobacillus and Clostridium and in the Firmicutes to Bacteroidetes ratio observed between the two groups could be related to the glycemic level in the group with diabetes. Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children. These findings could be useful for developing strategies to control the development of type 1 diabetes by modifying the gut microbiota. PMID:23433344

Molecular analysis of microbiota along the digestive tract of juvenile Atlantic salmon (Salmo salar L.).

PubMed

Navarrete, P; Espejo, R T; Romero, J

2009-04-01

Dominant bacterial microbiota of the gut of juvenile farmed Atlantic salmon was investigated using a combination of molecular approaches. Bacterial community composition from the stomach, the pyloric caeca, and the intestine was assessed by extracting DNA directly from each gut compartment. Temporal temperature gradient gel electrophoresis (TTGE) analysis of 16S ribosomal DNA (rDNA) amplicons showed very similar bacterial compositions throughout the digestive tract. Band sequencing revealed a narrow diversity of species with a dominance of Pseudomonas in the three compartments. However, cloning revealed more diversity among the Pseudomonas sequences. To confirm these results, we analyzed the bacterial community by amplifying the variable 16S-23S rDNA intergenic spacer region (ITS). Similar ITS profiles were observed among gastrointestinal compartments of salmon, confirming the TTGE results. Moreover, the dominant ITS band at 650 bp, identified as Pseudomonas, was observed in the ITS profile from fish collected in two seasons (July 2003 and 2004). In contrast, aerobic culture analysis revealed Shewanella spp. as the most prevalent isolate. This discrepancy was resolved by evaluating 16S rDNA and ITS polymerase chain reaction amplification efficiency from both Shewanella and Pseudomonas isolates. Very similar efficiencies were observed in the two bacteria. Hence, this discrepancy may be explained by preferential cultivation of Shewanella spp. under the experimental conditions. Also, we included analyses of pelleted feed and the water influent to explore environmental influences on the bacterial composition of the gut microbiota. Overall, these results indicate a homogeneous composition of the bacterial community composition along the gastrointestinal tract of reared juvenile salmon. This community is mainly composed of Pseudomonas spp., which could be derived from water influent and may be selectively associated with salmon in this hatchery.

Sex differences in gut microbiota in patients with major depressive disorder.

PubMed

Chen, Jian-Jun; Zheng, Peng; Liu, Yi-Yun; Zhong, Xiao-Gang; Wang, Hai-Yang; Guo, Yu-Jie; Xie, Peng

2018-01-01

Our previous studies found that disturbances in gut microbiota might have a causative role in the onset of major depressive disorder (MDD). The aim of this study was to investigate whether there were sex differences in gut microbiota in patients with MDD. First-episode drug-naïve MDD patients and healthy controls were included. 16S rRNA gene sequences extracted from the fecal samples of the included subjects were analyzed. Principal-coordinate analysis and partial least squares-discriminant analysis were used to assess whether there were sex-specific gut microbiota. A random forest algorithm was used to identify the differential operational taxonomic units. Linear discriminant-analysis effect size was further used to identify the dominant sex-specific phylotypes responsible for the differences between MDD patients and healthy controls. In total, 57 and 74 differential operational taxonomic units responsible for separating female and male MDD patients from their healthy counterparts were identified. Compared with their healthy counterparts, increased Actinobacteria and decreased Bacteroidetes levels were found in female and male MDD patients, respectively. The most differentially abundant bacterial taxa in female and male MDD patients belonged to phyla Actinobacteria and Bacteroidia, respectively. Meanwhile, female and male MDD patients had different dominant phylotypes. These results demonstrated that there were sex differences in gut microbiota in patients with MDD. The suitability of Actinobacteria and Bacteroidia as the sex-specific biomarkers for diagnosing MDD should be further explored.

Mucosal Interactions between Genetics, Diet, and Microbiome in Inflammatory Bowel Disease

PubMed Central

Basson, Abigail; Trotter, Ashley; Rodriguez-Palacios, Alex; Cominelli, Fabio

2016-01-01

Numerous reviews have discussed gut microbiota composition changes during inflammatory bowel diseases (IBD), particularly Crohn’s disease (CD). However, most studies address the observed effects by focusing on studying the univariate connection between disease and dietary-induced alterations to gut microbiota composition. The possibility that these effects may reflect a number of other interconnected (i.e., pantropic) mechanisms, activated in parallel, particularly concerning various bacterial metabolites, is in the process of being elucidated. Progress seems, however, hampered by various difficult-to-study factors interacting at the mucosal level. Here, we highlight some of such factors that merit consideration, namely: (1) the contribution of host genetics and diet in altering gut microbiome, and in turn, the crosstalk among secondary metabolic pathways; (2) the interdependence between the amount of dietary fat, the fatty acid composition, the effects of timing and route of administration on gut microbiota community, and the impact of microbiota-derived fatty acids; (3) the effect of diet on bile acid composition, and the modulator role of bile acids on the gut microbiota; (4) the impact of endogenous and exogenous intestinal micronutrients and metabolites; and (5) the need to consider food associated toxins and chemicals, which can introduce confounding immune modulating elements (e.g., antioxidant and phytochemicals in oils and proteins). These concepts, which are not mutually exclusive, are herein illustrated paying special emphasis on physiologically inter-related processes. PMID:27531998

Microencapsulated Bifidobacterium longum subsp. infantis ATCC 15697 Favorably Modulates Gut Microbiota and Reduces Circulating Endotoxins in F344 Rats

PubMed Central

Saha, Shyamali; Prakash, Satya

2014-01-01

The gut microbiota is a bacterial bioreactor whose composition is an asset for human health. However, circulating gut microbiota derived endotoxins cause metabolic endotoxemia, promoting metabolic and liver diseases. This study investigates the potential of orally delivered microencapsulated Bifidobacterium infantis ATCC 15697 to modulate the gut microbiota and reduce endotoxemia in F344 rats. The rats were gavaged daily with saline or microencapsulated B. infantis ATCC 15697. Following 38 days of supplementation, the treated rats showed a significant (P < 0.05) increase in fecal Bifidobacteria (4.34 ± 0.46 versus 2.45 ± 0.25% of total) and B. infantis (0.28 ± 0.21 versus 0.52 ± 0.12 % of total) and a significant (P < 0.05) decrease in fecal Enterobacteriaceae (0.80 ± 0.45 versus 2.83 ± 0.63% of total) compared to the saline control. In addition, supplementation with the probiotic formulation reduced fecal (10.52 ± 0.18 versus 11.29 ± 0.16 EU/mg; P = 0.01) and serum (0.33 ± 0.015 versus 0.30 ± 0.015 EU/mL; P = 0.25) endotoxins. Thus, microencapsulated B. infantis ATCC 15697 modulates the gut microbiota and reduces colonic and serum endotoxins. Future preclinical studies should investigate the potential of the novel probiotic formulation in metabolic and liver diseases. PMID:24967382

Visualization of Microbiota in Tick Guts by Whole-mount In Situ Hybridization.

PubMed

Moss, Caitlin E; Robson, Andrew; Fikrig, Erol; Narasimhan, Sukanya

2018-06-01

Infectious diseases transmitted by arthropod vectors continue to pose a significant threat to human health worldwide. The pathogens causing these diseases, do not exist in isolation when they colonize the vector; rather, they likely engage in interactions with resident microorganisms in the gut lumen. The vector microbiota has been demonstrated to play an important role in pathogen transmission for several vector-borne diseases. Whether resident bacteria in the gut of the Ixodes scapularis tick, the vector of several human pathogens including Borrelia burgdorferi, influence tick transmission of pathogens is not determined. We require methods for characterizing the composition of the bacteria associated with the tick gut to facilitate a better understanding of potential interspecies interactions in the tick gut. Using whole-mount in situ hybridization to visualize RNA transcripts associated with particular bacterial species allows for the collection of qualitative data regarding the abundance and distribution of the microbiota in intact tissue. This technique can be used to examine changes in the gut microbiota milieu over the course of tick feeding and can also be applied to analyze expression of tick genes. Staining of whole tick guts yield information about the gross spatial distribution of target RNA in the tissue without the need for three-dimensional reconstruction and is less affected by environmental contamination, which often confounds the sequencing-based methods frequently used to study complex microbial communities. Overall, this technique is a valuable tool that can be used to better understand vector-pathogen-microbiota interactions and their role in disease transmission.

Disentangling metabolic functions of bacteria in the honey bee gut

PubMed Central

Ellegaard, Kirsten M.; Troilo, Michaël; Sauer, Uwe

2017-01-01

It is presently unclear how much individual community members contribute to the overall metabolic output of a gut microbiota. To address this question, we used the honey bee, which harbors a relatively simple and remarkably conserved gut microbiota with striking parallels to the mammalian system and importance for bee health. Using untargeted metabolomics, we profiled metabolic changes in gnotobiotic bees that were colonized with the complete microbiota reconstituted from cultured strains. We then determined the contribution of individual community members in mono-colonized bees and recapitulated our findings using in vitro cultures. Our results show that the honey bee gut microbiota utilizes a wide range of pollen-derived substrates, including flavonoids and outer pollen wall components, suggesting a key role for degradation of recalcitrant secondary plant metabolites and pollen digestion. In turn, multiple species were responsible for the accumulation of organic acids and aromatic compound degradation intermediates. Moreover, a specific gut symbiont, Bifidobacterium asteroides, stimulated the production of host hormones known to impact bee development. While we found evidence for cross-feeding interactions, approximately 80% of the identified metabolic changes were also observed in mono-colonized bees, with Lactobacilli being responsible for the largest share of the metabolic output. These results show that, despite prolonged evolutionary associations, honey bee gut bacteria can independently establish and metabolize a wide range of compounds in the gut. Our study reveals diverse bacterial functions that are likely to contribute to bee health and provide fundamental insights into how metabolic activities are partitioned within gut communities. PMID:29232373

Disentangling metabolic functions of bacteria in the honey bee gut.

PubMed

Kešnerová, Lucie; Mars, Ruben A T; Ellegaard, Kirsten M; Troilo, Michaël; Sauer, Uwe; Engel, Philipp

2017-12-01

It is presently unclear how much individual community members contribute to the overall metabolic output of a gut microbiota. To address this question, we used the honey bee, which harbors a relatively simple and remarkably conserved gut microbiota with striking parallels to the mammalian system and importance for bee health. Using untargeted metabolomics, we profiled metabolic changes in gnotobiotic bees that were colonized with the complete microbiota reconstituted from cultured strains. We then determined the contribution of individual community members in mono-colonized bees and recapitulated our findings using in vitro cultures. Our results show that the honey bee gut microbiota utilizes a wide range of pollen-derived substrates, including flavonoids and outer pollen wall components, suggesting a key role for degradation of recalcitrant secondary plant metabolites and pollen digestion. In turn, multiple species were responsible for the accumulation of organic acids and aromatic compound degradation intermediates. Moreover, a specific gut symbiont, Bifidobacterium asteroides, stimulated the production of host hormones known to impact bee development. While we found evidence for cross-feeding interactions, approximately 80% of the identified metabolic changes were also observed in mono-colonized bees, with Lactobacilli being responsible for the largest share of the metabolic output. These results show that, despite prolonged evolutionary associations, honey bee gut bacteria can independently establish and metabolize a wide range of compounds in the gut. Our study reveals diverse bacterial functions that are likely to contribute to bee health and provide fundamental insights into how metabolic activities are partitioned within gut communities.

Gut Microbiota Contributes to the Growth of Fast-Growing Transgenic Common Carp (Cyprinus carpio L.)

PubMed Central

Xie, Shouqi; Hu, Wei; Yu, Yuhe; Hu, Zihua

2013-01-01

Gut microbiota has shown tight and coordinated connection with various functions of its host such as metabolism, immunity, energy utilization, and health maintenance. To gain insight into whether gut microbes affect the metabolism of fish, we employed fast-growing transgenic common carp (Cyprinus carpio L.) to study the connections between its large body feature and gut microbes. Metagenome-based fingerprinting and high-throughput sequencing on bacterial 16S rRNA genes indicated that fish gut was dominated by Proteobacteria, Fusobacteria, Bacteroidetes and Firmicutes, which displayed significant differences between transgenic fish and wild-type controls. Analyses to study the association of gut microbes with the fish metabolism discovered three major phyla having significant relationships with the host metabolic factors. Biochemical and histological analyses indicated transgenic fish had increased carbohydrate but decreased lipid metabolisms. Additionally, transgenic fish has a significantly lower Bacteroidetes:Firmicutes ratio than that of wild-type controls, which is similar to mammals between obese and lean individuals. These findings suggest that gut microbiotas are associated with the growth of fast growing transgenic fish, and the relative abundance of Firmicutes over Bacteroidetes could be one of the factors contributing to its fast growth. Since the large body size of transgenic fish displays a proportional body growth, which is unlike obesity in human, the results together with the findings from others also suggest that the link between obesity and gut microbiota is likely more complex than a simple Bacteroidetes:Firmicutes ratio change. PMID:23741344

Oral Administration of Live Exopolysaccharide-Producing Pediococcus parvulus, but Not Purified Exopolysaccharide, Suppressed Enterobacteriaceae without Affecting Bacterial Diversity in Ceca of Mice

PubMed Central

Xu, Jie; Öste, Rickard; Holst, Olle; Molin, Göran

2013-01-01

Growing evidence indicates that the gut microbiota could have an important role in the development of diet- and lifestyle-induced diseases. It has been shown that modulation of the gut microbiota by means of probiotics and prebiotics could improve host health. An oat-based product fermented by the exopolysaccharide (EPS)-producing organism Pediococcus parvulus 2.6 has been reported to have a bifidogenic effect. To find out whether the effect could be attributed to the EPS or the bacterium, mice were fed a diet supplemented with 2% purified EPS or 108 CFU/g of live P. parvulus 2.6 for 6 weeks. Both supplementations altered the gut microbiota composition but in different directions. Purified EPS not only significantly lowered the microbial diversity (P < 0.001) but decreased the bifidobacterial population (P = 0.01). In contrast, the live EPS-producing bacterium P. parvulus 2.6 antagonized Enterobacteriaceae without disturbing the homeostasis of the cecal microbiota. PMID:23770909

N-Acetyl-Cysteine Alleviates Gut Dysbiosis and Glucose Metabolic Disorder in High-Fat Diet-Induced Mice.

PubMed

Zheng, Junping; Yuan, Xubing; Zhang, Chen; Jia, Peiyuan; Jiao, Siming; Zhao, Xiaoming; Yin, Heng; Du, Yuguang; Liu, Hongtao

2018-05-30

N-acetyl cysteine (NAC), an anti-oxidative reagent for clinical diseases, shows potential application to diabetes and other metabolic diseases. However, it is unknown how NAC modulates the gut microbiota of mice with metabolic syndrome. In present study, we aim to demonstrate the preventive effect of NAC on intestinal dysbiosis and glucose metabolic disorder. C57BL/6J mice were fed with normal chow diet (NCD), NCD plus NAC, high-fat diet (HFD) or HFD plus NAC for five months. After the treatment, the glucose level, circulating endotoxin and metabolism-related key proteins were determined. The fecal samples were analyzed by 16S rRNA sequencing. A novel analysis was carried out to predict the functional changes of gut microbiota. In addition, Spearman's correlation between metabolic biomarkers and bacterial abundance was also assayed. The results show that NAC treatment significantly reversed the glucose intolerance, fasting glucose level, body weight and plasma endotoxin in HFD-fed mice. Further, NAC upregulated the levels of Occludin protein and mucin glycoproteins in proximal colons of HFD-treated mice. Noticeably, NAC promoted the growth of beneficial bacteria such as Akkermansia, Bifidobacterium, Lactobacillus and Allobaculum, and hampered the population of diabetes-related genera including Desulfovibrio and Blautia. Also, NAC may influence the metabolic pathways of intestinal bacteria including lipopolysaccharide biosynthesis, oxidative stress and bacterial motility. Finally, the modified gut microbiota showed close association with the metabolic changes of the NAC treated HFD-fed mice. In summary, NAC may be a potential drug to prevent glucose metabolic disturbance by reshaping the structure of gut microbiota. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Host-microbiota interactions within the fish intestinal ecosystem.

PubMed

Pérez, T; Balcázar, J L; Ruiz-Zarzuela, I; Halaihel, N; Vendrell, D; de Blas, I; Múzquiz, J L

2010-07-01

Teleost fish are in direct contact with the aquatic environment, and are therefore in continual contact with a complex and dynamic microbiota, some of which may have implications for health. Mucosal surfaces represent the main sites in which environmental antigens and intestinal microbiota interact with the host. Thus, the gut-associated lymphoid tissues (GALT) must develop mechanisms to discriminate between pathogenic and commensal microorganisms. Colonization of intestinal mucosal surfaces with a normal microbiota has a positive effect on immune regulatory functions of the gut, and disturbance in these immune regulatory functions by an imbalanced microbiota may contribute to the development of diseases. Significant attention has therefore been recently focused on the role of probiotics in the induction or restoration of a disturbed microbiota to its normal beneficial composition. Given this, this article explores the fascinating relationship between the fish immune system and the bacteria that are present in its intestinal microbiota, focusing on the bacterial effect on the development of certain immune responses.

A common core microbiota between obese individuals and their lean relatives? Evaluation of the predisposition to obesity on the basis of the fecal microflora profile.

PubMed

Elli, M; Colombo, O; Tagliabue, A

2010-10-01

Obesity represents a crucial social problem in developed countries as a cause of multiple metabolic abnormalities. The exact etiology of this multifactorial disease is still unknown. The impact of dietary habits and lifestyle is currently under investigation but the role of other predisposing factors, such as genetic determinants and familial history, needs still to be elucidated. Significant alterations in the composition of the intestinal microbiota have been recently identified in obese mice, suggesting an involvement of gut microbes in obesity. In humans, obese subjects are supposed to have a more efficient flora in energy extraction from food, due to the detection of quantitative differences in the major bacterial groups in obese subjects compared to lean ones. Despite these observations, the homologies in gut microbiota between obese adults and their lean relatives have never been investigated in details. Few reports about the detection of common microbial profiles between members of the same family have been published in the past but only one recent scientific article, investigating the presence of a common core microbiota between obese and lean twins, correlates genetic background and gut microflora as significant variables in obesity. The hypothesis suggested herein is that the identification of a familial-specific core microbiota could be precious in order to identify key-bacterial groups to be used as biomarkers for the evaluation of predisposition to obesity. Copyright 2010 Elsevier Ltd. All rights reserved.

Fructose: A Dietary Sugar in Crosstalk with Microbiota Contributing to the Development and Progression of Non-Alcoholic Liver Disease

PubMed Central

Lambertz, Jessica; Weiskirchen, Sabine; Landert, Silvano; Weiskirchen, Ralf

2017-01-01

Fructose is one of the key dietary catalysts in the development of non-alcoholic fatty liver disease (NAFLD). NAFLD comprises a complex disease spectrum, including steatosis (fatty liver), non-alcoholic steatohepatitis, hepatocyte injury, inflammation, and fibrosis. It is also the hepatic manifestation of the metabolic syndrome, which covers abdominal obesity, insulin resistance, dyslipidemia, glucose intolerance, or type 2 diabetes mellitus. Commensal bacteria modulate the host immune system, protect against exogenous pathogens, and are gatekeepers in intestinal barrier function and maturation. Dysbalanced intestinal microbiota composition influences a variety of NAFLD-associated clinical conditions. Conversely, nutritional supplementation with probiotics and preobiotics impacting composition of gut microbiota can improve the outcome of NAFLD. In crosstalk with the host immune system, the gut microbiota is able to modulate inflammation, insulin resistance, and intestinal permeability. Moreover, the composition of microbiota of an individual is a kind of fingerprint highly influenced by diet. In addition, not only the microbiota itself but also its metabolites influence the metabolism and host immune system. The gut microbiota can produce vitamins and a variety of nutrients including short-chain fatty acids. Holding a healthy balance of the microbiota is therefore highly important. In the present review, we discuss the impact of long-term intake of fructose on the composition of the intestinal microbiota and its biological consequences in regard to liver homeostasis and disease. In particular, we will refer about fructose-induced alterations of the tight junction proteins affecting the gut permeability, leading to the translocation of bacteria and bacterial endotoxins into the blood circulation. PMID:28970836

The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment

PubMed Central

Barfod, Kenneth Klingenberg; Vrankx, Katleen; Mirsepasi-Lauridsen, Hengameh Chloé; Hansen, Jitka Stilund; Hougaard, Karin Sørig; Larsen, Søren Thor; Ouwenhand, Arthur C.; Krogfelt, Karen Angeliki

2015-01-01

Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases. PMID:26668669

The gut microbiome as a virtual endocrine organ with implications for farm and domestic animal endocrinology.

PubMed

O'Callaghan, T F; Ross, R P; Stanton, C; Clarke, G

2016-07-01

The gut microbiome exerts a marked influence on host physiology, and manipulation of its composition has repeatedly been shown to influence host metabolism and body composition. This virtual endocrine organ also has a role in the regulation of the plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Control over the hypothalamic-pituitary-adrenal axis also appears to be under the influence of the gut microbiota. This is clear from studies in microbiota-deficient germ-free animals with exaggerated responses to psychological stress that can be normalized by monocolonization with certain bacterial species including Bifidobacterium infantis. Therapeutic targeting of the gut microbiota may thus be useful in treating or preventing stress-related microbiome-gut-brain axis disorders and metabolic diseases, much the same way as redirections of metabolopathies can be achieved through more traditional endocrine hormone-based interventions. Moreover, the implications of these findings need to be considered in the context of farm and domestic animal physiology, behavior, and food safety. Copyright © 2016 Elsevier Inc. All rights reserved.

Intestinal alkaline phosphatase: novel functions and protective effects.

PubMed

Lallès, Jean-Paul

2014-02-01

Important protective roles of intestinal alkaline phosphatase (IAP)--including regulation of intestinal surface pH, absorption of lipids, detoxification of free nucleotides and bacterial lipopolysaccharide, attenuation of intestinal inflammation, and possible modulation of the gut microbiota--have been reviewed recently. IAP is modulated by numerous nutritional factors. The present review highlights new findings on the properties of IAP and extends the list of its protective functions. Critical assessment of data suggests that some IAP properties are a direct result of dephosphorylation of proinflammatory moieties, while others (e.g., gut barrier protection and microbiota shaping) may be secondary to IAP-mediated downregulation of inflammation. IAP and tissue-nonspecific alkaline phosphatase isoforms characterize the small intestine and the colon, respectively. Gastrointestinal administration of exogenous IAP ameliorates gut inflammation and favors gut tissue regeneration, whereas enteral and systemic IAP administration attenuates systemic inflammation only. Finally, the IAP gene family has a strong evolutionary link to food-driven changes in gastrointestinal tract anatomy and microbiota composition. Therefore, stimulation of IAP activity by dietary intervention is a goal for preserving gut homeostasis and health by minimizing low-grade inflammation. © 2013 International Life Sciences Institute.

Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction.

PubMed

Catry, Emilie; Bindels, Laure B; Tailleux, Anne; Lestavel, Sophie; Neyrinck, Audrey M; Goossens, Jean-François; Lobysheva, Irina; Plovier, Hubert; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Bouzin, Caroline; Pachikian, Barbara D; Cani, Patrice D; Staels, Bart; Dessy, Chantal; Delzenne, Nathalie M

2018-02-01

To investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction. We examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe -/- ) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days. Mesenteric and carotid arteries were isolated to evaluate endothelium-dependent relaxation ex vivo. Caecal microbiota composition (Illumina Sequencing of the 16S rRNA gene) and key pathways/mediators involved in the control of vascular function, including bile acid (BA) profiling, gut and liver key gene expression, nitric oxide and gut hormones production were also assessed. ITF supplementation totally reverses endothelial dysfunction in mesenteric and carotid arteries of n-3 PUFA-depleted Apoe -/- mice via activation of the nitric oxide (NO) synthase/NO pathway. Gut microbiota changes induced by prebiotic treatment consist in increased NO-producing bacteria, replenishment of abundance in Akkermansia and decreased abundance in bacterial taxa involved in secondary BA synthesis. Changes in gut and liver gene expression also occur upon ITFs suggesting increased glucagon-like peptide 1 production and BA turnover as drivers of endothelium function preservation. We demonstrate for the first time that ITF improve endothelial dysfunction, implicating a short-term adaptation of both gut microbiota and key gut peptides. If confirmed in humans, prebiotics could be proposed as a novel approach in the prevention of metabolic disorders-related cardiovascular diseases. 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/.

Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs

PubMed Central

Honneffer, Julia B; Minamoto, Yasushi; Suchodolski, Jan S

2014-01-01

The intestinal microbiota is the collection of the living microorganisms (bacteria, fungi, protozoa, and viruses) inhabiting the gastrointestinal tract. Novel bacterial identification approaches have revealed that the gastrointestinal microbiota of dogs and cats is, similarly to humans, a highly complex ecosystem. Studies in dogs and cats have demonstrated that acute and chronic gastrointestinal diseases, including inflammatory bowel disease (IBD), are associated with alterations in the small intestinal and fecal microbial communities. Of interest is that these alterations are generally similar to the dysbiosis observed in humans with IBD or animal models of intestinal inflammation, suggesting that microbial responses to inflammatory conditions of the gut are conserved across mammalian host types. Studies have also revealed possible underlying susceptibilities in the innate immune system of dogs and cats with IBD, which further demonstrate the intricate relationship between gut microbiota and host health. Commonly identified microbiome changes in IBD are decreases in bacterial groups within the phyla Firmicutes and Bacteroidetes, and increases within Proteobacteia. Furthermore, a reduction in the diversity of Clostridium clusters XIVa and IV (i.e., Lachnospiraceae and Clostridium coccoides subgroups) are associated with IBD, suggesting that these bacterial groups may play an important role in maintenance of gastrointestinal health. Future studies are warranted to evaluate the functional changes associated with intestinal dysbiosis in dogs and cats. PMID:25469017

The Composition of Human Milk and Infant Faecal Microbiota Over the First Three Months of Life: A Pilot Study

PubMed Central

Murphy, Kiera; Curley, David; O’Callaghan, Tom F.; O’Shea, Carol-Anne; Dempsey, Eugene M.; O’Toole, Paul W.; Ross, R. Paul; Ryan, C. Anthony; Stanton, Catherine

2017-01-01

Human milk contains a diverse array of bioactives and is also a source of bacteria for the developing infant gut. The aim of this study was to characterize the bacterial communities in human milk and infant faeces over the first 3 months of life, in 10 mother-infant pairs. The presence of viable Bifidobacterium and Lactobacillus in human milk was also evaluated. MiSeq sequencing revealed a large diversity of the human milk microbiota, identifying over 207 bacterial genera in milk samples. The phyla Proteobacteria and Firmicutes and the genera Pseudomonas, Staphylococcus and Streptococcus were the predominant bacterial groups. A core of 12 genera represented 81% of the microbiota relative abundance in milk samples at week 1, 3 and 6, decreasing to 73% at week 12. Genera shared between infant faeces and human milk samples accounted for 70–88% of the total relative abundance in infant faecal samples, supporting the hypothesis of vertical transfer of bacteria from milk to the infant gut. In addition, identical strains of Bifidobacterium breve and Lactobacillus plantarum were isolated from the milk and faeces of one mother-infant pair. Vertical transfer of bacteria via breastfeeding may contribute to the initial establishment of the microbiota in the developing infant intestine. PMID:28094284

Microbiota, a key player in alcoholic liver disease.

PubMed

Cassard, Anne-Marie; Ciocan, Dragos

2017-12-22

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. Only 20% of heavy alcohol consumers develop alcoholic liver cirrhosis. The intestinal microbiota (IM) has been recently identified as a key player in the severity of liver injury in ALD. Common features of ALD include a decrease of gut epithelial tight junction protein expression, mucin production, and antimicrobial peptide levels. This disruption of the gut barrier, which is a prerequisite for ALD, leads to the passage of bacterial products into the blood stream (endotoxemia). Moreover, metabolites produced by bacteria, such as short chain fatty acids, volatile organic compounds (VOS), and bile acids (BA), are involved in ALD pathology. Probiotic treatment, IM transplantation, or the consumption of dietary fiber, such as pectin, which all alter the ratio of bacterial species, have been shown to improve liver injury in animal models of ALD and to be associated with an improvement in gut barrier function. Although the connections between the microbiota and the host in ALD are well established, the underlying mechanisms are still an active area of research. Targeting the microbiome through the use of prebiotic, probiotic, and postbiotic modalities could be an attractive new approach to manage ALD.

The bamboo-eating giant panda harbors a carnivore-like gut microbiota, with excessive seasonal variations.

PubMed

Xue, Zhengsheng; Zhang, Wenping; Wang, Linghua; Hou, Rong; Zhang, Menghui; Fei, Lisong; Zhang, Xiaojun; Huang, He; Bridgewater, Laura C; Jiang, Yi; Jiang, Chenglin; Zhao, Liping; Pang, Xiaoyan; Zhang, Zhihe

2015-05-19

The giant panda evolved from omnivorous bears. It lives on a bamboo-dominated diet at present, but it still retains a typical carnivorous digestive system and is genetically deficient in cellulose-digesting enzymes. To find out whether this endangered mammalian species, like other herbivores, has successfully developed a gut microbiota adapted to its fiber-rich diet, we conducted a 16S rRNA gene-based large-scale structural profiling of the giant panda fecal microbiota. Forty-five captive individuals were sampled in spring, summer, and late autumn within 1 year. Significant intraindividual variations in the diversity and structure of gut microbiota across seasons were observed in this population, which were even greater than the variations between individuals. Compared with published data sets involving 124 gut microbiota profiles from 54 mammalian species, these giant pandas, together with 9 captive and 7 wild individuals investigated previously, showed extremely low gut microbiota diversity and an overall structure that diverged from those of nonpanda herbivores but converged with those of carnivorous and omnivorous bears. The giant panda did not harbor putative cellulose-degrading phylotypes such as Ruminococcaceae and Bacteroides bacteria that are typically enriched in other herbivores, but instead, its microbiota was dominated by Escherichia/Shigella and Streptococcus bacteria. Members of the class Clostridia were common and abundant in the giant panda gut microbiota, but most of the members present were absent in other herbivores and were not phylogenetically related with known cellulolytic lineages. Therefore, the giant panda appears not to have evolved a gut microbiota compatible with its newly adopted diet, which may adversely influence the coevolutionary fitness of this herbivore. The giant panda, an endangered mammalian species endemic to western China, is well known for its unique bamboo diet. Unlike other herbivores that have successfully evolved anatomically specialized digestive systems to efficiently deconstruct fibrous plant matter, the giant panda still retains a gastrointestinal tract typical of carnivores. We characterized the fecal bacterial communities from a giant panda population to determine whether this animal relies on its symbiotic gut microbiota to cope with the complex carbohydrates that dominate its diet, as is common in other herbivores. We found that the giant panda gut microbiota is low in diversity and highly variable across seasons. It also shows an overall composition typical of bears and entirely differentiated from other herbivores, with low levels of putative cellulose-digesting bacteria. The gut microbiota of this herbivore, therefore, may not have well adapted to its highly fibrous diet, suggesting a potential link with its poor digestive efficiency. Copyright © 2015 Xue et al.

Analysis of Gut Microbiota in Patients with Parkinson's Disease.

PubMed

Petrov, V A; Saltykova, I V; Zhukova, I A; Alifirova, V M; Zhukova, N G; Dorofeeva, Yu B; Tyakht, A V; Kovarsky, B A; Alekseev, D G; Kostryukova, E S; Mironova, Yu S; Izhboldina, O P; Nikitina, M A; Perevozchikova, T V; Fait, E A; Babenko, V V; Vakhitova, M T; Govorun, V M; Sazonov, A E

2017-04-01

Gut microbiota of patients with Parkinson's disease and healthy volunteers was analyzed by the method of high throughput 16S rRNA sequencing of bacterial genomes. In patients with Parkinson's diseases, changes in the content of 9 genera and 15 species of microorganisms were revealed: reduced content of Dorea, Bacteroides, Prevotella, Faecalibacterium, Bacteroides massiliensis, Stoquefichus massiliensis, Bacteroides coprocola, Blautia glucerasea, Dorea longicatena, Bacteroides dorei, Bacteroides plebeus, Prevotella copri, Coprococcus eutactus, and Ruminococcus callidus, and increased content of Christensenella, Catabacter, Lactobacillus, Oscillospira, Bifidobacterium, Christensenella minuta, Catabacter hongkongensis, Lactobacillus mucosae, Ruminococcus bromii, and Papillibacter cinnamivorans. This microbiological pattern of gut microflora can trigger local inflammation followed by aggregation of α-synuclein and generation of Lewy bodies.

Gut microbiota in patients with Parkinson's disease in southern China.

PubMed

Lin, Aiqun; Zheng, Wenxia; He, Yan; Tang, Wenli; Wei, Xiaobo; He, Rongni; Huang, Wei; Su, Yuying; Huang, Yaowei; Zhou, Hongwei; Xie, Huifang

2018-05-16

Accumulating evidence has revealed alterations in the communication between the gut and brain in patients with Parkinson's disease (PD), and previous studies have confirmed that alterations in the gut microbiome play an important role in the pathogenesis of numerous diseases, including PD. The aim of this study was to determine whether the faecal microbiome of PD patients in southern China differs from that of control subjects and whether the gut microbiome composition alters among different PD motor phenotypes. We compared the gut microbiota composition of 75 patients with PD and 45 age-matched controls using 16S rRNA next-generation-sequencing. We observed significant increases in the abundance of four bacterial families and significant decreases in the abundance of seventeen bacterial families in patients with PD compared to those of the controls. In particular, the abundance of Lachnospiraceae was reduced by 42.9% in patients with PD, whereas Bifidobacteriaceae was enriched in patients with PD. We did not identify a significant difference in the overall microbial composition among different PD motor phenotypes, but we identified the association between specific taxas and different PD motor phenotypes. PD is accompanied by alterations in the abundance of specific gut microbes. The abundance of certain gut microbes was altered depending on clinical motor phenotypes. Based on our findings, the gut microbiome may be a potential PD biomarker. Copyright © 2018 Elsevier Ltd. All rights reserved.

Safety Evaluation of Neo Transgenic Pigs by Studying Changes in Gut Microbiota Using High-Throughput Sequencing Technology

PubMed Central

Jiang, Shengwang; Cai, Chunbo; Ma, Dezun; Gao, Pengfei; Li, Hegang; Jiang, Ke; Tang, Maoxue; Hou, Jian; Liu, Jie; Cui, Wentao

2016-01-01

The neo (neomycin phosphotransferase) gene is widely used as a selection marker in the production of genetically engineered animals and plants. Recent attention has been focused on safety concerns regarding neo transgene expression. In this study, neo transgenic and non-transgenic piglets were randomly assigned into Group A and Group B to evaluate effects of neo transgene by studying changes in gut microbiota using high-throughput sequencing. Group A pigs were fed a standard diet supplemented with antibiotic neomycin; Group B pigs were fed a standard diet. We examined horizontal transfer of exogenous neo gene using multiplex PCR; and investigated if the presence of secreted NPT II (neo expression product) in the intestine could lead to some protection against neomycin in transgenic pigs by monitoring different patterns of changes in gut microbiota in Group A animals. The unintended effects of neo transgene on gut microbiota were studied in Group B animals. Horizontal gene transfer was not detected in gut microbiota of any transgenic pigs. In Group A, a significant difference was observed between transgenic pigs and non-transgenic pigs in pattern of changes in Proteobacteria populations in fecal samples during and post neomycin feeding. In Group B, there were significant differences in the relative abundance of phyla Firmicutes, Bacteroidetes and Proteobacteria, and genera Lactobacillus and Escherichia-Shigella-Hafnia between transgenic pigs and non-transgenic pigs. We speculate that the secretion of NPT II from transgenic tissues/cells into gut microbiota results in the inhibition of neomycin activity and the different patterns of changes in bacterial populations. Furthermore, the neo gene also leads to unintended effects on gut microbiota in transgenic pigs that were fed with basic diet (not supplemented with neomycin). Thus, our data in this study caution that wide use of the neo transgene in genetically engineered animals should be carefully considered and fully assessed. PMID:26966911

Probiotics in prevention and treatment of obesity: a critical view.

PubMed

Kobyliak, Nazarii; Conte, Caterina; Cammarota, Giovanni; Haley, Andreana P; Styriak, Igor; Gaspar, Ludovit; Fusek, Jozef; Rodrigo, Luis; Kruzliak, Peter

2016-01-01

The worldwide prevalence of obesity more than doubled between 1980 and 2014. The obesity pandemic is tightly linked to an increase in energy availability, sedentariness and greater control of ambient temperature that have paralleled the socioeconomic development of the past decades. The most frequent cause which leads to the obesity development is a dysbalance between energy intake and energy expenditure. The gut microbiota as an environmental factor which influence whole-body metabolism by affecting energy balance but also inflammation and gut barrier function, integrate peripheral and central food intake regulatory signals and thereby increase body weight. Probiotics have physiologic functions that contribute to the health of gut microbiota, can affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community.

Fungal microbiota dysbiosis in IBD

PubMed Central

Sokol, Harry; Leducq, Valentin; Aschard, Hugues; Pham, Hang-Phuong; Jegou, Sarah; Landman, Cecilia; Cohen, David; Liguori, Giuseppina; Bourrier, Anne; Nion-Larmurier, Isabelle; Cosnes, Jacques; Seksik, Philippe; Langella, Philippe; Skurnik, David; Richard, Mathias L; Beaugerie, Laurent

2017-01-01

Objective The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Design Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. Results We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Conclusions Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis. PMID:26843508

Active migration is associated with specific and consistent changes to gut microbiota in Calidris shorebirds.

PubMed

Risely, Alice; Waite, David W; Ujvari, Beata; Hoye, Bethany J; Klaassen, Marcel

2018-03-01

Gut microbes are increasingly recognised for their role in regulating an animal's metabolism and immunity. However, identifying repeatable associations between host physiological processes and their gut microbiota has proved challenging, in part because microbial communities often respond stochastically to host physiological stress (e.g. fasting, forced exercise or infection). Migratory birds provide a valuable system in which to test host-microbe interactions under physiological extremes because these hosts are adapted to predictable metabolic and immunological challenges as they undergo seasonal migrations, including temporary gut atrophy during long-distance flights. These physiological challenges may either temporarily disrupt gut microbial ecosystems, or, alternatively, promote predictable host-microbe associations during migration. To determine the relationship between migration and gut microbiota, we compared gut microbiota composition between migrating and non-migrating ("resident") conspecific shorebirds sharing a flock. We performed this across two sandpiper species, Calidris ferruginea and Calidris ruficollis, in north-western Australia, and an additional C. ruficollis population 3,000 km away in southern Australia. We found that migrants consistently had higher abundances of the bacterial genus Corynebacterium (average 28% abundance) compared to conspecific residents (average <1% abundance), with this effect holding across both species and sites. However, other than this specific association, community structure and diversity was almost identical between migrants and residents, with migration status accounting for only 1% of gut community variation when excluding Corynebacterium. Our findings suggest a consistent relationship between Corynebacterium and Calidris shorebirds during migration, with further research required to identify causal mechanisms behind the association, and to elucidate functionality to the host. However, outside this specific association, migrating shorebirds broadly maintained gut community structure, which may allow them to quickly recover gut function after a migratory flight. This study provides a rare example of a repeatable and specific response of the gut microbiota to a major physiological challenge across two species and two distant populations. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Disrupted progression of the intestinal microbiota with age in children with cystic fibrosis.

PubMed

Nielsen, Shaun; Needham, Bronwen; Leach, Steven T; Day, Andrew S; Jaffe, Adam; Thomas, Torsten; Ooi, Chee Y

2016-05-04

Cystic fibrosis (CF) is a genetic disorder that leads to formation of thick epithelial secretions in affected organs. Chronic microbial infections associated with thick mucus secretions are the hallmarks of lung disease in CF. Despite similar conditions existing in the gastrointestinal tract, it is much less studied. We therefore examined the microbial communities within the gastrointestinal tract of children with and without CF (either pancreatic sufficient or insufficient) across a range of childhood ages (0.87-17 years). We observed a substantial reduction in the richness and diversity of gut bacteria associated with CF from early childhood (2 years) until late adolescence (17 years). A number of bacteria that establish themselves in the gut of healthy children were unable to do so in children with CF. In contrast, a few bacteria dominated the gut microbiota in children with CF and are unlikely to be beneficial for the metabolic function of the gut. A functioning pancreas (pancreatic sufficient) under a CF lifestyle showed little effect on microbial communities. Our results argue that any attempts to rectify the loss of bacterial diversity and provide normal bacterial function in the gut of CF patients should be conducted no later than early childhood.

Functional metagenomic profiling of intestinal microbiome in extreme ageing

PubMed Central

Rampelli, Simone; Candela, Marco; Turroni, Silvia; Biagi, Elena; Collino, Sebastiano; Franceschi, Claudio; O'Toole, Paul W; Brigidi, Patrizia

2013-01-01

Age-related alterations in human gut microbiota composition have been thoroughly described, but a detailed functional description of the intestinal bacterial coding capacity is still missing. In order to elucidate the contribution of the gut metagenome to the complex mosaic of human longevity, we applied shotgun sequencing to total fecal bacterial DNA in a selection of samples belonging to a well-characterized human ageing cohort. The age-related trajectory of the human gut microbiome was characterized by loss of genes for shortchain fatty acid production and an overall decrease in the saccharolytic potential, while proteolytic functions were more abundant than in the intestinal metagenome of younger adults. This altered functional profile was associated with a relevant enrichment in “pathobionts”, i.e. opportunistic pro-inflammatory bacteria generally present in the adult gut ecosystem in low numbers. Finally, as a signature for long life we identified 116 microbial genes that significantly correlated with ageing. Collectively, our data emphasize the relationship between intestinal bacteria and human metabolism, by detailing the modifications in the gut microbiota as a consequence of and/or promoter of the physiological changes occurring in the human host upon ageing. PMID:24334635

Dynamic In Vitro Models of the Human Gastrointestinal Tract as Relevant Tools to Assess the Survival of Probiotic Strains and Their Interactions with Gut Microbiota

PubMed Central

Cordonnier, Charlotte; Thévenot, Jonathan; Etienne-Mesmin, Lucie; Denis, Sylvain; Alric, Monique; Livrelli, Valérie; Blanquet-Diot, Stéphanie

2015-01-01

The beneficial effects of probiotics are conditioned by their survival during passage through the human gastrointestinal tract and their ability to favorably influence gut microbiota. The main objective of this study was to use dynamic in vitro models of the human digestive tract to investigate the effect of fasted or fed state on the survival kinetics of the new probiotic Saccharomyces cerevisiae strain CNCM I-3856 and to assess its influence on intestinal microbiota composition and activity. The probiotic yeast showed a high survival rate in the upper gastrointestinal tract whatever the route of admistration, i.e., within a glass of water or a Western-type meal. S. cerevisiae CNCM I-3856 was more sensitive to colonic conditions, as the strain was not able to colonize within the bioreactor despite a twice daily administration. The main bacterial populations of the gut microbiota, as well as the production of short chain fatty acids were not influenced by the probiotic treatment. However, the effect of the probiotic on the gut microbiota was found to be individual dependent. This study shows that dynamic in vitro models can be advantageously used to provide useful insight into the behavior of probiotic strains in the human digestive environment. PMID:27682114

Molecular analysis of the gut microbiota of identical twins with Crohn's disease

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

Jansson, Janet; Dicksved, Johan; Halfvarson, Jonas

2008-03-14

Increasing evidence suggests that a combination of host genetics and the composition of the gut microbiota are important for development of Crohn's disease (CD). Our aim was to study identical twins with CD to determine microbial factors independently of host genetics. Fecal samples were studied from 10 monozygotic twin pairs with CD (discordant n=6, concordant n=4) and 8 healthy twin pairs. DNA was extracted, 16S rRNA genes were PCR amplified and T-RFLP fingerprints generated using general bacterial and Bacteroides group specific primers. The microbial communities were also profiled based on their % G+C contents. Bacteroides 16S rRNA genes were clonedmore » and sequenced from a subset of the samples. The bacterial diversity in each sample and similarity indices between samples were estimated based on the T-RFLP data using a combination of statistical approaches. Healthy individuals had a significantly higher bacterial diversity compared to individuals with CD. The fecal microbial communities were more similar between healthy twins than between twins with CD, especially when these were discordant for the disease. The microbial community profiles of individuals with ileal CD were significantly different from healthy individuals and those with colonic CD. Also, CD individuals had a lower relative abundance of B. uniformis and higher relative abundances of B. ovatus and B. vulgatus. Our results suggest that genetics and/or environmental exposure during childhood in part determine the gut microbial composition. However, CD is associated with dramatic changes in the gut microbiota and this was particularly evident for individuals with ileal CD.« less

Unveiling the gut microbiota composition and functionality associated with constipation through metagenomic analyses.

PubMed

Mancabelli, Leonardo; Milani, Christian; Lugli, Gabriele Andrea; Turroni, Francesca; Mangifesta, Marta; Viappiani, Alice; Ticinesi, Andrea; Nouvenne, Antonio; Meschi, Tiziana; van Sinderen, Douwe; Ventura, Marco

2017-08-29

Functional constipation (FC) is a gastrointestinal disorder with a high prevalence among the general population. The precise causes of FC are still unknown and are most likely multifactorial. Growing evidence indicates that alterations of gut microbiota composition contribute to constipation symptoms. Nevertheless, many discrepancies exist in literature and no clear link between FC and gut microbiota composition has as yet been identified. In this study, we performed 16 S rRNA-based microbial profiling analysis of 147 stool samples from 68 FC individuals and compared their microbial profiles with those of 79 healthy subjects (HS). Notably, the gut microbiota of FC individuals was shown to be depleted of members belonging to Bacteroides, Roseburia and Coprococcus 3. Furthermore, the metabolic capabilities of the gut microbiomes of five FC and five HS individuals were evaluated through shotgun metagenomics using a MiSeq platform, indicating that HS are enriched in pathways involved in carbohydrate, fatty acid and lipid metabolism as compared to FC. In contrast, the microbiomes corresponding to FC were shown to exhibit high abundance of genes involved in hydrogen production, methanogenesis and glycerol degradation. The identified differences in bacterial composition and metabolic capabilities may play an important role in development of FC symptoms.

Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 reduces bacterial translocation in rats treated with carbon tetrachloride

PubMed Central

Sánchez, Elisabet; Nieto, Juan C.; Vidal, Silvia; Santiago, Alba; Martinez, Xavier; Sancho, Francesc J.; Sancho-Bru, Pau; Mirelis, Beatriz; Corominola, Helena; Juárez, Candido; Manichanh, Chaysavanh; Guarner, Carlos; Soriano, German

2017-01-01

Probiotics can prevent pathological bacterial translocation by modulating intestinal microbiota and improving the gut barrier. The aim was to evaluate the effect of a fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 on bacterial translocation in rats with carbon tetrachloride (CCl4)-induced cirrhosis. Sprague-Dawley rats treated with CCl4 were randomized into a probiotic group that received fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 in drinking water or a water group that received water only. Laparotomy was performed one week after ascites development. We evaluated bacterial translocation, intestinal microbiota, the intestinal barrier and cytokines in mesenteric lymph nodes and serum. Bacterial translocation decreased and gut dysbiosis improved in the probiotic group compared to the water group. The ileal β-defensin-1 concentration was higher and ileal malondialdehyde levels were lower in the probiotic group than in water group. There were no differences between groups in serum cytokines but TNF-α levels in mesenteric lymph nodes were lower in the probiotic group than in the water group. Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 decreases bacterial translocation, gut dysbiosis and ileal oxidative damage and increases ileal β-defensin-1 expression in rats treated with CCl4, suggesting an improvement in the intestinal barrier integrity. PMID:28368023

The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease.

PubMed

Torres, J; Palmela, C; Brito, H; Bao, X; Ruiqi, H; Moura-Santos, P; Pereira da Silva, J; Oliveira, A; Vieira, C; Perez, K; Itzkowitz, S H; Colombel, J F; Humbert, L; Rainteau, D; Cravo, M; Rodrigues, C M; Hu, J

2018-02-01

Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients.

PubMed

Xu, Kai-Yu; Xia, Geng-Hong; Lu, Jun-Qi; Chen, Mu-Xuan; Zhen, Xin; Wang, Shan; You, Chao; Nie, Jing; Zhou, Hong-Wei; Yin, Jia

2017-05-03

Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions. CKD patients had higher percentages of opportunistic pathogens from gamma-Proteobacteria and reduced percentages of beneficial microbes, such as Roseburia, Coprococcus, and Ruminococcaceae. The PICRUSt analysis demonstrated that eight genes involved in choline, betaine, L-carnitine and trimethylamine (TMA) metabolism were changed in the CKD patients. Moreover, we transferred faecal samples from CKD patients and healthy controls into antibiotic-treated C57BL/6 mice and found that the mice that received gut microbes from the CKD patients had significantly higher plasma TMAO levels and different composition of gut microbiota than did the comparative mouse group. Our present study demonstrated that CKD patients had increased plasma TMAO levels due to contributions from both impaired renal functions and dysbiosis of the gut microbiota.

Ability of the gut microbiota to produce PUFA-derived bacterial metabolites: Proof of concept in germ-free versus conventionalized mice.

PubMed

Druart, Céline; Bindels, Laure B; Schmaltz, Robert; Neyrinck, Audrey M; Cani, Patrice D; Walter, Jens; Ramer-Tait, Amanda E; Delzenne, Nathalie M

2015-08-01

The gut microbiota is able to modulate host physiology through the production of bioactive metabolites. Our recent studies suggest that changes in gut microbiota composition upon prebiotics supplementation alter tissue levels of PUFA-derived metabolites in mice. However, in vivo evidence that gut microbes produces PUFA-derived metabolites is lacking. This study aimed to decipher the contribution of gut microbes versus that of the host in PUFA-derived metabolite production. To achieve this goal, we compared the proportion of PUFA-derived metabolites and the expression of fatty acid desaturases in germ-free (GF) and conventionalized (CONV) mice fed either a low fat or Western diet. Higher concentrations of PUFA-derived metabolites were found in the colonic contents of conventionalized mice (CONV) mice compared to GF mice. The abundance of these metabolites in host tissues was modulated by dietary treatments but not by microbial status. Although microbial status did significantly influence desaturase expression, no correlations between host enzymes and tissue PUFA-derived metabolite levels were observed. Together, these results highlight the ability of the gut microbiota to produce PUFA-derived metabolites from dietary PUFA. However, microbial production of these metabolites in colonic contents is not necessarily associated with modifications of their concentration in host tissues. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation.

PubMed

Bates, Jennifer M; Mittge, Erika; Kuhlman, Julie; Baden, Katrina N; Cheesman, Sarah E; Guillemin, Karen

2006-09-15

All animals exist in intimate associations with microorganisms that play important roles in the hosts' normal development and tissue physiology. In vertebrates, the most populous and complex community of microbes resides in the digestive tract. Here, we describe the establishment of the gut microbiota and its role in digestive tract differentiation in the zebrafish model vertebrate, Danio rerio. We find that in the absence of the microbiota, the gut epithelium is arrested in aspects of its differentiation, as revealed by the lack of brush border intestinal alkaline phosphatase activity, the maintenance of immature patterns of glycan expression and a paucity of goblet and enteroendocrine cells. In addition, germ-free intestines fail to take up protein macromolecules in the distal intestine and exhibit faster motility. Reintroduction of a complex microbiota at later stages of development or mono-association of germ-free larvae with individual constituents of the microbiota reverses all of these germ-free phenotypes. Exposure of germ-free zebrafish to heat-killed preparations of the microbiota or bacterial lipopolysaccharide is sufficient to restore alkaline phosphatase activity but not mature patterns of Gal alpha1,3Gal containing glycans, indicating that the host perceives and responds to its associated microbiota by at least two distinct pathways.

Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift

PubMed Central

Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”. PMID:24098410

Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift.

PubMed

Ren, Zhigang; Cui, Guangying; Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the "gut-liver axis".

The abundance and variety of carbohydrate-active enzymes in the human gut microbiota.

PubMed

El Kaoutari, Abdessamad; Armougom, Fabrice; Gordon, Jeffrey I; Raoult, Didier; Henrissat, Bernard

2013-07-01

Descriptions of the microbial communities that live on and in the human body have progressed at a spectacular rate over the past 5 years, fuelled primarily by highly parallel DNA-sequencing technologies and associated advances in bioinformatics, and by the expectation that understanding how to manipulate the structure and functions of our microbiota will allow us to affect health and prevent or treat diseases. Among the myriad of genes that have been identified in the human gut microbiome, those that encode carbohydrate-active enzymes (CAZymes) are of particular interest, as these enzymes are required to digest most of our complex repertoire of dietary polysaccharides. In this Analysis article, we examine the carbohydrate-digestive capacity of a simplified but representative mini-microbiome in order to highlight the abundance and variety of bacterial CAZymes that are represented in the human gut microbiota.

Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla

PubMed Central

Mahowald, Michael A.; Rey, Federico E.; Seedorf, Henning; Turnbaugh, Peter J.; Fulton, Robert S.; Wollam, Aye; Shah, Neha; Wang, Chunyan; Magrini, Vincent; Wilson, Richard K.; Cantarel, Brandi L.; Coutinho, Pedro M.; Henrissat, Bernard; Crock, Lara W.; Russell, Alison; Verberkmoes, Nathan C.; Hettich, Robert L.; Gordon, Jeffrey I.

2009-01-01

The adult human distal gut microbial community is typically dominated by 2 bacterial phyla (divisions), the Firmicutes and the Bacteroidetes. Little is known about the factors that govern the interactions between their members. Here, we examine the niches of representatives of both phyla in vivo. Finished genome sequences were generated from Eubacterium rectale and E. eligens, which belong to Clostridium Cluster XIVa, one of the most common gut Firmicute clades. Comparison of these and 25 other gut Firmicutes and Bacteroidetes indicated that the Firmicutes possess smaller genomes and a disproportionately smaller number of glycan-degrading enzymes. Germ-free mice were then colonized with E. rectale and/or a prominent human gut Bacteroidetes, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling, high-resolution proteomic analysis, and biochemical assays of microbial–microbial and microbial–host interactions. B. thetaiotaomicron adapts to E. rectale by up-regulating expression of a variety of polysaccharide utilization loci encoding numerous glycoside hydrolases, and by signaling the host to produce mucosal glycans that it, but not E. rectale, can access. E. rectale adapts to B. thetaiotaomicron by decreasing production of its glycan-degrading enzymes, increasing expression of selected amino acid and sugar transporters, and facilitating glycolysis by reducing levels of NADH, in part via generation of butyrate from acetate, which in turn is used by the gut epithelium. This simplified model of the human gut microbiota illustrates niche specialization and functional redundancy within members of its major bacterial phyla, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability. PMID:19321416

Susceptibility and tolerance of human gut culturable aerobic microbiota to wine polyphenols.

PubMed

Cueva, Carolina; Bartolomé, Begoña; Moreno-Arribas, M Victoria; Bustos, Irene; Requena, Teresa; González-Manzano, Susana; Santos-Buelga, Celestino; Turrientes, María-Carmen; del Campo, Rosa

2015-02-01

Diet is one of the main factors that could affect quantitatively and qualitatively the stability of the gut microbiota. Polyphenols are abundantly present in the human diet and have an antimicrobial effect inducing selective changes in the microbiota composition, with potential beneficial effects for the human health. Our aim was to determine the human gut microbiota susceptibility toward wine polyphenols. Susceptibility to two commercial wine phenolic extracts (Vitaflavan(®) and Provinols™) was determined in isolates from fecal samples from 36 gastrointestinal healthy volunteers. To select the polyphenol-resistant isolates, feces were seeded in plates containing 1 mg/ml of phenolic extract. The minimal inhibitory concentration to polyphenols in the collected isolates was assessed by the agar dilution method. Overall results showed that Gram-negative isolates are most tolerant to the presence of both grape seed and red wine extracts. Furthermore, we purified to homogeneity the phenolic fractions by high-performance liquid chromatography (HPLC) to determine their antimicrobial effect and their influence on bacterial growth in four selected ATCC strains using the BioScreen apparatus. Results showed that the antimicrobial activity of the wine polyphenols is the result of the interaction of both the flavan-3-ol type and the bacteria. Bacterial Intraspecies differences in the phenolic susceptibility suggest the existence of polyphenol-resistant mechanisms that are uncharacterized as yet.

Gut Microbiota Linked to Sexual Preference and HIV Infection

PubMed Central

Noguera-Julian, Marc; Rocafort, Muntsa; Guillén, Yolanda; Rivera, Javier; Casadellà, Maria; Nowak, Piotr; Hildebrand, Falk; Zeller, Georg; Parera, Mariona; Bellido, Rocío; Rodríguez, Cristina; Carrillo, Jorge; Mothe, Beatriz; Coll, Josep; Bravo, Isabel; Estany, Carla; Herrero, Cristina; Saz, Jorge; Sirera, Guillem; Torrela, Ariadna; Navarro, Jordi; Crespo, Manel; Brander, Christian; Negredo, Eugènia; Blanco, Julià; Guarner, Francisco; Calle, Maria Luz; Bork, Peer; Sönnerborg, Anders; Clotet, Bonaventura; Paredes, Roger

2016-01-01

The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction. PMID:27077120

Decreased Bacterial Diversity Characterizes an Altered Gut Microbiota in Psoriatic Arthritis and Resembles Dysbiosis of Inflammatory Bowel Disease

PubMed Central

Scher, Jose U.; Ubeda, Carles; Artacho, Alejandro; Attur, Mukundan; Isaac, Sandrine; Reddy, Soumya M.; Marmon, Shoshana; Neimann, Andrea; Brusca, Samuel; Patel, Tejas; Manasson, Julia; Pamer, Eric G.; Littman, Dan R.; Abramson, Steven B.

2014-01-01

Objective To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). Methods High-throughput 16S rRNA pyrosequencing was utilized to compare community composition of gut microbiota in PsA patients (n=16), subjects with psoriasis of the skin (Ps) (n=15) and healthy, matched-controls (n=17). Samples were further assessed for the presence and levels of fecal and serum secretory immunoglobulin A (sIgA), pro-inflammatory proteins and fatty-acids. Results The gut microbiota observed in PsA and Ps patients was less diverse when compared to healthy controls. These could be attributed to the reduced presence of several taxa. While both groups showed a relative decrease in Coprococcus spp., PsA samples were characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA and a decrease in receptor activator of nuclear factor kappa-B ligand (RANKL) levels. Fatty acid analysis revealed low levels of hexanoate and heptanoate in PsA and Ps patients. Conclusion PsA and Ps patients had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that published for patients with IBD and was associated with changes in specific inflammatory proteins unique to this group, and distinct from Ps and controls. Thus, the role of gut microbiota in the continuum of Ps-PsA pathogenesis and the associated immune response merits further study. PMID:25319745

Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers.

PubMed

Ticinesi, Andrea; Milani, Christian; Guerra, Angela; Allegri, Franca; Lauretani, Fulvio; Nouvenne, Antonio; Mancabelli, Leonardo; Lugli, Gabriele Andrea; Turroni, Francesca; Duranti, Sabrina; Mangifesta, Marta; Viappiani, Alice; Ferrario, Chiara; Dodi, Rossella; Dall'Asta, Margherita; Del Rio, Daniele; Ventura, Marco; Meschi, Tiziana

2018-04-28

The involvement of the gut microbiota in the pathogenesis of calcium nephrolithiasis has been hypothesised since the discovery of the oxalate-degrading activity of Oxalobacter formigenes , but never comprehensively studied with metagenomics. The aim of this case-control study was to compare the faecal microbiota composition and functionality between recurrent idiopathic calcium stone formers (SFs) and controls. Faecal samples were collected from 52 SFs and 48 controls (mean age 48±11). The microbiota composition was analysed through 16S rRNA microbial profiling approach. Ten samples (five SFs, five controls) were also analysed with deep shotgun metagenomics sequencing, with focus on oxalate-degrading microbial metabolic pathways. Dietary habits, assessed through a food-frequency questionnaire, and 24-hour urinary excretion of prolithogenic and antilithogenic factors, including calcium and oxalate, were compared between SFs and controls, and considered as covariates in the comparison of microbiota profiles. SFs exhibited lower faecal microbial diversity than controls (Chao1 index 1460±363vs 1658±297, fully adjusted p=0.02 with stepwise backward regression analysis). At multivariate analyses, three taxa ( Faecalibacterium , Enterobacter , Dorea ) were significantly less represented in faecal samples of SFs. The Oxalobacter abundance was not different between groups. Faecal samples from SFs exhibited a significantly lower bacterial representation of genes involved in oxalate degradation, with inverse correlation with 24-hour oxalate excretion (r=-0.87, p=0.002). The oxalate-degrading genes were represented in several bacterial species, whose cumulative abundance was inversely correlated with oxaluria (r=-0.85, p=0.02). Idiopathic calcium SFs exhibited altered gut microbiota composition and functionality that could contribute to nephrolithiasis physiopathology. © 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.

Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity.

PubMed

Evans, Christian C; LePard, Kathy J; Kwak, Jeff W; Stancukas, Mary C; Laskowski, Samantha; Dougherty, Joseph; Moulton, Laura; Glawe, Adam; Wang, Yunwei; Leone, Vanessa; Antonopoulos, Dionysios A; Smith, Dan; Chang, Eugene B; Ciancio, Mae J

2014-01-01

Diet-induced obesity (DIO) is a significant health concern which has been linked to structural and functional changes in the gut microbiota. Exercise (Ex) is effective in preventing obesity, but whether Ex alters the gut microbiota during development with high fat (HF) feeding is unknown. Determine the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and in HF-DIO. Male C57BL/6 littermates (5 weeks) were distributed equally into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12 weeks and used for bacterial DNA isolation. DNA was subjected both to quantitative PCR using primers specific to the 16S rRNA encoding genes for Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification using the Illumina MiSeq platform. Data were analyzed using a one or two-way ANOVA or Pearson correlation. HF diet resulted in significantly greater body weight and adiposity as well as decreased glucose tolerance that were prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with principal coordinates analysis indicated clustering by both diet and Ex at week 12. Sequencing demonstrated Ex-induced changes in the percentage of major bacterial phyla at 12 weeks. A correlation between total Ex distance and the ΔCt Bacteroidetes: ΔCt Firmicutes ratio from qPCR demonstrated a significant inverse correlation (r2 = 0.35, p = 0.043). Ex induces a unique shift in the gut microbiota that is different from dietary effects. Microbiota changes may play a role in Ex prevention of HF-DIO.

Exercise Prevents Weight Gain and Alters the Gut Microbiota in a Mouse Model of High Fat Diet-Induced Obesity

PubMed Central

Evans, Christian C.; LePard, Kathy J.; Kwak, Jeff W.; Stancukas, Mary C.; Laskowski, Samantha; Dougherty, Joseph; Moulton, Laura; Glawe, Adam; Wang, Yunwei; Leone, Vanessa; Antonopoulos, Dionysios A.; Smith, Dan; Chang, Eugene B.; Ciancio, Mae J.

2014-01-01

Background Diet-induced obesity (DIO) is a significant health concern which has been linked to structural and functional changes in the gut microbiota. Exercise (Ex) is effective in preventing obesity, but whether Ex alters the gut microbiota during development with high fat (HF) feeding is unknown. Objective Determine the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and in HF-DIO. Methods Male C57BL/6 littermates (5 weeks) were distributed equally into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12 weeks and used for bacterial DNA isolation. DNA was subjected both to quantitative PCR using primers specific to the 16S rRNA encoding genes for Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification using the Illumina MiSeq platform. Data were analyzed using a one or two-way ANOVA or Pearson correlation. Results HF diet resulted in significantly greater body weight and adiposity as well as decreased glucose tolerance that were prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with principal coordinates analysis indicated clustering by both diet and Ex at week 12. Sequencing demonstrated Ex-induced changes in the percentage of major bacterial phyla at 12 weeks. A correlation between total Ex distance and the ΔCt Bacteroidetes: ΔCt Firmicutes ratio from qPCR demonstrated a significant inverse correlation (r2 = 0.35, p = 0.043). Conclusion Ex induces a unique shift in the gut microbiota that is different from dietary effects. Microbiota changes may play a role in Ex prevention of HF-DIO. PMID:24670791

Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria.

PubMed

Stecher, Bärbel; Chaffron, Samuel; Käppeli, Rina; Hapfelmeier, Siegfried; Freedrich, Susanne; Weber, Thomas C; Kirundi, Jorum; Suar, Mrutyunjay; McCoy, Kathy D; von Mering, Christian; Macpherson, Andrew J; Hardt, Wolf-Dietrich

2010-01-01

The intestinal ecosystem is formed by a complex, yet highly characteristic microbial community. The parameters defining whether this community permits invasion of a new bacterial species are unclear. In particular, inhibition of enteropathogen infection by the gut microbiota ( = colonization resistance) is poorly understood. To analyze the mechanisms of microbiota-mediated protection from Salmonella enterica induced enterocolitis, we used a mouse infection model and large scale high-throughput pyrosequencing. In contrast to conventional mice (CON), mice with a gut microbiota of low complexity (LCM) were highly susceptible to S. enterica induced colonization and enterocolitis. Colonization resistance was partially restored in LCM-animals by co-housing with conventional mice for 21 days (LCM(con21)). 16S rRNA sequence analysis comparing LCM, LCM(con21) and CON gut microbiota revealed that gut microbiota complexity increased upon conventionalization and correlated with increased resistance to S. enterica infection. Comparative microbiota analysis of mice with varying degrees of colonization resistance allowed us to identify intestinal ecosystem characteristics associated with susceptibility to S. enterica infection. Moreover, this system enabled us to gain further insights into the general principles of gut ecosystem invasion by non-pathogenic, commensal bacteria. Mice harboring high commensal E. coli densities were more susceptible to S. enterica induced gut inflammation. Similarly, mice with high titers of Lactobacilli were more efficiently colonized by a commensal Lactobacillus reuteri(RR) strain after oral inoculation. Upon examination of 16S rRNA sequence data from 9 CON mice we found that closely related phylotypes generally display significantly correlated abundances (co-occurrence), more so than distantly related phylotypes. Thus, in essence, the presence of closely related species can increase the chance of invasion of newly incoming species into the gut ecosystem. We provide evidence that this principle might be of general validity for invasion of bacteria in preformed gut ecosystems. This might be of relevance for human enteropathogen infections as well as therapeutic use of probiotic commensal bacteria.

Bacteria from diverse habitats colonize and compete in the mouse gut.

PubMed

Seedorf, Henning; Griffin, Nicholas W; Ridaura, Vanessa K; Reyes, Alejandro; Cheng, Jiye; Rey, Federico E; Smith, Michelle I; Simon, Gabriel M; Scheffrahn, Rudolf H; Woebken, Dagmar; Spormann, Alfred M; Van Treuren, William; Ursell, Luke K; Pirrung, Megan; Robbins-Pianka, Adam; Cantarel, Brandi L; Lombard, Vincent; Henrissat, Bernard; Knight, Rob; Gordon, Jeffrey I

2014-10-09

To study how microbes establish themselves in a mammalian gut environment, we colonized germ-free mice with microbial communities from human, zebrafish, and termite guts, human skin and tongue, soil, and estuarine microbial mats. Bacteria from these foreign environments colonized and persisted in the mouse gut; their capacity to metabolize dietary and host carbohydrates and bile acids correlated with colonization success. Cohousing mice harboring these xenomicrobiota or a mouse cecal microbiota, along with germ-free "bystanders," revealed the success of particular bacterial taxa in invading guts with established communities and empty gut habitats. Unanticipated patterns of ecological succession were observed; for example, a soil-derived bacterium dominated even in the presence of bacteria from other gut communities (zebrafish and termite), and human-derived bacteria colonized germ-free bystander mice before mouse-derived organisms. This approach can be generalized to address a variety of mechanistic questions about succession, including succession in the context of microbiota-directed therapeutics. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome

PubMed Central

Theodorou, Vassilia; Belgnaoui, Afifa Ait; Agostini, Simona; Eutamene, Helene

2014-01-01

The last ten years’ wide progress in the gut microbiota phylogenetic and functional characterization has been made evidencing dysbiosis in several gastrointestinal diseases including inflammatory bowel diseases and irritable bowel syndrome (IBS). IBS is a functional gut disease with high prevalence and negative impact on patient’s quality of life characterized mainly by visceral pain and/or discomfort, representing a good paradigm of chronic gut hypersensitivity. The IBS features are strongly regulated by bidirectional gut-brain interactions and there is increasing evidence for the involvement of gut bacteria and/or their metabolites in these features, including visceral pain. Further, gut microbiota modulation by antibiotics or probiotics has been promising in IBS. Mechanistic data provided mainly by animal studies highlight that commensals or probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier, the mucosal and/or systemic immune activation, and subsequent neuronal sensitization and/or activation. PMID:25184834

Spatial organization of a model 15-member human gut microbiota established in gnotobiotic mice

PubMed Central

Mark Welch, Jessica L.; Hasegawa, Yuko; McNulty, Nathan P.; Gordon, Jeffrey I.; Borisy, Gary G.

2017-01-01

Knowledge of the spatial organization of the gut microbiota is important for understanding the physical and molecular interactions among its members. These interactions are thought to influence microbial succession, community stability, syntrophic relationships, and resiliency in the face of perturbations. The complexity and dynamism of the gut microbiota pose considerable challenges for quantitative analysis of its spatial organization. Here, we illustrate an approach for addressing this challenge, using (i) a model, defined 15-member consortium of phylogenetically diverse, sequenced human gut bacterial strains introduced into adult gnotobiotic mice fed a polysaccharide-rich diet, and (ii) in situ hybridization and spectral imaging analysis methods that allow simultaneous detection of multiple bacterial strains at multiple spatial scales. Differences in the binding affinities of strains for substrates such as mucus or food particles, combined with more rapid replication in a preferred microhabitat, could, in principle, lead to localized clonally expanded aggregates composed of one or a few taxa. However, our results reveal a colonic community that is mixed at micrometer scales, with distinct spatial distributions of some taxa relative to one another, notably at the border between the mucosa and the lumen. Our data suggest that lumen and mucosa in the proximal colon should be conceptualized not as stratified compartments but as components of an incompletely mixed bioreactor. Employing the experimental approaches described should allow direct tests of whether and how specified host and microbial factors influence the nature and functional contributions of “microscale” mixing to the dynamic operations of the microbiota in health and disease. PMID:29073107

Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers.

PubMed

Queipo-Ortuño, María Isabel; Boto-Ordóñez, María; Murri, Mora; Gomez-Zumaquero, Juan Miguel; Clemente-Postigo, Mercedes; Estruch, Ramon; Cardona Diaz, Fernando; Andrés-Lacueva, Cristina; Tinahones, Francisco J

2012-06-01

Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota, and they focused mainly on single polyphenol molecules and select bacterial populations. The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits. Ten healthy male volunteers underwent a randomized, crossover, controlled intervention study. After a washout period, all of the subjects received red wine, the equivalent amount of de-alcoholized red wine, or gin for 20 d each. Total fecal DNA was submitted to polymerase chain reaction(PCR)-denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota. Several biochemical markers were measured. The dominant bacterial composition did not remain constant over the different intake periods. Compared with baseline, the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides-Eubacterium rectale groups (P < 0.05). In parallel, systolic and diastolic blood pressures and triglyceride, total cholesterol, HDL cholesterol, and C-reactive protein concentrations decreased significantly (P < 0.05). Moreover, changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number. This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans, which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet. This trial was registered at controlled-trials.com as ISRCTN88720134.

Diet, Environments, and Gut Microbiota. A Preliminary Investigation in Children Living in Rural and Urban Burkina Faso and Italy.

PubMed

De Filippo, Carlotta; Di Paola, Monica; Ramazzotti, Matteo; Albanese, Davide; Pieraccini, Giuseppe; Banci, Elena; Miglietta, Franco; Cavalieri, Duccio; Lionetti, Paolo

2017-01-01

Diet is one of the main factors that affects the composition of gut microbiota. When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso ( n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children ( n = 13). We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. Microbiota of rural children retain a geographically unique bacterial reservoir ( Prevotella , Treponema , and Succinivibrio ), assigned to ferment fiber and polysaccharides from vegetables. Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle.

DNA-sensing inflammasomes: regulation of bacterial host defense and the gut microbiota.

PubMed

Man, Si Ming; Karki, Rajendra; Kanneganti, Thirumala-Devi

2016-06-01

DNA sensors are formidable immune guardians of the host. At least 14 cytoplasmic DNA sensors have been identified in recent years, each with specialized roles in driving inflammation and/or cell death. Of these, AIM2 is a sensor of dsDNA, and forms an inflammasome complex to activate the cysteine protease caspase-1, mediates the release of the proinflammatory cytokines IL-1β and IL-18, and induces pyroptosis. The inflammasome sensor NLRP3 can also respond to DNA in the forms of oxidized mitochondrial DNA and the DNA derivative RNA:DNA hybrids produced by bacteria, whereas the putative inflammasome sensor IFI16 responds to viral DNA in the nucleus. Although inflammasomes provoke inflammation for anti-microbial host defense, they must also maintain homeostasis with commensal microbiota. Here, we outline recent advances highlighting the complex relationship between DNA-sensing inflammasomes, bacterial host defense and the gut microbiota. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dynamic Distribution of the Gut Microbiota and the Relationship with Apparent Crude Fiber Digestibility and Growth Stages in Pigs

PubMed Central

Niu, Qing; Li, Pinghua; Hao, Shuaishuai; Zhang, Yeqiu; Kim, Sung Woo; Li, Huizhi; Ma, Xiang; Gao, Shuo; He, Lichun; Wu, WangJun; Huang, Xuegen; Hua, Jindi; Zhou, Bo; Huang, Ruihua

2015-01-01

The gut microbiota plays an important role in nutrient digestibility in animals. To examine changes in the pig gut microbiota across growth stages and its effects on nutrient digestion, the gut microbiota population in pigs at 28 days (before weaning), and 60, 90, and 150 days of age was assessed by 16S rDNA gene sequencing. The apparent digestibility of crude fiber (CF), neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP) and ether extract (EE) was also assessed in these pigs. A total of 19,875 operational taxonomic units (OTUs) were identified from all samples. Both bacterial abundance and diversity increased with age. A total of 22 phyla and 249 genera were identified from all fecal samples; Firmicutes and Bacteroidetes were the most dominant phyla in all samples. With increasing age, the proportion of TM7 and Tenericutes increased, whereas the proportion of Lentisphaerae and Synergistetes decreased. The abundance of 36 genera varied with age, and the apparent digestibility of CF increased with age. Three phyla, Proteobacteria, Tenericutes and TM7, and 11 genera, including Anaeroplasma, Campylobacter, and Clostridium, were correlated with apparent CF digestibility. PMID:25898122

Gut microbiota in MS: possible influence of immunomodulators

PubMed Central

Cantarel, Brandi L.; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z.; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M.; Mowry, Ellen M.

2015-01-01

Objectives Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in multiple sclerosis patients and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Methods Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Multiple sclerosis patients were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5,000 IU/day) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. Results While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in multiple sclerosis patients. Glatiramer acetate-treated MS subjects showed differences in community composition compared to untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and Other Clostridiales. Compared to the other groups, untreated multiple sclerosis subjects had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. Conclusions While overall bacterial communities were similar, specific operational taxonomic units differed between healthy and multiple sclerosis subjects. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results. PMID:25775034

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

PubMed

Cantarel, Brandi L; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M; Mowry, Ellen M

2015-06-01

Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

Assessment of metabolic diversity within the intestinal microbiota from healthy humans using combined molecular and cultural approaches.

PubMed

Chassard, Christophe; Scott, Karen P; Marquet, Perrine; Martin, Jennifer C; Del'homme, Christophe; Dapoigny, Michel; Flint, Harry J; Bernalier-Donadille, Annick

2008-12-01

The human gut harbours a wide range of bacterial communities that play key roles in supplying nutrients and energy to the host through anaerobic fermentation of dietary components and host secretions. This fermentative process involves different functional groups of microorganisms linked in a trophic chain. Although the diversity of the intestinal microbiota has been studied extensively using molecular techniques, the functional aspects of this biodiversity remain mostly unexplored. The aim of the present work was to enumerate the principal metabolic groups of microorganisms involved in the fermentative process in the gut of healthy humans. These functional groups of microorganisms were quantified by a cultural approach, while the taxonomic composition of the microbiota was assessed by in situ hybridization on the same faecal samples. The functional groups of microorganisms that predominated in the gut were the polysaccharide-degrading populations involved in the breakdown of the most readily available exogenous and endogenous substrates and the predominant butyrate-producing species. Most of the functional groups of microorganisms studied appeared to be present at rather similar levels in all healthy volunteers, suggesting that optimal numbers of these various bacterial groups are crucial for efficient gut fermentation, as well as for host nutrition and health. Significant interindividual differences were, however, confirmed with respect to the numbers of methanogenic archaea, filter paper-degrading and acetogenic bacteria and the products formed by lactate-utilizing bacteria.

Diversification of Type VI Secretion System Toxins Reveals Ancient Antagonism among Bee Gut Microbes.

PubMed

Steele, Margaret I; Kwong, Waldan K; Whiteley, Marvin; Moran, Nancy A

2017-12-12

Microbial communities are shaped by interactions among their constituent members. Some Gram-negative bacteria employ type VI secretion systems (T6SSs) to inject protein toxins into neighboring cells. These interactions have been theorized to affect the composition of host-associated microbiomes, but the role of T6SSs in the evolution of gut communities is not well understood. We report the discovery of two T6SSs and numerous T6SS-associated Rhs toxins within the gut bacteria of honey bees and bumble bees. We sequenced the genomes of 28 strains of Snodgrassella alvi , a characteristic bee gut microbe, and found tremendous variability in their Rhs toxin complements: altogether, these strains appear to encode hundreds of unique toxins. Some toxins are shared with Gilliamella apicola , a coresident gut symbiont, implicating horizontal gene transfer as a source of toxin diversity in the bee gut. We use data from a transposon mutagenesis screen to identify toxins with antibacterial function in the bee gut and validate the function and specificity of a subset of these toxin and immunity genes in Escherichia coli Using transcriptome sequencing, we demonstrate that S. alvi T6SSs and associated toxins are upregulated in the gut environment. We find that S. alvi Rhs loci have a conserved architecture, consistent with the C-terminal displacement model of toxin diversification, with Rhs toxins, toxin fragments, and cognate immunity genes that are expressed and confer strong fitness effects in vivo Our findings of T6SS activity and Rhs toxin diversity suggest that T6SS-mediated competition may be an important driver of coevolution within the bee gut microbiota. IMPORTANCE The structure and composition of host-associated bacterial communities are of broad interest, because these communities affect host health. Bees have a simple, conserved gut microbiota, which provides an opportunity to explore interactions between species that have coevolved within their host over millions of years. This study examined the role of type VI secretion systems (T6SSs)-protein complexes used to deliver toxic proteins into bacterial competitors-within the bee gut microbiota. We identified two T6SSs and diverse T6SS-associated toxins in bacterial strains from bees. Expression of these genes is increased in bacteria in the bee gut, and toxin and immunity genes demonstrate antibacterial and protective functions, respectively, when expressed in Escherichia coli Our results suggest that coevolution among bacterial species in the bee gut has favored toxin diversification and maintenance of T6SS machinery, and demonstrate the importance of antagonistic interactions within host-associated microbial communities. Copyright © 2017 Steele et al.

Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis.

PubMed

So, Daniel; Whelan, Kevin; Rossi, Megan; Morrison, Mark; Holtmann, Gerald; Kelly, Jaimon T; Shanahan, Erin R; Staudacher, Heidi M; Campbell, Katrina L

2018-06-01

Dysfunction of the gut microbiota is frequently reported as a manifestation of chronic diseases, and therefore presents as a modifiable risk factor in their development. Diet is a major regulator of the gut microbiota, and certain types of dietary fiber may modify bacterial numbers and metabolism, including short-chain fatty acid (SCFA) generation. A systematic review and meta-analysis were undertaken to assess the effect of dietary fiber interventions on gut microbiota composition in healthy adults. A systematic search was conducted across MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials using culture and/or molecular microbiological techniques evaluating the effect of fiber intervention on gut microbiota composition in healthy adults. Meta-analyses via a random-effects model were performed on alpha diversity, prespecified bacterial abundances including Bifidobacterium and Lactobacillus spp., and fecal SCFA concentrations comparing dietary fiber interventions with placebo/low-fiber comparators. A total of 64 studies involving 2099 participants were included. Dietary fiber intervention resulted in higher abundance of Bifidobacterium spp. (standardized mean difference (SMD): 0.64; 95% CI: 0.42, 0.86; P < 0.00001) and Lactobacillus spp. (SMD: 0.22; 0.03, 0.41; P = 0.02) as well as fecal butyrate concentration (SMD: 0.24; 0.00, 0.47; P = 0.05) compared with placebo/low-fiber comparators. Subgroup analysis revealed that fructans and galacto-oligosaccharides led to significantly greater abundance of both Bifidobacterium spp. and Lactobacillus spp. compared with comparators (P < 0.00001 and P = 0.002, respectively). No differences in effect were found between fiber intervention and comparators for α-diversity, abundances of other prespecified bacteria, or other SCFA concentrations. Dietary fiber intervention, particularly involving fructans and galacto-oligosaccharides, leads to higher fecal abundance of Bifidobacterium and Lactobacillus spp. but does not affect α-diversity. Further research is required to better understand the role of individual fiber types on the growth of microbes and the overall gut microbial community. This review was registered at PROSPERO as CRD42016053101.

Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet.

PubMed

Kang, Chao; Wang, Bin; Kaliannan, Kanakaraju; Wang, Xiaolan; Lang, Hedong; Hui, Suocheng; Huang, Li; Zhang, Yong; Zhou, Ming; Chen, Mengting; Mi, Mantian

2017-05-23

Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI) responsible for the development of obesity. Capsaicin (CAP) is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD) supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA) measurements, and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae , while it caused lower levels of members of the lipopolysaccharide (LPS)-producing family S24_7. Predicted function analysis (PICRUSt) showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB 1 ) by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation. IMPORTANCE Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of chronic low-grade inflammation (CLGI), which primarily mediates the development of obesity. A dietary strategy to reduce endotoxemia appears to be an effective approach for addressing the issue of obesity. Capsaicin (CAP) is the major pungent component in red chili (genus Capsicum ). Little is known about the role of gut microbiota in the anti-obesity effect of CAP. High-throughput 16S rRNA gene sequencing revealed that CAP significantly increased butyragenic bacteria and decreased LPS-producing bacteria (e.g., members of the S24-7 family) and LPS biosynthesis. By using antibiotics and microbiota transplantation, we prove that gut microbiota plays a causal role in dietary CAP-induced protective phenotype against high-fat-diet-induced CLGI and obesity. Moreover, CB 1 inhibition was partially involved in the beneficial effect of CAP. Together, these data suggest that the gut microbiome is a critical factor for the anti-obesity effects of CAP. Copyright © 2017 Kang et al.

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.

Stability and phylogenetic correlation in gut microbiota: lessons from ants and apes.

PubMed

Sanders, Jon G; Powell, Scott; Kronauer, Daniel J C; Vasconcelos, Heraldo L; Frederickson, Megan E; Pierce, Naomi E

2014-03-01

Correlation between gut microbiota and host phylogeny could reflect codiversification over shared evolutionary history or a selective environment that is more similar in related hosts. These alternatives imply substantial differences in the relationship between host and symbiont, but can they be distinguished based on patterns in the community data themselves? We explored patterns of phylogenetic correlation in the distribution of gut bacteria among species of turtle ants (genus Cephalotes), which host a dense gut microbial community. We used 16S rRNA pyrosequencing from 25 Cephalotes species to show that their gut community is remarkably stable, from the colony to the genus level. Despite this overall similarity, the existing differences among species' microbiota significantly correlated with host phylogeny. We introduced a novel analytical technique to test whether these phylogenetic correlations are derived from recent bacterial evolution, as would be expected in the case of codiversification, or from broader shifts more likely to reflect environmental filters imposed by factors such as diet or habitat. We also tested this technique on a published data set of ape microbiota, confirming earlier results while revealing previously undescribed patterns of phylogenetic correlation. Our results indicated a high degree of partner fidelity in the Cephalotes microbiota, suggesting that vertical transmission of the entire community could play an important role in the evolution and maintenance of the association. As additional comparative microbiota data become available, the techniques presented here can be used to explore trends in the evolution of host-associated microbial communities. © 2014 John Wiley & Sons Ltd.

Noninvasive photoacoustic identification and imaging of gut microbes.

PubMed

Huang, Xiaoxiao; Shi, Ying; Liu, Yajing; Xu, Hongzhi; Liu, Yu; Xiao, Chuanxing; Ren, Jianlin; Nie, Liming

2017-08-01

Homeostasis of the gut microbiota is indispensable for various physiological functions. Its composition and activity co-develop with the host, and especially associate with human colorectal cancer. However, current composition identification methods are complicated and not timely without spatial distribution information. In this Letter, we explored the photoacoustic imaging (PAI) technique to characterize the composition and quantify the proportions of the gut microbes after optical probe labeling. Our experimental results demonstrated that PAI has the potential to identify different gut bacterial species on the spot.

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.

Decreased Diversity of the Oral Microbiota of Patients with Hepatitis B Virus-Induced Chronic Liver Disease: A Pilot Project

PubMed Central

Ling, Zongxin; Liu, Xia; Cheng, Yiwen; Jiang, Xiawei; Jiang, Haiyin; Wang, Yuezhu; Li, Lanjuan

2015-01-01

Increasing evidence suggests that altered gut microbiota is implicated in the pathogenesis of hepatitis B virus-induced chronic liver disease (HBV-CLD). However, the structure and composition of the oral microbiota of patients with HBV-CLD remains unclear. High-throughput pyrosequencing showed that decreased oral bacterial diversity was found in patients with HBV-CLD. The Firmicutes/Bacteroidetes ratio was increased significantly, which indicated that dysbiosis of the oral microbiota participated in the process of HBV-CLD development. However, the changing patterns of the oral microbiota in patients with HBV-induced liver cirrhosis (LC) were almost similar to patients with chronic hepatitis B (CHB). HBV infection resulted in an increase in potential H2S- and CH3SH-producing phylotypes such as Fusobacterium, Filifactor, Eubacterium, Parvimonas and Treponema, which might contribute to the increased oral malodor. These key oral-derived phylotypes might invade into the gut as opportunistic pathogens and contribute to altering the composition of the gut microbiota. This study provided important clues that dysbiosis of the oral microbiota might be involved in the development of HBV-CLD. Greater understanding of the relationships between the dysbiosis of oral microbiota and the development of HBV-CLD might facilitate the development of non-invasive differential diagnostic procedures and targeted treatments of HBV-CLD patients harbouring specific oral phylotypes. PMID:26606973

Gut microbiota: puppeteer of the host juvenile growth.

PubMed

Schwarzer, Martin

2018-05-01

This review focuses on the recent discoveries about the impact of intestinal microbiota on mammalian host juvenile growth. Intestinal microbiota is a powerful modulator of many facets of multicellular host's physiology. Recent results from human field studies and animal research have clearly shown that not only the nutrition, but also the intestinal microbiota impacts host postnatal growth kinetics. Absence of microbiome leads to stunted growth in mammalian gnotobiotic models and changes in the composition of the intestinal microbiota can impact the postnatal growth kinetics both positively and negatively under normal nutritional conditions as well as in undernutrition. Strikingly, specific bacterial strains are able to interact with GH/IGF-1 somatotropic axis activity, thus directly impacting host juvenile development. Intestinal microbiota dictates the pace of host postnatal growth. This newly described role envisages that therapy with specific bacterial strains, together with re-nutritional strategies, might successfully alleviate the long-term sequelae of undernutrition during childhood in humans.

Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection.

PubMed

Vincent, Caroline; Miller, Mark A; Edens, Thaddeus J; Mehrotra, Sudeep; Dewar, Ken; Manges, Amee R

2016-03-14

Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk of developing CDI because they are exposed to C. difficile spores through contact with the hospital environment and often receive antibiotics and other medications that can disrupt the integrity of the indigenous intestinal microbiota and impair colonization resistance. Using whole metagenome shotgun sequencing, we examined the diversity and composition of the fecal microbiota in a prospective cohort study of 98 hospitalized patients. Four patients had asymptomatic C. difficile colonization, and four patients developed CDI. We observed dramatic shifts in the structure of the gut microbiota during hospitalization. In contrast to CDI cases, asymptomatic patients exhibited elevated relative abundance of potentially protective bacterial taxa in their gut at the onset of C. difficile colonization. Use of laxatives was associated with significant reductions in the relative abundance of Clostridium and Eubacterium; species within these genera have previously been shown to enhance resistance to CDI via the production of secondary bile acids. Cephalosporin and fluoroquinolone exposure decreased the frequency of Clostridiales Family XI Incertae Sedis, a bacterial family that has been previously associated with decreased CDI risk. This study underscores the detrimental impact of antibiotics as well as other medications, particularly laxatives, on the intestinal microbiota and suggests that co-colonization with key bacterial taxa may prevent C. difficile overgrowth or the transition from asymptomatic C. difficile colonization to CDI.

Functional microbiomics: Evaluation of gut microbiota-bile acid metabolism interactions in health and disease.

PubMed

Mullish, Benjamin H; Pechlivanis, Alexandros; Barker, Grace F; Thursz, Mark R; Marchesi, Julian R; McDonald, Julie A K

2018-04-26

There is an ever-increasing recognition that bile acids are not purely simple surfactant molecules that aid in lipid digestion, but are a family of molecules contributing to a diverse range of key systemic functions in the host. It is now also understood that the specific composition of the bile acid milieu within the host is related to the expression and activity of bacterially-derived enzymes within the gastrointestinal tract, as such creating a direct link between the physiology of the host and the gut microbiota. Coupled to the knowledge that perturbation of the structure and/or function of the gut microbiota may contribute to the pathogenesis of a range of diseases, there is a high level of interest in the potential for manipulation of the gut microbiota-host bile acid axis as a novel approach to therapeutics. Much of the growing understanding of the biology of this area reflects the recent development and refinement of a range of novel techniques; this study applies a number of those techniques to the analysis of human samples, aiming to illustrate their strengths, drawbacks and biological significance at all stages. Specifically, we used microbial profiling (using 16S rRNA gene sequencing), bile acid profiling (using liquid chromatography-mass spectrometry), bsh and baiCD qPCR, and a BSH enzyme activity assay to demonstrate differences in the gut microbiota and bile metabolism in stool samples from healthy and antibiotic-exposed individuals. Copyright © 2018 Elsevier Inc. All rights reserved.

Involvement of gut microbiota in association between GLP-1/GLP-1 receptor expression and gastrointestinal motility.

PubMed

Yang, Mo; Fukui, Hirokazu; Eda, Hirotsugu; Xu, Xin; Kitayama, Yoshitaka; Hara, Ken; Kodani, Mio; Tomita, Toshihiko; Oshima, Tadayuki; Watari, Jiro; Miwa, Hiroto

2017-04-01

The microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expressed in myenteric neural cells throughout the GI wall. GLP-1R-positive cells throughout the GI wall were significantly fewer in GF mice with FT than in GF mice without gut microbiota reconstitution. GITT was significantly shorter in GF mice with FT than in control GF mice without FT and correlated with the number of GLP-1R-positive cells throughout the GI wall. GITT was significantly longer in GF control mice than in SPF mice. When those mice were treated with GLP-1 agonist extendin4, GITT was significantly longer in the GF mice. The gut microbiota may accelerate or at least modify GI motility while suppressing GLP-1R expression in myenteric neural cells throughout the GI tract. NEW & NOTEWORTHY The gut microbiota has been intensively studied, because it plays a pivotal role in various aspects of host physiology. On the other hand, glucagon-like peptide 1 (GLP-1) plays important roles in metabolism as well as gastrointestinal motility. In the present study, we have suggested that the gut microbiota accelerates gastrointestinal motility while suppressing the expression of GLP-1 receptor in myenteric neural cells throughout the gastrointestinal tract. We believe that this article is very timely and suggestive work. Copyright © 2017 the American Physiological Society.

Starring role of toll-like receptor-4 activation in the gut-liver axis

PubMed Central

Carotti, Simone; Guarino, Michele Pier Luca; Vespasiani-Gentilucci, Umberto; Morini, Sergio

2015-01-01

Since the introduction of the term “gut-liver axis”, many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4 (TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types. PMID:26600967

Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome.

PubMed

Maldonado-Gómez, María X; Martínez, Inés; Bottacini, Francesca; O'Callaghan, Amy; Ventura, Marco; van Sinderen, Douwe; Hillmann, Benjamin; Vangay, Pajau; Knights, Dan; Hutkins, Robert W; Walter, Jens

2016-10-12

Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30% of individuals for at least 6 months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota. AH1206 engraftment was associated with low abundance of resident B. longum and underrepresentation of specific carbohydrate utilization genes in the pre-treatment microbiome. Thus, phylogenetic limiting and resource availability are two factors that control the niche opportunity for AH1206 colonization. These findings suggest that bacterial species and functional genes absent in the gut microbiome of individual humans can be reestablished, providing opportunities for precise and personalized microbiome reconstitution. Copyright © 2016 Elsevier Inc. All rights reserved.

Long Term Development of Gut Microbiota Composition in Atopic Children: Impact of Probiotics

PubMed Central

Rutten, N. B. M. M.; Gorissen, D. M. W.; Eck, A.; Niers, L. E. M.; Vlieger, A. M.; Besseling-van der Vaart, I.; Budding, A. E.; Savelkoul, P. H. M.; van der Ent, C. K.; Rijkers, G. T.

2015-01-01

Introduction Imbalance of the human gut microbiota in early childhood is suggested as a risk factor for immune-mediated disorders such as allergies. With the objective to modulate the intestinal microbiota, probiotic supplementation during infancy has been used for prevention of allergic diseases in infants, with variable success. However, not much is known about the long-term consequences of neonatal use of probiotics on the microbiota composition. The aim of this study was to assess the composition and microbial diversity in stool samples of infants at high-risk for atopic disease, from birth onwards to six years of age, who were treated with probiotics or placebo during the first year of life. Methods In a double-blind, randomized, placebo-controlled trial, a probiotic mixture consisting of B. bifidum W23, B. lactis W52 and Lc. Lactis W58 (Ecologic® Panda) was administered to pregnant women during the last 6 weeks of pregnancy and to their offspring during the first year of life. During follow-up, faecal samples were collected from 99 children over a 6-year period with the following time points: first week, second week, first month, three months, first year, eighteen months, two years and six years. Bacterial profiling was performed by IS-pro. Differences in bacterial abundance and diversity were assessed by conventional statistics. Results The presence of the supplemented probiotic strains in faecal samples was confirmed, and the probiotic strains had a higher abundance and prevalence in the probiotic group during supplementation. Only minor and short term differences in composition of microbiota were found between the probiotic and placebo group and between children with or without atopy. The diversity of Bacteroidetes was significantly higher after two weeks in the placebo group, and at the age of two years atopic children had a significantly higher Proteobacteria diversity (p < 0.05). Gut microbiota development continued between two and six years, whereby microbiota composition at phylum level evolved more and more towards an adult-like configuration. Conclusion Perinatal supplementation with Ecologic® Panda, to children at high-risk for atopic disease, had minor effects on gut microbiota composition during the supplementation period. No long lasting differences were identified. Regardless of intervention or atopic disease status, children had a shared microbiota development over time determined by age that continued to develop between two and six years. PMID:26378926

Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment.

PubMed

Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

2016-01-01

The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being.

Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment

PubMed Central

Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

2016-01-01

The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being. PMID:27416027

Role of the gut microbiota in host appetite control: bacterial growth to animal feeding behaviour.

PubMed

Fetissov, Sergueï O

2017-01-01

The life of all animals is dominated by alternating feelings of hunger and satiety - the main involuntary motivations for feeding-related behaviour. Gut bacteria depend fully on their host for providing the nutrients necessary for their growth. The intrinsic ability of bacteria to regulate their growth and to maintain their population within the gut suggests that gut bacteria can interfere with molecular pathways controlling energy balance in the host. The current model of appetite control is based mainly on gut-brain signalling and the animal's own needs to maintain energy homeostasis; an alternative model might also involve bacteria-host communications. Several bacterial components and metabolites have been shown to stimulate intestinal satiety pathways; at the same time, their production depends on bacterial growth cycles. This short-term bacterial growth-linked modulation of intestinal satiety can be coupled with long-term regulation of appetite, controlled by the neuropeptidergic circuitry in the hypothalamus. Indeed, several bacterial products are detected in the systemic circulation, which might act directly on hypothalamic neurons. This Review analyses the data relevant to possible involvement of the gut bacteria in the regulation of host appetite and proposes an integrative homeostatic model of appetite control that includes energy needs of both the host and its gut bacteria.

Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.

PubMed

Quagliariello, Andrea; Del Chierico, Federica; Russo, Alessandra; Reddel, Sofia; Conte, Giulia; Lopetuso, Loris R; Ianiro, Gianluca; Dallapiccola, Bruno; Cardona, Francesco; Gasbarrini, Antonio; Putignani, Lorenza

2018-01-01

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides , Odoribacter , and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter . In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.

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.

Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients.

PubMed

Moreno-Indias, Isabel; Sánchez-Alcoholado, Lidia; Pérez-Martínez, Pablo; Andrés-Lacueva, Cristina; Cardona, Fernando; Tinahones, Francisco; Queipo-Ortuño, María Isabel

2016-04-01

This study evaluated the possible prebiotic effect of a moderate intake of red wine polyphenols on the modulation of the gut microbiota composition and the improvement in the risk factors for the metabolic syndrome in obese patients. Ten metabolic syndrome patients and ten healthy subjects were included in a randomized, crossover, controlled intervention study. After a washout period, the subjects consumed red wine and de-alcoholized red wine over a 30 day period for each. The dominant bacterial composition did not differ significantly between the study groups after the two red wine intake periods. In the metabolic syndrome patients, red wine polyphenols significantly increased the number of fecal bifidobacteria and Lactobacillus (intestinal barrier protectors) and butyrate-producing bacteria (Faecalibacterium prausnitzii and Roseburia) at the expense of less desirable groups of bacteria such as LPS producers (Escherichia coli and Enterobacter cloacae). The changes in gut microbiota in these patients could be responsible for the improvement in the metabolic syndrome markers. Modulation of the gut microbiota by using red wine could be an effective strategy for managing metabolic diseases associated with obesity.

Microbiome/microbiota and allergies.

PubMed

Inoue, Yuzaburo; Shimojo, Naoki

2015-01-01

Allergies are characterized by a hypersensitive immune reaction to originally harmless antigens. In recent decades, the incidence of allergic diseases has markedly increased, especially in developed countries. The increase in the frequency of allergic diseases is thought to be primarily due to environmental changes related to a westernized lifestyle, which affects the commensal microbes in the human body. The human gut is the largest organ colonized by bacteria and contains more than 1000 bacterial species, called the "gut microbiota." The recent development of sequencing technology has enabled researchers to genetically investigate and clarify the diversity of all species of commensal microbes. The collective genomes of commensal microbes are together called the "microbiome." Although the detailed mechanisms remain unclear, it has been proposed that the microbiota/microbiome, especially that in the gut, impacts the systemic immunity and metabolism, thus affecting the development of various immunological diseases, including allergies. In this review, we summarize the recent findings regarding the importance of the microbiome/microbiota in the development of allergic diseases and also the results of interventional studies using probiotics or prebiotics to prevent allergies.

Antiviral effect of vitamin A on norovirus infection via modulation of the gut microbiome

PubMed Central

Lee, Heetae; Ko, GwangPyo

2016-01-01

The effect and underlying mechanism of vitamin A on norovirus infection are largely unknown. This study aimed to investigate how vitamin A administration affects the gut microbiome after norovirus infection. Here, we demonstrate that treatment with either retinol or retinoic acid (RA) inhibits murine norovirus (MNV) replication using both in vitro and in vivo models. Compositional changes in the gut microbiome associated with RA administration and/or norovirus infection were also investigated. Oral administration of RA and/or MNV significantly altered intestinal microbiome profiles. Particularly, bacterial species belonging to the Lactobacillaceae families were remarkably increased by MNV inoculation and RA administration, suggesting that the antiviral effects of RA occur via the modulation of specific microbiota. The antiviral causal effect of Lactobacillus was identified and demonstrated using in vitro models in RAW264.7 cells. The antiviral immune response to MNV was mediated by IFN-β upregulation. This study represents the first comprehensive profiling of gut microbiota in response to RA treatment against norovirus infection. Moreover, we conclude that the abundance of Lactobacillus through gut microbiota modulation by RA is at least partially responsible for norovirus inhibition. PMID:27180604

Effect of caloric restriction on gut permeability, inflammation markers, and fecal microbiota in obese women.

PubMed

Ott, Beate; Skurk, Thomas; Hastreiter, Ljiljana; Lagkouvardos, Ilias; Fischer, Sandra; Büttner, Janine; Kellerer, Teresa; Clavel, Thomas; Rychlik, Michael; Haller, Dirk; Hauner, Hans

2017-09-20

Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue. Plasma high-molecular weight adiponectin (HMW adiponectin) was significantly increased after VLCD. Plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipopolysaccharide-binding protein (LBP) were significantly decreased after 28 days of VLCD. Using three different methods, gut paracellular permeability was decreased after VLCD. These changes in clinical parameters were not associated with major consistent changes in dominant bacterial communities in feces. In summary, a 4-week caloric restriction resulted in significant weight loss, improved gut barrier integrity and reduced systemic inflammation in obese women.

Effects of Whole-Grain Rice and Wheat on Composition of Gut Microbiota and Short-Chain Fatty Acids in Rats.

PubMed

Han, Fei; Wang, Yong; Han, Yangyang; Zhao, Jianxin; Han, Fenli; Song, Ge; Jiang, Ping; Miao, Haijiang

2018-05-29

Diets rich in whole grain (WG) cereals bring lower disease risks compared with refined grain-based diets. We investigated the effects of polished rice (PR), refined wheat (RW), unpolished rice (UPR), and whole wheat (WW) on short-chain fatty acids (SCFAs) and gut microbiota in ileal, cecal, and colonic digesta of normal rats. Animals fed with UPR and WW diets exhibited higher total SCFA in cecal and colonic digesta compared with those fed with PR and RW diets. Wheat diets contributed higher total SCFA than rice diets. In cecal and colonic digesta, animals fed with UPR and WW diets demonstrated higher acetate and butyrate contents than those given PR and RW. Firmicutes were the dominant eumycota in rat ileum digesta (>92% abundance). Cecal and colonic digesta were dominated by Firmicutes, Verrucomicrobia, and Bacteroidetes. UPR and WW affected gut microbiota, decreasing the proportion of Firmicutes to Bacteroidetes. SMB53, Lactobacillus, and Faecalibacterium were the main bacterial genera in ileal digesta. Akkermansia was highest in cecal and colonic digesta. In the colonic digesta of rats, the relative abundance of Akkermansia in rats on wheat diets was higher than that in rats on rice diets ( P < 0.05). Thus, UPR and WW could modulate gut microbiota composition and increase the SCFA concentration. Wheat diet was superior to rice diet in terms of intestinal microbiota adjustment.

Diet and microbiota in inflammatory bowel disease: The gut in disharmony.

PubMed

Rapozo, Davy C M; Bernardazzi, Claudio; de Souza, Heitor Siffert Pereira

2017-03-28

Bacterial colonization of the gut shapes both the local and the systemic immune response and is implicated in the modulation of immunity in both healthy and disease states. Recently, quantitative and qualitative changes in the composition of the gut microbiota have been detected in Crohn's disease and ulcerative colitis, reinforcing the hypothesis of dysbiosis as a relevant mechanism underlying inflammatory bowel disease (IBD) pathogenesis. Humans and microbes have co-existed and co-evolved for a long time in a mutually beneficial symbiotic association essential for maintaining homeostasis. However, the microbiome is dynamic, changing with age and in response to environmental modifications. Among such environmental factors, food and alimentary habits, progressively altered in modern societies, appear to be critical modulators of the microbiota, contributing to or co-participating in dysbiosis. In addition, food constituents such as micronutrients are important regulators of mucosal immunity, with direct or indirect effects on the gut microbiota. Moreover, food constituents have recently been shown to modulate epigenetic mechanisms, which can result in increased risk for the development and progression of IBD. Therefore, it is likely that a better understanding of the role of different food components in intestinal homeostasis and the resident microbiota will be essential for unravelling the complex molecular basis of the epigenetic, genetic and environment interactions underlying IBD pathogenesis as well as for offering dietary interventions with minimal side effects.

Diet and microbiota in inflammatory bowel disease: The gut in disharmony

PubMed Central

Rapozo, Davy C M; Bernardazzi, Claudio; de Souza, Heitor Siffert Pereira

2017-01-01

Bacterial colonization of the gut shapes both the local and the systemic immune response and is implicated in the modulation of immunity in both healthy and disease states. Recently, quantitative and qualitative changes in the composition of the gut microbiota have been detected in Crohn’s disease and ulcerative colitis, reinforcing the hypothesis of dysbiosis as a relevant mechanism underlying inflammatory bowel disease (IBD) pathogenesis. Humans and microbes have co-existed and co-evolved for a long time in a mutually beneficial symbiotic association essential for maintaining homeostasis. However, the microbiome is dynamic, changing with age and in response to environmental modifications. Among such environmental factors, food and alimentary habits, progressively altered in modern societies, appear to be critical modulators of the microbiota, contributing to or co-participating in dysbiosis. In addition, food constituents such as micronutrients are important regulators of mucosal immunity, with direct or indirect effects on the gut microbiota. Moreover, food constituents have recently been shown to modulate epigenetic mechanisms, which can result in increased risk for the development and progression of IBD. Therefore, it is likely that a better understanding of the role of different food components in intestinal homeostasis and the resident microbiota will be essential for unravelling the complex molecular basis of the epigenetic, genetic and environment interactions underlying IBD pathogenesis as well as for offering dietary interventions with minimal side effects. PMID:28405140

Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity.

PubMed

Sen, Tanusree; Cawthon, Carolina R; Ihde, Benjamin Thomas; Hajnal, Andras; DiLorenzo, Patricia M; de La Serre, Claire B; Czaja, Krzysztof

2017-05-01

Obesity is one of the major health issues in the United States. Consumption of diets rich in energy, notably from fats and sugars (high-fat/high-sugar diet: HF/HSD) is linked to the development of obesity and a popular dietary approach for weight loss is to reduce fat intake. Obesity research traditionally uses low and high fat diets and there has been limited investigation of the potential detrimental effects of a low-fat/high-sugar diet (LF/HSD) on body fat accumulation and health. Therefore, in the present study, we investigated the effects of HF/HSD and LF/HSD on microbiota composition, gut inflammation, gut-brain vagal communication and body fat accumulation. Specifically, we tested the hypothesis that LF/HSD changes the gut microbiota, induces gut inflammation and alters vagal gut-brain communication, associated with increased body fat accumulation. Sprague-Dawley rats were fed an HF/HSD, LF/HSD or control low-fat/low-sugar diet (LF/LSD) for 4weeks. Body weight, caloric intake, and body composition were monitored daily and fecal samples were collected at baseline, 1, 6 and 27days after the dietary switch. After four weeks, blood and tissues (gut, brain, liver and nodose ganglia) were sampled. Both HF/HSD and LF/HSD-fed rats displayed significant increases in body weight and body fat compared to LF/LSD-fed rats. 16S rRNA sequencing showed that both HF/HSD and LF/HSD-fed animals exhibited gut microbiota dysbiosis characterized by an overall decrease in bacterial diversity and an increase in Firmicutes/Bacteriodetes ratio. Dysbiosis was typified by a bloom in Clostridia and Bacilli and a marked decrease in Lactobacillus spp. LF/HSD-fed animals showed a specific increase in Sutterella and Bilophila, both Proteobacteria, abundances of which have been associated with liver damage. Expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNFα, was upregulated in the cecum while levels of tight junction protein occludin were downregulated in both HF/HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation. © 2016.

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

Perturbations of gut microbiome genes in infants with atopic dermatitis according to feeding type.

PubMed

Lee, Min-Jung; Kang, Mi-Jin; Lee, So-Yeon; Lee, Eun; Kim, Kangjin; Won, Sungho; Suh, Dong In; Kim, Kyung Won; Sheen, Youn Ho; Ahn, Kangmo; Kim, Bong-Soo; Hong, Soo-Jong

2018-04-01

Perturbations of the infant gut microbiota can shape development of the immune system and link to the risk of allergic diseases. We sought to understand the role of the gut microbiome in patients with atopic dermatitis (AD). The metagenome of the infant gut microbiome was analyzed according to feeding types. Composition of the gut microbiota was analyzed in fecal samples from 129 infants (6 months old) by using pyrosequencing, including 66 healthy infants and 63 infants with AD. The functional profile of the gut microbiome was analyzed by means of whole-metagenome sequencing (20 control subjects and 20 patients with AD). In addition, the total number of bacteria in the feces was determined by using real-time PCR. The gut microbiome of 6-month-old infants was different based on feeding types, and 2 microbiota groups (Bifidobacterium species-dominated and Escherichia/Veillonella species-dominated groups) were found in breast-fed and mixed-fed infants. Bacterial cell amounts in the feces were lower in infants with AD than in control infants. Although no specific taxa directly correlated with AD in 16S rRNA gene results, whole-metagenome analysis revealed differences in functional genes related to immune development. The reduction in genes for oxidative phosphorylation, phosphatidylinositol 3-kinase-Akt signaling, estrogen signaling, nucleotide-binding domain-like receptor signaling, and antigen processing and presentation induced by reduced colonization of mucin-degrading bacteria (Akkermansia muciniphila, Ruminococcus gnavus, and Lachnospiraceae bacterium 2_1_58FAA) was significantly associated with stunted immune development in the AD group compared with the control group (P < .05). Alterations in the gut microbiome can be associated with AD because of different bacterial genes that can modulate host immune cell function. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

Effect of artesunate supplementation on bacterial translocation and dysbiosis of gut microbiota in rats with liver cirrhosis.

PubMed

Chen, Yun-Xia; Lai, Li-Na; Zhang, Hui-Ying; Bi, Yang-Hui; Meng, Li; Li, Xu-Jiong; Tian, Xiao-Xia; Wang, Li-Min; Fan, Yi-Min; Zhao, Zhong-Fu; Han, De-Wu; Ji, Cheng

2016-03-14

To evaluate the effect of artesunate (AS) supplementation on bacterial translocation (BT) and gut microbiota in a rat model of liver cirrhosis. Fifty-four male Sprague-Dawley rats were randomly divided into a normal control group (N), a liver cirrhosis group (M) and a liver cirrhosis group intervened with AS (MA). Each group was sampled at 4, 6 and 8 wk. Liver cirrhosis was induced by injection of carbon tetrachloride (CCl4), intragastric administration of 10% ethanol, and feeding a high fat diet. Rats in the MA group were intragastrically administered with AS (25 mg/kg body weight, once daily). Injuries of the liver and intestinal mucosa were assessed by hematoxylin-eosin or Masson's trichrome staining. Liver index was calculated as a ratio of the organ weight (g) to body weight (g). The gut microbiota was examined by automated ribosomal intergenic-spacer analysis of fecal DNA. BT was assessed by standard microbiological techniques in the blood, mesenteric lymph nodes (MLNs), liver, spleen, and kidney. Compared to group N, the body weight was reduced significantly in groups M and MA due to the development of liver cirrhosis over the period of 8 wk. The body weight was higher in group MA than in group M. The liver indices were significantly elevated at 4, 6 and 8 wk in groups M and MA compared to group N. AS supplementation partially decreased the liver indices in group MA. Marked histopathologic changes in the liver and small intestinal mucosa in group M were observed, which were alleviated in group MA. Levels of pro-inflammatory interleukin-6 and tumor necrosis factor-α were significantly elevated at 8 wk in ileal homogenates in group M compared to group N, which were decreased after AS supplementation in group MA. The dysbiosis of gut microbiota indicated by the mean diversity (Shannon index) and mean similarity (Sorenson index) was severe as the liver cirrhosis developed, and AS supplementation had an apparent intervention effect on the dysbiosis of gut microbiota at 4 wk. The occurrence of BT was increased in the liver of group M compared to that of group N. AS supplementation reduced BT in group MA at 8 wk. BT also occurred in the MLNs, spleen, and kidney, which was reduced by AS supplementation. BT was not detected in the blood in any group. Dysbiosis of gut microbiota, injury of intestinal mucosal barrier and BT occurred as liver cirrhosis progressed, which might enhance inflammation and aggravate liver injury. AS may have other non-antimalarial effects that modulate gut microbiota, inhibit BT and alleviate inflammation, resulting in a reduction in CCl4, alcohol and high fat-caused damages to the liver and intestine.

Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

PubMed Central

Pamer, Eric G.

2016-01-01

The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care–associated infections caused by highly antibiotic-resistant bacteria. PMID:27126035

Effect of room temperature transport vials on DNA quality and phylogenetic composition of faecal microbiota of elderly adults and infants.

PubMed

Hill, Cian J; Brown, Jillian R M; Lynch, Denise B; Jeffery, Ian B; Ryan, C Anthony; Ross, R Paul; Stanton, Catherine; O'Toole, Paul W

2016-05-10

Alterations in intestinal microbiota have been correlated with a growing number of diseases. Investigating the faecal microbiota is widely used as a non-invasive and ethically simple proxy for intestinal biopsies. There is an urgent need for collection and transport media that would allow faecal sampling at distance from the processing laboratory, obviating the need for same-day DNA extraction recommended by previous studies of freezing and processing methods for stool. We compared the faecal bacterial DNA quality and apparent phylogenetic composition derived using a commercial kit for stool storage and transport (DNA Genotek OMNIgene GUT) with that of freshly extracted samples, 22 from infants and 20 from older adults. Use of the storage vials increased the quality of extracted bacterial DNA by reduction of DNA shearing. When infant and elderly datasets were examined separately, no differences in microbiota composition were observed due to storage. When the two datasets were combined, there was a difference according to a Wilcoxon test in the relative proportions of Faecalibacterium, Sporobacter, Clostridium XVIII, and Clostridium XlVa after 1 week's storage compared to immediately extracted samples. After 2 weeks' storage, Bacteroides abundance was also significantly different, showing an apparent increase from week 1 to week 2. The microbiota composition of infant samples was more affected than that of elderly samples by storage, with significantly higher Spearman distances between paired freshly extracted and stored samples (p < 0.001). When the microbiota profiles were analysed at the operational taxonomic unit (OTU) level, three infant datasets in the study did not cluster together, while only one elderly dataset did not. The lower microbiota diversity of the infant gut microbiota compared to the elderly gut microbiota (p < 0.001) means that any alteration in the infant datasets has a proportionally larger effect. The commercial storage vials appear to be suitable for high diversity microbiota samples, but may be less appropriate for lower diversity samples. Differences between fresh and stored samples mean that where storage is unavoidable, a consistent storage regime should be used. We would recommend extraction ideally within the first week of storage.

Alterations in the Fecal Microbiota of Patients with HIV-1 Infection: An Observational Study in A Chinese Population

PubMed Central

Ling, Zongxin; Jin, Changzhong; Xie, Tiansheng; Cheng, Yiwen; Li, Lanjuan; Wu, Nanping

2016-01-01

The available evidence suggests that alterations in gut microbiota may be tightly linked to the increase in microbial translocation and systemic inflammation in patients with human immunodeficiency virus 1 (HIV-1) infection. We profiled the fecal microbiota as a proxy of gut microbiota by parallel barcoded 454-pyrosequencing in 67 HIV-1-infected patients (32 receiving highly active antiretroviral therapy [HAART] and 35 HAART naïve) and 16 healthy controls from a Chinese population. We showed that α-diversity indices did not differ significantly between the healthy control and HIV-1-infected patients. The ratio of Firmicutes/Bacteroidetes increased significantly in HIV-1-infected patients. Several key bacterial phylotypes, including Prevotella, were prevalent in HIV-1-infected patients; whereas Phascolarctobacterium, Clostridium XIVb, Dialister and Megamonas were significantly correlated with systemic inflammatory cytokines. After short-term, effective HAART, the viral loads of HIV-1 were reduced; however, the diversity and composition of the fecal microbiota were not completely restored. and the dysbiosis remained among HIV-1-infected subjects undergoing HAART. Our detailed analysis demonstrated that dysbiosis of fecal microbiota might play an active role in HIV-1 infection. Thus, new insights may be provided into therapeutics that target the microbiota to attenuate the progression of HIV disease and to reduce the risk of gut-linked disease in HIV-1-infected patients. PMID:27477587

The Intersection Between Colonization Resistance, Antimicrobial Stewardship, and Clostridium difficile.

PubMed

Rosa, Rossana; Donskey, Curtis J; Munoz-Price, L Silvia

2018-06-07

Colonization resistance refers to the innate defense provided by the indigenous microbiota against colonization by pathogenic organisms. We aim to describe how this line of defense is deployed against Clostridium difficile and what the implications are for interventions directed by Antimicrobial Stewardship Programs. The indigenous microbiota provides colonization resistance through depletion of nutrients, prevention of access to adherence sites within the gut mucosa, production of inhibitory substances, and stimulation of the host's immune system. The ability to quantify colonization resistance could provide information regarding periods of maximal vulnerability to colonization with pathogens and also allow the identification of mechanisms of restoration of colonization resistance. Methods utilized to determine the composition of the gut microbiota include sequencing technologies and measurement of concentration of specific bacterial metabolites. Use of innovations in the quantification of colonization resistance can expand the role of Antimicrobial Stewardship from prevention of disruption of the indigenous microbiota to restoration of colonization resistance.

Impacts of canine distemper virus infection on the giant panda population from the perspective of gut microbiota

PubMed Central

Zhao, Na; Li, Meng; Luo, Jing; Wang, Supen; Liu, Shelan; Wang, Shan; Lyu, Wenting; Chen, Lin; Su, Wen; Ding, Hua; He, Hongxuan

2017-01-01

The recent increase in infectious disease outbreaks has been directly linked to the global loss of biodiversity and the decline of some endangered species populations. Between December 2014 and March 2015, five captive giant pandas died due to canine distemper virus (CDV) infection in China. CDV has taken a heavy toll on tigers and lions in recent years. Here, we describe the first gut microbiome diversity study of CDV-infected pandas. By investigating the influence of CDV infection on gut bacterial communities in infected and uninfected individuals and throughout the course of infection, we found that CDV infection distorted the gut microbiota composition by reducing the prevalence of the dominant genera, Escherichia and Clostridium, and increasing microbial diversity. Our results highlight that increases in intestinal inflammation and changes in the relative abundances of pathogen-containing gut communities occur when individuals become infected with CDV. These results may provide new insights into therapeutics that target the microbiota to attenuate the progression of CDV disease and to reduce the risk of gut-linked disease in individuals with CDV. In addition, our findings underscore the need for better information concerning the dynamics of infection and the damage caused by pathogens in panda populations. PMID:28051146

High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE-/- mice.

PubMed

Chan, Yee Kwan; Brar, Manreetpal Singh; Kirjavainen, Pirkka V; Chen, Yan; Peng, Jiao; Li, Daxu; Leung, Frederick Chi-Ching; El-Nezami, Hani

2016-11-08

Atherosclerosis appears to have multifactorial causes - microbial component like lipopolysaccharides (LPS) and other pathogen associated molecular patterns may be plausible factors. The gut microbiota is an ample source of such stimulants, and its dependent metabolites and altered gut metagenome has been an established link to atherosclerosis. In this exploratory pilot study, we aimed to elucidate whether microbial intervention with probiotics L. rhamnosus GG (LGG) or pharmaceuticals telmisartan (TLM) could improve atherosclerosis in a gut microbiota associated manner. Atherosclerotic phenotype was established by 12 weeks feeding of high fat (HF) diet as opposed to normal chow diet (ND) in apolipoprotein E knockout (ApoE -/- ) mice. LGG or TLM supplementation to HF diet was studied. Both LGG and TLM significantly reduced atherosclerotic plaque size and improved various biomarkers including endotoxin to different extents. Colonial microbiota analysis revealed that TLM restored HF diet induced increase in Firmicutes/Bacteroidetes ratio and decrease in alpha diversity; and led to a more distinct microbial clustering closer to ND in PCoA plot. Eubacteria, Anaeroplasma, Roseburia, Oscillospira and Dehalobacteria appeared to be protective against atherosclerosis and showed significant negative correlation with atherosclerotic plaque size and plasma adipocyte - fatty acid binding protein (A-FABP) and cholesterol. LGG and TLM improved atherosclerosis with TLM having a more distinct alteration in the colonic gut microbiota. Altered bacteria genera and reduced alpha diversity had significant correlations to atherosclerotic plaque size, plasma A-FABP and cholesterol. Future studies on such bacterial functional influence in lipid metabolism will be warranted.

Gut microbiota and allergy: the importance of the pregnancy period.

PubMed

Abrahamsson, Thomas R; Wu, Richard You; Jenmalm, Maria C

2015-01-01

Limited microbial exposure is suggested to underlie the increase of allergic diseases in affluent countries, and bacterial diversity seems to be more important than specific bacteria taxa. Prospective studies indicate that the gut microbiota composition during the first months of life influences allergy development, and support the theory that factors influencing the early maturation of the immune system might be important for subsequent allergic disease. However, recent research indicates that microbial exposure during pregnancy may be even more important for the preventative effects against allergic disease. This review gives a background of the epidemiology, immunology, and microbiology literature in this field. It focuses on possible underlying mechanisms such as immune-regulated epigenetic imprinting and bacterial translocation during pregnancy, potentially providing the offspring with a pioneer microbiome. We suggest that a possible reason for the initial exposure of bacterial molecular patterns to the fetus in utero is to prime the immune system and/or the epithelium to respond appropriately to pathogens and commensals after birth.

The possible mechanisms of the human microbiome in allergic diseases.

PubMed

Ipci, Kagan; Altıntoprak, Niyazi; Muluk, Nuray Bayar; Senturk, Mehmet; Cingi, Cemal

2017-02-01

In the present paper, we discuss the importance of the microbiome in allergic disease. In this review paper, the data from the Medline (PubMed) and search engine of Kirikkale University were systematically searched for all relevant articles in June 15th, 2015 for the past 30 years. The keywords of "microbiome", "dysbiosis", "allergy", "allergic rhinitis", "allergic disease", "mechanisms" and "treatment" were used alone or together. In this paper, microbiomes were presented in terms of "Definition", "Influence of \\the human microbiome on health", "The microbiome and allergic diseases", and "Modulation of the gut microbiota in terms of treatment and prevention". Microbiological dysbiosis is also reviewed. The microbiome is the genetic material of all microbes (bacteria, fungi, protozoa, and viruses) that live on or in the human body. Microbes outnumber human cells in a 10:1 ratio. Most microbes live in the gut, particularly the large intestine. Changes in the immune function of the respiratory tract are (at least in theory) linked to the immunomodulatory activity of the gut microbiota via the concept of a "common mucosal response". The gut microbiota shapes systemic immunity, thus affecting the lung mucosa. Alternatively, changes in the gut microbiota may reflect alterations in the oropharyngeal microbiota, which may in turn directly affect the lung microbiota and host immune responses via microaspiration. Dysbiosis is defined as qualitative and quantitative changes in the intestinal flora; and modern diet and lifestyle, antibiotics, psychological and physical stress result in alterations in bacterial metabolism, as well as the overgrowth of potentially pathogenic microorganisms. All immune system components are directly or indirectly regulated by the microbiota. The nature of microbial exposure early in life appears to be important for the development of robust immune regulation; disruption of either the microbiota or the host response can trigger chronic inflammation. Dysbiosis is also an important clinical entity. Antibiotics, psychological and physical stress, and dietary factors contribute to intestinal dysbiosis.

In Vitro Continuous Fermentation Model (PolyFermS) of the Swine Proximal Colon for Simultaneous Testing on the Same Gut Microbiota

PubMed Central

Tanner, Sabine A.; Zihler Berner, Annina; Rigozzi, Eugenia; Grattepanche, Franck; Chassard, Christophe; Lacroix, Christophe

2014-01-01

In vitro gut modeling provides a useful platform for a fast and reproducible assessment of treatment-related changes. Currently, pig intestinal fermentation models are mainly batch models with important inherent limitations. In this study we developed a novel in vitro continuous fermentation model, mimicking the porcine proximal colon, which we validated during 54 days of fermentation. This model, based on our recent PolyFermS design, allows comparing different treatment effects on the same microbiota. It is composed of a first-stage inoculum reactor seeded with immobilized fecal swine microbiota and used to constantly inoculate (10% v/v) five second-stage reactors, with all reactors fed with fresh nutritive chyme medium and set to mimic the swine proximal colon. Reactor effluents were analyzed for metabolite concentrations and bacterial composition by HPLC and quantitative PCR, and microbial diversity was assessed by 454 pyrosequencing. The novel PolyFermS featured stable microbial composition, diversity and metabolite production, consistent with bacterial activity reported for swine proximal colon in vivo. The constant inoculation provided by the inoculum reactor generated reproducible microbial ecosystems in all second-stage reactors, allowing the simultaneous investigation and direct comparison of different treatments on the same porcine gut microbiota. Our data demonstrate the unique features of this novel PolyFermS design for the swine proximal colon. The model provides a tool for efficient, reproducible and cost-effective screening of environmental factors, such as dietary additives, on pig colonic fermentation. PMID:24709947

In vitro continuous fermentation model (PolyFermS) of the swine proximal colon for simultaneous testing on the same gut microbiota.

PubMed

Tanner, Sabine A; Zihler Berner, Annina; Rigozzi, Eugenia; Grattepanche, Franck; Chassard, Christophe; Lacroix, Christophe

2014-01-01

In vitro gut modeling provides a useful platform for a fast and reproducible assessment of treatment-related changes. Currently, pig intestinal fermentation models are mainly batch models with important inherent limitations. In this study we developed a novel in vitro continuous fermentation model, mimicking the porcine proximal colon, which we validated during 54 days of fermentation. This model, based on our recent PolyFermS design, allows comparing different treatment effects on the same microbiota. It is composed of a first-stage inoculum reactor seeded with immobilized fecal swine microbiota and used to constantly inoculate (10% v/v) five second-stage reactors, with all reactors fed with fresh nutritive chyme medium and set to mimic the swine proximal colon. Reactor effluents were analyzed for metabolite concentrations and bacterial composition by HPLC and quantitative PCR, and microbial diversity was assessed by 454 pyrosequencing. The novel PolyFermS featured stable microbial composition, diversity and metabolite production, consistent with bacterial activity reported for swine proximal colon in vivo. The constant inoculation provided by the inoculum reactor generated reproducible microbial ecosystems in all second-stage reactors, allowing the simultaneous investigation and direct comparison of different treatments on the same porcine gut microbiota. Our data demonstrate the unique features of this novel PolyFermS design for the swine proximal colon. The model provides a tool for efficient, reproducible and cost-effective screening of environmental factors, such as dietary additives, on pig colonic fermentation.

Gut Bacterial Communities in the Giant Land Snail Achatina fulica and Their Modification by Sugarcane-Based Diet

PubMed Central

Cardoso, Alexander M.; Cavalcante, Janaína J. V.; Vieira, Ricardo P.; Lima, Joyce L.; Grieco, Maria Angela B.; Clementino, Maysa M.; Vasconcelos, Ana Tereza R.; Garcia, Eloi S.; de Souza, Wanderley; Albano, Rodolpho M.; Martins, Orlando B.

2012-01-01

The invasive land snail Achatina fulica is one of the most damaging agricultural pests worldwide representing a potentially serious threat to natural ecosystems and human health. This species is known to carry parasites and harbors a dense and metabolically active microbial community; however, little is known about its diversity and composition. Here, we assessed for the first time the complexity of bacterial communities occurring in the digestive tracts of field-collected snails (FC) by using culture-independent molecular analysis. Crop and intestinal bacteria in FC were then compared to those from groups of snails that were reared in the laboratory (RL) on a sugarcane-based diet. Most of the sequences recovered were novel and related to those reported for herbivorous gut. Changes in the relative abundance of Bacteroidetes and Firmicutes were observed when the snails were fed a high-sugar diet, suggesting that the snail gut microbiota can influence the energy balance equation. Furthermore, this study represents a first step in gaining a better understanding of land snail gut microbiota and shows that this is a complex holobiont system containing diverse, abundant and active microbial communities. PMID:22438932

Gut bacterial communities in the giant land snail Achatina fulica and their modification by sugarcane-based diet.

PubMed

Cardoso, Alexander M; Cavalcante, Janaína J V; Vieira, Ricardo P; Lima, Joyce L; Grieco, Maria Angela B; Clementino, Maysa M; Vasconcelos, Ana Tereza R; Garcia, Eloi S; de Souza, Wanderley; Albano, Rodolpho M; Martins, Orlando B

2012-01-01

The invasive land snail Achatina fulica is one of the most damaging agricultural pests worldwide representing a potentially serious threat to natural ecosystems and human health. This species is known to carry parasites and harbors a dense and metabolically active microbial community; however, little is known about its diversity and composition. Here, we assessed for the first time the complexity of bacterial communities occurring in the digestive tracts of field-collected snails (FC) by using culture-independent molecular analysis. Crop and intestinal bacteria in FC were then compared to those from groups of snails that were reared in the laboratory (RL) on a sugarcane-based diet. Most of the sequences recovered were novel and related to those reported for herbivorous gut. Changes in the relative abundance of Bacteroidetes and Firmicutes were observed when the snails were fed a high-sugar diet, suggesting that the snail gut microbiota can influence the energy balance equation. Furthermore, this study represents a first step in gaining a better understanding of land snail gut microbiota and shows that this is a complex holobiont system containing diverse, abundant and active microbial communities.

Characterization of the gut bacterial community in Manduca sexta and effect of antibiotics on bacterial diversity and nematode reproduction.

PubMed

van der Hoeven, Ransome; Betrabet, Geeta; Forst, Steven

2008-09-01

The tobacco hornworm, Manduca sexta, is a model lepidopteran insect used to study the pathogenic and mutualistic phases of entomopathogenic nematodes (EPNs) and their bacterial symbionts. While intestinal microbial communities could potentially compete with the EPN and its bacterial partner for nutrient resources of the insect, the microbial gut community had not been characterized previously. Here, we show that the midgut of M. sexta raised on an artificial diet contained mostly Gram-positive cocci and coryneforms including Staphylococcus, Pediococcus, Micrococcus and Corynebacterium. Major perturbation in the gut community was observed on addition of antibiotics to the diet. Paenibacillus and several Proteobacteria such as Methylobacterium, Sphingomonas and Acinetobacter were primary genera identified under these conditions. Furthermore, the reproduction of the nematode Steinernema carpocapsae was less efficient, and the level of nematode colonization by its symbiont Xenorhabdus nematophila reduced, in insects reared on a diet containing antibiotics. The effect of antibiotics and perturbation of gut microbiota on nematode reproduction is discussed.

Necessary Sequencing Depth and Clustering Method to Obtain Relatively Stable Diversity Patterns in Studying Fish Gut Microbiota.

PubMed

Xiao, Fanshu; Yu, Yuhe; Li, Jinjin; Juneau, Philippe; Yan, Qingyun

2018-05-25

The 16S rRNA gene is one of the most commonly used molecular markers for estimating bacterial diversity during the past decades. However, there is no consistency about the sequencing depth (from thousand to millions of sequences per sample), and the clustering methods used to generate OTUs may also be different among studies. These inconsistent premises make effective comparisons among studies difficult or unreliable. This study aims to examine the necessary sequencing depth and clustering method that would be needed to ensure a stable diversity patterns for studying fish gut microbiota. A total number of 42 samples dataset of Siniperca chuatsi (carnivorous fish) gut microbiota were used to test how the sequencing depth and clustering may affect the alpha and beta diversity patterns of fish intestinal microbiota. Interestingly, we found that the sequencing depth (resampling 1000-11,000 per sample) and the clustering methods (UPARSE and UCLUST) did not bias the estimates of the diversity patterns during the fish development from larva to adult. Although we should acknowledge that a suitable sequencing depth may differ case by case, our finding indicates that a shallow sequencing such as 1000 sequences per sample may be also enough to reflect the general diversity patterns of fish gut microbiota. However, we have shown in the present study that strict pre-processing of the original sequences is required to ensure reliable results. This study provides evidences to help making a strong scientific choice of the sequencing depth and clustering method for future studies on fish gut microbiota patterns, but at the same time reducing as much as possible the costs related to the analysis.