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Sample records for intestinal microbial antigens

  1. Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice

    PubMed Central

    Natividad, Jane M.; Huang, Xianxi; Slack, Emma; Jury, Jennifer; Sanz, Yolanda; David, Chella; Denou, Emmanuel; Yang, Pinchang; Murray, Joseph

    2009-01-01

    Background and Aims Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice. Methodology/Principal Findings HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by in-vitro antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-γ in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota. Conclusion Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-γ production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota. PMID:19649259

  2. Intestinal Antigen-Presenting Cells

    PubMed Central

    Flannigan, Kyle L.; Geem, Duke; Harusato, Akihito; Denning, Timothy L.

    2016-01-01

    The microbiota that populate the mammalian intestine are critical for proper host physiology, yet simultaneously pose a potential danger. Intestinal antigen-presenting cells, namely macrophages and dendritic cells (DCs), are integral components of the mucosal innate immune system that maintain co-existence with the microbiota in face of this constant threat. Intestinal macrophages and DCs integrate signals from the microenvironment to orchestrate innate and adaptive immune responses that ultimately lead to durable tolerance of the microbiota. Tolerance is not a default response, however, because macrophages and DCs remain poised to vigorously respond to pathogens that breach the epithelial barrier. In this review, we summarize the salient features of macrophages and DCs in the healthy and inflamed intestine and discuss how signals from the microbiota can influence their function. PMID:25976247

  3. Phenotypic and functional profiling of mouse intestinal antigen presenting cells

    PubMed Central

    Harusato, Akihito; Flannigan, Kyle L.; Geem, Duke; Denning, Timothy L.

    2015-01-01

    The microbiota that populates the mammalian intestine consists of hundreds of trillions of bacteria that are separated from underlying immune cells by a single layer of epithelial cells. The intestinal immune system effectively tolerates components of the microbiota that provide benefit to the host while remaining poised to eliminate those that are harmful. Antigen presenting cells, especially macrophages and dendritic cells, play important roles in maintaining intestinal homeostasis via their ability to orchestrate appropriate responses to the microbiota. Paramount to elucidating intestinal macrophage- and dendritic cell-mediated functions is the ability to effectively isolate and identify these cells from a complex cellular environment. In this review, we summarize methodology for the isolation and phenotypic characterization of macrophages and DCs from the mouse intestine and discuss how this may be useful for gaining insight into the mechanisms by which mucosal immune tolerance is maintained. PMID:25891794

  4. Reduction of T-Helper Cell Responses to Recall Antigen Mediated by Codelivery with Peptidoglycan via the Intestinal Nanomineral–Antigen Pathway

    PubMed Central

    Hewitt, Rachel E.; Robertson, Jack; Haas, Carolin T.; Pele, Laetitia C.; Powell, Jonathan J.

    2017-01-01

    Naturally occurring intestinal nanomineral particles constituently form in the mammalian gut and trap luminal protein and microbial components. These cargo loaded nanominerals are actively scavenged by M cells of intestinal immune follicles, such as Peyer’s patches and are passed to antigen-presenting cells. Using peripheral blood mononuclear cell populations as an in vitro model of nanomineral uptake and antigen presentation, we show that monocytes avidly phagocytose nanomineral particles bearing antigen and peptidoglycan (PGN), and that the presence of PGN within particles downregulates their cell surface MHC class II and upregulates programmed death receptor ligand 1. Nanomineral delivery of antigen suppresses antigen-specific CD4+ T cell responses, an effect that is enhanced in the presence of PGN. Blocking the interleukin-10 receptor restores CD4+ T cell responses to antigen codelivered with PGN in nanomineral form. Using human intestinal specimens, we have shown that the in vivo nanomineral pathway operates in an interleukin-10 rich environment. Consequently, the delivery of a dual antigen–PGN cargo by endogenous nanomineral in vivo is likely to be important in the establishment of intestinal tolerance, while their synthetic mimetics present a potential delivery system for therapeutic applications targeting the modulation of Peyer’s patch T cell responses. PMID:28367148

  5. The outer mucus layer hosts a distinct intestinal microbial niche

    PubMed Central

    Li, Hai; Limenitakis, Julien P.; Fuhrer, Tobias; Geuking, Markus B.; Lawson, Melissa A.; Wyss, Madeleine; Brugiroux, Sandrine; Keller, Irene; Macpherson, Jamie A.; Rupp, Sandra; Stolp, Bettina; Stein, Jens V.; Stecher, Bärbel; Sauer, Uwe; McCoy, Kathy D.; Macpherson, Andrew J.

    2015-01-01

    The overall composition of the mammalian intestinal microbiota varies between individuals: within each individual there are differences along the length of the intestinal tract related to host nutrition, intestinal motility and secretions. Mucus is a highly regenerative protective lubricant glycoprotein sheet secreted by host intestinal goblet cells; the inner mucus layer is nearly sterile. Here we show that the outer mucus of the large intestine forms a unique microbial niche with distinct communities, including bacteria without specialized mucolytic capability. Bacterial species present in the mucus show differential proliferation and resource utilization compared with the same species in the intestinal lumen, with high recovery of bioavailable iron and consumption of epithelial-derived carbon sources according to their genome-encoded metabolic repertoire. Functional competition for existence in this intimate layer is likely to be a major determinant of microbiota composition and microbial molecular exchange with the host. PMID:26392213

  6. Dysregulation of Systemic and Mucosal Humoral Responses to Microbial and Food Antigens as a Factor Contributing to Microbial Translocation and Chronic Inflammation in HIV-1 Infection.

    PubMed

    Hel, Zdenek; Xu, Jun; Denning, Warren L; Helton, E Scott; Huijbregts, Richard P H; Heath, Sonya L; Overton, E Turner; Christmann, Benjamin S; Elson, Charles O; Goepfert, Paul A; Mestecky, Jiri

    2017-01-01

    HIV-1 infection is associated with an early and profound depletion of mucosal memory CD4+ T cells, a population that plays an indispensable role in the regulation of isotype switching and transepithelial transport of antibodies. In this study, we addressed whether the depletion of CD4+ T cell in HIV-1-infected individuals results in altered humoral responses specific to antigens encountered at mucosal surfaces. Comprehensive protein microarray of systemic humoral responses to intestinal microbiota demonstrated reduced IgG responses to antigens derived from Proteobacteria and Firmicutes but not Bacteroidetes. Importantly, intestinal secretions of antiretroviral therapy-treated HIV-1-infected individuals exhibited a significant elevation of IgM levels and decreased IgA/IgM and IgG/IgM ratios of antibodies specific to a variety of microbial and food antigens. The presented findings indicate reduced competence of mucosal B cells for class switch recombination from IgM to other isotypes limiting their capacity to react to changing antigenic variety in the gut lumen. Decreased availability of microbiota-specific IgA and IgG may be an important factor contributing to the translocation of microbial antigens across the intestinal mucosal barrier and their systemic dissemination that drives chronic inflammation in HIV-1-infected individuals.

  7. Dysregulation of Systemic and Mucosal Humoral Responses to Microbial and Food Antigens as a Factor Contributing to Microbial Translocation and Chronic Inflammation in HIV-1 Infection

    PubMed Central

    Hel, Zdenek; Xu, Jun; Denning, Warren L.; Huijbregts, Richard P. H.; Heath, Sonya L.; Overton, E. Turner; Elson, Charles O.; Goepfert, Paul A.; Mestecky, Jiri

    2017-01-01

    HIV-1 infection is associated with an early and profound depletion of mucosal memory CD4+ T cells, a population that plays an indispensable role in the regulation of isotype switching and transepithelial transport of antibodies. In this study, we addressed whether the depletion of CD4+ T cell in HIV-1-infected individuals results in altered humoral responses specific to antigens encountered at mucosal surfaces. Comprehensive protein microarray of systemic humoral responses to intestinal microbiota demonstrated reduced IgG responses to antigens derived from Proteobacteria and Firmicutes but not Bacteroidetes. Importantly, intestinal secretions of antiretroviral therapy-treated HIV-1-infected individuals exhibited a significant elevation of IgM levels and decreased IgA/IgM and IgG/IgM ratios of antibodies specific to a variety of microbial and food antigens. The presented findings indicate reduced competence of mucosal B cells for class switch recombination from IgM to other isotypes limiting their capacity to react to changing antigenic variety in the gut lumen. Decreased availability of microbiota-specific IgA and IgG may be an important factor contributing to the translocation of microbial antigens across the intestinal mucosal barrier and their systemic dissemination that drives chronic inflammation in HIV-1-infected individuals. PMID:28125732

  8. A Microbial Feed Additive Abates Intestinal Inflammation in Atlantic Salmon

    PubMed Central

    Vasanth, Ghana; Kiron, Viswanath; Kulkarni, Amod; Dahle, Dalia; Lokesh, Jep; Kitani, Yoichiro

    2015-01-01

    The efficacy of a microbial feed additive (Bactocell®) in countering intestinal inflammation in Atlantic salmon was examined in this study. Fish were fed either the additive-coated feed (probiotic) or feed without it (control). After an initial 3-week feeding, an inflammatory condition was induced by anally intubating all the fish with oxazolone. The fish were offered the feeds for 3 more weeks. Distal intestine from the groups was obtained at 4 h, 24 h, and 3 weeks, after oxazolone treatment. Inflammatory responses were prominent in both groups at 24 h, documented by changes in intestinal micromorphology, expression of inflammation-related genes, and intestinal proteome. The control group was characterized by edema, widening of intestinal villi and lamina propria, infiltration of granulocytes and lymphocytes, and higher expression of genes related to inflammatory responses, mul1b, il1b, tnfa, ifng, compared to the probiotic group or other time points of the control group. Further, the protein expression in the probiotic group at 24 h after inducing inflammation revealed five differentially regulated proteins – Calr, Psma5, Trp1, Ctsb, and Naga. At 3 weeks after intubation, the inflammatory responses subsided in the probiotic group. The findings provide evidence that the microbial additive contributes to intestinal homeostasis in Atlantic salmon. PMID:26347738

  9. Microbial imbalance and intestinal pathologies: connections and contributions

    PubMed Central

    Yang, Ye; Jobin, Christian

    2014-01-01

    Microbiome analysis has identified a state of microbial imbalance (dysbiosis) in patients with chronic intestinal inflammation and colorectal cancer. The bacterial phylum Proteobacteria is often overrepresented in these individuals, with Escherichia coli being the most prevalent species. It is clear that a complex interplay between the host, bacteria and bacterial genes is implicated in the development of these intestinal diseases. Understanding the basic elements of these interactions could have important implications for disease detection and management. Recent studies have revealed that E. coli utilizes a complex arsenal of virulence factors to colonize and persist in the intestine. Some of these virulence factors, such as the genotoxin colibactin, were found to promote colorectal cancer in experimental models. In this Review, we summarize key features of the dysbiotic states associated with chronic intestinal inflammation and colorectal cancer, and discuss how the dysregulated interplay between host and bacteria could favor the emergence of E. coli with pathological traits implicated in these pathologies. PMID:25256712

  10. New diagnostic antigens for early trichinellosis: the excretory-secretory antigens of Trichinella spiralis intestinal infective larvae.

    PubMed

    Sun, Ge Ge; Liu, Ruo Dan; Wang, Zhong Quan; Jiang, Peng; Wang, Li; Liu, Xiao Lin; Liu, Chun Yin; Zhang, Xi; Cui, Jing

    2015-12-01

    The excretory-secretory (ES) antigens from Trichinella spiralis muscle larvae (ML) are the most commonly used diagnostic antigens for trichinellosis, but anti-Trichinella IgG antibodies cannot be detected until 2-3 weeks after infection; there is an obvious window period between Trichinella infection and antibody positivity. Intestinal infective larvae (IIL) are the first invasive stage during Trichinella infection, and their ES antigens are firstly exposed to the immune system and might be the early diagnostic markers of trichinellosis. The aim of this study was to evaluate the early diagnostic values of IIL ES antigens for trichinellosis. The IIL were collected from intestines of infected mice at 6 h postinfection (hpi), and IIL ES antigens were prepared by incubation for 18 h. Anti-Trichinella IgG antibodies in mice infected with 100 ML were detectable by ELISA with IIL ES antigens as soon as 10 days postinfection (dpi), but ELISA with ML ES antigens did not permit detection of infected mice before 12 dpi. When the sera of patients with trichinellosis at 19 dpi were assayed, the sensitivity (100 %) of ELISA with IIL ES antigens was evidently higher than 75 % of ELISA with ML ES antigens (P < 0.05) The specificity (96.86 %) of ELISA with IIL ES antigens was also higher than 89.31 % of ELISA with ML ES antigens (P < 0.05). The IIL ES antigens provided a new source of diagnostic antigens and could be considered as a potential early diagnostic antigen for trichinellosis.

  11. [Microbial diversity in scorpion intestine (Buthus martensii Karsch)].

    PubMed

    Wang, Bao-Jun; Liu, Ying; Jiang, Jia-Tong; Liu, Bin; Liu, Shuang-Jiang

    2007-10-01

    Scorpion is an important officinal animal, and has a high nutritional value. In this study, the culture-independent and culture-dependent methods were used to investigate the microbial diversity in the scorpion's intestine. Results based on culture-independent method showed the bacteria to be related to alpha, beta, gamma-proteobacteria. Bacteria isolated by the culture-dependent method were high G + C, gram-positive bacteria. The genera Enterobacter, Serratia and Ochrobactrum were detected by both methods. To sum up the results from the two methods, the bacteria in scorpion intestine belong to 23 genera, which are Enterobacter, Serratia, Pseudomonas, Acinetobacter, Aeromonas, Citrobacter, Pedobacter, Delftia, Ralstonia, Ochrobactrum, Sphingomonas, Exiguobacterium, Gordonia, Nocardia, Rhodococcus, Janibacte, Kocuria, Micrococcus, Agromyces, Microbacterium, Agrococcus, Deinococcus, Ornithinimicrobium, and some uncultured species. The two methods have both advantages and shortcomings. However, when used simultaneously, they complement each other.

  12. Microbial DNA extraction from intestinal biopsies is improved by avoiding mechanical cell disruption

    PubMed Central

    Carbonero, Franck; Nava, Gerardo M.; Benefiel, Ann C.; Greenberg, Eugene; Gaskins, H. Rex

    2011-01-01

    Currently, standard protocols for microbial DNA extraction from intestinal tissues do not exist. We assessed the efficiency of a commercial kit with and without mechanical disruption. Better quality DNA was obtained without mechanical disruption. Thus, it appears that bead-beating is not required for efficient microbial DNA extraction from intestinal biopsies. PMID:21820015

  13. Dietary synbiotic application modulates Atlantic salmon (Salmo salar) intestinal microbial communities and intestinal immunity.

    PubMed

    Abid, A; Davies, S J; Waines, P; Emery, M; Castex, M; Gioacchini, G; Carnevali, O; Bickerdike, R; Romero, J; Merrifield, D L

    2013-12-01

    A feeding trial was conducted to determine the effect of dietary administration of Pediococcus acidilactici MA18/5M and short chain fructooligosaccharides (scFOS) on Atlantic salmon (Salmo salar L.) intestinal health. Salmon (initial average weight 250 g) were allocated into triplicate sea pens and were fed either a control diet (commercial diet: 45% protein, 20% lipid) or a synbiotic treatment diet (control diet + P. acidilactici at 3.5 g kg(-1) and 7 g kg(-1) scFOS) for 63 days. At the end of this period, fish were sampled for intestinal microbiology, intestinal histology and the expression of selected immune-related genes (IL1β, TNFα, IL8, TLR3 and MX-1) in the intestine. Compared to the control fish, the total bacterial levels were significantly lower in the anterior mucosa, posterior mucosa and posterior digesta of the synbiotic fed fish. qPCR revealed good recovery (log 6 bacteria g(-1)) of the probiotic in the intestinal digesta of the synbiotic fed fish and PCR-DGGE revealed that the number of OTUs, as well as the microbial community diversity and richness were significantly higher in the anterior digesta of the synbiotic fed fish than the control. Compared to the control fed fish, the mucosal fold (villi) length and the infiltration of epithelial leucocytes were significantly higher in the anterior and posterior intestine, respectively, in the synbiotic group. Real-time PCR demonstrated that all of the genes investigated were significantly up-regulated in the anterior and posterior intestine of the synbiotic fed salmon, compared to the control group. At the systemic level, serum lysozyme activity was significantly higher in the synbiotic fed fish and growth performance, feed utilisation and biometric measurements (condition factor, gutted weight and gut loss) were not affected. Together these results suggest that the synbiotic modulation of the gut microbiota has a protective action on the intestinal mucosal cells, improving morphology and stimulating

  14. Intestinal Intraepithelial Lymphocyte-Enterocyte Crosstalk Regulates Production of Bactericidal Angiogenin 4 by Paneth Cells upon Microbial Challenge

    PubMed Central

    Dalton, Jane E.; Overweg, Karin; Egan, Charlotte E.; Bongaerts, Roy J.; Newton, Darren J.; Cruickshank, Sheena M.; Andrew, Elizabeth M.; Carding, Simon R.

    2013-01-01

    Antimicrobial proteins influence intestinal microbial ecology and limit proliferation of pathogens, yet the regulation of their expression has only been partially elucidated. Here, we have identified a putative pathway involving epithelial cells and intestinal intraepithelial lymphocytes (iIELs) that leads to antimicrobial protein (AMP) production by Paneth cells. Mice lacking γδ iIELs (TCRδ-/-) express significantly reduced levels of the AMP angiogenin 4 (Ang4). These mice were also unable to up-regulate Ang4 production following oral challenge by Salmonella, leading to higher levels of mucosal invasion compared to their wild type counterparts during the first 2 hours post-challenge. The transfer of γδ iIELs from wild type (WT) mice to TCRδ-/- mice restored Ang4 production and Salmonella invasion levels were reduced to those obtained in WT mice. The ability to restore Ang4 production in TCRδ-/- mice was shown to be restricted to γδ iIELs expressing Vγ7-encoded TCRs. Using a novel intestinal crypt co-culture system we identified a putative pathway of Ang4 production initiated by exposure to Salmonella, intestinal commensals or microbial antigens that induced intestinal epithelial cells to produce cytokines including IL‑23 in a TLR-mediated manner. Exposure of TCR-Vγ7+ γδ iIELs to IL-23 promoted IL‑22 production, which triggered Paneth cells to secrete Ang4. These findings identify a novel role for γδ iIELs in mucosal defence through sensing immediate epithelial cell cytokine responses and influencing AMP production. This in turn can contribute to the maintenance of intestinal microbial homeostasis and epithelial barrier function, and limit pathogen invasion. PMID:24358364

  15. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens.

    PubMed

    Yang, Yi; Torchinsky, Miriam B; Gobert, Michael; Xiong, Huizhong; Xu, Mo; Linehan, Jonathan L; Alonzo, Francis; Ng, Charles; Chen, Alessandra; Lin, Xiyao; Sczesnak, Andrew; Liao, Jia-Jun; Torres, Victor J; Jenkins, Marc K; Lafaille, Juan J; Littman, Dan R

    2014-06-05

    T-helper-17 (TH17) cells have critical roles in mucosal defence and in autoimmune disease pathogenesis. They are most abundant in the small intestine lamina propria, where their presence requires colonization of mice with microbiota. Segmented filamentous bacteria (SFB) are sufficient to induce TH17 cells and to promote TH17-dependent autoimmune disease in animal models. However, the specificity of TH17 cells, the mechanism of their induction by distinct bacteria, and the means by which they foster tissue-specific inflammation remain unknown. Here we show that the T-cell antigen receptor (TCR) repertoire of intestinal TH17 cells in SFB-colonized mice has minimal overlap with that of other intestinal CD4(+) T cells and that most TH17 cells, but not other T cells, recognize antigens encoded by SFB. T cells with antigen receptors specific for SFB-encoded peptides differentiated into RORγt-expressing TH17 cells, even if SFB-colonized mice also harboured a strong TH1 cell inducer, Listeria monocytogenes, in their intestine. The match of T-cell effector function with antigen specificity is thus determined by the type of bacteria that produce the antigen. These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines.

  16. Effect of dietary alginic acid on juvenile tilapia (Oreochromis niloticus) intestinal microbial balance, intestinal histology and growth performance.

    PubMed

    Merrifield, Daniel L; Harper, Glenn M; Mustafa, Sanaa; Carnevali, Oliana; Picchietti, Simona; Davies, Simon J

    2011-04-01

    The aim of the present study was to assess the effect of a commercial alginic acid source (Ergosan) on tilapia Oreochromis niloticus intestinal microbial balance, intestinal morphology, and growth parameters. Fish were fed a basal control diet or the basal diet plus a source of alginic acid (5 g kg(-1) Ergosan; Schering-Plough Aquaculture, UK) for 9 weeks. At the end of the trial, light and electron microscopy demonstrated that the morphology of the intestinal tract at the gross and ultra-structural level was not affected by dietary alginic acid inclusion. Both groups of fish displayed healthy, normal morphology with no signs of disease, cell or tissue damage. Intestinal epithelial leucocyte infiltration was not affected by dietary alginic acid. Molecular bacterial profiles derived from PCR-DGGE illustrated highly similar microbial communities (both within the lumen and associated with the intestinal mucosa) in the respective treatment groups. Microbial ecological parameters (e.g. species diversity and richness) also remained unaffected. Although not significant, trends towards elevated survival and body protein content were observed in the alginic acid-fed fish. These results are suggestive that alginic acid does not adversely impact the indigenous gastrointestinal microbial balance and subsequently does not impact upon the epithelial brush border integrity. Validation of non-detrimental impacts of immunostimulatory products on gastric microbiota and epithelial integrity should be pursued in future studies as maintaining microbial balance and epithelial integrity is essential for proper gut functionality.

  17. Prostate stem cell antigen gene TT genotype and development of intestinal metaplasia in Helicobacter pylori infection

    PubMed Central

    Uotani, Takahiro; Sugimoto, Mitsushige; Ichikawa, Hitomi; Tanaka, Shingo; Nagashima, Hiroyuki; Uchida, Tomohisa; Graham, David Y.; Yamaoka, Yoshio

    2016-01-01

    Aim Gastric cancer is etiologically related to interactions between Helicobacter pylori infection, environmental, and host factors. Gastric carcinoma is associated with a cascade of increasing atrophic gastric mucosal damage. Prostate stem cell antigen polymorphisms have been associated with an increased risk of gastric cancer. Here, we examined the interaction between prostate stem cell antigen polymorphisms and H. pylori in the progression of H. pylori gastritis. Methods Prostate stem cell antigen polymorphisms (TT, TC and CC) among H. pylori infected and uninfected Bhutanese were compared with the severity of H. pylori gastritis (neutrophils, monocytes, atrophy scores, H. pylori density, and the presence and extent of intestinal metaplasia) using the updated Sydney system. Results Biopsies from 339 patients were included. The proportion of biopsies with intestinal metaplasia was also significantly (P<0.05) greater among those with the TT genotype than with either the CT or CC genotype. Despite no significant differences in inflammation or H. pylori density scores, the scores for the premalignant condition, intestinal metaplasia in both the gastric corpus and antrum, among H. pylori infected with the TT genotype was significantly (P <0.05) greater than C allele carriers. Conclusions Prostate stem cell antigen TT genotype was associated with more than a 3-fold increase in the prevalence and extent of gastric mucosal intestinal metaplasia compared to C allele carriers among H. pylori infected Bhutanese. PMID:26706772

  18. Intestinal Antigen-Presenting Cells: Key Regulators of Immune Homeostasis and Inflammation.

    PubMed

    Flannigan, Kyle L; Geem, Duke; Harusato, Akihito; Denning, Timothy L

    2015-07-01

    The microbiota that populate the mammalian intestine are critical for proper host physiology, yet simultaneously pose a potential danger. Intestinal antigen-presenting cells, namely macrophages and dendritic cells (DCs), are integral components of the mucosal innate immune system that maintain co-existence with the microbiota in face of this constant threat. Intestinal macrophages and DCs integrate signals from the microenvironment to orchestrate innate and adaptive immune responses that ultimately lead to durable tolerance of the microbiota. Tolerance is not a default response, however, because macrophages and DCs remain poised to vigorously respond to pathogens that breach the epithelial barrier. In this review, we summarize the salient features of macrophages and DCs in the healthy and inflamed intestine and discuss how signals from the microbiota can influence their function.

  19. Identification of a potent microbial lipid antigen for diverse Natural Killer T cells1

    PubMed Central

    Wolf, Benjamin J.; Tatituri, Raju V. V.; Almeida, Catarina F.; Le Nours, Jérôme; Bhowruth, Veemal; Johnson, Darryl; Uldrich, Adam P.; Hsu, Fong-Fu; Brigl, Manfred; Besra, Gurdyal S.; Rossjohn, Jamie; Godfrey, Dale I.; Brenner, Michael B.

    2016-01-01

    Invariant Natural Killer T (iNKT) cells are a well-characterized CD1d-restricted T cell subset. The availability of potent antigens and tetramers for iNKT cells has allowed this population to be extensively studied and has revealed their central roles in infection, autoimmunity, and tumor immunity. In contrast, diverse Natural Killer T (dNKT) cells are poorly understood because the lipid antigens they recognize are largely unknown. We sought to identify dNKT cell lipid antigen(s) by interrogating a panel of dNKT mouse cell hybridomas with lipid extracts from the pathogen Listeria monocytogenes. We identified Listeria phosphatidylglycerol (PG) as a microbial antigen that was significantly more potent than a previously characterized dNKT cell antigen, mammalian PG. Further, while mammalian PG loaded CD1d tetramers did not stain dNKT cells, the Listeria-derived PG loaded tetramers did. The structure of Listeria PG was distinct from mammalian PG since it contained shorter, fully-saturated anteiso fatty acid lipid tails. CD1d binding lipid displacement studies revealed that the microbial PG antigen binds significantly better to CD1d than counterparts with the same headgroup. These data reveal a highly-potent microbial lipid antigen for a subset of dNKT cells and provide an explanation for its increased antigen potency compared to the mammalian counterpart. PMID:26254340

  20. Permeability of milk protein antigens across the intestinal epithelium in vitro.

    PubMed

    Marcon-Genty, D; Tomé, D; Dumontier, A M; Kheroua, O; Desjeux, J F

    1989-01-01

    Degradations by proteolytic enzymes and intestinal epithelial permeability represent two major drawbacks to the transfer of food protein antigens to blood. These steps were studied in vitro for the milk protein antigens beta-lactoglobulin (beta-Lg), alpha-Lactalbumin (alpha-La) and beta-casein (beta-cas). Pepsin-trypsin hydrolysis and permeability in isolated rabbit ileum in Ussing chamber were suited by ELISA and radiolabelled-protein measurement. Pepsin-trypsin hydrolysis showed an increasing resistance in the order beta-cas less than alpha-La less than beta-Lg. The rate of absorption of the antigenic proteins by isolated rabbit ileum was in the same order, and the rate of absorption of the whole proteins (degraded and antigenic forms) was significantly higher for beta-Lg than for alpha-La and beta-cas. These results suggest a selective intestinal permeability for milk protein antigens. This selectivity is probably important in the mechanism of food protein sensitization via the oral route.

  1. Sialic acid catabolism drives intestinal inflammation and microbial dysbiosis in mice

    PubMed Central

    Huang, Yen-Lin; Chassard, Christophe; Hausmann, Martin; von Itzstein, Mark; Hennet, Thierry

    2015-01-01

    Rapid shifts in microbial composition frequently occur during intestinal inflammation, but the mechanisms underlying such changes remain elusive. Here we demonstrate that an increased caecal sialidase activity is critical in conferring a growth advantage for some bacteria including Escherichia coli (E. coli) during intestinal inflammation in mice. This sialidase activity originates among others from Bacteroides vulgatus, whose intestinal levels expand after dextran sulphate sodium administration. Increased sialidase activity mediates the release of sialic acid from intestinal tissue, which promotes the outgrowth of E. coli during inflammation. The outburst of E. coli likely exacerbates the inflammatory response by stimulating the production of pro-inflammatory cytokines by intestinal dendritic cells. Oral administration of a sialidase inhibitor and low levels of intestinal α2,3-linked sialic acid decrease E. coli outgrowth and the severity of colitis in mice. Regulation of sialic acid catabolism opens new perspectives for the treatment of intestinal inflammation as manifested by E. coli dysbiosis. PMID:26303108

  2. The composition of the zebrafish intestinal microbial community varies across development

    PubMed Central

    Zac Stephens, W; Burns, Adam R; Stagaman, Keaton; Wong, Sandi; Rawls, John F; Guillemin, Karen; Bohannan, Brendan J M

    2016-01-01

    The assembly of resident microbial communities is an important event in animal development; however, the extent to which this process mirrors the developmental programs of host tissues is unknown. Here we surveyed the intestinal bacteria at key developmental time points in a sibling group of 135 individuals of a model vertebrate, the zebrafish (Danio rerio). Our survey revealed stage-specific signatures in the intestinal microbiota and extensive interindividual variation, even within the same developmental stage. Microbial community shifts were apparent during periods of constant diet and environmental conditions, as well as in concert with dietary and environmental change. Interindividual variation in the intestinal microbiota increased with age, as did the difference between the intestinal microbiota and microbes in the surrounding environment. Our results indicate that zebrafish intestinal microbiota assemble into distinct communities throughout development, and that these communities are increasingly different from the surrounding environment and from one another. PMID:26339860

  3. Transport phenomena of microbial flora in the small intestine with peristalsis.

    PubMed

    Ishikawa, T; Sato, T; Mohit, G; Imai, Y; Yamaguchi, T

    2011-06-21

    The gastrointestinal tract of humans is colonized by indigenous prokaryotic and eukaryotic microbial cells that form a complex ecological system called microbial flora. Although the microbial flora has diverse functions, its homeostasis inside the gastrointestinal tract is still largely unknown. Therefore, creating a model for investigating microbial flora in the gastrointestinal tract is important. In this study, we developed a novel numerical model to explore the transport phenomena of microbial flora in the small intestine. By simultaneously solving the flow field generated by peristalsis, the concentrations of oxygen and nutrient, and the densities of moderate anaerobes and aerobes, the effects of fluid mechanics on the transport phenomena of microbial flora are discussed. The results clearly illustrated that fluid mechanics have considerable influence not only on the bacterial population, but also on the concentration distributions of oxygen and nutrient. Especially, the flow field enhances the radial variation of the concentration fields. We also show scaling arguments for bacterial growth and oxygen consumption, which capture the main features of the results. Additionally, we investigated the transport phenomena of microbial flora in a long tube with 40 constrictions. The results showed a high growth rate of aerobes in the upstream side and a high growth rate of anaerobes in the downstream side, which qualitatively agrees with experimental observations of human intestines. These new findings provide the fundamental basis for a better understanding of the transport phenomena of microbial flora in the intestine.

  4. An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells

    NASA Astrophysics Data System (ADS)

    Powell, Jonathan J.; Thomas-McKay, Emma; Thoree, Vinay; Robertson, Jack; Hewitt, Rachel E.; Skepper, Jeremy N.; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A.; Gomez-Morilla, Inmaculada; Grime, Geoffrey W.; Kirkby, Karen J.; Mabbott, Neil A.; Donaldson, David S.; Williams, Ifor R.; Rios, Daniel; Girardin, Stephen E.; Haas, Carolin T.; Bruggraber, Sylvaine F. A.; Laman, Jon D.; Tanriver, Yakup; Lombardi, Giovanna; Lechler, Robert; Thompson, Richard P. H.; Pele, Laetitia C.

    2015-05-01

    In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule ‘programmed death-ligand 1’, whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.

  5. An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells.

    PubMed

    Powell, Jonathan J; Thomas-McKay, Emma; Thoree, Vinay; Robertson, Jack; Hewitt, Rachel E; Skepper, Jeremy N; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A; Gomez-Morilla, Inmaculada; Grime, Geoffrey W; Kirkby, Karen J; Mabbott, Neil A; Donaldson, David S; Williams, Ifor R; Rios, Daniel; Girardin, Stephen E; Haas, Carolin T; Bruggraber, Sylvaine F A; Laman, Jon D; Tanriver, Yakup; Lombardi, Giovanna; Lechler, Robert; Thompson, Richard P H; Pele, Laetitia C

    2015-04-01

    In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.

  6. An Endogenous Nanomineral Chaperones Luminal Antigen and Peptidoglycan to Intestinal Immune Cells

    PubMed Central

    Powell, Jonathan J; Thomas-McKay, Emma; Thoree, Vinay; Robertson, Jack; Hewitt, Rachel E; Skepper, Jeremy N; Brown, Andy; Hernandez-Garrido, Juan Carlos; Midgley, Paul A; Gomez-Morilla, Inmaculada; Grime, Geoffrey W; Kirkby, Karen J; Mabbott, Neil A; Donaldson, David S; Williams, Ifor R; Rios, Daniel; Girardin, Stephen E; Haas, Carolin T; Bruggraber, Sylvaine FA; Laman, Jon D; Tanriver, Yakup; Lombardi, Giovanna; Lechler, Robert; Thompson, Richard P H; Pele, Laetitia C

    2015-01-01

    In humans and other mammals, it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally-fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer’s patches - small areas of the intestine concentrated with particle-scavenging immune cells. In wild type mice, intestinal immune cells containing these naturally-formed nanoparticles expressed the immune tolerance-associated molecule ‘programmed death-ligand 1 (PD-L1)’, whereas in NOD1/2 double knock-out mice, which cannot recognize peptidoglycan, PD-L1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and how this helps to shape intestinal immune homeostasis. PMID:25751305

  7. Use of circulating cathodic antigen (CCA) dipsticks for detection of intestinal and urinary schistosomiasis.

    PubMed

    Stothard, J Russell; Kabatereine, Narcis B; Tukahebwa, Edridah M; Kazibwe, Francis; Rollinson, David; Mathieson, William; Webster, Joanne P; Fenwick, Alan

    2006-02-01

    An evaluation of a commercially available antigen capture dipstick that detects schistosome circulating cathodic antigen (CCA) in urine was conducted in representative endemic areas for intestinal and urinary schistosomiasis in Uganda and Zanzibar, respectively. Under field-based conditions, the sensitivity (SS) and specificity (SP) of the dipstick was 83 and 81% for detection of Schistosoma mansoni infections while positive predictive (PPV) and negative predictive values (NPV) were 84%. Light egg-positive infections were sometimes CCA-negative while CCA-positives included egg-negative children. A positive association between faecal egg output and intensity of CCA test band was observed. Estimating prevalence of intestinal schistosomiasis by school with dipsticks was highly correlated (r=0.95) with Kato-Katz stool examinations, typically within +/-8.5%. In Zanzibar, however, dipsticks totally failed to detect S. haematobium despite examining children with egg-patent schistosomiasis. This was also later corroborated by further surveys in Niger and Burkina Faso. Laboratory testing of dipsticks with aqueous adult worm lysates from several reference species showed correct functioning, however, dipsticks failed to detect CCA in urine from S. haematobium-infected hamsters. While CCA dipsticks are a good alternative, or complement, to stool microscopy for field diagnosis of intestinal schistosomiasis, they have no proven value for field diagnosis of urinary schistosomiasis. At approximately 2.6 US dollars per dipstick, they are presently too expensive to be cost-effective for wide scale use in disease mapping surveys unless Lot Quality Assurance Sampling (LQAS) strategies are developed.

  8. Mechanism of Action of Probiotic Bacteria on Intestinal and Systemic Immunities and Antigen-Presenting Cells.

    PubMed

    Fong, Fiona Long Yan; Shah, Nagendra P; Kirjavainen, Pirkka; El-Nezami, Hani

    2016-05-03

    Immunomodulation has been shown to be one of the major functions of probiotic bacteria. This review is presented to provide detailed information on the immunomodulatory properties of probiotics in various animal models and clinical practices. Probiotics can regulate helper T (Th) responses and release of cytokines in a strain-specific manner. For example, Lactobacillus rhamnosus GG can induce beneficial Th1 immunomodulatory effect in infants with cow's milk allergy and relieve intestinal inflammation in atopic children by promoting IL-10 generation. Mechanism of action of probiotics on antigen-presenting cells at gastrointestinal tract is also postulated in this review. Probiotic bacterial cells and their soluble factors may activate dendritic cells, macrophages, and to certain extent monocytes via toll-like-receptor recognition and may further provoke specific Th responses. They are speculated to elicit immunomodulatory effects on intestinal and systemic immunities.

  9. Intestinal antigen-presenting cells in mucosal immune homeostasis: crosstalk between dendritic cells, macrophages and B-cells.

    PubMed

    Mann, Elizabeth R; Li, Xuhang

    2014-08-07

    The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota. Inflammatory bowel disease (IBD) involves a breakdown in tolerance towards the microbiota. Dendritic cells (DC), macrophages (MΦ) and B-cells are known as professional antigen-presenting cells (APC) due to their specialization in presenting processed antigen to T-cells, and in turn shaping types of T-cell responses generated. Intestinal DC are migratory cells, unique in their ability to generate primary T-cell responses in mesenteric lymph nodes or Peyer's patches, whilst MΦ and B-cells contribute to polarization and differentiation of secondary T-cell responses in the gut lamina propria. The antigen-sampling function of gut DC and MΦ enables them to sample bacterial antigens from the gut lumen to determine types of T-cell responses generated. The primary function of intestinal B-cells involves their secretion of large amounts of immunoglobulin A, which in turn contributes to epithelial barrier function and limits immune responses towards to microbiota. Here, we review the role of all three types of APC in intestinal immunity, both in the steady state and in inflammation, and how these cells interact with one another, as well as with the intestinal microenvironment, to shape mucosal immune responses. We describe mechanisms of maintaining intestinal immune tolerance in the steady state but also inappropriate responses of APC to components of the gut microbiota that contribute to pathology in IBD.

  10. Yeast culture supplement during nursing and transport affects immunity and intestinal microbial ecology of weanling pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weaning and transport stress can have a negative impact on the piglet's immune system and intestinal microbiota. The objective of this study was to determine the influence of a yeast product on innate immunity and microbial ecology of the gastrointestinal tract following stress of weaning and trans...

  11. [Microbial ecology of the intestines in health and in pathology].

    PubMed

    Goncharova, G I; Dorofeĭchuk, V G; Smolianskaia, A Z; Sokolova, K Ia

    1989-06-01

    Bifidoflora constitute 85--95 per cent of the large intestine microbiocenosis in children under 1 year of age. Bacteroides are not specific of children under 6 months of age. Lactobacilli, lactic acid streptococci, colon bacilli, enterococci and staphylococci (saprophytic, epidermal) constitute not more than 15 per cent. The predominating group peculiar of eubiosis in adults includes bifidobacteria and bacteroides. Changes in human autoflora are often induced by such factors as impaired ecology, stress, uncontrolled use of antibacterial drugs, radio- and chemotherapy, etc. Dysbacteriosis (first of all lower quantitative contents of bifidoflora) has an unfavourable effect on the intestine secretory function, absorption and certain indices of protein, lipid and mineral metabolism, vitamin synthesizing and fermentative functions and leads to disfunction of the gastrointestinal tract. It is a cause of persisting and relapsing infections in children and adults. High and optimal levels of bifidoflora in the intestine usually prevent the pathogenic action of pathogens. Lysozyme of digestive secretion and secretory immunity with immunoglobulin A prevalence also play an important role in the complicated mechanism of the protective barrier. The use of bacterial preparations such as bifidumbacterin, lactobacterin or bifilact for stabilization and recovery of high bifidoflora levels is indicated in all the cases with impaired microbiocenosis of the intestine.

  12. Role of the Host Defense System and Intestinal Microbial Flora in the Pathogenesis of Necrotizing Enterocolitis

    PubMed Central

    Emami, Claudia N.; Petrosyan, Mikael; Giuliani, Stefano; Williams, Monica; Hunter, Catherine; Prasadarao, Nemani V.

    2009-01-01

    Abstract Background Necrotizing enterocolitis (NEC) is a devastating disease that affects primarily the intestine of premature infants. Despite recent advances in neonatology, NEC remains a major cause of morbidity and mortality in neonates. Neonatal mucosal defenses and adherence of bacterial pathogens may play an important role in the pathogenesis of NEC. Methods Review and synthesis of pertinent literature. Results Putative factors that have been implicated in the pathogenesis of NEC include abnormal patterns of gut colonization by bacteria, immaturity of the host immune system and mucosal defense mechanisms, intestinal ischemia, formula feeding, and loss of intestinal epithelial barrier integrity. Conclusion Host defenses and intestinal microbial ecology are believed to play important roles in the pathogenesis of NEC. Commensal bacteria and probiotic therapy may be of therapeutic utility in the maintenance of the gut epithelial barrier. PMID:19943775

  13. Antibody responses to Toxoplasma gondii in sera, intestinal secretions, and milk from orally infected mice and characterization of target antigens.

    PubMed Central

    Chardès, T; Bourguin, I; Mevelec, M N; Dubremetz, J F; Bout, D

    1990-01-01

    Toxoplasma gondii-specific antibody responses in serum, intestinal secretions, and milk were identified with an enzyme-linked immunosorbent assay following a single oral infection of mice with strain 76K cysts of T. gondii. Immunoglobulin A (IgA) production began during week 2 of infection in serum and milk and during week 3 of infection in intestinal secretions and persisted in all three throughout the experiment (17 weeks). IgG but not IgM antibodies were detected in intestinal secretions later in the infection. Serum and milk IgG and IgM production began at the same time after infection as did the IgA response. In Western blotting (immunoblotting), intestinal IgA antibodies were shown to react with antigens comigrating with the T. gondii proteins p22, p23, p30, and p43, the 28-kilodalton antigen, and the 55- and 60-kilodalton rhoptry proteins, as recognized by specific monoclonal antibodies. Milk IgA antibodies reacted with antigens comigrating with p30 and p43. Most of the antigens recognized by IgA antibodies were also detected by IgG antibodies. IgA antibodies from all three biological samples detected the same major T. gondii antigens; thus, there was apparently no specific antibody production unique to one locality. Images PMID:2323815

  14. PCR-DGGE analysis of intestinal bacteria and effect of Bacillus spp. on intestinal microbial diversity in kuruma shrimp ( Marsupenaeus japonicus)

    NASA Astrophysics Data System (ADS)

    Liu, Huaide; Liu, Mei; Wang, Baojie; Jiang, Keyong; Jiang, Shan); Sun, Shujuan; Wang, Lei

    2010-07-01

    In this study, the intestinal microbiota of kuruma shrimp ( Marsupenaeus japonicus) was examined by molecular analysis of the 16S rDNA to identify the dominant intestinal bacteria and to investigate the effects of Bacillus spp. on intestinal microbial diversity. Samples of the intestines of kuruma shrimp fed normal feed and Bacillus spp. amended feed. PCR and denaturing gradient gel electrophoresis (DGGE) analyses were then performed on DNA extracted directly from the guts. Population fingerprints of the predominant organisms were generated by DGGE analysis of the universal V3 16S rDNA amplicons, and distinct bands in the gels were sequenced. The results suggested that the gut of kuruma shrimp was dominated by Vibrio sp. and uncultured gamma proteobacterium. Overall, the results of this study suggest that PCR-DGGE is a possible method of studying the intestinal microbial diversity of shrimp.

  15. [The Amben correction of disorders in the intestinal microbial colonization of newborn infants with perinatal pathology].

    PubMed

    Iakushenko, M N; Tkhagapsoeva, Zh A; Bondarenko, V M

    1998-01-01

    The examination of 49 newborn infants revealed that at the early neonatal period the character of the microbial colonization of the intestine depended on the kind of perinatal pathology: in lesions of the central nervous system and conjugation jaundice the deficiency of Bifidobacterium and Escherichia was detected; in hemolytic disease opportunistic bacteria were dominant simultaneously with the deficiency of lactoflora. The study of these infants, divided into two groups differing in the administration of Amben (an inhibitor of proteolytic enzymes), showed the efficiency of Amben which stimulated the growth and development of resident microflora in the intestine, thus contributing to the maintenance of eubiosis in a given group of infants with perinatal pathology.

  16. Regulatory T cells occupy an isolated niche in the intestine that is antigen independent.

    PubMed

    Korn, Lisa L; Hubbeling, Harper G; Porrett, Paige M; Yang, Qi; Barnett, Lisa G; Laufer, Terri M

    2014-12-11

    Regulatory T cells (Tregs) are CD4(+) T cells that maintain immune homeostasis and prevent autoimmunity. Like all CD4(+) T cells, Tregs require antigen-specific signals via T cell receptor-major histocompatibility complex class II (TCR-MHCII) interactions for their development. However, the requirement for MHCII in Treg homeostasis in tissues such as intestinal lamina propria (LP) is unknown. We examined LP Treg homeostasis in a transgenic mouse model that lacks peripheral TCR-MHCII interactions and generation of extrathymic Tregs (iTregs). Thymically generated Tregs entered the LP of weanlings and proliferated independently of MHCII to fill the compartment. The adult LP was a closed niche; new thymic Tregs were excluded, and Tregs in parabiotic pairs were LP resident. The isolated LP niche was interleukin-2 (IL-2) independent but dependent on commensal bacteria. Thus, an LP Treg niche can be filled, isolated, and maintained independently of antigen signals and iTregs. This niche may represent a tissue-specific mechanism for maintaining immune tolerance.

  17. Deregulation of intestinal anti-microbial defense by the dietary additive, maltodextrin.

    PubMed

    Nickerson, Kourtney P; Chanin, Rachael; McDonald, Christine

    2015-01-01

    Inflammatory bowel disease (IBD) is a complex, multi-factorial disease thought to arise from an inappropriate immune response to commensal bacteria in a genetically susceptible person that results in chronic, cyclical, intestinal inflammation. Dietary and environmental factors are implicated in the initiation and perpetuation of IBD; however, a singular causative agent has not been identified. As of now, the role of environmental priming or triggers in IBD onset and pathogenesis are not well understood, but these factors appear to synergize with other disease susceptibility factors. In previous work, we determined that the polysaccharide dietary additive, maltodextrin (MDX), impairs cellular anti-bacterial responses and suppresses intestinal anti-microbial defense mechanisms. In this addendum, we review potential mechanisms for dietary deregulation of intestinal homeostasis, postulate how dietary and genetic risk factors may combine to result in disease pathogenesis, and discuss these ideas in the context of recent findings related to dietary interventions for IBD.

  18. The intestinal proteome of diabetic and control children is enriched with different microbial and host proteins.

    PubMed

    Pinto, Elsa; Anselmo, Marisol; Calha, Manuela; Bottrill, Andrew; Duarte, Isabel; Andrew, Peter W; Faleiro, Maria L

    2017-02-01

    In this study, the intestinal microbial proteome of children with established type 1 diabetes (T1D) was compared with the proteome of healthy children (Control) with the aim to identify differences in the activity of the intestinal microbiota that not only will contribute to a deeper knowledge of the functionality of the gut in these children but also may provide new approaches to improve the control of the disease. Faecal protein extracts collected from three T1D children (aged 9.3±0.6 years) and three Control children (aged 9.3±1.5 years) were analysed using a combination of 2D gel electrophoresis and spectral counting. The results evidenced markedly differences between the intestinal proteome of T1D children and the Control. The T1D microbial intestinal proteome was enriched with proteins of clostridial cluster XVa and cluster IV and Bacteroides. In contrast, the Control proteome was enriched with bifidobacterial proteins. In both groups, proteins with moonlight function were observed. Human proteins also distinguished the two groups with T1D children depleted in exocrine pancreatic enzymes.

  19. Antigen sampling by intestinal M cells is the principal pathway initiating mucosal IgA production to commensal enteric bacteria

    PubMed Central

    Rios, D; Wood, M B; Li, J; Chassaing, B; Gewirtz, A T; Williams, I R

    2016-01-01

    Secretory IgA (SIgA) directed against gut resident bacteria enables the mammalian mucosal immune system to establish homeostasis with the commensal gut microbiota after weaning. Germinal centers (GCs) in Peyer's patches (PPs) are the principal inductive sites where naive B cells specific for bacterial antigens encounter their cognate antigens and receive T-cell help driving their differentiation into IgA-producing plasma cells. We investigated the role of antigen sampling by intestinal M cells in initiating the SIgA response to gut bacteria by developing mice in which receptor activator of nuclear factor-κB ligand (RANKL)-dependent M-cell differentiation was abrogated by conditional deletion of Tnfrsf11a in the intestinal epithelium. Mice without intestinal M cells had profound delays in PP GC maturation and emergence of lamina propria IgA plasma cells, resulting in diminished levels of fecal SIgA that persisted into adulthood. We conclude that M-cell-mediated sampling of commensal bacteria is a required initial step for the efficient induction of intestinal SIgA. PMID:26601902

  20. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation.

    PubMed

    Hashimoto, Tatsuo; Perlot, Thomas; Rehman, Ateequr; Trichereau, Jean; Ishiguro, Hiroaki; Paolino, Magdalena; Sigl, Verena; Hanada, Toshikatsu; Hanada, Reiko; Lipinski, Simone; Wild, Birgit; Camargo, Simone M R; Singer, Dustin; Richter, Andreas; Kuba, Keiji; Fukamizu, Akiyoshi; Schreiber, Stefan; Clevers, Hans; Verrey, Francois; Rosenstiel, Philip; Penninger, Josef M

    2012-07-25

    Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea.

  1. Intestinal M cells

    PubMed Central

    Ohno, Hiroshi

    2016-01-01

    We have an enormous number of commensal bacteria in our intestine, moreover, the foods that we ingest and the water we drink is sometimes contaminated with pathogenic microorganisms. The intestinal epithelium is always exposed to such microbes, friend or foe, so to contain them our gut is equipped with specialized gut-associated lymphoid tissue (GALT), literally the largest peripheral lymphoid tissue in the body. GALT is the intestinal immune inductive site composed of lymphoid follicles such as Peyer’s patches. M cells are a subset of intestinal epithelial cells (IECs) residing in the region of the epithelium covering GALT lymphoid follicles. Although the vast majority of IEC function to absorb nutrients from the intestine, M cells are highly specialized to take up intestinal microbial antigens and deliver them to GALT for efficient mucosal as well as systemic immune responses. I will discuss recent advances in our understanding of the molecular mechanisms of M-cell differentiation and functions. PMID:26634447

  2. Host-microbial interactions and regulation of intestinal epithelial barrier function: From physiology to pathology

    PubMed Central

    Yu, Linda Chia-Hui; Wang, Jin-Town; Wei, Shu-Chen; Ni, Yen-Hsuan

    2012-01-01

    The gastrointestinal tract is the largest reservoir of commensal bacteria in the human body, providing nutrients and space for the survival of microbes while concurrently operating mucosal barriers to confine the microbial population. The epithelial cells linked by tight junctions not only physically separate the microbiota from the lamina propria, but also secrete proinflammatory cytokines and reactive oxygen species in response to pathogen invasion and metabolic stress and serve as a sentinel to the underlying immune cells. Accumulating evidence indicates that commensal bacteria are involved in various physiological functions in the gut and microbial imbalances (dysbiosis) may cause pathology. Commensal bacteria are involved in the regulation of intestinal epithelial cell turnover, promotion of epithelial restitution and reorganization of tight junctions, all of which are pivotal for fortifying barrier function. Recent studies indicate that aberrant bacterial lipopolysaccharide-mediated signaling in gut mucosa may be involved in the pathogenesis of chronic inflammation and carcinogenesis. Our perception of enteric commensals has now changed from one of opportunistic pathogens to active participants in maintaining intestinal homeostasis. This review attempts to explain the dynamic interaction between the intestinal epithelium and commensal bacteria in disease and health status. PMID:22368784

  3. T-cell activation by transitory neo-antigens derived from distinct microbial pathways.

    PubMed

    Corbett, Alexandra J; Eckle, Sidonia B G; Birkinshaw, Richard W; Liu, Ligong; Patel, Onisha; Mahony, Jennifer; Chen, Zhenjun; Reantragoon, Rangsima; Meehan, Bronwyn; Cao, Hanwei; Williamson, Nicholas A; Strugnell, Richard A; Van Sinderen, Douwe; Mak, Jeffrey Y W; Fairlie, David P; Kjer-Nielsen, Lars; Rossjohn, Jamie; McCluskey, James

    2014-05-15

    T cells discriminate between foreign and host molecules by recognizing distinct microbial molecules, predominantly peptides and lipids. Riboflavin precursors found in many bacteria and yeast also selectively activate mucosal-associated invariant T (MAIT) cells, an abundant population of innate-like T cells in humans. However, the genesis of these small organic molecules and their mode of presentation to MAIT cells by the major histocompatibility complex (MHC)-related protein MR1 (ref. 8) are not well understood. Here we show that MAIT-cell activation requires key genes encoding enzymes that form 5-amino-6-d-ribitylaminouracil (5-A-RU), an early intermediate in bacterial riboflavin synthesis. Although 5-A-RU does not bind MR1 or activate MAIT cells directly, it does form potent MAIT-activating antigens via non-enzymatic reactions with small molecules, such as glyoxal and methylglyoxal, which are derived from other metabolic pathways. The MAIT antigens formed by the reactions between 5-A-RU and glyoxal/methylglyoxal were simple adducts, 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), respectively, which bound to MR1 as shown by crystal structures of MAIT TCR ternary complexes. Although 5-OP-RU and 5-OE-RU are unstable intermediates, they became trapped by MR1 as reversible covalent Schiff base complexes. Mass spectra supported the capture by MR1 of 5-OP-RU and 5-OE-RU from bacterial cultures that activate MAIT cells, but not from non-activating bacteria, indicating that these MAIT antigens are present in a range of microbes. Thus, MR1 is able to capture, stabilize and present chemically unstable pyrimidine intermediates, which otherwise convert to lumazines, as potent antigens to MAIT cells. These pyrimidine adducts are microbial signatures for MAIT-cell immunosurveillance.

  4. Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity.

    PubMed

    Dhawan, Shobhit; De Palma, Giada; Willemze, Rose A; Hilbers, Francisca W; Verseijden, Caroline; Luyer, Misha D; Nuding, Sabine; Wehkamp, Jan; Souwer, Yuri; de Jong, Esther C; Seppen, J; van den Wijngaard, René M; Wehner, Sven; Verdu, Elena; Bercik, Premek; de Jonge, Wouter J

    2016-11-01

    The cholinergic anti-inflammatory pathway reduces systemic tumor necrosis factor (TNF) via acetylcholine-producing memory T cells in the spleen. These choline acetyltransferase (ChAT)-expressing T cells are also found in the intestine, where their function is unclear. We aimed to characterize these cells in mouse and human intestine and delineate their function. We made use of the ChAT-enhanced green fluorescent protein (eGFP) reporter mice. CD4(Cre) mice were crossed to ChAT(fl/fl) mice to achieve specific deletion of ChAT in CD4(+) T cells. We observed that the majority of ChAT-expressing T cells in the human and mouse intestine have characteristics of Th17 cells and coexpress IL17A, IL22, and RORC The generation of ChAT-expressing T cells was skewed by dendritic cells after activation of their adrenergic receptor β2 To evaluate ChAT T cell function, we generated CD4-specific ChAT-deficient mice. CD4ChAT(-/-) mice showed a reduced level of epithelial antimicrobial peptides lysozyme, defensin A, and ang4, which was associated with an enhanced bacterial diversity and richness in the small intestinal lumen in CD4ChAT(-/-) mice. We conclude that ChAT-expressing T cells in the gut are stimulated by adrenergic receptor activation on dendritic cells. ChAT-expressing T cells may function to mediate the host AMP secretion, microbial growth and expansion.

  5. Effects of alfalfa meal on the intestinal microbial diversity and immunity of growing ducks.

    PubMed

    Jiang, J F; Song, X M; Wu, J L; Jiang, Y Q

    2014-12-01

    This study was conducted to investigate the effects of alfalfa meal diets on the intestinal microbial diversity and immunity of growing egg-type ducks. A total of 128 healthy 7-week-old female egg-type Shaoxing ducks were selected and randomly assigned into four dietary treatments: 0%, 3%, 6% and 9% alfalfa meal for 8 weeks. Each treatment consisted of four replicates of eight ducks each. Polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) was used to characterize the microbiota. The results showed that the DGGE fingerprints of the V6-V8 fragments of the 16S rRNA from the caeca and faeces of ducks fed 3%, 6% and 9% alfalfa meal had significantly higher microbiota species richness than those fed 0% alfalfa meal (p < 0.05). The Shannon-Weiner index of the microbiota from the caeca and faeces of ducks fed 3%, 6% and 9% alfalfa meal was significantly higher than those fed 0% alfalfa meal (p < 0.05). Molecular analysis of the caecal and faecal DNA extracts showed that the alfalfa meal diet promotes the intestinal microbial diversity, as indicated by their higher species richness and Shannon-Weiner index. However, the groups did not significantly differ in terms of average daily gain, feed intake and gain-to-feed ratio (p > 0.05), and the 3-9% alfalfa meal did not affect the growth performance of the growing egg-type ducks. The proliferation of T and B lymphocytes was significantly greater (p < 0.05) in the groups supplemented with 3%, 6% and 9% of alfalfa meal than the unsupplemented control group, and alfalfa meal promoted the lymphocytes proliferation of the growing egg-type ducks. Dietary alfalfa meal supplementation increases intestinal microbial community diversity and improves of the immune response growing egg-type ducks.

  6. Emerging role of intestinal microbiota and microbial metabolites in metabolic control.

    PubMed

    Herrema, Hilde; IJzerman, Richard G; Nieuwdorp, Max

    2017-04-01

    The role of the intestinal microbiota and microbial metabolites in the maintenance of host health and development of metabolic disease has gained significant attention over the past decade. Mechanistic insight revealing causality, however, is scarce. Work by Ussar and co-workers demonstrates that a complex interaction between microbiota, host genetics and environmental factors is involved in metabolic disease development in mice. In addition, Perry and co-workers show that the microbial metabolite acetate augments insulin resistance in rats. These studies underscore an important role of the microbiota in the development of obesity and symptoms of type 2 diabetes in rodents. If causality can be demonstrated in humans, development of novel diagnostic and therapeutic tools that target the gut microbiota will have high potential.

  7. Diet and host-microbial crosstalk in postnatal intestinal immune homeostasis.

    PubMed

    Jain, Nitya; Walker, W Allan

    2015-01-01

    Neonates face unique challenges in the period following birth. The postnatal immune system is in the early stages of development and has a range of functional capabilities that are distinct from the mature adult immune system. Bidirectional immune-microbial interactions regulate the development of mucosal immunity and alter the composition of the microbiota, which contributes to overall host well-being. In the past few years, nutrition has been highlighted as a third element in this interaction that governs host health by modulating microbial composition and the function of the immune system. Dietary changes and imbalances can disturb the immune-microbiota homeostasis, which might alter susceptibility to several autoimmune and metabolic diseases. Major changes in cultural traditions, socioeconomic status and agriculture are affecting the nutritional status of humans worldwide, which is altering core intestinal microbial communities. This phenomenon is especially relevant to the neonatal and paediatric populations, in which the microbiota and immune system are extremely sensitive to dietary influences. In this Review, we discuss the current state of knowledge regarding early-life nutrition, its effects on the microbiota and the consequences of diet-induced perturbation of the structure of the microbial community on mucosal immunity and disease susceptibility.

  8. Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice

    PubMed Central

    Tai, Ningwen; Peng, Jian; Liu, Fuqiang; Hu, Youjia; Zhang, Xiaojun; Chen, Li

    2016-01-01

    Both animal model and human studies indicate that commensal bacteria may modify type 1 diabetes (T1D) development. However, the underlying mechanisms by which gut microbes could trigger or protect from diabetes are not fully understood, especially the interaction of commensal bacteria with pathogenic CD8 T cells. In this study, using islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP)–reactive CD8 T cell receptor NY8.3 transgenic nonobese diabetic mice, we demonstrated that MyD88 strongly modulates CD8+ T cell–mediated T1D development via the gut microbiota. Some microbial protein peptides share significant homology with IGRP. Both the microbial peptide mimic of Fusobacteria and the bacteria directly activate IGRP-specific NY8.3 T cells and promote diabetes development. Thus, we provide evidence of molecular mimicry between microbial antigens and an islet autoantigen and a novel mechanism by which the diabetogenicity of CD8+ T cells can be regulated by innate immunity and the gut microbiota. PMID:27621416

  9. Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats.

    PubMed

    Lam, Vy; Su, Jidong; Hsu, Anna; Gross, Garrett J; Salzman, Nita H; Baker, John E

    2016-01-01

    Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host's metabolism. Hierarchical clustering of dissimilarities separated the levels of 284 identified metabolites from treated vs. untreated rats; 193 were altered by the antibiotic treatments with a tendency towards decreased metabolite levels. Catabolism of the aromatic amino acids phenylalanine, tryptophan and tyrosine was the most affected pathway comprising 33 affected metabolites. Both antibiotic treatments decreased the severity of an induced myocardial infarction in vivo by 27% and 29%, respectively. We then determined whether microbial metabolites of the amino acids phenylalanine, tryptophan and tyrosine were linked to decreased severity of myocardial infarction. Vancomycin-treated rats were administered amino acid metabolites prior to ischemia/reperfusion studies. Oral or intravenous pretreatment of rats with these amino acid metabolites abolished the decrease in infarct size conferred by vancomycin. Inhibition of JAK-2 (AG-490, 10 μM), Src kinase (PP1, 20 μM), Akt/PI3 kinase (Wortmannin, 100 nM), p44/42 MAPK (PD98059, 10 μM), p38 MAPK (SB203580, 10 μM), or KATP channels (glibenclamide, 3 μM) abolished cardioprotection by vancomycin, indicating microbial metabolites are interacting with cell surface receptors to transduce their signals through Src kinase, cell survival pathways and KATP channels. These inhibitors have no effect on myocardial infarct size in

  10. Intestine.

    PubMed

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

  11. Proliferative cell nuclear antigen (PCNA) expression in the intestine of Salmo trutta trutta naturally infected with an acanthocephalan

    PubMed Central

    2012-01-01

    Background Changes in the production of proliferating cell nuclear antigen (PCNA), a 36 kd protein involved in protein synthesis, within intestinal epithelia can provide an early indication of deviations to normal functioning. Inhibition or stimulation of cell proliferation and PCNA can be determined through immunohistochemical staining of intestinal tissue. Changes in the expression of PCNA act as an early warning system of changes to the gut and this application has not been applied to the fields of aquatic parasitology and fish health. The current study set out to determine whether a population of wild brown trout, Salmo trutta trutta (L.) harbouring an infection of the acanthocephalan Dentitruncus truttae Sinzar, 1955 collected from Lake Piediluco in Central Italy also effected changes in the expression of PCNA. Methods A total of 29 brown trout were investigated, 19 of which (i.e. 65.5%) were found to harbour acanthocephalans (5–320 worms fish-1). Histological sections of both uninfected and infected intestinal material were immunostained for PCNA. Results The expression of PCNA was observed in the epithelial cells in the intestinal crypts and within the mast cells and fibroblasts in the submucosa layer which is consistent with its role in cell proliferation and DNA synthesis. The number of PCNA-positive cells in both the intestinal epithelium and the submucosa layer in regions close to the point of parasite attachment were significantly higher than the number observed in uninfected individuals and in infected individuals in zones at least 0.7 cm from the point of parasite attachment (ANOVA, p < 0.05). Conclusions An infection of the acanthocephalan D. truttae within the intestinal tract of S. t. trutta effected a significant increase in the number of PCNA positive cells (mast cells and fibroblasts) at the site of parasite attachment when compared to the number of positive cells found in uninfected conspecifics and in tissue zones away from the point

  12. Transcriptome profiles of chicken intestinal intraepithelial lymphocytes altered by the intake of a multi-strain direct-fed microbials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The current study was conducted to investigate the effects of the direct-fed microbials (DFM) including three Bacillus subtilis strains on the modulation of transcriptional profile in chicken intestinal intraepithelial lymphocytes (IEL). The multiple-strain DFM product modified 453 probes from 1,98...

  13. Cell surface phenotype and ultramicroscopic analysis of purified human enterocytes: a possible antigen-presenting cell in the intestine.

    PubMed

    Martín-Villa, J M; Ferre-López, S; López-Suárez, J C; Corell, A; Pérez-Blas, M; Arnaiz-Villena, A

    1997-12-01

    Epithelial cells of the intestine seem to act as antigen-presenting cells to surrounding lymphoid tissue and may be crucial to maintain the pool of peripheral T lymphocytes. The scope of this study was to carry out an immunophenotypic and ultramicroscopic analysis of purified human enterocytes to elucidate their role as antigen-presenting cells, in the immune responses in the gut-associated lymphoid tissue. A method has been developed to obtain purified and viable human enterocyte populations, later labeled with relevant monoclonal antibodies directed to leukocyte antigens and subjected to cytofluorometric analysis. Phenotypic analysis revealed the presence of markers common to "classical" antigen-presenting cells (CD14, CD35, CD39, CD43, CD63 and CD64), reinforcing the idea that enterocytes may act as such. Moreover, several integrins (CD11b, CD11c, CD18, CD41a, CD61 and CD29) were also found. CD25 (IL-2 receptor alpha chain) and CD28, characteristic of T cells, were detected on the surface of these cells; this latter finding rises the possibility that enterocytes could be activated by IL-2 and/or via CD28 through binding to its ligands CD80 or CD86. Finally, the presence of CD21, CD32, CD35 and CD64 that may bind immune complexes via Fc or C3, suggests their participation in the metabolism of immune complexes. Furthermore, the finding of a Birbeck's-like granule in the cytoplasm of the cells, shows that enterocytes contain an ultramicroscopic feature previously thought to be characteristic of Langerhans' cells, an antigen-presenting cell. The phenotype detected on the surface of enterocytes, along with their ultramicroscopic characteristics, suggests that they may play an important role in the immune responses elicited in the gut, presenting antigens to surrounding lymphoid cells, and establishing cognate interactions with them.

  14. Plasmid-mediated susceptibility to intestinal microbial antagonisms in Escherichia coli.

    PubMed

    Andremont, A; Gerbaud, G; Tancrède, C; Courvalin, P

    1985-09-01

    Self-transferable plasmid pIP1100 confers to Escherichia coli an unusually high level of resistance (1 to 2 mg/ml) to erythromycin by production of an erythromycin esterase. The effect of pIP1100 on the destiny of E. coli strains in the intestines of gnotobiotic mice was studied. In germfree mice, pIP1100 was efficiently transferred to a plasmid-free E. coli recipient. Intestinal counts of the donor, the recipient, and the transconjugants were greater than 8.5 log CFU/g of feces. When erythromycin was added to the diet of the mice, counts of the plasmid-bearing strains were only slightly lowered and partial inactivation of erythromycin was observed in the feces. Transfer of pIP1100 also occurred in human-flora-associated mice. In this model all the E. coli strains were subject to microbial antagonisms caused by the anaerobic components of the flora. However, strains harboring pIP1100 were strongly inhibited (less than 2.5 log CFU/g of feces), whereas their plasmid-free counterparts persisted at much higher population levels (greater than 5.2 log CFU/g of feces). The ecological disadvantage conferred by pIP1100 to E. coli when a complex human flora was concomitantly present in the intestine of the mice persisted during erythromycin administration. These results provide an explanation for the low incidence of isolation of highly erythromycin-resistant E. coli strains despite the extensive use of the antibiotic.

  15. Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class.

    PubMed

    Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera; Linninge, Caroline; Ahrné, Siv; Højberg, Ole; Licht, Tine Rask; Bahl, Martin Iain

    2015-01-01

    Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group) were dosed by oral gavage with either amoxicillin (AMX), cefotaxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10-11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in permeability did

  16. Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats

    PubMed Central

    Lam, Vy; Su, Jidong; Hsu, Anna; Gross, Garrett J.; Salzman, Nita H.

    2016-01-01

    Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host’s metabolism. Hierarchical clustering of dissimilarities separated the levels of 284 identified metabolites from treated vs. untreated rats; 193 were altered by the antibiotic treatments with a tendency towards decreased metabolite levels. Catabolism of the aromatic amino acids phenylalanine, tryptophan and tyrosine was the most affected pathway comprising 33 affected metabolites. Both antibiotic treatments decreased the severity of an induced myocardial infarction in vivo by 27% and 29%, respectively. We then determined whether microbial metabolites of the amino acids phenylalanine, tryptophan and tyrosine were linked to decreased severity of myocardial infarction. Vancomycin-treated rats were administered amino acid metabolites prior to ischemia/reperfusion studies. Oral or intravenous pretreatment of rats with these amino acid metabolites abolished the decrease in infarct size conferred by vancomycin. Inhibition of JAK-2 (AG-490, 10 μM), Src kinase (PP1, 20 μM), Akt/PI3 kinase (Wortmannin, 100 nM), p44/42 MAPK (PD98059, 10 μM), p38 MAPK (SB203580, 10 μM), or KATP channels (glibenclamide, 3 μM) abolished cardioprotection by vancomycin, indicating microbial metabolites are interacting with cell surface receptors to transduce their signals through Src kinase, cell survival pathways and KATP channels. These inhibitors have no effect on myocardial infarct size in

  17. Dietary inclusion of feathers affects intestinal microbiota and microbial metabolites in growing Leghorn-type chickens.

    PubMed

    Meyer, B; Bessei, W; Bessei, A W; Vahjen, W; Zentek, J; Harlander-Matauschek, A

    2012-07-01

    Feather pecking in laying hens is a serious behavioral problem that is often associated with feather eating. The intake of feathers may influence the gut microbiota and its metabolism. The aim of this study was to determine the effect of 2 different diets, with or without 5% ground feathers, on the gut microbiota and the resulting microbial fermentation products and to identify keratin-degrading bacteria in chicken digesta. One-day-old Lohmann-Selected Leghorn chicks were divided into 3 feeding groups: group A (control), B (5% ground feathers in the diet), and C, in which the control diet was fed until wk 12 and then switched to the 5% feather diet to study the effect of time of first feather ingestion. The gut microbiota was analyzed by cultivation and denaturing gradient gel electrophoresis of ileum and cecum digesta. Short-chain fatty acids, ammonia, and lactate concentrations were measured as microbial metabolites. The concentration of keratinolytic bacteria increased after feather ingestion in the ileum (P < 0.001) and cecum (P = 0.033). Bacterial species that hydrolyzed keratin were identified as Enterococcus faecium, Lactobacillus crispatus, Lactobacillus reuteri-like species (97% sequence homology), and Lactobacillus salivarius-like species (97% sequence homology). Molecular analysis of cecal DNA extracts showed that the feather diet lowered the bacterial diversity indicated by a reduced richness (P < 0.001) and shannon (P = 0.012) index. The pattern of microbial metabolites indicated some changes, especially in the cecum. This study showed that feather intake induced an adaptation of the intestinal microbiota in chickens. It remains unclear to what extent the changed metabolism of the microbiota reflects the feather intake and could have an effect on the behavior of the hens.

  18. Altered expression of intestinal human leucocyte antigen D-related and immune signalling molecules in juvenile idiopathic arthritis

    PubMed Central

    Arvonen, M; Vähäsalo, P; Turunen, S; Salo, H M; Mäki, M; Laurila, K; Vaarala, O; Karttunen, T J

    2012-01-01

    We aimed to study intestinal immune activation status in juvenile idiopathic arthritis (JIA) by assessing intestinal human leucocyte antigen (HLA) class II expression and the mRNA expression levels of the pro- and anti-inflammatory mediators and pattern recognition receptors. HLA-D-related (HLA-DR) expression was assessed using immunohistochemical staining of frozen sections in 11 children with JIA and 17 controls. The gene expression levels of the anti- and proinflammatory cytokines, lymphocyte recognition receptors and pattern recognition receptors were studied with reverse transcription–polymerase chain reaction (RT–PCR) in 14 children with JIA and 12 controls. All subjects had various gastrointestinal (GI) symptoms indicating endoscopic examinations, but eventually were not diagnosed with GI disease. In JIA patients, the expression of HLA-DR was increased in the crypt epithelial cells and in the epithelial basement membrane of the ileum when compared with the controls. Positive HLA-DR staining in the ileal mucosa was associated with the presence of high clinical disease activity of JIA and low mRNA expression of anti-inflammatory mediators, such as forkhead box protein P3 (FoxP3), glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) and transforming growth factor (TGF)-beta. Low ileal expression of interleukin (IL)-10, TGF-β, FoxP3, Toll-like receptor 2 (TLR-2) and TLR-4 transcripts correlated significantly with a high clinical disease activity in the JIA patients. The increased HLA-DR expression suggests enhanced intestinal antigen presentation in JIA. A correlation between clinical disease activity and low gene expression of tolerogenic mediators in the ileum supports the hypothesis that a link exists between the gut immune system and JIA. PMID:23121667

  19. Immunobiotic Lactobacillus rhamnosus strains differentially modulate antiviral immune response in porcine intestinal epithelial and antigen presenting cells

    PubMed Central

    2014-01-01

    Background Previous findings suggested that Lactobacillus rhamnosus CRL1505 is able to increase resistance of children to intestinal viral infections. However, the intestinal cells, cytokines and receptors involved in the immunoregulatory effect of this probiotic strain have not been fully characterized. Results We aimed to gain insight into the mechanisms involved in the immunomodulatory effect of the CRL1505 strain and therefore evaluated in vitro the crosstalk between L. rhamnosus CRL1505, porcine intestinal epithelial cells (IECs) and antigen presenting cells (APCs) from swine Peyer’s patches in order to deepen our knowledge about the mechanisms, through which this strain may help preventing viral diarrhoea episodes. L. rhamnosus CRL1505 was able to induce IFN–α and –β in IECs and improve the production of type I IFNs in response to poly(I:C) challenge independently of Toll-like receptor (TLR)-2 or TLR9 signalling. In addition, the CRL1505 strain induced mRNA expression of IL-6 and TNF-α via TLR2 in IECs. Furthermore, the strain significantly increased surface molecules expression and cytokine production in intestinal APCs. The improved Th1 response induced by L. rhamnosus CRL1505 was triggered by TLR2 signalling and included augmented expression of MHC-II and co-stimulatory molecules and expression of IL-1β, IL-6, and IFN-γ in APCs. IL-10 was also significantly up-regulated by CRL1505 in APCs. Conclusions It was recently reviewed the emergence of TLR agonists as new ways to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies. The use of L. rhamnosus CRL1505 as modulator of innate immunity and inductor of antiviral type I IFNs, IFN-γ, and regulatory IL-10 clearly offers the potential to overcome this challenge. PMID:24886142

  20. Effects of feed additives and mixed eimeria species infection on intestinal microbial ecology of broilers.

    PubMed

    Hume, M E; Clemente-Hernández, S; Oviedo-Rondón, E O

    2006-12-01

    Evaluation of digestive microbial ecology is necessary to understand effects of growth-promoting feed. In the current study, the dynamics of intestinal microbial communities (MC) were examined in broilers fed diets supplemented with a combination of antibiotic (bacitracin methylene disalicylate) and ionophore (Coban 60), and diets containing 1 of 2 essential oil (EO) blends, Crina Poultry (CP) and Crina Alternate (CA). Five treatments were analyzed: 1) unmedicated uninfected control; 2) unmedicated infected control; 3) feed additives monensin (bacitracin methylene disalicylate) + monensin (Coban 60; AI); 4) EO blend CP; and 5) EO blend CA. Additives were mixed into a basal feed mixture, and EO were adjusted to 100 ppm. Chicks were infected by oral gavage at 19 d of age with Eimeria acervulina, Eimeria maxima, and Eimeria tenella. Duodenal, ileal, and cecal samples were taken from 12 birds per treatment just before and 7 d after challenge; 2 samples each were pooled to give a final number of 6 samples total; and all pooled samples were frozen until used for DNA extraction. Denaturing gradient gel electrophoresis was used to examine PCR-amplified fragments of the bacterial 16S ribosomal DNA variable region. Results are presented as percentages of similarity coefficients (SC). Dendrograms of PCR amplicon or band patterns indicated MC differences due to intestinal location, feed additives, and cocci challenge. Essential oil blends CP and CA affected MC in all gut sections. Each EO had different effects over MC, and they differed in most instances from the AI group. The cocci challenge caused drastic MC population shifts in duodenal, ileal, and cecal sections (36.7, 55.4, and 36.2% SC, respectively). Diets supplemented with CP supported higher SC between pre- and postchallenge MC (89.9, 83.3, and 76.4%) than AI (81.8., 57.4, and 60.0%). We concluded that mixed coccidia challenge caused drastic shifts in MC. These EO blends modulated MC better than AI, avoiding drastic

  1. Microbial Population Differentials between Mucosal and Submucosal Intestinal Tissues in Advanced Crohn's Disease of the Ileum.

    PubMed

    Chiodini, Rodrick J; Dowd, Scot E; Chamberlin, William M; Galandiuk, Susan; Davis, Brian; Glassing, Angela

    2015-01-01

    Since Crohn's disease is a transmural disease, we hypothesized that examination of deep submucosal tissues directly involved in the inflammatory disease process may provide unique insights into bacterial populations transgressing intestinal barriers and bacterial populations more representative of the causes and agents of the disease. We performed deep 16s microbiota sequencing on isolated ilea mucosal and submucosal tissues on 20 patients with Crohn's disease and 15 non-inflammatory bowel disease controls with a depth of coverage averaging 81,500 sequences in each of the 70 DNA samples yielding an overall resolution down to 0.0001% of the bacterial population. Of the 4,802,328 total sequences generated, 98.9% or 4,749,183 sequences aligned with the Kingdom Bacteria that clustered into 8545 unique sequences with <3% divergence or operational taxonomic units enabling the identification of 401 genera and 698 tentative bacterial species. There were significant differences in all taxonomic levels between the submucosal microbiota in Crohn's disease compared to controls, including organisms of the Order Desulfovibrionales that were present within the submucosal tissues of most Crohn's disease patients but absent in the control group. A variety of organisms of the Phylum Firmicutes were increased in the subjacent submucosa as compared to the parallel mucosal tissue including Ruminococcus spp., Oscillospira spp., Pseudobutyrivibrio spp., and Tumebacillus spp. In addition, Propionibacterium spp. and Cloacibacterium spp. were increased as well as large increases in Proteobacteria including Parasutterella spp. and Methylobacterium spp. This is the first study to examine the microbial populations within submucosal tissues of patients with Crohn's disease and to compare microbial communities found deep within the submucosal tissues with those present on mucosal surfaces. Our data demonstrate the existence of a distinct submucosal microbiome and ecosystem that is not well

  2. Microbial Population Differentials between Mucosal and Submucosal Intestinal Tissues in Advanced Crohn's Disease of the Ileum

    PubMed Central

    Chiodini, Rodrick J.; Dowd, Scot E.; Chamberlin, William M.; Galandiuk, Susan; Davis, Brian; Glassing, Angela

    2015-01-01

    Since Crohn's disease is a transmural disease, we hypothesized that examination of deep submucosal tissues directly involved in the inflammatory disease process may provide unique insights into bacterial populations transgressing intestinal barriers and bacterial populations more representative of the causes and agents of the disease. We performed deep 16s microbiota sequencing on isolated ilea mucosal and submucosal tissues on 20 patients with Crohn's disease and 15 non-inflammatory bowel disease controls with a depth of coverage averaging 81,500 sequences in each of the 70 DNA samples yielding an overall resolution down to 0.0001% of the bacterial population. Of the 4,802,328 total sequences generated, 98.9% or 4,749,183 sequences aligned with the Kingdom Bacteria that clustered into 8545 unique sequences with <3% divergence or operational taxonomic units enabling the identification of 401 genera and 698 tentative bacterial species. There were significant differences in all taxonomic levels between the submucosal microbiota in Crohn's disease compared to controls, including organisms of the Order Desulfovibrionales that were present within the submucosal tissues of most Crohn's disease patients but absent in the control group. A variety of organisms of the Phylum Firmicutes were increased in the subjacent submucosa as compared to the parallel mucosal tissue including Ruminococcus spp., Oscillospira spp., Pseudobutyrivibrio spp., and Tumebacillus spp. In addition, Propionibacterium spp. and Cloacibacterium spp. were increased as well as large increases in Proteobacteria including Parasutterella spp. and Methylobacterium spp. This is the first study to examine the microbial populations within submucosal tissues of patients with Crohn's disease and to compare microbial communities found deep within the submucosal tissues with those present on mucosal surfaces. Our data demonstrate the existence of a distinct submucosal microbiome and ecosystem that is not well

  3. Effects of direct-fed microbial supplementation on broiler performance, intestinal nutrient transport and integrity under experimental conditions with increased microbial challenge.

    PubMed

    Murugesan, G R; Gabler, N K; Persia, M E

    2014-02-01

    1. The effects of Aspergillus oryzae- and Bacillus subtilis-based direct-fed microbials (DFM) were investigated on the performance, ileal nutrient transport and intestinal integrity of broiler chickens, raised under experimental conditions, with increased intestinal microbial challenge. 2. The first study was a 3 × 2 factorial experiment, with 3 dietary treatments (control (CON), CON + DFM and CON + antibiotic growth promoter) with and without challenge. Chicks were fed experimental diets from 1 to 28 d, while the challenge was provided by vaccinating with 10 times the normal dose of commercial coccidial vaccine on d 9. In a second experiment, two groups of 1 d-old broilers, housed on built-up litter (uncleaned from two previous flocks), were fed the same CON and CON + DFM diets from 1 to 21 d. 3. The challenge in the first experiment reduced performance, but no differences were observed among dietary treatments from 8 to 28 d. The challenge reduced the ileal epithelial flux for D-glucose, L-lysine, DL-methionine and phosphorus on d 21. Epithelial flux for D-glucose, L-lysine and DL-methionine were increased by DFM. Ileal trans-epithelial electrical resistance (TER) was increased in challenged broilers fed DFM, although this was not observed in unchallenged birds as indicated by a significant interaction. 4. Ileal mucin mRNA expression and colon TER were increased, and colon endotoxin permeability was reduced by DFM on d 21 in the second experiment. 5. It was concluded that the addition of DFM in the diet improved the intestinal integrity of broiler chickens raised under experimental conditions designed to provide increased intestinal microbial challenge.

  4. Arabinoxylan‐oligosaccharides (AXOS) affect the protein/carbohydrate fermentation balance and microbial population dynamics of the Simulator of Human Intestinal Microbial Ecosystem

    PubMed Central

    Sanchez, J. I.; Marzorati, M.; Grootaert, C.; Baran, M.; Van Craeyveld, V.; Courtin, C. M.; Broekaert, W. F.; Delcour, J. A.; Verstraete, W.; Van de Wiele, T.

    2009-01-01

    Summary Arabinoxylan‐oligosaccharides (AXOS) are a recently newly discovered class of candidate prebiotics as – depending on their structure – they are fermented in different regions of gastrointestinal tract. This can have an impact on the protein/carbohydrate fermentation balance in the large intestine and, thus, affect the generation of potentially toxic metabolites in the colon originating from proteolytic activity. In this study, we screened different AXOS preparations for their impact on the in vitro intestinal fermentation activity and microbial community structure. Short‐term fermentation experiments with AXOS with an average degree of polymerization (avDP) of 29 allowed part of the oligosaccharides to reach the distal colon, and decreased the concentration of proteolytic markers, whereas AXOS with lower avDP were primarily fermented in the proximal colon. Additionally, prolonged supplementation of AXOS with avDP 29 to the Simulator of Human Intestinal Microbial Ecosystem (SHIME) reactor decreased levels of the toxic proteolytic markers phenol and p‐cresol in the two distal colon compartments and increased concentrations of beneficial short‐chain fatty acids (SCFA) in all colon vessels (25–48%). Denaturant gradient gel electrophoresis (DGGE) analysis indicated that AXOS supplementation only slightly modified the total microbial community, implying that the observed effects on fermentation markers are mainly caused by changes in fermentation activity. Finally, specific quantitative PCR (qPCR) analysis showed that AXOS supplementation significantly increased the amount of health‐promoting lactobacilli as well as of Bacteroides–Prevotella and Clostridium coccoides–Eubacterium rectale groups. These data allow concluding that AXOS are promising candidates to modulate the microbial metabolism in the distal colon. PMID:21261885

  5. Expression of the aryl hydrocarbon receptor contributes to the establishment of intestinal microbial community structure in mice

    PubMed Central

    Murray, Iain A.; Nichols, Robert G.; Zhang, Limin; Patterson, Andrew D.; Perdew, Gary H.

    2016-01-01

    Environmental and genetic factors represent key components in the establishment/maintenance of the intestinal microbiota. The aryl hydrocarbon receptor (AHR) is emerging as a pleiotropic factor, modulating pathways beyond its established role as a xenobiotic sensor. The AHR is known to regulate immune surveillance within the intestine through retention of intraepithelial lymphocytes, functional redistribution of Th17/Treg balance. Consequently, environmental/genetic manipulation of AHR activity likely influences host-microbe homeostasis. Utilizing C57BL6/J Ahr−/+ and Ahr−/− co-housed littermates followed by 18 days of genotypic segregation, we examined the influence of AHR expression upon intestinal microbe composition/functionality and host physiology. 16S sequencing/quantitative PCR (qPCR) revealed significant changes in phyla abundance, particularly Verrucomicrobia together with segmented filamentous bacteria, and an increase in species diversity in Ahr−/− mice following genotypic segregation. Metagenomics/metabolomics indicate microbial composition is associated with functional shifts in bacterial metabolism. Analysis identified Ahr−/−-dependent increases in ileal gene expression, indicating increased inflammatory tone. Transfer of Ahr−/− microbiota to wild-type germ-free mice recapitulated the increase Verrucomicrobia and inflammatory tone, indicating Ahr−/−-microbial dependence. These data suggest a role for the AHR in influencing the community structure of the intestinal microbiota. PMID:27659481

  6. The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice

    PubMed Central

    Wisniewski, Paul J.; Noji, Michael; McGuinness, Lora R.; Lightfoot, Stanley A.

    2016-01-01

    Background The gut microbiota is now known to play an important role contributing to inflammatory-based chronic diseases. This study examined intestinal integrity/inflammation and the gut microbial communities in sedentary and exercising mice presented with a normal or high-fat diet. Methods Thirty-six, 6-week old C57BL/6NTac male mice were fed a normal or high-fat diet for 12-weeks and randomly assigned to exercise or sedentary groups. After 12 weeks animals were sacrificed and duodenum/ileum tissues were fixed for immunohistochemistry for occludin, E-cadherin, and cyclooxygenase-2 (COX-2). The bacterial communities were assayed in fecal samples using terminal restriction fragment length polymorphism (TRFLP) analysis and pyrosequencing of 16S rRNA gene amplicons. Results Lean sedentary (LS) mice presented normal histologic villi while obese sedentary (OS) mice had similar villi height with more than twice the width of the LS animals. Both lean (LX) and obese exercise (OX) mice duodenum and ileum were histologically normal. COX-2 expression was the greatest in the OS group, followed by LS, LX and OX. The TRFLP and pyrosequencing indicated that members of the Clostridiales order were predominant in all diet groups. Specific phylotypes were observed with exercise, including Faecalibacterium prausnitzi, Clostridium spp., and Allobaculum spp. Conclusion These data suggest that exercise has a strong influence on gut integrity and host microbiome which points to the necessity for more mechanistic studies of the interactions between specific bacteria in the gut and its host. PMID:26954359

  7. Yeast culture supplement during nursing and transport affects immunity and intestinal microbial ecology of weanling pigs.

    PubMed

    Weedman, S M; Rostagno, M H; Patterson, J A; Yoon, I; Fitzner, G; Eicher, S D

    2011-06-01

    The objectives of this study were to determine the influence of a Saccharomyces cerevisiae fermentation product on innate immunity and intestinal microbial ecology after weaning and transport stress. In a randomized complete block design, before weaning and in a split-plot analysis of a 2 × 2 factorial arrangement of yeast culture (YY) and transport (TT) after weaning, 3-d-old pigs (n = 108) were randomly assigned within litter (block) to either a control (NY, milk only) or yeast culture diet (YY; delivered in milk to provide 0.1 g of yeast culture product/kg of BW) from d 4 to 21. At weaning (d 21), randomly, one-half of the NY and YY pigs were assigned to a 6-h transport (NY-TT and YY-TT) before being moved to nursery housing, and the other one-half were moved directly to nursery housing (NY-NT and YY-NT, where NT is no transport). The yeast treatment was a 0.2% S. cerevisiae fermentation product and the control treatment was a 0.2% grain blank in feed for 2 wk. On d 1 before transport and on d 1, 4, 7, and 14 after transport, blood was collected for leukocyte assays, and mesenteric lymph node, jejunal, and ileal tissue, and jejunal, ileal, and cecal contents were collected for Toll-like receptor expression (TLR); enumeration of Escherichia coli, total coliforms, and lactobacilli; detection of Salmonella; and microbial analysis. After weaning, a yeast × transport interaction for ADG was seen (P = 0.05). Transport affected (P = 0.09) ADFI after weaning. Yeast treatment decreased hematocrit (P = 0.04). A yeast × transport interaction was found for counts of white blood cells (P = 0.01) and neutrophils (P = 0.02) and for the neutrophil-to-lymphocyte ratio (P = 0.02). Monocyte counts revealed a transport (P = 0.01) effect. Interactions of yeast × transport (P = 0.001) and yeast × transport × day (P = 0.09) for TLR2 and yeast × transport (P = 0.08) for TLR4 expression in the mesenteric lymph node were detected. Day affected lactobacilli, total coliform, and E

  8. Early Changes in Microbial Colonization Selectively Modulate Intestinal Enzymes, but Not Inducible Heat Shock Proteins in Young Adult Swine

    PubMed Central

    Arnal, Marie-Edith; Zhang, Jing; Messori, Stefano; Bosi, Paolo; Smidt, Hauke; Lallès, Jean-Paul

    2014-01-01

    Metabolic diseases and obesity are developing worldwide in a context of plethoric intake of high energy diets. The intestine may play a pivotal role due to diet-induced alterations in microbiota composition and increased permeability to bacterial lipopolysaccharide inducing metabolic inflammation. Early programming of metabolic disorders appearing in later life is also suspected, but data on the intestine are lacking. Therefore, we hypothesized that early disturbances in microbial colonization have short- and long-lasting consequences on selected intestinal components including key digestive enzymes and protective inducible heat shock proteins (HSP). The hypothesis was tested in swine offspring born to control mothers (n = 12) or mothers treated with the antibiotic amoxicillin around parturition (n = 11), and slaughtered serially at 14, 28 and 42 days of age to assess short-term effects. To evaluate long-term consequences, young adult offspring from the same litters were offered a normal or a fat-enriched diet for 4 weeks between 140 and 169 days of age and were then slaughtered. Amoxicillin treatment transiently modified both mother and offspring microbiota. This was associated with early but transient reduction in ileal alkaline phosphatase, HSP70 (but not HSP27) and crypt depth, suggesting a milder or delayed intestinal response to bacteria in offspring born to antibiotic-treated mothers. More importantly, we disclosed long-term consequences of this treatment on jejunal alkaline phosphatase (reduced) and jejunal and ileal dipeptidylpeptidase IV (increased and decreased, respectively) of offspring born to antibiotic-treated dams. Significant interactions between early antibiotic treatment and later diet were observed for jejunal alkaline phosphatase and sucrase. By contrast, inducible HSPs were not affected. In conclusion, our data suggest that early changes in bacterial colonization not only modulate intestinal architecture and function transiently, but

  9. Metabolic and Microbial Modulation of the Large Intestine Ecosystem by Non-Absorbed Diet Phenolic Compounds: A Review.

    PubMed

    Mosele, Juana I; Macià, Alba; Motilva, Maria-José

    2015-09-18

    Phenolic compounds represent a diverse group of phytochemicals whose intake is associated with a wide spectrum of health benefits. As consequence of their low bioavailability, most of them reach the large intestine where, mediated by the action of local microbiota, a series of related microbial metabolites are accumulated. In the present review, gut microbial transformations of non-absorbed phenolic compounds are summarized. Several studies have reached a general consensus that unbalanced diets are associated with undesirable changes in gut metabolism that could be detrimental to intestinal health. In terms of explaining the possible effects of non-absorbed phenolic compounds, we have also gathered information regarded their influence on the local metabolism. For this purpose, a number of issues are discussed. Firstly, we consider the possible implications of phenolic compounds in the metabolism of colonic products, such as short chain fatty acids (SCFA), sterols (cholesterol and bile acids), and microbial products of non-absorbed proteins. Due to their being recognized as affective antioxidant and anti-inflammatory agents, the ability of phenolic compounds to counteract or suppress pro-oxidant and/or pro-inflammatory responses, triggered by bowel diseases, is also presented. The modulation of gut microbiota through dietetic maneuvers including phenolic compounds is also commented on. Although the available data seems to assume positive effects in terms of gut health protection, it is still insufficient for solid conclusions to be extracted, basically due to the lack of human trials to confirm the results obtained by the in vitro and animal studies. We consider that more emphasis should be focused on the study of phenolic compounds, particularly in their microbial metabolites, and their power to influence different aspects of gut health.

  10. Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis.

    PubMed

    Czaja, Albert J

    2016-11-14

    The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora (dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens (molecular mimicry). Activated gut-derived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as adjunctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies.

  11. Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis

    PubMed Central

    Czaja, Albert J

    2016-01-01

    The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora (dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens (molecular mimicry). Activated gut-derived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as adjunctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies. PMID:27895415

  12. Differences in intestinal microbial metabolites in laying hens with high and low levels of repetitive feather-pecking behavior.

    PubMed

    Meyer, Beatrice; Zentek, Jürgen; Harlander-Matauschek, Alexandra

    2013-02-17

    Feather pecking in laying hens is a serious behavioral problem and is often associated with feather eating. There is some evidence that ingested feathers affect gut function. The aim of the present study was to explore whether differences in intestinal microbial metabolites in laying hens with high and low levels of repetitive feather-pecking behavior exist. Sixty high feather-pecking birds (H) and sixty low feather-pecking birds (L) of the White Leghorn breed were used for behavioral recordings of feather pecking. Feather pecking activity was observed for 5 weeks, after which 22 H birds with the highest and 22 L birds with the lowest feather pecking activity were chosen. The number of whole feathers and feather parts in the gizzard and intestinal microbial metabolites in the ileum and ceca of these laying hens was examined. Biogenic amines, short-chain fatty acids, ammonia and lactate were measured as microbial metabolites. A higher number of feather parts and particles were found in H than in L birds. Putrescine and cadaverine concentrations were higher in the ileum of the hens with low pecking activity (P<0.001 and P=0.012). In the cecum the amounts of l-lactate, d-lactate and total lactate and SCFA were higher in H birds (P=0.007, P=0.005, P=0.006, and P<0.001). Acetate, i-butyrate, i-valeriate and n-valeriate all displayed significantly higher molar ratios in the cecal contents of L birds (P=0.001, P=0.003, P=0.001, and P<0.001). Propionate and n-butyrate showed higher molar ratios in H birds (P<0.001 and P=0.034). Ammonia was higher in the ileum and cecum of the L birds (P<0.001 and P=0.004). For the first time, this study shows that birds with high and low numbers of repetitive pecking movements to the plumage of other birds differ in their intestinal microbial metabolism. Further experiments should be conducted to investigate whether these differences alter behavior in H and L feather pecking birds. The present results, however, open new avenues of research

  13. Effects of dietary supplementation with fermented ginkgo leaves on antioxidant capacity, intestinal morphology and microbial ecology in broiler chicks.

    PubMed

    Zhang, X H; Sun, Z Y; Cao, F L; Ahmad, H; Yang, X H; Zhao, L G; Wang, T

    2015-01-01

    1. The purpose of this study was to evaluate the effects of supplementing diets with three types of fermented Ginkgo-leaves (FGL) on growth, antioxidant capacity, intestinal morphology and microbial ecology in broiler chicks. 2. A total of 300 d-old broilers were randomly allocated to 4 dietary treatments with 6 replications of 10 birds each. Birds were fed on basal diets (Control) or basal diets supplemented with 0.5% FGL with Candida utilis (CF group), Aspergillus niger (AF group) or their combined fermentation (CAF group), respectively, for a 42 d feeding trial. 3. AF and CAF supplementation improved body weight gain (BWG) (22-42 d) and feed conversion ratio (22-42 d and 1-42 d). Concentrations of serum α-tocopherol in CAF group, as well as hepatic α-tocopherol in the three FGL groups were increased, while hepatic reactive oxygen species (ROS) levels were greatly decreased in group AF and CAF. Chickens in AF and CAF groups had decreased hepatic protein carbonyls and malondialdehyde (MDA), as well as jejunal and ileal protein carbonyls. The total superoxide dismutase (T-SOD) activities and glutathione (GSH) of both jejunum and ileum of the CAF group were higher than the other groups. 4. Duodenal and jejunal villous height of birds fed on the AF and CAF diets were increased, while jejunal crypt depth (CD) was decreased. Furthermore, birds fed on AF and CAF supplemented diets had increased ileal lactobacilli populations. Decreased ileal and caecal Escherichia coli and Salmonellas populations was found for the birds fed on CAF supplemented diets. 5. The present study may indicate that the improved feed efficiency and intestinal functions in the group supplemented with AF and CAF are directly connected with the improved antioxidant capacity and intestinal microbial ecology.

  14. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment.

    PubMed

    Vaziri, Nosratola D; Zhao, Ying-Yong; Pahl, Madeleine V

    2016-05-01

    Chronic kidney disease (CKD) results in systemic inflammation and oxidative stress which play a central role in CKD progression and its adverse consequences. Although many of the causes and consequences of oxidative stress and inflammation in CKD have been extensively explored, little attention had been paid to the intestine and its microbial flora as a potential source of these problems. Our recent studies have revealed significant disruption of the colonic, ileal, jejunal and gastric epithelial tight junction in different models of CKD in rats. Moreover, the disruption of the epithelial barrier structure and function found in uremic animals was replicated in cultured human colonocytes exposed to uremic human plasma in vitro We have further found significant changes in the composition and function of colonic bacterial flora in humans and animals with advanced CKD. Together, uremia-induced impairment of the intestinal epithelial barrier structure and function and changes in composition of the gut microbiome contribute to the systemic inflammation and uremic toxicity by accommodating the translocation of endotoxin, microbial fragments and other noxious luminal products in the circulation. In addition, colonic bacteria are the main source of several well-known pro-inflammatory uremic toxins such as indoxyl sulfate, p-cresol sulfate, trimethylamine-N-oxide and many as-yet unidentified retained compounds in end-stage renal disease patients. This review is intended to provide an overview of the effects of CKD on the gut microbiome and intestinal epithelial barrier structure and their role in the pathogenesis of systemic inflammation and uremic toxicity. In addition, potential interventions aimed at mitigating these abnormalities are briefly discussed.

  15. Modulatory Effects of Vasoactive Intestinal Peptide on Intestinal Mucosal Immunity and Microbial Community of Weaned Piglets Challenged by an Enterotoxigenic Escherichia coli (K88)

    PubMed Central

    Xu, Chunlan; Wang, Youming; Sun, Rui; Qiao, Xiangjin; Shang, Xiaoya; Niu, Weining

    2014-01-01

    Toll-like receptors (TLRs) recognize microbial pathogens and trigger immune response, but their regulation by neuropeptide-vasoactive intestinal peptide (VIP) in weaned piglets infected by enterotoxigenic Escherichia coli (ETEC) K88 remains unexplored. Therefore, the study was conducted to investigate its role using a model of early weaned piglets infected by ETEC K88. Male Duroc×Landrace×Yorkshire piglets (n = 24) were randomly divided into control, ETEC K88, VIP, and ETEC K88+VIP groups. On the first three days, ETEC K88 and ETEC K88+VIP groups were orally administrated with ETEC K88, other two groups were given sterile medium. Then each piglet from VIP and ETEC K88+VIP group received 10 nmol VIP intraperitoneally (i.p.) once daily, on day four and six. On the seventh day, the piglets were sacrificed. The results indicated that administration of VIP improved the growth performance, reduced diarrhea incidence of ETEC K88 challenged pigs, and mitigated the histopathological changes of intestine. Serum levels of IL-2, IL-6, IL-12p40, IFN-γ and TNF-α in the ETEC K88+ VIP group were significantly reduced compared with those in the ETEC group. VIP significantly increased IL-4, IL-10, TGF-β and S-IgA production compared with the ETEC K88 group. Besides, VIP could inhibit the expression of TLR2, TLR4, MyD88, NF-κB p65 and the phosphorylation of IκB-α, p-ERK, p-JNK, and p-38 induced by ETEC K88. Moreover, VIP could upregulate the expression of occludin in the ileum mucosa compared with the ETEC K88 group. Colon and caecum content bacterial richness and diversity were lower for pigs in the ETEC group than the unchallenged groups. These results demonstrate that VIP is beneficial for the maturation of the intestinal mucosal immune system and elicited local immunomodulatory activities. The TLR2/4-MyD88 mediated NF-κB and MAPK signaling pathway may be critical to the mechanism underlying the modulatory effect of VIP on intestinal mucosal immune function and

  16. Detection of monoclonality in intestinal lymphoma with polymerase chain reaction for antigen receptor gene rearrangement analysis to differentiate from enteritis in dogs.

    PubMed

    Ohmura, S; Leipig, M; Schöpper, I; Hergt, F; Weber, K; Rütgen, B C; Tsujimoto, H; Hermanns, W; Hirschberger, J

    2017-03-01

    The diagnosis of canine intestinal lymphoma by morphological examination is challenging, especially when endoscopic tissue specimens are used. The utility of detection of antigen receptor gene rearrangement by polymerase chain reaction (PARR) in canine lymphoma has been well established, but its usefulness to distinguish enteritis and intestinal lymphoma remains unclear. In this retrospective study we assessed clonality of 29 primary canine intestinal lymphoma, 14 enteritis and 15 healthy control cases by PARR analysis, using formalin-fixed, paraffin-embedded full-thickness tissue specimens. We could detect monoclonal rearrangements in 22 of 29 canine intestinal lymphomas [76%; 95% confidence interval (CI) 56-90%] and polyclonal rearrangements in all of the enteritis and healthy control cases (100%; CI 88-100%). We revealed a predominance of T-cell phenotype compared to B-cell phenotype (85%; CI 65-96% and 15%; CI 4-35%, respectively). We showed that PARR analysis contributes to differentiation of canine intestinal lymphoma from enteritis and to phenotyping of lymphomas.

  17. The Urine Circulating Cathodic Antigen (CCA) Dipstick: A Valid Substitute for Microscopy for Mapping and Point-Of-Care Diagnosis of Intestinal Schistosomiasis

    PubMed Central

    Sousa-Figueiredo, José Carlos; Betson, Martha; Kabatereine, Narcis B.; Stothard, J. Russell

    2013-01-01

    Background The World Health Organization now recommends the provision of praziquantel treatment to preschool-aged children infected with schistosomiasis. For intestinal schistosomiasis the current operational field diagnostic standard is examination of a thick Kato-Katz smear by microscopy prepared from a single stool specimen, and although pragmatic, this methodology has well-known shortcomings. Here, as a potential alternative, the performance of the urine circulating cathodic antigen (CCA) dipstick test was assessed in terms of disease-mapping and point-of-care diagnosis for intestinal schistosomiasis in preschool-aged children. Our manuscript reports on findings at baseline and at the end of a one-year longitudinal treatment study. Methodology/Principal Findings A total of 925 children (mean age 2.8 years) were initially recruited from six lakeshore villages representative of high, moderate and low levels of disease transmission. At baseline, all children were tested for intestinal schistosomiasis by microscopic examination of duplicate Kato-Katz smears prepared from a single stool faecal, by antigen detection with the urine CCA dipstick test and by serology with a commercially available ELISA test (as ‘gold-standard’) that measures host antibody titres to soluble egg antigens. As a point-of-care diagnosis, the urine CCA dipstick test achieved sensitivity and specificity values ranging from 52.5–63.2% and 57.7–75.6%, respectively, with faecal microscopy achieving very high specificities (>87%) but sensitivities as low as 16.7% in the low transmission setting. Conclusion/Significance The urine CCA test was shown to be more effective than faecal microscopy especially in lower transmission settings. The diagnostic performance of this test was not significantly impacted by treatment history or co-infections with other intestinal helminths. PMID:23359826

  18. Influence of porcine intestinal pH and gastric digestion on antigenicity of F4 fimbriae for oral immunisation.

    PubMed

    Snoeck, Veerle; Cox, Eric; Verdonck, Frank; Joensuu, Jussi J; Goddeeris, Bruno M

    2004-01-14

    Newly weaned piglets can be orally immunised against F4+ enterotoxigenic Escherichia coli (ETEC) infection with F4 fimbriae. However, to efficiently develop a vaccine against ETEC induced postweaning diarrhoea, knowledge of the stability of the F4 fimbriae to different pH and gastric digestion is needed. The gastrointestinal pH in suckling and recently weaned piglets was measured and the stability of F4 fimbriae to different pH and to pepsin was assessed in vitro. In the stomach the lowest pH was found in the fundus gland region. Gastric pH values below 2.5 were not found in suckling piglets or at the day of weaning, in contrast to piglets 1 and 2 weeks postweaning. Along the first half of the small intestine and in the caecum, a negative correlation was found between pH and age. The F4 fimbriae were stable to pH 1.5 and 2 for 2 h, whereas longer incubation periods resulted in conversion of the multimeric forms into monomers. The F4 fimbriae were partially degraded by incubation for 15-30 min in simulated gastric fluid at pH 1.5 and 2, and completely digested from 3 h onwards. At pH 3, the fimbriae maintained their antigenicity for at least 4h. The results demonstrate that gastric digestion will only have a limited impact on oral immunisation since liquid passes through the stomach relatively quickly (50% within 2 h). However, we previously demonstrated that the transit times are prolonged shortly after weaning. Shortly after weaning it could be necessary to protect the F4 fimbriae against gastric digestion to obtain efficient oral immunisation of the piglets.

  19. Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus

    PubMed Central

    Hewitson, James P.; Nguyen, D. Linh; van Diepen, Angela; Smit, Cornelis H.; Koeleman, Carolien A.; McSorley, Henry J.; Murray, Janice; Maizels, Rick M.; Hokke, Cornelis H.

    2016-01-01

    Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory–secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. We used MALDI-TOF-MS and LC–MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory–secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1–4GlcNAc) structure, respectively. We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory–secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory–secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory–secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. PMID:26688390

  20. Reduced microbial diversity and high numbers of one single Escherichia coli strain in the intestine of colitic mice.

    PubMed

    Wohlgemuth, Steffen; Haller, Dirk; Blaut, Michael; Loh, Gunnar

    2009-06-01

    Commensal bacteria play a role in the aetiology of inflammatory bowel diseases (IBD). High intestinal numbers of Escherichia coli in IBD patients suggest a role of this organism in the initiation or progression of chronic gut inflammation. In addition, some E. coli genotypes are more frequently detected in IBD patients than others. We aimed to find out whether gut inflammation in an IBD mouse model is associated with a particular E. coli strain. Intestinal contents and tissue material were taken from 1-, 8-, 16- and 24-week-old interleukin 10-deficient (IL-10(-/-)) mice and the respective wild-type animals. Caecal and colonic inflammation was observed in IL-10(-/-) animals from the 8 weeks of life on accompanied by a lower intestinal microbial diversity than in the respective wild-type animals. Culture- based and molecular approaches revealed that animals with gut inflammation harboured significantly higher numbers of E. coli than healthy controls. Phylogenetic grouping according to the E. coli Reference Collection (ECOR) system and strain typing by random-amplified polymorphic DNA and pulsed-field gel electrophoresis revealed that all mice were colonized by one single E. coli strain. The strain was shown to have the O7:H7:K1 serotype and to belong to the virulence-associated phylogenetic group B2. In a co-association experiment with gnotobiotic mice, the strain outnumbered E. coli ECOR strains belonging to the phylogenetic group A and B2 respectively. A high number of virulence- and fitness-associated genes were detected in the strain's genome possibly involved in the bacterial adaptation to the murine intestine.

  1. Effects of mannan oligosaccharide and virginiamycin on the cecal microbial community and intestinal morphology of chickens raised under suboptimal conditions.

    PubMed

    Pourabedin, Mohsen; Xu, Zhengxin; Baurhoo, Bushansingh; Chevaux, Eric; Zhao, Xin

    2014-05-01

    There is an increasing movement against use of antibiotic growth promoters in animal feed. Prebiotic supplementation is a potential alternative to enhance the host's natural defense through modulation of gut microbiota. In the present study, the effect of mannan oligosaccharide (MOS) and virginiamycin (VIRG) on cecal microbial ecology and intestinal morphology of broiler chickens raised under suboptimal conditions was evaluated. MOS and VIRG induced different bacterial community structures, as revealed by denaturing gradient gel electrophoresis of 16S rDNA. The antibiotic treatment reduced cecal microbial diversity while the community equitability increased. A higher bacterial diversity was observed in the cecum of MOS-supplemented birds. Quantitative polymerase chain reaction results indicated that MOS changed the cecal microbiota in favor of the Firmicutes population but not the Bacteroidetes population. No difference was observed in total bacterial counts among treatments. MOS promoted the growth of Lactobacillus spp. and Bifidobacterium spp. in the cecum and increased villus height and goblet cell numbers in the ileum and jejunum. These results provide a deeper insight into the microbial ecological changes after supplementation of MOS prebiotic in poultry diets.

  2. Microbial fingerprinting detects intestinal microbiota dysbiosis in Zebrafish models with chemically-induced enterocolitis

    PubMed Central

    2013-01-01

    Background Inflammatory bowel disease (IBD) involves a breakdown in interactions between the host immune response and the resident commensal microbiota. Recent studies have suggested gut physiology and pathology relevant to human IBD can be rapidly modeled in zebrafish larvae. The aim of this study was to investigate the dysbiosis of intestinal microbiota in zebrafish models with IBD-like enterocolitis using culture-independent techniques. Results IBD-like enterocolitis was induced by exposing larval zebrafish to trinitrobenzenesulfonic acid (TNBS). Pathology was assessed by histology and immunofluorescence. Changes in intestinal microbiota were evaluated by denaturing gradient gel electrophoresis (DGGE) and the predominant bacterial composition was determined with DNA sequencing and BLAST and confirmed by real-time polymerase chain reaction. Larval zebrafish exposed to TNBS displayed intestinal-fold architecture disruption and inflammation reminiscent of human IBD. In this study, we defined a reduced biodiversity of gut bacterial community in TNBS-induced coliitis. The intestinal microbiota dysbiosis in zebrafish larvae with IBD-like colitis was characterized by an increased proportion of Proteobacteria (especially Burkholderia) and a decreased of Firmicutes(Lactobacillus group), which were significantly correlated with enterocolitis severity(Pearson correlation p < 0.01). Conclusions This is the first description of intestinal microbiota dysbiosis in zebrafish IBD-like models, and these changes correlate with TNBS-induced enterocolitis. Prevention or reversal of this dysbiosis may be a viable option for reducing the incidence and severity of human IBD. PMID:24325678

  3. Antigen-Presenting Human γδ T Cells Promote Intestinal CD4(+) T Cell Expression of IL-22 and Mucosal Release of Calprotectin.

    PubMed

    Tyler, Christopher J; McCarthy, Neil E; Lindsay, James O; Stagg, Andrew J; Moser, Bernhard; Eberl, Matthias

    2017-03-22

    The cytokine IL-22 plays a critical role in mucosal barrier defense, but the mechanisms that promote IL-22 expression in the human intestine remain poorly understood. As human microbe-responsive Vγ9/Vδ2 T cells are abundant in the gut and recognize microbiota-associated metabolites, we assessed their potential to induce IL-22 expression by intestinal CD4(+) T cells. Vγ9/Vδ2 T cells with characteristics of APCs were generated from human blood and intestinal organ cultures, then cocultured with naive and memory CD4(+) T cells obtained from human blood or the colon. The potency of blood and intestinal γδ T-APCs was compared with that of monocytes and dendritic cells, by assessing CD4(+) T cell phenotypes and proliferation as well as cytokine and transcription factor profiles. Vγ9/Vδ2 T cells in human blood, colon, and terminal ileum acquired APC functions upon microbial activation in the presence of microenvironmental signals including IL-15, and were capable of polarizing both blood and colonic CD4(+) T cells toward distinct effector fates. Unlike monocytes or dendritic cells, gut-homing γδ T-APCs employed an IL-6 independent mechanism to stimulate CD4(+) T cell expression of IL-22 without upregulating IL-17. In human intestinal organ cultures, microbial activation of Vγ9/Vδ2 T cells promoted mucosal secretion of IL-22 and ICOSL/TNF-α-dependent release of the IL-22 inducible antimicrobial protein calprotectin without modulating IL-17 expression. In conclusion, human γδ T-APCs stimulate CD4(+) T cell responses distinct from those induced by myeloid APCs to promote local barrier defense via mucosal release of IL-22 and calprotectin. Targeting of γδ T-APC functions may lead to the development of novel gut-directed immunotherapies and vaccines.

  4. Controlling Salmonella infection in weanling pigs through water delivery of direct-fed microbials or organic acids: Part II. Effects on intestinal histology and active nutrient transport

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to evaluate the effects of water-delivered direct-fed microbials (DFM) or organic acids on intestinal morphology and active nutrient absorption in weanling pigs following deliberate Salmonella infection. Pigs (n = 88) were weaned at 19 ± 2 d of age and assigned to one...

  5. Intestinal microbial affects of yeast products on weaned and transport stressed pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Study objectives were to determine effects of a commercially available yeast product (XPC, Diamond-V Mills) and stress of transportation on total Enterobacteriaceae, Escherichia coli, coliforms, and Lactobacilli populations in the intestine of weaning pigs. In a RCB design with a 2 x 2 factorial ar...

  6. Colonization of porcine small intestine by Escherichia coli: ileal colonization and adhesion by pig enteropathogens that lack K88 antigen and by some acapsular mutants.

    PubMed

    Nagy, B; Moon, H W; Isaacson, R E

    1976-04-01

    Seven K88-negative porcine enteropathogenic Escherichia coli, representing three different serogroups, caused severe diarrhea and characteristically colonized the ileum, but not the jejunum, of intragastrically exposed newborn pigs. Bacterial counts of intestinal contents and wall, fluorescence, and scanning electron microscopy all suggested that these strains colonized the ileum by adhesion to the villous epithelium. However, in ligated intestinal loops, these enteropathogenic E. coli strains adhered to jejunal epithelium as well as to ileal epithelium. Acapsular (K-) mutants, derived from one of the principal strains, retained their colonizing and adhesive abilities, whereas K- mutants from three other enteropathogenic E. coli strains did not. It is suggested that: (i) these K88-negative enteropathogenic E. coli colonize the ileum by adhesion, and (ii) the adhesion of some K-88-negative strains is mediated by surface factors other than, or in addition to, the polysaccharide K antigen.

  7. Nutritional Keys for Intestinal Barrier Modulation

    PubMed Central

    De Santis, Stefania; Cavalcanti, Elisabetta; Mastronardi, Mauro; Jirillo, Emilio; Chieppa, Marcello

    2015-01-01

    The intestinal tract represents the largest interface between the external environment and the human body. Nutrient uptake mostly happens in the intestinal tract, where the epithelial surface is constantly exposed to dietary antigens. Since inflammatory response toward these antigens may be deleterious for the host, a plethora of protective mechanisms take place to avoid or attenuate local damage. For instance, the intestinal barrier is able to elicit a dynamic response that either promotes or impairs luminal antigens adhesion and crossing. Regulation of intestinal barrier is crucial to control intestinal permeability whose increase is associated with chronic inflammatory conditions. The cross talk among bacteria, immune, and dietary factors is able to modulate the mucosal barrier function, as well as the intestinal permeability. Several nutritional products have recently been proposed as regulators of the epithelial barrier, even if their effects are in part contradictory. At the same time, the metabolic function of the microbiota generates new products with different effects based on the dietary content. Besides conventional treatments, novel therapies based on complementary nutrients are now growing. Fecal therapy has been recently used for the clinical treatment of refractory Clostridium difficile infection instead of the classical antibiotic therapy. In the present review, we will outline the epithelial response to nutritional components derived from dietary intake and microbial fermentation focusing on the consequent effects on the integrity of the epithelial barrier. PMID:26697008

  8. Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

    PubMed Central

    Cui, Tao; Hurtig, Monica; Elgue, Graciela; Li, Su-Chen; Veronesi, Giulia; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Pelosi, Giuseppe; Alimohammadi, Mohammad; Öberg, Kjell; Giandomenico, Valeria

    2010-01-01

    Background Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. Methodology/Principal Findings A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Conclusion Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors. PMID:21209860

  9. T helper cell IL-4 drives intestinal Th2 priming to oral peanut antigen, under the control of OX40L and independent of innate-like lymphocytes.

    PubMed

    Chu, D K; Mohammed-Ali, Z; Jiménez-Saiz, R; Walker, T D; Goncharova, S; Llop-Guevara, A; Kong, J; Gordon, M E; Barra, N G; Gillgrass, A E; Van Seggelen, H; Khan, W I; Ashkar, A A; Bramson, J L; Humbles, A A; Kolbeck, R; Waserman, S; Jordana, M

    2014-11-01

    Intestinal T helper type 2 (Th2) immunity in food allergy results in IgG1 and IgE production, and antigen re-exposure elicits responses such as anaphylaxis and eosinophilic inflammation. Although interleukin-4 (IL-4) is critically required for allergic sensitization, the source and control of IL-4 during the initiation of Th2 immunity in vivo remains unclear. Non-intestinal and non-food allergy systems have suggested that natural killer-like T (NKT) or γδ T-cell innate lymphocytes can supply the IL-4 required to induce Th2 polarization. Group 2 innate lymphoid cells (ILCs) are a novel IL-4-competent population, but their contribution to initiating adaptive Th2 immunity is unclear. There are also reports of IL-4-independent Th2 responses. Here, we show that IL-4-dependent peanut allergic Th2 responses are completely intact in NKT-deficient, γδ T-deficient or ILC-deficient mice, including antigen-specific IgG1/IgE production, anaphylaxis, and cytokine production. Instead, IL-4 solely from CD4(+) Th cells induces full Th2 immunity. Further, CD4(+) Th cell production of IL-4 in vivo is dependent on OX40L, a costimulatory molecule on dendritic cells (DCs) required for intestinal allergic priming. However, both Th2 cells and ILCs orchestrated IL-13-dependent eosinophilic inflammation. Thus, intestinal Th2 priming is initiated by an autocrine/paracrine acting CD4(+) Th cell-intrinsic IL-4 program that is controlled by DC OX40L, and not by NKT, γδ T, or ILC cells.

  10. Regulatory effect of monocytes on T cell proliferative responses to oral microbial antigens.

    PubMed Central

    Stashenko, P

    1982-01-01

    Mononuclear cell preparations isolated by Ficoll-Hypaque centrifugation from human peripheral blood were found to vary considerably in the number of monocytes they contained (mean, 20.3%; range, 13 to 33%). The regulatory role of monocytes in T cell proliferative responses to sonic extracts of a panel of oral microorganisms was therefore investigated. T cells were fractionated by anti-immunoglobulin chromatography and depleted of monocytes by treatment with a monoclonal anti-human Ia-like (DR locus antigen) antibody and complement. Purified populations of monocytes were obtained by extensive adherence procedures. The resultant cell populations were greater than 95% pure, as judged by indirect immunofluorescence on a fluorescence-activated cell sorter. Monocyte-depleted T cells failed to respond by proliferation to the nonoral antigen tetanus toxoid, as well as to any oral microorganism, but retained responsiveness to phytohemagglutinin. Readdition of monocytes in final concentrations of from 5 to 15% resulted in the restoration of maximal T cell proliferation. Monocytes in greater numbers suppressed T cell responses to all sonic extracts tested. PMID:6984019

  11. Intestinal microbial metabolism of phosphatidylcholine: a novel insight in the cardiovascular risk scenario

    PubMed Central

    Sorrentino, Claudia; Principi, Mariabeatrice; Giorgio, Floriana; Losurdo, Giuseppe; Di Leo, Alfredo

    2015-01-01

    Intestinal microbiota is a “dynamic organ” influencing host metabolism, nutrition, physiology and immune system. Among its several interactions, the role of a phosphatidylcholine metabolite derived by gut flora activity, i.e., trimethylamine-N-oxide (TMAO), allows perceiving a novel insight in the cardiovascular risk scenario, being a strong predictor of this condition. Based on current reports, including the paper of Tang et al., we describe here: the possible role of intestinal microbiota in cardiovascular risk as well as potential interventions to reduce gut flora TMAO production by diet, probiotics and antibiotics. Finally, we highlight the possibility of evaluating, monitoring and modulating TMAO in order to use its serum levels as a marker of cardiovascular risk in the next future, when the need of controlled studies on large series will be satisfied. PMID:26312245

  12. Therapeutic modulation of intestinal dysbiosis.

    PubMed

    Walker, Alan W; Lawley, Trevor D

    2013-03-01

    The human gastrointestinal tract is home to an extremely numerous and diverse collection of microbes, collectively termed the "intestinal microbiota". This microbiota is considered to play a number of key roles in the maintenance of host health, including aiding digestion of otherwise indigestible dietary compounds, synthesis of vitamins and other beneficial metabolites, immune system regulation and enhanced resistance against colonisation by pathogenic microorganisms. Conversely, the intestinal microbiota is also a potent source of antigens and potentially harmful compounds. In health, humans can therefore be considered to exist in a state of natural balance with their microbial inhabitants. A shift in the balance of microbiota composition such that it may become deleterious to host health is termed "dysbiosis". Dysbiosis of the gut microbiota has been implicated in numerous disorders, ranging from intestinal maladies such as inflammatory bowel diseases and colorectal cancer to disorders with more systemic effects such as diabetes, metabolic syndrome and atopy. Given the far reaching influence of the intestinal microbiota on human health a clear future goal must be to develop reliable means to alter the composition of the microbiota and restore a healthy balance of microbial species. While it is clear that much fundamental research remains to be done, potentially important therapeutic options include narrow spectrum antibiotics, novel probiotics, dietary interventions and more radical techniques such as faecal transplantation, all of which aim to suppress clinical dysbiosis, restore intestinal microbiota diversity and improve host health.

  13. Comparative analysis of fecal microbiota and intestinal microbial metabolic activity in captive polar bears.

    PubMed

    Schwab, Clarissa; Gänzle, Michael

    2011-03-01

    The composition of the intestinal microbiota depends on gut physiology and diet. Ursidae possess a simple gastrointestinal system composed of a stomach, small intestine, and indistinct hindgut. This study determined the composition and stability of fecal microbiota of 3 captive polar bears by group-specific quantitative PCR and PCR-DGGE (denaturing gradient gel electrophoresis) using the 16S rRNA gene as target. Intestinal metabolic activity was determined by analysis of short-chain fatty acids in feces. For comparison, other Carnivora and mammals were included in this study. Total bacterial abundance was approximately log 8.5 DNA gene copies·(g feces)-1 in all 3 polar bears. Fecal polar bear microbiota was dominated by the facultative anaerobes Enterobacteriaceae and enterococci, and the Clostridium cluster I. The detection of the Clostridium perfringens α-toxin gene verified the presence of C. perfringens. Composition of the fecal bacterial population was stable on a genus level; according to results obtained by PCR-DGGE, dominant bacterial species fluctuated. The total short-chain fatty acid content of Carnivora and other mammals analysed was comparable; lactate was detected in feces of all carnivora but present only in trace amounts in other mammals. In comparison, the fecal microbiota and metabolic activity of captive polar bears mostly resembled the closely related grizzly and black bears.

  14. Intestinal microbial ecology of broilers vaccinated and challenged with mixed Eimeria species, and supplemented with essential oil blends.

    PubMed

    Oviedo-Rondón, E O; Hume, M E; Hernández, C; Clemente-Hernández, S

    2006-05-01

    Intestinal microbiota is an important component in the development of defense mechanisms in the gut mucosa. This project determined the dynamics of intestinal microbial communities (MC) of broilers vaccinated at first day of age with live oocysts of Eimeria species and fed diets supplemented with 2 specific essential oil (EO) blends, Crina Poultry (CP) and Crina Alternate (CA). Five treatments were analyzed: 1) unmedicated-uninfected (UU) control; 2) unmedicated-infected (UI) control; 3) vaccinated with Advent cocci-vaccine and without feed additive (COV) supplements; 4) vaccinated with Advent and supplemented with CP; and 5) vaccinated with Advent and supplemented with CA. The EO blends were added at 100 ppm to the same basal diets. Chicks were gavage-infected at 19 d of age with Eimeria acervulina, Eimeria maxima, and Eimeria tenella. Duodenal, ileal, and cecal samples were taken from 12 birds per treatment just before the infection and 7 d after the challenge, pooled in 6 samples, and frozen. Denaturing gradient gel electrophoresis was used to examine PCR-amplified fragments of the bacterial 16S ribosomal DNA variable region. Results are presented as percentages of similarity coefficients (SC). Dendrograms of amplicon patterns indicated MC differences due to intestinal location, feed additives, and cocci infection. The EO blends CP and CA did affect MC in all gut sections. The cocci-infection caused drastic MC population shifts in duodenal, ileal, and cecal sections (36.7, 55.4, and 36.2% SC, respectively). The CP-supplemented birds had higher SC between pre- and postchallenge MC in duodenal and ileal (73.3, 81.8%) than COV (66.4, 66.5%). However, COV broilers had the smallest changes in cecal MC after infection (79.5% SC). We concluded that cocci-vaccination causes small changes in intestinal MC, but challenge causes drastic shifts. The EO blend supplementation modulates MC in cocci-vaccinated broilers, avoiding drastic shifts after a mixed coccidia infection

  15. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation.

    PubMed

    Read, S; Malmström, V; Powrie, F

    2000-07-17

    It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25(+)CD45RB(low)CD4(+)) as those that control autoimmunity. Previous studies have failed to identify how CD25(+) Treg cells function in vivo. Our studies reveal that the immune-suppressive function of these cells in vivo is dependent on signaling via the negative regulator of T cell activation cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as secretion of the immune-suppressive cytokine transforming growth factor beta. Strikingly, constitutive expression of CTLA-4 among CD4(+) cells was restricted primarily to Treg cells, suggesting that CTLA-4 expression by these cells is involved in their immune-suppressive function. These findings raise the possibility that Treg cell function contributes to the immune suppression characteristic of CTLA-4 signaling. Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases.

  16. [Optimization of treatment of children with acute intestinal infections by application of Russian biological microbial preparations].

    PubMed

    Feklisova, L V

    2005-01-01

    The article presents the results of long-term (several years) use of Russian bifido- and lactocontaing probiotics and data on the clinicolaboratory effectiveness of bifidumbacterin forte, probifor, bifidin, bifilis, calcidum, florin forte, acipol and acilact in children with various intestinal infections of known and unknown etiology. The presented results were obtained by studies conducted according to the requirements of The Governmental Program of L. A. Tarasevich State Institute of Standartization and Medical Biological Preparation Control, which included randomization of groups of patients receiving codified preparations or placebo according to their age, nosology, the degree of the process severity, premorbid status, and the time when the treatment was started. Each of the programs included several hundreds of children, receiving probiotics; in which of the programs the studies were multicentered. The courses of treatment with probiotics were short (1 to 2 weeks). No significant adverse effects were observed.

  17. Correlation between lack of norovirus replication and histo-blood group antigen expression in 3D-intestinal epithelial cultures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Noroviruses (NoV) are a leading cause of gastroenteritis worldwide. An in vitro model for NoV replication remains elusive, making study of the virus difficult. One publication utilizing a 3-dimensional (3D) intestinal model derived from Int407 cells reported NoV replication and extensive cytopathi...

  18. Prebiotic effect of fructooligosaccharide in the simulator of the human intestinal microbial ecosystem (SHIME® model).

    PubMed

    Sivieri, Katia; Morales, Martha L Villarreal; Saad, Susana M I; Adorno, Maria A Tallarico; Sakamoto, Isabel Kimiko; Rossi, Elizeu A

    2014-08-01

    Maintaining "gut health" is a goal for scientists throughout the world. Therefore, microbiota management models for testing probiotics, prebiotics, and synbiotics have been developed. The SHIME(®) model was used to study the effect of fructooligosaccharide (FOS) on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2 weeks using a culture medium. This stabilization period was followed by a 2-week control period during which the microbiota was monitored. The microbiota was then subjected to a 4-week treatment period by adding 5 g/day-1 FOS to vessel one (the "stomach" compartment). Plate counts, Denaturing Gradient Gel Electrophoresis (DGGE), short-chain fatty acid (SCFA), and ammonium analyses were used to observe the influence of FOS treatment in simulated colon compartments. A significant increase (P<.01) in the Lactobacillus spp. and Bifidobacterium spp. populations was observed during the treatment period. The DGGE obtained showed the overall microbial community was changed in the ascending colon compartment of the SHIME reactor. FOS induced increase of the SCFA concentration (P<.05) during the treatment period, mainly due to significant increased levels of acetic and butyric acids. However, ammonium concentrations increased during the same period (P<.01). This study indicates the usefulness of in vitro methods that simulate the colon region as part of research towards the improvement of human health.

  19. Performance of circulating cathodic antigen (CCA) urine-dipsticks for rapid detection of intestinal schistosomiasis in schoolchildren from shoreline communities of Lake Victoria

    PubMed Central

    2010-01-01

    For disease surveillance and mapping within large-scale control programmes, RDTs are becoming popular. For intestinal schistosomiasis, a commercially available urine-dipstick which detects schistosome circulating cathodic antigen (CCA) in host urine is being increasingly applied, however, further validation is needed. In this study, we compared the CCA urine-dipstick test against double thick Kato-Katz faecal smears from 171 schoolchildren examined along the Tanzanian and Kenyan shorelines of Lake Victoria. Diagnostic methods were in broad agreement; the mean prevalence of intestinal schistosomiasis inferred by Kato-Katz examination was 68.6% (95% confidence intervals (CIs) = 60.7-75.7%) and 71.3% (95% CIs = 63.9-78.8%) by CCA urine-dipsticks. There were, however, difficulties in precisely 'calling' the CCA test result, particularly in discrimination of 'trace' reactions as either putative infection positive or putative infection negative, which has important bearing upon estimation of mean infection prevalence; considering 'trace' as infection positive mean prevalence was 94.2% (95% CIs = 89.5-97.2%). A positive association between increasing intensity of the CCA urine-dipstick test band and faecal egg count was observed. Assigning trace reactions as putative infection negative, overall diagnostic sensitivity (SS) of the CCA urine-dipstick was 87.7% (95% CIs = 80.6-93.0%), specificity (SP) was 68.1% (95% CIs = 54.3-80.0%), positive predictive value (PPV) was 86.1% (95% CIs = 78.8-91.7%) and negative predictive value (NPV) was 71.1% (95% CIs = 57.2-82.8%). To assist in objective defining of the CCA urine-dipstick result, we propose the use of a simple colour chart and conclude that the CCA urine-dipstick is a satisfactory alternative, or supplement, to Kato-Katz examination for rapid detection of intestinal schistosomiasis. PMID:20181101

  20. Gamma delta T cells recognize a microbial encoded B Cell antigen to initiate a rapid antigen-specific Interleukin-17 response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gamma delta T cells contribute uniquely to host immune defense, but the way in which they do so remains an enigma. Here we show that an algae protein, phycoerythrin (PE) is recognized by gamma delta T cells from mice, bovine and humans and binds directly to specific gamma delta T cell antigen recept...

  1. Effects of Fruit Toxins on Intestinal and Microbial β-Glucosidase Activities of Seed-Predating and Seed-Dispersing Rodents (Acomys spp.).

    PubMed

    Kohl, Kevin D; Samuni-Blank, Michal; Lymberakis, Petros; Kurnath, Patrice; Izhaki, Ido; Arad, Zeev; Karasov, William H; Dearing, M Denise

    2016-01-01

    Plant secondary compounds (PSCs) have profound influence on the ecological interaction between plants and their consumers. Glycosides, a class of PSC, are inert in their intact form and become toxic on activation by either plant β-glucosidase enzymes or endogenous β-glucosidases produced by the intestine of the plant-predator or its microbiota. Many insect herbivores decrease activities of endogenous β-glucosidases to limit toxin exposure. However, such an adaptation has never been investigated in nonmodel mammals. We studied three species of spiny mice (Acomys spp.) that vary in their feeding behavior of the glycoside-rich fruit of Ochradenus baccatus. Two species, the common (Acomys cahirinus) and Crete (Acomys minous) spiny mice, behaviorally avoid activating glycosides, while the golden spiny mouse (Acomys russatus) regularly consumes activated glycosides. We fed each species a nontoxic diet of inert glycosides or a toxic diet of activated fruit toxins and investigated the responses of intestinal and microbial β-glucosidase activities. We found that individuals feeding on activated toxins had lower intestinal β-glucosidase activity and that the species that behaviorally avoid activating glycosides also had lower intestinal β-glucosidase activity regardless of treatment. The microbiota represented a larger source of toxin liberation, and the toxin-adapted species (golden spiny mouse) exhibited almost a fivefold increase in microbial β-glucosidase when fed activated toxins, while other species showed slight decreases. These results are contrary to those in insects, where glycoside-adapted species have lower β-glucosidase activity. The glycoside-adapted golden spiny mouse may have evolved tolerance mechanisms such as enhanced detoxification rather than avoidance mechanisms.

  2. Effects of encapsulated Lactobacillus acidophilus along with pasteurized longan juice on the colon microbiota residing in a dynamic simulator of the human intestinal microbial ecosystem.

    PubMed

    Chaikham, Pittaya; Apichartsrangkoon, Arunee

    2014-01-01

    The effect of encapsulated Lactobacillus acidophilus LA5 along with pasteurized longan juice on the colon microbiota was investigated by applying a dynamic model of the human gastrointestinal tract. Encapsulated L. acidophilus LA5 in pasteurized longan juice or sole encapsulated L. acidophilus LA5 exhibited the efficiency of colonizing the colon and enabling the growth of colon lactobacilli as well as beneficial bifidobacteria but inhibited the growth of fecal coliforms and clostridia. Moreover, these treatments gave rise to a significant increase of lactic acid and short-chain fatty acids such as acetate, propionate, and butyrate. Although acetate displayed the highest quantity, it was likely that after incorporating encapsulated L. acidophilus LA5 plus pasteurized longan juice, quantity of butyrate exceed propionate, and acetate in comparison with their controls. Denaturant gradient gel electrophoresis patterns confirmed that various treatments affected the alteration of microbial community within the simulator of the human intestinal microbial ecosystem.

  3. A Gut Microbial Metabolite of Linoleic Acid, 10-Hydroxy-cis-12-octadecenoic Acid, Ameliorates Intestinal Epithelial Barrier Impairment Partially via GPR40-MEK-ERK Pathway*

    PubMed Central

    Miyamoto, Junki; Mizukure, Taichi; Park, Si-Bum; Kishino, Shigenobu; Kimura, Ikuo; Hirano, Kanako; Bergamo, Paolo; Rossi, Mauro; Suzuki, Takuya; Arita, Makoto; Ogawa, Jun; Tanabe, Soichi

    2015-01-01

    Gut microbial metabolites of polyunsaturated fatty acids have attracted much attention because of their various physiological properties. Dysfunction of tight junction (TJ) in the intestine contributes to the pathogenesis of many disorders such as inflammatory bowel disease. We evaluated the effects of five novel gut microbial metabolites on tumor necrosis factor (TNF)-α-induced barrier impairment in Caco-2 cells and dextran sulfate sodium-induced colitis in mice. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a gut microbial metabolite of linoleic acid, suppressed TNF-α and dextran sulfate sodium-induced changes in the expression of TJ-related molecules, occludin, zonula occludens-1, and myosin light chain kinase. HYA also suppressed the expression of TNF receptor 2 (TNFR2) mRNA and protein expression in Caco-2 cells and colonic tissue. In addition, HYA suppressed the protein expression of TNFR2 in murine intestinal epithelial cells. Furthermore, HYA significantly up-regulated G protein-coupled receptor (GPR) 40 expression in Caco-2 cells. It also induced [Ca2+]i responses in HEK293 cells expressing human GPR40 with higher sensitivity than linoleic acid, its metabolic precursor. The barrier-recovering effects of HYA were abrogated by a GPR40 antagonist and MEK inhibitor in Caco-2 cells. Conversely, 10-hydroxyoctadacanoic acid, which is a gut microbial metabolite of oleic acid and lacks a carbon-carbon double bond at Δ12 position, did not show these TJ-restoring activities and down-regulated GPR40 expression. Therefore, HYA modulates TNFR2 expression, at least partially, via the GPR40-MEK-ERK pathway and may be useful in the treatment of TJ-related disorders such as inflammatory bowel disease. PMID:25505251

  4. Antigen independent differentiation and maintenance of effector-like resident memory T cells in tissues

    PubMed Central

    Casey, Kerry A; Fraser, Kathryn A; Schenkel, Jason M; Moran, Amy; Abt, Michael C; Beura, Lalit K; Lucas, Philip J; Artis, David; Wherry, E John; Hogquist, Kristin; Vezys, Vaiva; Masopust, David

    2012-01-01

    Differentiation and maintenance of recirculating effector memory CD8 T cells (TEM) depends on prolonged cognate antigen stimulation. Whether similar pathways of differentiation exist for recently identified tissue-resident effector memory T cells (TRM), which contribute to rapid local protection upon pathogen re-exposure, is unknown. Memory CD8αβ+ T cells within small intestine epithelium are well-characterized examples of TRM and they maintain a long-lived effector-like phenotype that is highly suggestive of persistent antigen stimulation. This study sought to define the sources and requirements for prolonged Ag-stimulation in programming this differentiation state, including local stimulation via cognate or cross-reactive antigens derived from pathogens, microbial flora, or dietary proteins. Contrary to expectations, we found that prolonged cognate Ag-stimulation was dispensable for intestinal TRM ontogeny. In fact, chronic antigenic stimulation skewed differentiation away from the canonical intestinal T cell phenotype. Resident memory signatures, CD69 and CD103, were expressed in many non-lymphoid tissues including intestine, stomach, kidney, reproductive tract, pancreas, brain, heart, and salivary gland, and could be driven by cytokines. Moreover, TGFβ driven CD103 expression was required for TRM maintenance within intestinal epithelium in vivo. Thus, induction and maintenance of long-lived effector-like intestinal TRM differed from classic models of TEM ontogeny, and were programmed through a novel location-dependent pathway that was required for the persistence of local immunological memory. PMID:22504644

  5. Modulation of intestinal barrier by intestinal microbiota: pathological and therapeutic implications.

    PubMed

    Natividad, Jane M M; Verdu, Elena F

    2013-03-01

    Mammals and their intestinal microbiota peacefully coexist in a mutualistic relationship. Commensal bacteria play an active role in shaping and modulating physiological processes in the host, which include, but are not restricted to, the immune system and the intestinal barrier. Both play a crucial role in containing intestinal bacteria and other potentially noxious luminal antigens within the lumen and mucosal compartment. Although mutualism defines the relationship between the host and the intestinal microbiota, disruptions in this equilibrium may promote disease. Thus, alterations in gut microbiota (dysbiosis) have been linked to the recent increased expression of obesity, allergy, autoimmunity, functional and inflammatory disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). In this article, we review the evidence supporting a role of gut microbiota in regulating intestinal barrier function. We discuss the hypothesis that microbial factors can modulate the barrier in ways that can prevent or promote gastrointestinal disease. A better understanding of the role of the intestinal microbiota in maintaining a functional intestinal barrier may help develop targeted strategies to prevent and treat disease.

  6. Pigs that are divergent in feed efficiency, differ in intestinal enzyme and nutrient transporter gene expression, nutrient digestibility and microbial activity.

    PubMed

    Vigors, S; Sweeney, T; O'Shea, C J; Kelly, A K; O'Doherty, J V

    2016-11-01

    Feed efficiency is an important trait in the future sustainability of pig production, however, the mechanisms involved are not fully elucidated. The objective of this study was to examine nutrient digestibility, organ weights, select bacterial populations, volatile fatty acids (VFA's), enzyme and intestinal nutrient transporter gene expression in a pig population divergent in feed efficiency. Male pigs (n=75; initial BW 22.4 kg SEM 2.03 kg) were fed a standard finishing diet for 43 days before slaughter to evaluate feed intake and growth for the purpose of calculating residual feed intake (RFI). Phenotypic RFI was calculated as the residuals from a regression model regressing average daily feed intake (ADFI) on average daily gain (ADG) and midtest BW0.60 (MBW). On day 115, 16 pigs (85 kg SEM 2.8 kg), designated as high RFI (HRFI) and low RFI (LRFI) were slaughtered and digesta was collected to calculate the coefficient of apparent ileal digestibility (CAID), total tract nutrient digestibility (CATTD), microbial populations and VFA's. Intestinal tissue was collected to examine intestinal nutrient transporter and enzyme gene expression. The LRFI pigs had lower ADFI (P<0.001), improved feed conversion ratio (P<0.001) and an improved RFI value relative to HRFI pigs (0.19 v. -0.14 SEM 0.08; P<0.001). The LRFI pigs had an increased CAID of gross energy (GE), and an improved CATTD of GE, nitrogen and dry matter compared to HRFI pigs (P<0.05). The LRFI pigs had higher relative gene expression levels of fatty acid binding transporter 2 (FABP2) (P<0.01), the sodium/glucose co-transporter 1 (SGLT1) (P<0.05), the glucose transporter GLUT2 (P<0.10), and the enzyme sucrase-isomaltase (SI) (P<0.05) in the jejunum. The LRFI pigs had increased populations of lactobacillus spp. in the caecum compared with HRFI pigs. In colonic digesta HRFI pigs had increased acetic acid concentrations (P<0.05). Differences in nutrient digestibility, intestinal microbial populations and gene

  7. Comparison of Yacon (Smallanthus sonchifolius) Tuber with Commercialized Fructo-oligosaccharides (FOS) in Terms of Physiology, Fermentation Products and Intestinal Microbial Communities in Rats

    PubMed Central

    UTAMI, Ni Wayan Arya; SONE, Teruo; TANAKA, Michiko; NAKATSU, Cindy H; SAITO, Akihiko; ASANO, Kozo

    2013-01-01

    The yacon (Smallanthus sonchifolius) tuber was examined with regard to its prebiotic effects compared with commercialized fructo-oligosaccharides (FOS). A feed containing 10% yacon tuber, which is equivalent to 5% commercialized FOS in terms of the amount of fructo-oligosaccharides (GF2, GF3 and GF4), was administrated to rats for 28 days. The yacon diet changed the intestinal microbial communities beginning in the first week, resulting in a twofold greater concentration of cecal short-chain fatty acids (SCFAs). The SCFA composition differed, but the cecal pH in rats fed yacon tuber was equal to that in rats fed FOS. Serum triglycerides were lower in rats fed yacon compared with rats fed FOS and the control diet. Cecal size was greater with the yacon tuber diet compared with the control diet. The abundant fermentation in the intestines created a selective environment for the intestinal microbiota, which included Lactobacillus acidophilus, Bifidobacterium pseudolongum, Bifidobacterium animalis and Barnesiella spp. according to identification with culture-independent analysis, 16S rRNA gene PCR-DGGE combined with cloning and sequencing. Barnesiella spp. and B. pseudolongum were only found in the rats fed the yacon diet, while L. acidophilus and B. animalis were found in abundance in rats fed both the yacon and FOS diets. The genus Barnesiella has not previously been reported to be associated with yacon or FOS fermentation. We concluded that the physiological and microbiological effects of the yacon tuber were different from those of FOS. Differences in cecal size, blood triglycerides and microbial community profiles including their metabolites (SCFAs) between the yacon tuber and FOS were shown to be more greatly affected by the yacon tuber rather than FOS. PMID:24936376

  8. Comparison of Yacon (Smallanthus sonchifolius) Tuber with Commercialized Fructo-oligosaccharides (FOS) in Terms of Physiology, Fermentation Products and Intestinal Microbial Communities in Rats.

    PubMed

    Utami, Ni Wayan Arya; Sone, Teruo; Tanaka, Michiko; Nakatsu, Cindy H; Saito, Akihiko; Asano, Kozo

    2013-01-01

    The yacon (Smallanthus sonchifolius) tuber was examined with regard to its prebiotic effects compared with commercialized fructo-oligosaccharides (FOS). A feed containing 10% yacon tuber, which is equivalent to 5% commercialized FOS in terms of the amount of fructo-oligosaccharides (GF2, GF3 and GF4), was administrated to rats for 28 days. The yacon diet changed the intestinal microbial communities beginning in the first week, resulting in a twofold greater concentration of cecal short-chain fatty acids (SCFAs). The SCFA composition differed, but the cecal pH in rats fed yacon tuber was equal to that in rats fed FOS. Serum triglycerides were lower in rats fed yacon compared with rats fed FOS and the control diet. Cecal size was greater with the yacon tuber diet compared with the control diet. The abundant fermentation in the intestines created a selective environment for the intestinal microbiota, which included Lactobacillus acidophilus, Bifidobacterium pseudolongum, Bifidobacterium animalis and Barnesiella spp. according to identification with culture-independent analysis, 16S rRNA gene PCR-DGGE combined with cloning and sequencing. Barnesiella spp. and B. pseudolongum were only found in the rats fed the yacon diet, while L. acidophilus and B. animalis were found in abundance in rats fed both the yacon and FOS diets. The genus Barnesiella has not previously been reported to be associated with yacon or FOS fermentation. We concluded that the physiological and microbiological effects of the yacon tuber were different from those of FOS. Differences in cecal size, blood triglycerides and microbial community profiles including their metabolites (SCFAs) between the yacon tuber and FOS were shown to be more greatly affected by the yacon tuber rather than FOS.

  9. Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway.

    PubMed

    Sun, Runbin; Yang, Na; Kong, Bo; Cao, Bei; Feng, Dong; Yu, Xiaoyi; Ge, Chun; Huang, Jingqiu; Shen, Jianliang; Wang, Pei; Feng, Siqi; Fei, Fei; Guo, Jiahua; He, Jun; Aa, Nan; Chen, Qiang; Pan, Yang; Schumacher, Justin D; Yang, Chung S; Guo, Grace L; Aa, Jiye; Wang, Guangji

    2017-02-01

    Previous studies suggest that the lipid-lowering effect of berberine (BBR) involves actions on the low-density lipoprotein receptor and the AMP-activated protein kinase signaling pathways. However, the implication of these mechanisms is unclear because of the low bioavailability of BBR. Because the main action site of BBR is the gut and intestinal farnesoid X receptor (FXR) plays a pivotal role in the regulation of lipid metabolism, we hypothesized that the effects of BBR on intestinal FXR signaling pathway might account for its pharmacological effectiveness. Using wild type (WT) and intestine-specific FXR knockout (FXR(int-/-)) mice, we found that BBR prevented the development of high-fat-diet-induced obesity and ameliorated triglyceride accumulation in livers of WT, but not FXR(int-/-) mice. BBR increased conjugated bile acids in serum and their excretion in feces. Furthermore, BBR inhibited bile salt hydrolase (BSH) activity in gut microbiota, and significantly increased the levels of tauro-conjugated bile acids, especially tauro-cholic acid(TCA), in the intestine. Both BBR and TCA treatment activated the intestinal FXR pathway and reduced the expression of fatty-acid translocase Cd36 in the liver. These results indicate that BBR may exert its lipid-lowering effect primarily in the gut by modulating the turnover of bile acids and subsequently the ileal FXR signaling pathway. In summary, we provide the first evidence to suggest a new mechanism of BBR action in the intestine that involves, sequentially, inhibiting BSH, elevating TCA, and activating FXR, which lead to the suppression of hepatic expression of Cd36 that results in reduced uptake of long-chain fatty acids in the liver.

  10. An organotypic slice model for ex vivo study of neural, immune, and microbial interactions of mouse intestine.

    PubMed

    Schwerdtfeger, Luke A; Ryan, Elizabeth P; Tobet, Stuart A

    2016-02-15

    Organotypic tissue slices provide seminatural, three-dimensional microenvironments for use in ex vivo study of specific organs and have advanced investigative capabilities compared with isolated cell cultures. Several characteristics of the gastrointestinal tract have made in vitro models for studying the intestine challenging, such as maintaining the intricate structure of microvilli, the intrinsic enteric nervous system, Peyer's patches, the microbiome, and the active contraction of gut muscles. In the present study, an organotypic intestinal slice model was developed that allows for functional investigation across regions of the intestine. Intestinal tissue slices were maintained ex vivo for several days in a physiologically relevant environment that preserved normal enterocyte structure, intact and proliferating crypt cells, submucosal organization, and muscle wall composure. Cell death was measured by a membrane-impermeable DNA binding indicator, ethidium homodimer, and less than 5% of cells were labeled in all regions of the villi and crypt epithelia at 24 h ex vivo. This tissue slice model demonstrated intact myenteric and submucosal neuronal plexuses and functional interstitial cells of Cajal to the extent that nonstimulated, segmental contractions occurred for up to 48 h ex vivo. To detect changes in physiological responses, slices were also assessed for segmental contractions in the presence and absence of antibiotic treatment, which resulted in slices with lesser or greater amounts of commensal bacteria, respectively. Segmental contractions were significantly greater in slices without antibiotics and increased native microbiota. This model renders mechanisms of neuroimmune-microbiome interactions in a complex gut environment available to direct observation and controlled perturbation.

  11. Laxative treatment with polyethylene glycol decreases microbial primary bile salt dehydroxylation and lipid metabolism in the intestine of rats.

    PubMed

    van der Wulp, Mariëtte Y M; Derrien, Muriel; Stellaard, Frans; Wolters, Henk; Kleerebezem, Michiel; Dekker, Jan; Rings, Edmond H H M; Groen, Albert K; Verkade, Henkjan J

    2013-10-01

    Polyethylene glycol (PEG) is a frequently used osmotic laxative that accelerates gastrointestinal transit. It has remained unclear, however, whether PEG affects intestinal functions. We aimed to determine the effect of PEG treatment on intestinal sterol metabolism. Rats were treated with PEG in drinking water (7%) for 2 wk or left untreated (controls). We studied the enterohepatic circulation of the major bile salt (BS) cholate with a plasma stable isotope dilution technique and determined BS profiles and concentrations in bile, intestinal lumen contents, and feces. We determined the fecal excretion of cholesterol plus its intestinally formed metabolites. Finally, we determined the cytolytic activity of fecal water (a surrogate marker of colorectal cancer risk) and the amount and composition of fecal microbiota. Compared with control rats, PEG treatment increased the pool size (+51%; P < 0.01) and decreased the fractional turnover of cholate (-32%; P < 0.01). PEG did not affect the cholate synthesis rate, corresponding with an unaffected fecal primary BS excretion. PEG reduced fecal excretion of secondary BS and of cholesterol metabolites (each P < 0.01). PEG decreased the cytolytic activity of fecal water [54 (46-62) vs. 87 (85-92)% erythrocyte potassium release in PEG-treated and control rats, respectively; P < 0.01]. PEG treatment increased the contribution of Verrucomicrobia (P < 0.01) and decreased that of Firmicutes (P < 0.01) in fecal flora. We concluded that PEG treatment changes the intestinal bacterial composition, decreases the bacterial dehydroxylation of primary BS and the metabolism of cholesterol, and increases the pool size of the primary BS cholate in rats.

  12. Microbes and microbial Toxins: paradigms for microbial-mucosal toxins. V. Cholera: invasion of the intestinal epithelial barrier by a stably folded protein toxin.

    PubMed

    Lencer, W I

    2001-05-01

    Cholera toxin (CT) produced by Vibrio cholerae is the virulence factor responsible for the massive secretory diarrhea seen in Asiatic cholera. To cause disease, CT enters the intestinal epithelial cell as a stably folded protein by co-opting a lipid-based membrane receptor, ganglioside G(M1). G(M1) sorts the toxin into lipid rafts and a retrograde trafficking pathway to the endoplasmic reticulum, where the toxin unfolds and transfers its enzymatic subunit to the cytosol, probably by dislocation through the translocon sec61p. The molecular determinants that drive entry of CT into this pathway are encoded entirely within the structure of the protein toxin itself.

  13. Dietary protein concentration affects intestinal microbiota of adult cats: a study using DGGE and qPCR to evaluate differences in microbial populations in the feline gastrointestinal tract.

    PubMed

    Lubbs, D C; Vester, B M; Fastinger, N D; Swanson, K S

    2009-02-01

    The objective of this study was to identify qualitative and quantitative differences in microbial populations of adult cats fed diets containing different protein concentrations. Following a 4 week baseline period, eight healthy adult domestic short-hair queens (>1-year-old) were randomly allotted to a moderate-protein (MP; n = 4) or high-protein (HP; n = 4) diet for 8 weeks. Fresh faecal samples were collected after baseline and 8 weeks on treatment and stored at -80 degrees C. Following DNA extraction, samples were analyzed using denaturing gradient gel electrophoresis to distinguish qualitative changes between diets. Quantitative polymerase chain reaction was used to measure E. coli, Bifidobacterium, Clostridium perfringens, and Lactobacillus populations. Compared to baseline, cats fed MP had a bacterial similarity index of 66.7% as opposed to 40.6% similarity for those fed HP, exhibiting marked changes in intestinal bacteria of cats fed HP. Bifidobacterium populations were greater (p < 0.05) in cats fed MP versus HP (9.44 vs. 5.63 CFU/g). Clostridium perfringens populations were greater (p < 0.05) in cats fed HP than MP (12.39 vs. 10.83 CFU/g). In this experiment, a high-protein diet resulted in a dramatic shift in microbial populations. Decreased Bifidobacterium population in cats fed HP may justify prebiotic supplementation for such diets.

  14. Effects of diets containing different concentrations of mannanoligosaccharide or antibiotics on growth performance, intestinal development, cecal and litter microbial populations, and carcass parameters of broilers.

    PubMed

    Baurhoo, B; Ferket, P R; Zhao, X

    2009-11-01

    The effects of 2 levels of mannanoligosaccharide (MOS) in feed were compared with antibiotic growth promoters on growth performance, intestinal morphology, cecal and litter microbial populations, and carcass parameters in broilers raised in a sanitary environment. Dietary treatments included: 1) antibiotic growth promoter-free diet (control), 2) VIRG (diet 1 + 16.5 mg/kg of virginiamycin), 3) BACT (diet 1 + 55 mg/kg of bacitracin), 4) LMOS (diet 1 + 0.2% MOS), and 5) HMOS (diet 1 + 0.5% MOS). Birds were randomly assigned to 3 replicate pens/treatment (n = 55/pen). Body weight and feed intake were recorded weekly throughout 38 d. At d 14, 24, and 34, a 1-cm segment of duodenum, jejunum, and ileum was used in morphological analysis (n = 9 birds/d per treatment). At the same bird ages, cecal contents were assayed for lactobacilli, bifidobacteria, Salmonella, Campylobacter, and Escherichia coli, whereas litter was analyzed for Salmonella, Campylobacter, and E. coli. Carcass yields (breast fillet and tenders, thigh, drumstick, and wing) were determined at d 38. Body weight, feed conversion, and carcass yields did not differ among treatments. In contrast to birds fed VIRG or BACT, LMOS and HMOS consistently increased (P < 0.05) villi height and goblet cell number per villus in all intestinal segments at d 24 and 34. Bifidobacteria concentrations were higher (P < 0.05) in LMOS- and HMOS-fed birds at all time points. Birds and litter from all treatments were free of Salmonella. At d 14 and 24, cecal E. coli and Campylobacter counts were not different among treatments. In comparison to birds fed control, at d 34, BACT, LMOS, and HMOS significantly reduced (P < 0.05) cecal E. coli concentrations, whereas Campylobacter counts were reduced (P < 0.05) by VIRG, BACT, and LMOS. Litter bacterial counts were not altered by dietary treatments. In conclusion, under conditions of this study, MOS conferred intestinal health benefits to chickens by improving its morphological

  15. An organotypic slice model for ex vivo study of neural, immune, and microbial interactions of mouse intestine

    PubMed Central

    Schwerdtfeger, Luke A.; Ryan, Elizabeth P.

    2015-01-01

    Organotypic tissue slices provide seminatural, three-dimensional microenvironments for use in ex vivo study of specific organs and have advanced investigative capabilities compared with isolated cell cultures. Several characteristics of the gastrointestinal tract have made in vitro models for studying the intestine challenging, such as maintaining the intricate structure of microvilli, the intrinsic enteric nervous system, Peyer's patches, the microbiome, and the active contraction of gut muscles. In the present study, an organotypic intestinal slice model was developed that allows for functional investigation across regions of the intestine. Intestinal tissue slices were maintained ex vivo for several days in a physiologically relevant environment that preserved normal enterocyte structure, intact and proliferating crypt cells, submucosal organization, and muscle wall composure. Cell death was measured by a membrane-impermeable DNA binding indicator, ethidium homodimer, and less than 5% of cells were labeled in all regions of the villi and crypt epithelia at 24 h ex vivo. This tissue slice model demonstrated intact myenteric and submucosal neuronal plexuses and functional interstitial cells of Cajal to the extent that nonstimulated, segmental contractions occurred for up to 48 h ex vivo. To detect changes in physiological responses, slices were also assessed for segmental contractions in the presence and absence of antibiotic treatment, which resulted in slices with lesser or greater amounts of commensal bacteria, respectively. Segmental contractions were significantly greater in slices without antibiotics and increased native microbiota. This model renders mechanisms of neuroimmune-microbiome interactions in a complex gut environment available to direct observation and controlled perturbation. PMID:26680736

  16. Eggshell membrane powder ameliorates intestinal inflammation by facilitating the restitution of epithelial injury and alleviating microbial dysbiosis.

    PubMed

    Jia, Huijuan; Hanate, Manaka; Aw, Wanping; Itoh, Hideomi; Saito, Kenji; Kobayashi, Shoko; Hachimura, Satoshi; Fukuda, Shinji; Tomita, Masaru; Hasebe, Yukio; Kato, Hisanori

    2017-03-08

    Gut microbiota is an essential factor in the shaping of intestinal immune system development and driving inflammation in inflammatory bowel disease (IBD). We report the effects and microbe-host interactions underlying an intervention using fine powder of eggshell membrane (ESM) against IBD. ESM attenuated lipopolysaccharide-induced inflammatory cytokine production and promoted the Caco-2 cell proliferation by up-regulating growth factors in vitro. In a murine model of dextran sodium sulphate-induced colitis, ESM significantly suppressed the disease activity index and colon shortening. These effects were associated with significant ameliorations of gene expressions of inflammatory mediators, intestinal epithelial cell proliferation, restitution-related factors and antimicrobial peptides. Multifaceted integrated omics analyses revealed improved levels of energy metabolism-related genes, proteins and metabolites. Concomitantly, cecal metagenomic information established an essential role of ESM in improving dysbiosis characterized by increasing the diversity of bacteria and decreasing absolute numbers of pathogenic bacteria such as Enterobacteriaceae and E. coli, as well as in the regulation of the expansion of Th17 cells by suppressing the overgrowth of segmented filamentous bacteria. Such modulations have functional effects on the host; i.e., repairing the epithelium, regulating energy requirements and eventually alleviating mucosal inflammation. These findings are first insights into ESM's modulation of microbiota and IBD suppression, providing new perspectives on the prevention/treatment of IBD.

  17. Eggshell membrane powder ameliorates intestinal inflammation by facilitating the restitution of epithelial injury and alleviating microbial dysbiosis

    PubMed Central

    Jia, Huijuan; Hanate, Manaka; Aw, Wanping; Itoh, Hideomi; Saito, Kenji; Kobayashi, Shoko; Hachimura, Satoshi; Fukuda, Shinji; Tomita, Masaru; Hasebe, Yukio; Kato, Hisanori

    2017-01-01

    Gut microbiota is an essential factor in the shaping of intestinal immune system development and driving inflammation in inflammatory bowel disease (IBD). We report the effects and microbe-host interactions underlying an intervention using fine powder of eggshell membrane (ESM) against IBD. ESM attenuated lipopolysaccharide-induced inflammatory cytokine production and promoted the Caco-2 cell proliferation by up-regulating growth factors in vitro. In a murine model of dextran sodium sulphate-induced colitis, ESM significantly suppressed the disease activity index and colon shortening. These effects were associated with significant ameliorations of gene expressions of inflammatory mediators, intestinal epithelial cell proliferation, restitution-related factors and antimicrobial peptides. Multifaceted integrated omics analyses revealed improved levels of energy metabolism-related genes, proteins and metabolites. Concomitantly, cecal metagenomic information established an essential role of ESM in improving dysbiosis characterized by increasing the diversity of bacteria and decreasing absolute numbers of pathogenic bacteria such as Enterobacteriaceae and E. coli, as well as in the regulation of the expansion of Th17 cells by suppressing the overgrowth of segmented filamentous bacteria. Such modulations have functional effects on the host; i.e., repairing the epithelium, regulating energy requirements and eventually alleviating mucosal inflammation. These findings are first insights into ESM’s modulation of microbiota and IBD suppression, providing new perspectives on the prevention/treatment of IBD. PMID:28272447

  18. Immunochemical and immunohistological expression of Lewis histo-blood group antigens in small intestine including individuals of the Le(a+b+) and Le(a-b-) nonsecretor phenotypes.

    PubMed

    Henry, S M; Samuelsson, B E; Oriol, R

    1994-12-01

    Histological samples and total non-acid glycosphingolipids were prepared from small intestine of human cadavers with the Le(a+b+) and Le(a-b-) nonsecretor phenotypes and contrasted with the more common Lewis phenotypes. Glycolipid fractions were analysed by thin-layer chromatography and tested for Lewis activity with monoclonal antibodies reactive to Lewis epitopes. Paraffin-embedded small intestine sections were also fluorescently immunostained with anti-Lewis antibodies. Unlike the common Lewis positive phenotypes, we were immunochemically able to demonstrate the copresence of large amounts of Lea and Leb glycolipids in the Le(a+b+) sample. In addition we demonstrated increased formation of extended Lewis structures in this phenotype. By immunohistochemistry Lea, Leb and type 1 precursor chain epitopes could be demonstrated in the brush border. These results show that the expression of the Le(a+b+) phenotype at the erythrocyte phenotyping level parallels the small intestinal expression of this phenotype, and the patterns of Lewis antigen expressions are unique to this phenotype. By immunohistochemistry and immunochemistry we also demonstrated the presence of trace amounts of Lewis active glycoconjugates in the small intestine of the Le(a-b-) nonsecretor and Le(a+b-) samples. In the Le(a-b-) nonsecretor Lea and Leb activity was absent and type 1 precursor was present in brush border, while Leb activity was immunohistologically demonstrated in the Golgi apparatus of the deep glands. Trace amounts of both Lea and Leb glycolipids were identified in this sample. In parallel trace Leb activity could also be detected in the glycolipids of the Le(a+b-) sample and could be immunohistologically demonstrated to be fully expressed in occasional cells in the deep glands of the small intestine, a pattern quite dissimilar to that of the Le(a-b-) nonsecretor.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Adding mucins to an in vitro batch fermentation model of the large intestine induces changes in microbial population isolated from porcine feces depending on the substrate.

    PubMed

    Tran, T H T; Boudry, C; Everaert, N; Théwis, A; Portetelle, D; Daube, G; Nezer, C; Taminiau, B; Bindelle, J

    2016-02-01

    Adding mucus to in vitro fermentation models of the large intestine shows that some genera, namely lactobacilli, are dependent on host-microbiota interactions and that they rely on mucosal layers to increase their activity. This study investigated whether this dependence on mucus is substrate dependent and to what extent other genera are impacted by the presence of mucus. Inulin and cellulose were fermented in vitro by a fecal inoculum from pig in the presence or not of mucin beads in order to compare fermentation patterns and bacterial communities. Mucins increased final gas production with inulin and shifted short-chain fatty acid molar ratios (P < 0.001). Quantitative real-time PCR analyses revealed that Lactobacillus spp. and Bifidobacterium spp. decreased with mucins, but Bacteroides spp. increased when inulin was fermented. A more in-depth community analysis indicated that the mucins increased Proteobacteria (0.55 vs 0.25%, P = 0.013), Verrucomicrobia (5.25 vs 0.03%, P = 0.032), Ruminococcaceae, Bacteroidaceae and Akkermansia spp. Proteobacteria (5.67 vs 0.55%, P < 0.001) and Lachnospiraceae (33 vs 10.4%) were promoted in the mucus compared with the broth, while Ruminococcaceae decreased. The introduction of mucins affected many microbial genera and fermentation patterns, but from PCA results, the impact of mucus was independent of the fermentation substrate.

  20. Medium-chain triglyceride as an alternative of in-feed colistin sulfate to improve growth performance and intestinal microbial environment in newly weaned pigs.

    PubMed

    Yen, Hung-Che; Lai, Wei-Kang; Lin, Chuan-Shun; Chiang, Shu-Hsing

    2015-01-01

    Five hundred and twenty-eight newly weaned pigs were given four treatments, with eight replicates per treatment. Sixteen to 18 pigs were assigned per replicate and were fed diets supplemented with 0 or 3% medium-chain triglyceride (MCT) and 0 or 40 ppm colistin sulfate (CS) in a 2 × 2 factorial arrangement for 2 weeks. The results showed that dietary supplementation with MCT improved the gain-to-feed ratio during days 3-7 and in the overall period (P < 0.05). Dietary supplementation with MCT decreased coliforms counts (C) in colon and rectum content (P < 0.05). Dietary supplementation with CS decreased C and lactic acid bacteria plus C counts (L + C) in cecum (P < 0.05), and C, L + C (P < 0.01) and ratio of L and C (P < 0.05) in colon and rectum contents. The lack of interactions between MCT and CS indicates different modes of action and additive effects between the two supplementations. In conclusion, supplementation with MCT in diet with or without CS could improve the intestinal microbial environment and the feed utilization efficiency of newly weaned pigs.

  1. Interleukin-19: A Constituent of the Regulome That Controls Antigen Presenting Cells in the Lungs and Airway Responses to Microbial Products

    PubMed Central

    Hoffman, Carol; Park, Sung-Hyun; Daley, Eleen; Emson, Claire; Louten, Jennifer; Sisco, Maureen; de Waal Malefyt, Rene; Grunig, Gabriele

    2011-01-01

    Background Interleukin (IL)-19 has been reported to enhance chronic inflammatory diseases such as asthma but the in vivo mechanism is incompletely understood. Because IL-19 is produced by and regulates cells of the monocyte lineage, our studies focused on in vivo responses of CD11c positive (CD11c+) alveolar macrophages and lung dendritic cells. Methodology/Principal Findings IL-19-deficient (IL-19-/-) mice were studied at baseline (naïve) and following intranasal challenge with microbial products, or recombinant cytokines. Naïve IL-19-/- mixed background mice had a decreased percentage of CD11c+ cells in the bronchoalveolar-lavage (BAL) due to the deficiency in IL-19 and a trait inherited from the 129-mouse strain. BAL CD11c+ cells from fully backcrossed IL-19-/- BALB/c or C57BL/6 mice expressed significantly less Major Histocompatibility Complex class II (MHCII) in response to intranasal administration of lipopolysaccharide, Aspergillus antigen, or IL-13, a pro-allergic cytokine. Neurogenic-locus-notch-homolog-protein-2 (Notch2) expression by lung monocytes, the precursors of BAL CD11c+ cells, was dysregulated: extracellular Notch2 was significantly decreased, transmembrane/intracellular Notch2 was significantly increased in IL-19-/- mice relative to wild type. Instillation of recombinant IL-19 increased extracellular Notch2 expression and dendritic cells cultured from bone marrow cells in the presence of IL-19 showed upregulated extracellular Notch2. The CD205 positive subset among the CD11c+ cells was 3-5-fold decreased in the airways and lungs of naïve IL-19-/- mice relative to wild type. Airway inflammation and histological changes in the lungs were ameliorated in IL-19-/- mice challenged with Aspergillus antigen that induces T lymphocyte-dependent allergic inflammation but not in IL-19-/- mice challenged with lipopolysaccharide or IL-13. Conclusions/Significance Because MHCII is the molecular platform that displays peptides to T lymphocytes and Notch2

  2. Microbial DNA recognition by cGAS-STING and other sensors in dendritic cells in inflammatory bowel diseases.

    PubMed

    Liu, Song; Zhang, Ying; Ren, Jianan; Li, Jieshou

    2015-04-01

    Recognition of microbial nucleic acid initiates host immune defenses against pathogens. Impaired recognition of nucleic acid is involved in the pathogenesis of inflammatory bowel diseases. In contrast to the relatively well-established mechanism of microbial RNA sensing and associated signaling cascades, very little is known on how microbial DNA activates intracellular DNA sensors and controls the function of antigen-presenting cells (especially dendritic cells) to shape mucosal immune responses in intestine. In this review, we will introduce mucosal dendritic cell population, describe various putative DNA sensors, emphasize on newly identified cGAS-cGAMP-STING complex, and discuss how the detection of foreign DNA by mucosal dendritic cells activates innate and adaptive immune responses in intestine. Finally, we will identify certain inflammatory bowel disease-susceptibility genes that associate with impaired microbial DNA recognition in human.

  3. Intestinal Microbial Dysbiosis and Colonic Epithelial Cell Hyperproliferation by Dietary α-Mangostin is Independent of Mouse Strain

    PubMed Central

    Gutierrez-Orozco, Fabiola; Thomas-Ahner, Jennifer M.; Galley, Jeffrey D.; Bailey, Michael T.; Clinton, Steven K.; Lesinski, Gregory B.; Failla, Mark L.

    2015-01-01

    Beverages and supplements prepared from mangosteen fruit are claimed to support gut health and immunity, despite the absence of supporting evidence from clinical trials. We recently reported that α-mangostin (α-MG), the most abundant xanthone in mangosteen fruit, altered the intestinal microbiome, promoted dysbiosis, and exacerbated colitis in C57BL/6J mice. The objective of this study was to determine whether induction of dysbiosis by dietary α-MG is limited to the C57BL/6J strain or represents a more generic response to chronic intake of the xanthone on the gut microbiota of mice. C3H, Balb/c, Nude FoxN1nu, and C57BL/6J mice, each demonstrating unique microbiomes, were fed standard diet or diet containing 0.1% α-MG for four weeks. Dietary α-MG significantly altered the cecal and colonic microbiota in all four strains of mice, promoting a reduction in generally assumed beneficial bacterial groups while increasing the abundance of pathogenic bacteria. Consumption of α-MG was associated with reduced abundance of Firmicutes and increased abundance of Proteobacteria. The abundance of Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae was reduced in α-MG-fed mice, while that of Enterobacteriaceae and Enterococcaceae was increased. Dietary α-MG also was associated with increased proliferation of colonic epithelial cells, infiltration of immune cells, infiltration of immune cells and increased fluid content in stool. These results suggest that ingestion of pharmacologic doses of xanthones in mangosteen-containing supplements may adversely alter the gut microbiota and should be used with caution. PMID:25621505

  4. Mixed culture models for predicting intestinal microbial interactions between Escherichia coli and Lactobacillus in the presence of probiotic Bacillus subtilis.

    PubMed

    Yang, J J; Niu, C C; Guo, X H

    2015-01-01

    Bacillus has been proposed as a probiotic due to its in vivo effectiveness in the gastrointestinal tract through antimicrobial activities. The present study investigates the effects of Lactobacillus alone or in the presence of Bacillus subtilis MA139 on the inhibition of pathogenic Escherichia coli K88. Mixed cultures were used to predict the possible interactions among these bacteria within the intestinal tract of animals. B. subtilis MA139 was first assayed for its inhibition against E. coli K88 both under shaking and static culture conditions. A co-culture assay was employed under static conditions to test the inhibitory effects of Lactobacillus reuteri on E. coli K88, with or without addition of B. subtilis MA139. The results showed that B. subtilis MA139 had marked inhibition against E. coli K88 under shaking conditions and weak inhibition under static conditions. Lactobacillus alone as well as in combination with B. subtilis MA139 spores exerted strong inhibition against E. coli K88 under static conditions. However, the inhibition by Lactobacillus in combination with B. subilis spores was much higher than that by Lactobacillus alone (P<0.01). B. subtilis MA139 significantly decreased the pH and oxidation-reduction potential values of the co-culture broth compared to that of Lactobacillus alone (P<0.05). The viability of Lactobacillus increased when co-cultured with B. subtilis MA139 because of significantly higher Lactobacillus counts and lower pH values in the broth (P<0.05). The role of Bacillus in the mixed culture models suggests that Bacillus may produce beneficial effects by increasing the viability of lactobacilli and subsequently inhibiting the growth of pathogenic E. coli. Therefore, the combination of Bacillus and Lactobacillus species as a probiotic is recommended.

  5. Perturbations of mucosal homeostasis through interactions of intestinal microbes with myeloid cells

    PubMed Central

    Schey, Regina; Danzer, Claudia; Mattner, Jochen

    2014-01-01

    Mucosal surfaces represent the largest areas of interactions of the host with its environment. Subsequently, the mucosal immune system has evolved complex strategies to maintain the integrity of the host by inducing protective immune responses against pathogenic and tolerance against dietary and commensal microbial antigens within the broad range of molecules the intestinal epithelium is exposed to. Among many other specialized cell subsets, myeloid cell populations - due to their strategic location in the subepithelial lamina propria - are the first ones to scavenge and process these intestinal antigens and to send consecutive signals to other immune and non-immune cell subsets. Thus, myeloid cell populations represent attractive targets for clinical intervention in chronic inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD) as they initiate and modulate inflammatory or regulatory immune response and shape the intestinal T cell pool. Here, we discuss the interactions of the intestinal microbiota with dendritic cell and macrophage populations and review in this context the literature on four promising candidate molecules that are critical for the induction and maintenance of intestinal homeostasis on the one hand, but also for the initiation and propagation of chronic intestinal inflammation on the other. PMID:25466587

  6. Perturbations of mucosal homeostasis through interactions of intestinal microbes with myeloid cells.

    PubMed

    Schey, Regina; Danzer, Claudia; Mattner, Jochen

    2015-02-01

    Mucosal surfaces represent the largest areas of interactions of the host with its environment. Subsequently, the mucosal immune system has evolved complex strategies to maintain the integrity of the host by inducing protective immune responses against pathogenic and tolerance against dietary and commensal microbial antigens within the broad range of molecules the intestinal epithelium is exposed to. Among many other specialized cell subsets, myeloid cell populations - due to their strategic location in the subepithelial lamina propria - are the first ones to scavenge and process these intestinal antigens and to send consecutive signals to other immune and non-immune cell subsets. Thus, myeloid cell populations represent attractive targets for clinical intervention in chronic inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD) as they initiate and modulate inflammatory or regulatory immune response and shape the intestinal T cell pool. Here, we discuss the interactions of the intestinal microbiota with dendritic cell and macrophage populations and review in this context the literature on four promising candidate molecules that are critical for the induction and maintenance of intestinal homeostasis on the one hand, but also for the initiation and propagation of chronic intestinal inflammation on the other.

  7. Controlling Salmonella infection in weanling pigs through water delivery of direct-fed microbials or organic acids: Part II. Effects on intestinal histology and active nutrient transport.

    PubMed

    Walsh, M C; Rostagno, M H; Gardiner, G E; Sutton, A L; Richert, B T; Radcliffe, J S

    2012-08-01

    The objective of this study was to evaluate the effects of water-delivered, direct-fed microbials (DFM) or organic acids on intestinal morphology and active nutrient absorption in weanling pigs after deliberate Salmonella infection. Pigs (n = 88) were weaned at 19 ± 2 d of age and assigned to 1 of the following treatments, which were administered for 14 d: 1) control diet; 2) control diet + DFM (Enterococcus faecium, Bacillus subtilis, and Bacillus licheniformis) in drinking water at 10(9) cfu/L for each strain of bacteria; 3) control diet + organic acid-based blend (predominantly propionic, acetic, and benzoic acids) in drinking water at 2.58 mL/L; and 4) control diet + 55 mg/kg carbadox. Pigs were challenged with 10(10) cfu Salmonella enterica var Typhimurium 6 d after commencement of treatments. Pigs (n = 22/d) were harvested before Salmonella challenge and on d 2, 4, and 8 after challenge. Duodenal, jejunal, and ileal mucosal tissues were sampled for measurement of villus height and crypt depth. Jejunal tissue was sampled for determination of active nutrient absorption in modified Ussing chambers. Duodenal villus height was greater in pigs fed in-feed antibiotic before infection (P < 0.05). Jejunal crypts were deeper in DFM- and acid-treated pigs on d 4 after infection compared with all other treatments (P < 0.05). Salmonella infection resulted in a linear decrease in phosphorus (P < 0.001) and glucose (P < 0.05) active transport, and an increase (P < 0.001) in glutamine uptake immediately after challenge. Salmonella infection reduced basal short-circuit current (I(sc)); however, water-delivered DFM or organic acid treatments caused greater basal I(sc) on d 2 after challenge than did carbadox. Carbachol-induced chloride ion secretion was greatest in negative control pigs before infection (P < 0.01) and DFM-treated pigs (P < 0.05) after infection. In conclusion, both the DFM and acidification treatments induced increases in basal active ion movement and jejunal

  8. Effect of Scrophularia striata and Ferulago angulata, as alternatives to virginiamycin, on growth performance, intestinal microbial population, immune response, and blood constituents of broiler chickens.

    PubMed

    Rostami, Farhad; Ghasemi, Hossein A; Taherpour, Kamran

    2015-09-01

    An experiment was conducted to investigate the comparative effect of Scrophularia striata, Ferulago angulata, and virginiamycin (VM) on performance, intestinal microbial population, immune response, and blood constituents of broilers. A total of 300 Ross 308 male broiler chickens were randomly assigned to 5 treatments, with 5 replicates/treatment (10 chickens/pen). Birds were fed either a corn-soybean meal basal diet (control) or the basal diet supplemented with 200 mg/kg VM; 4 g/kg S. striata (SS1); 8 g/kg S. striata (SS2); 4 g/kg F. angulata (FA1); or 8 g/kg F. angulata (FA2). After 6 wk, the BW, ADG, and feed-to-gain ratio (F:G) of the VM, SS1, and FA1 groups were better (P<0.01) compared with the control group. At 42 d, cecal lactobacillus counts were higher (P=0.032) in SS2 and FA2 groups compared with the control and VM groups. In addition, broilers fed any of the diets exhibited lower coliform counts (P<0.05) in the ileum and ceca than those fed the control diet. Total and IgG antibody titers against SRBC for secondary responses, relative spleen weight, and lymphocyte counts were higher (P<0.05) in birds fed the SS2 or FA2 diet compared with the control group. Moreover, feeding the SS2 or FA2 diet decreased (P<0.05) the blood heterophil/lymphocyte ratio and plasma triglyceride level, whereas only the SS2 diet increased (P=0.037) the white blood cell counts compared with the control diet. All diets, except for the VM diet, decreased (P=0.009) the plasma cholesterol level compared to the control treatment. The plasma high-density lipoprotein cholesterol level was also increased (P=0.042) in the SS2 and FA2 groups. In conclusion, dietary S. striata or F. angulata at a level of 4 g/kg diet enhanced growth performance, which was comparable to that of VM used as an antibiotic growth promoter. Furthermore, a high dose of both herbs (8 g/kg diet) could beneficially affect the intestinal health and immune status of broilers.

  9. Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.

    PubMed

    Peer, Xavier; An, Gary

    2014-10-01

    Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the C. difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, fecal microbial transplant. The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of

  10. Intestinal Microbiota and Microbial Metabolites Are Changed in a Pig Model Fed a High-Fat/Low-Fiber or a Low-Fat/High-Fiber Diet

    PubMed Central

    Heinritz, Sonja N.; Weiss, Eva; Eklund, Meike; Aumiller, Tobias; Louis, Sandrine; Rings, Andreas; Messner, Sabine; Camarinha-Silva, Amélia; Seifert, Jana; Bischoff, Stephan C.; Mosenthin, Rainer

    2016-01-01

    The intestinal microbiota and its metabolites appear to be an important factor for gastrointestinal function and health. However, research is still needed to further elaborate potential relationships between nutrition, gut microbiota and host’s health by means of a suitable animal model. The present study examined the effect of two different diets on microbial composition and activity by using the pig as a model for humans. Eight pigs were equally allotted to two treatments, either fed a low-fat/high-fiber (LF), or a high-fat/low-fiber (HF) diet for 7 weeks. Feces were sampled at day 7 of every experimental week. Diet effects on fecal microbiota were assessed using quantitative real-time PCR, DNA fingerprinting and metaproteomics. Furthermore, fecal short-chain fatty acid (SCFA) profiles and ammonia concentrations were determined. Gene copy numbers of lactobacilli, bifidobacteria (P<0.001) and Faecalibacterium prausnitzii (P<0.05) were higher in the LF pigs, while Enterobacteriaceae were more abundant in the HF pigs (P<0.001). Higher numbers of proteins affiliated to Enterobacteriaceae were also present in the HF samples. Proteins for polysaccharide breakdown did almost exclusively originate from Prevotellaceae. Total and individual fecal SCFA concentrations were higher for pigs of the LF treatment (P<0.05), whereas fecal ammonia concentrations did not differ between treatments (P>0.05). Results provide evidence that beginning from the start of the experiment, the LF diet stimulated beneficial bacteria and SCFA production, especially butyrate (P<0.05), while the HF diet fostered those bacterial groups which have been associated with a negative impact on health conditions. These findings correspond to results in humans and might strengthen the hypothesis that the response of the porcine gut microbiota to a specific dietary modulation is in support of using the pig as suitable animal model for humans to assess diet-gut-microbiota interactions. Data are available

  11. Intestinal Colonization by Enterotoxigenic ’Escherichia Coli’

    DTIC Science & Technology

    1976-12-01

    Growth of enterotoxigenic E . coli in porcine small intestine selects for piliated forms which adhere to the intestinal epithelium. Surface antigen...K99 on enterotoxigenic E . coli is a pilus. Antigen K99 occurs on porcine enterotoxigenic E . coli strains and is produced in pig small intestine.

  12. Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation.

    PubMed

    Byrd, Wyatt; Boedeker, Edgar C

    2013-03-15

    Although enterotoxigenic Escherichia coli (ETEC) infections are important causes of infantile and traveler's diarrhea there is no licensed vaccine available for those at-risk. Our goal is to develop a safe, live attenuated ETEC vaccine. We used an attenuated E. coli strain (O157:H7, Δ-intimin, Stx1-neg, Stx2-neg) as a vector (ZCR533) to prepare two vaccine strains, one strain expressing colonization factor antigen I (ZCR533-CFA/I) and one strain expressing CFA/I and a detoxified heat-labile enterotoxin (ZCR533-CFA/I+LThK63) to deliver ETEC antigens to mucosal sites in BALB/c mice. Following intranasal and intragastric immunization with the vaccine strains, serum IgG and IgA antibodies were measured to the CFA/I antigen, however, only serum IgG antibodies were detected to the heat-labile enterotoxin. Intranasal administration of the vaccine strains induced respiratory and intestinal antibody responses to the CFA/I and LT antigens, while intragastric administration induced only intestinal antibody responses with no respiratory antibodies detected to the CFA/I and LT antigens. Mice immunized intranasally with the vaccine strains showed enhanced clearance of wild-type (wt) ETEC bacteria from the lungs. Mice immunized intranasally and intragastrically with the vaccine strains were protected from intestinal colonization following oral challenge with ETEC wt bacteria. Mice immunized intragastrically with the ZCR533-CFA/I+LThK63 vaccine strain had less fluid accumulate in their intestine following challenge with ETEC wt bacteria or with purified LT as compared to the sham mice indicating that the immunized mice were protected from LT-induced intestinal fluid accumulation. Thus, mice intragastrically immunized with the ZCR533-CFA/I+LThK63 vaccine strain were able to effectively neutralize the activity of the LT enterotoxin. However, no difference in intestinal fluid accumulation was detected in the mice immunized intranasally with the vaccine strain as compared to the sham

  13. Eliciting Epitope-Specific CD8+ T Cell Response by Immunization with Microbial Protein Antigens Formulated with α-Galactosylceramide: Theory, Practice, and Protocols.

    PubMed

    Gilchuk, Pavlo; Knight, Frances C; Wilson, John T; Joyce, Sebastian

    2017-01-01

    CD8+ cytotoxic T lymphocytes confer protection against infectious diseases caused by viruses, bacteria, and parasites. Hence, significant efforts have been invested into devising ways to generate CD8+ T cell-targeted vaccines. Generation of microbe-free protein subunit vaccines requires a thorough knowledge of protective target antigens. Such antigens are proteolytically processed peptides presented by MHC class I molecules. To induce a robust antigen-specific CD8+ T cell response through vaccination, it is essential to formulate the antigen with an effective adjuvant. Here, we describe a versatile method for generating high-frequency antigen-specific CD8+ T cells through immunization of mice using the invariant natural killer T cell agonist α-galactosylceramide as the adjuvant.

  14. Quantitative immunohistochemical assessment of IgA, IgM, IgG and antigen-specific immunoglobulin secreting plasma cells in pig small intestinal lamina propria.

    PubMed

    Bianco, C; Felice, V; Panarese, S; Marrocco, R; Ostanello, F; Brunetti, B; Muscatello, L V; Leotti, G; Vila, T; Joisel, F; Sarli, G

    2014-08-15

    Intestinal immune response plays an important defensive role for pathogens, particularly for those transmitted by the oro-faecal route or for foecal shedding modulation. This work examined three parts of intestine from twelve gilts experimentally infected with PCV2-spiked semen, six vaccinated (V group) and six unvaccinated (NV group) against PCV2, 29 and 53 days post infection (DPI). An immunohistochemical investigation for IgA-, IgG- and IgM-antibody bearing plasma cells (PCs) was run on intestinal samples coupled with a sandwich immunohistochemical method to reveal anti-PCV2 antibody-secreting PCs. Plasma cell density was compared in the two groups of animals at 29 and 53 DPI. The IgA, IgG and IgM PC density did not differ between groups but displayed an increase from the upper (villus) to the lower part of the crypts while a decreasing trend in PC density was identified from duodenum to ileum. In the NV group, no increase in anti-PCV2 PC density was demonstrable in the two sampling moment: the amounts of lamina propria PCV2-specific antibody-producing PCs remained constant, 10.55 ± 4.24 and 10.06 ± 5.01 at 29 DPI and 53 DPI, respectively. In the V group a significant increase in PCV2-specific antibody-producing PCs was observed over time. The amounts of PCV2-specific antibody-producing PCs increased from 9.37 ± 13.36 at 29 DPI to 18.76 ± 15.83 at 53 DPI. The data on IgA, IgM and IgG PC counts can be considered reference values in a population of adult pigs. The sandwich method can be proposed as a technique able to identify specific antibody-secreting PCs in formalin-fixed paraffin-embedded tissues. A practical application of the sandwich method is the demonstration of a "booster-like" response of the lamina propria in vaccinated compared to unvaccinated animals. After virus challenge, vaccination induced an increase in the number of PCs containing specific anti-PCV2 antibodies at the level of intestinal mucosa.

  15. Intestinal Cancer

    MedlinePlus

    ... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

  16. Intestinal leiomyoma

    MedlinePlus

    Leiomyoma - intestine ... McLaughlin P, Maher MM. The duodenum and small intestine. In: Adam A, Dixon AK, Gillard JH, Schaefer- ... Roline CE, Reardon RF. Disorders of the small intestine. In: Marx JA, Hockberger RS, Walls RM, et ...

  17. Intestinal obstruction

    MedlinePlus

    Paralytic ileus; Intestinal volvulus; Bowel obstruction; Ileus; Pseudo-obstruction - intestinal; Colonic ileus ... objects that are swallowed and block the intestines) Gallstones (rare) Hernias Impacted stool Intussusception (telescoping of 1 ...

  18. Intestinal Obstruction

    MedlinePlus

    An intestinal obstruction occurs when food or stool cannot move through the intestines. The obstruction can be complete or partial. ... abdomen Inability to pass gas Constipation A complete intestinal obstruction is a medical emergency. It often requires surgery. ...

  19. TREATMENT OF LONG-EVANS RATS WITH A DEFINED MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS IMPACTS INTESTINAL MICROBIAL METABOLISM.

    EPA Science Inventory

    Water treatment results in the production of numerous halogenated disinfection by-products (DBPs), and has been associated with human colorectal cancer. Because the intestinal microbiota can bioactivate promutagens and procarcinogens, several studies have been done to examine the...

  20. Role of the intestinal microbiome in liver disease.

    PubMed

    Henao-Mejia, Jorge; Elinav, Eran; Thaiss, Christoph A; Licona-Limon, Paula; Flavell, Richard A

    2013-10-01

    The liver integrates metabolic outcomes with nutrient intake while preventing harmful signals derived from the gut to spread throughout the body. Direct blood influx from the gastrointestinal tract through the portal vein makes the liver a critical firewall equipped with a broad array of immune cells and innate immune receptors that recognize microbial-derived products, microorganisms, toxins and food antigens that have breached the intestinal barrier. An overwhelming amount of evidence obtained in the last decade indicates that the intestinal microbiota is a key component of a wide variety of physiological processes, and alterations in the delicate balance that represents the intestinal bacterial communities are now considered important determinants of metabolic syndrome and immunopathologies. Moreover, it is now evident that the interaction between the innate immune system and the intestinal microbiota during obesity or autoimmunity promotes chronic liver disease progression and therefore it might lead to novel and individualized therapeutic approaches. In this review, we discuss a growing body of evidence that highlights the central relationship between the immune system, the microbiome, and chronic liver disease initiation and progression.

  1. Human seroreactivity to gut microbiota antigens

    PubMed Central

    Christmann, Benjamin S.; Abrahamsson, Thomas R.; Bernstein, Charles N.; Duck, L. Wayne; Mannon, Peter J.; Berg, Göran; Björkstén, Bengt; Jenmalm, Maria C.; Elson, Charles O.

    2015-01-01

    Background While immune responses directed against antigens from the intestinal microbiota are observed in certain diseases, the normal human adaptive immune response to intestinal microbiota is poorly defined. Objective Our goal was to assess the adaptive immune response to the intestinal microbiota present in 143 healthy adults and compare this response to the immune response observed in 52 children and their mothers at risk of having allergic disease. Methods Human serum was collected from adults and from children followed from birth to seven years of age, and the serum IgG response to a panel of intestinal microbiota antigens was assessed using a novel protein microarray. Results Nearly every individual tested, regardless of health status, had serum IgG that recognized a common set of antigens. Seroreactivity to the panel of antigens was significantly lower in atopic adults. Healthy infants expressed the highest level of IgG seroreactivity to intestinal microbiota antigens. This adaptive response developed between 6 and 12 months of age, and peaked around 2 years of age. Low IgG responses to certain clusters of microbiota antigens during infancy were associated with allergy development during childhood. Conclusions There is an observed perturbation of the adaptive response to antigens from the microbiota in allergic individuals. These perturbations are observable even in childhood, suggesting that optimal stimulation of the adaptive immune system by the microbiota may be needed to prevent certain immune-mediated diseases. PMID:26014812

  2. Changes in gut microbial populations, intestinal morphology, expression of tight junction proteins, and cytokine production between two pig breeds after challenge with Escherichia coli K88: a comparative study.

    PubMed

    Gao, Y; Han, F; Huang, X; Rong, Y; Yi, H; Wang, Y

    2013-12-01

    This study hypothesized that the gut microbial populations, intestinal morphology, and cytokine production are differentially altered in 2 different pig breeds, namely, Chinese native Jinhua pigs and European Landrace pigs, after orally challenge with enterotoxigenic Escherichia coli (ETEC) K88. A total of 12 Jinhua pigs and 12 Landrace pigs were allocated to either the nonchallenged or the challenged groups (6 pigs per group). The challenged pigs were orally administered ETEC K88, and their nonchallenged counterparts were given sterile Luria-Bertani broth. Selected gut microbial populations, intestinal morphology, mRNA expression of tight junction proteins, and the levels of ileal cytokines and secretory immunoglobulin A (sIgA) production were measured in Jinhua and Landrace pigs. The results showed that the challenged Jinhua pigs exhibited a significantly (P < 0.05) lower incidence of diarrhea compared with their Landrace counterparts. The Escherichia coli (E.coli) population and the percentage of E. coli in the total bacteria population were increased in response to ETEC K88 challenge in both Jinhua and Landrace pigs. The challenged Landrace pigs shed more E. coli (P < 0.05) and had higher percentage of E. coli in the total bacteria population in the colon (P < 0.05) compared with their Jinhua counterparts. Both pig breeds tended to exhibit greater villous atrophy and crypt depth reduction in all of the intestinal segments with challenge. The expression of tight junction proteins decreased in response to ETEC K88 challenge in both pig breeds. The levels of the proinflammatory cytokines interferon (IFN)-γ, tumor necrosis factor-α, and IL-6 and the secretion of sIgA were positively altered whereas the levels of the anti-inflammatory cytokine IL-4 and transforming growth factor (TGF)-β were negatively altered by ETEC K88 challenge in both breeds. Jinhua pigs exhibited significantly higher levels of IFN-γ and TGF-β (P < 0.05) in the challenged group. Our

  3. Oral exposure to environmental pollutant benzo[a]pyrene impacts the intestinal epithelium and induces gut microbial shifts in murine model

    PubMed Central

    Ribière, Céline; Peyret, Pierre; Parisot, Nicolas; Darcha, Claude; Déchelotte, Pierre J.; Barnich, Nicolas; Peyretaillade, Eric; Boucher, Delphine

    2016-01-01

    Gut microbiota dysbiosis are associated with a wide range of human diseases, including inflammatory bowel diseases. The physiopathology of these diseases has multifactorial aetiology in which environmental factors, particularly pollution could play a crucial role. Among the different pollutants listed, Polycyclic Aromatic Hydrocarbons (PAHs) are subject to increased monitoring due to their wide distribution and high toxicity on Humans. Here, we used 16S rRNA gene sequencing to investigate the impact of benzo[a]pyrene (BaP, most toxic PAH) oral exposure on the faecal and intestinal mucosa-associated bacteria in C57BL/6 mice. Intestinal inflammation was also evaluated by histological observations. BaP oral exposure significantly altered the composition and the abundance of the gut microbiota and led to moderate inflammation in ileal and colonic mucosa. More severe lesions were observed in ileal segment. Shifts in gut microbiota associated with moderate inflammatory signs in intestinal mucosa would suggest the establishment of a pro-inflammatory intestinal environment following BaP oral exposure. Therefore, under conditions of genetic susceptibility and in association with other environmental factors, exposure to this pollutant could trigger and/or accelerate the development of inflammatory pathologies. PMID:27503127

  4. Acute ethanol administration inhibits Toll-like receptor 4 signaling pathway in rat intestinal epithelia.

    PubMed

    Zhou, Chao; Zhao, Ji; Li, Jing; Wang, Haiying; Tang, Chengwei

    2013-05-01

    Excess alcohol intake, as in binge drinking, increases susceptibility to microbial pathogens. Alcohol impairs macrophage function by suppression of the Toll-like receptor 4 (TLR4) pathway. This study investigated the effects of acute ethanol intake on the TLR4 pathway in rat intestinal epithelia, which usually encounters luminal antigens at first and participates in the development of intestinal immunity. Twenty Wistar rats were randomly assigned to an ethanol group given ethanol as a 25% (v/v) solution in water at 7.5 g/kg, or a control group given saline, by oral gavage daily for 3 days. The epithelial histology and ultrastructure, the intestinal microflora, peripheral and portal venous plasma lipopolysaccharide (LPS) levels, and somatostatin (SST) levels in the peripheral plasma and small intestine were evaluated. Somatostatin receptor 2 (SSTR2), TLR4, TANK binding kinase-1 (TBK1), activated nuclear factor-κB (NF-κB), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the intestinal mucosa were assayed. LPS responsiveness with or without SST pretreatment was assayed in vitro by quantification of TLR4, TBK1, activated NF-κB, IFN-γ and TNF-α in isolated intestinal epithelia. Mucosal damage was observed in the ethanol group by light and electron microscopy. Escherichia coli cultures were unchanged in rat intestine of the ethanol group compared with controls, but lactobacilli cultures were reduced (p < 0.05). LPS levels increased in peripheral and portal venous plasma (p < 0.05), but mucosal TLR4, TBK1, nuclear NF-κB, IFN-γ and TNF-α were unchanged in the ethanol group. LPS treatment in vitro up-regulated the level of TLR4, TBK1 and nuclear NF-κB as well as the production of IFN-γ and TNF-α in isolated intestinal epithelia in the control (p < 0.05), but not the ethanol group. The stimulatory effects of LPS on intestinal epithelia isolated from the control group were significantly inhibited by SST pretreatment (p < 0.05). The

  5. High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

    PubMed Central

    Tomas, Julie; Mulet, Céline; Saffarian, Azadeh; Cavin, Jean-Baptiste; Ducroc, Robert; Regnault, Béatrice; Kun Tan, Chek; Duszka, Kalina; Burcelin, Rémy; Wahli, Walter; Sansonetti, Philippe J.; Pédron, Thierry

    2016-01-01

    Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum—which is usually described as free of bacteria—became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus. A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ–deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses. PMID:27638207

  6. Intestinal Obstruction

    MedlinePlus

    ... Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of the Digestive ... Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of the Digestive ...

  7. Simultaneous UPLC-MS/MS analysis of native catechins and procyanidins and their microbial metabolites in intestinal contents and tissues of male Wistar Furth inbred rats.

    PubMed

    Goodrich, Katheryn M; Neilson, Andrew P

    2014-05-01

    Procyanidins have been extensively investigated for their potential health protective activities. However, the potential bioactivities of procyanidins are limited by their poor bioavailability. The majority of the ingested dose remains unabsorbed and reaches the colon where extensive microbial metabolism occurs. Most existing analytical methods measure either native compounds (catechins and procyanidins), or their microbial metabolites. The objectives of this study were to develop a high-throughput extraction and UPLC-MS/MS method for simultaneous measurement of both native procyanidins and their metabolites, facilitating high-throughput analysis of native and metabolite profiles in various regions of the colon. The present UPLC-MS/MS method facilitates simultaneous resolution and detection of authentic standards of 14 native catechin monomers and procyanidins, as well as 24 microbial metabolites. Detection and resolution of an additional 3 procyanidin dimers and 10 metabolites for which standards were not available was achieved. Elution and adequate resolution of both native compounds and metabolites were achieved within 10min. The intraday repeatability for native compounds was between 1.1 and 16.5%, and the interday repeatability for native compounds was between 2.2 and 25%. Intraday and interday repeatability for metabolites was between 0.6 and 24.1% and 1 and 23.9%, respectively. Observed lower limits of quantification for native compounds were ∼9-350fmol on-column, and for the microbial metabolites were ∼0.8-12,000fmol on-column. Observed lower limits of detection for native compounds were ∼4.5-190fmol on-column, and for metabolites were 0.304-6020fmol on-column. For native monomers and procyanidins, extraction recoveries ranged from 38 to 102%. Extraction recoveries for the 9 microbial metabolites tested ranged from 41 to 95%. Data from tissue analysis of rats gavaged with grape seed extract indicate fairly high accumulation of native compounds

  8. Simultaneous multicolor detection system of the single-molecular microbial antigen by total internal reflection fluorescence microscopy with fluorescent nanocrystal quantum dots

    NASA Astrophysics Data System (ADS)

    Hoshino, Akiyoshi; Fujioka, Kouki; Yamamoto, Mayu; Manabe, Noriyoshi; Yasuhara, Masato; Suzuki, Kazuo; Yamamoto, Kenji

    2005-11-01

    Immunological diagnostic methods have been widely performed and showed high performance in molecular and cellular biology, molecular imaging, and medical diagnostics. We have developed novel methods for the fluorescent labeling of several antibodies coupled with fluorescent nanocrystals QDs. In this study we demonstrated that two bacterial toxins, diphtheria toxin and tetanus toxin, were detected simultaneously in the same view field of a cover slip by using directly QD-conjugated antibodies. We have succeeded in detecting bacterial toxins by counting luminescent spots on the evanescent field with using primary antibody conjugated to QDs. In addition, each bacterial toxin in the mixture can be separately detected by single excitation laser with emission band pass filters, and simultaneously in situ pathogen quantification was performed by calculating the luminescent density on the surface of the cover slip. Our results demonstrate that total internal reflection fluorescence microscopy (TIRFM) enables us to distinguish each antigen from mixed samples and can simultaneously quantitate multiple antigens by QD-conjugated antibodies. Bioconjugated QDs could have great potentialities for in practical biomedical applications to develop various high-sensitivity detection systems.

  9. Immunity to intestinal pathogens: lessons learned from Salmonella

    PubMed Central

    McSorley, Stephen J.

    2014-01-01

    Summary Salmonella are a common source of food or water-borne infection and cause a wide range of clinical disease in human and animal hosts. Salmonella are relatively easy to culture and manipulate in a laboratory setting, and the infection of laboratory animals induces robust innate and adaptive immune responses. Thus, immunologists have frequently turned to Salmonella infection models to expand understanding of immunity to intestinal pathogens. In this review, I summarize current knowledge of innate and adaptive immunity to Salmonella and highlight features of this response that have emerged from recent studies. These include the heterogeneity of the antigen-specific T-cell response to intestinal infection, the prominence of microbial mechanisms to impede T and B-cell responses, and the contribution of non-cognate pathways for elicitation of T-cell effector functions. Together, these different issues challenge an overly simplistic view of host-pathogen interaction during mucosal infection but also allow deeper insight into the real-world dynamic of protective immunity to intestinal pathogens. PMID:24942689

  10. Regulation of antigenic variation in Giardia lamblia.

    PubMed

    Prucca, César G; Rivero, Fernando D; Luján, Hugo D

    2011-01-01

    Antigenic variation, a clonal phenotypic variation developed by microorganisms, involves the permanent switching of homologous, antigenically different cell surface molecules. In pathogenic microorganisms, antigenic variation is often described as a mechanism to evade the host immune system and therefore is responsible for the generation of chronic and/or recurrent infections. However, antigenic variation has also been involved in expanding host diversity and differential courses of the diseases. The intestinal protozoan parasite Giardia lamblia undergoes antigenic variation through the continuous exchange of approximately 200 variant-specific surface proteins. Here we review the principal issues regarding the significance of antigenic variation during Giardia infections, the particular features of the variant-specific surface proteins, and the current knowledge on the mechanisms that regulate this process, as well as the relevance of disrupting antigenic variation as a novel approach to design effective antiparasitic vaccines.

  11. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease.

    PubMed

    Lerner, Aaron; Matthias, Torsten

    2015-06-01

    The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression.

  12. Synthetic Small Intestinal Scaffolds for Improved Studies of Intestinal Differentiation

    PubMed Central

    Costello, Cait M.; Hongpeng, Jia; Shaffiey, Shahab; Yu, Jiajie; Jain, Nina K.; Hackam, David

    2014-01-01

    In vitro intestinal models can provide new insights into small intestinal function, including cellular growth and proliferation mechanisms, drug absorption capabilities, and host-microbial interactions. These models are typically formed with cells cultured on 2D scaffolds or transwell inserts, but it is widely understood that epithelial cells cultured in 3D environments exhibit different phenotypes that are more reflective of native tissue. Our focus was to develop a porous, synthetic 3D tissue scaffold with villous features that could support the culture of epithelial cell types to mimic the natural microenvironment of the small intestine. We demonstrated that our scaffold could support the co-culture of Caco-2 cells with a mucus-producing cell line, HT29-MTX, as well as small intestinal crypts from mice for extended periods. By recreating the surface topography with accurately sized intestinal villi, we enable cellular differentiation along the villous axis in a similar manner to native intestines. In addition, we show that the biochemical microenvironments of the intestine can be further simulated via a combination of apical and basolateral feeding of intestinal cell types cultured on the 3D models. PMID:24390638

  13. Characterization of AfaE adhesins produced by extraintestinal and intestinal human Escherichia coli isolates: PCR assays for detection of Afa adhesins that do or do not recognize Dr blood group antigens.

    PubMed

    Le Bouguénec, C; Lalioui, L; du Merle, L; Jouve, M; Courcoux, P; Bouzari, S; Selvarangan, R; Nowicki, B J; Germani, Y; Andremont, A; Gounon, P; Garcia, M I

    2001-05-01

    Operons of the afa family are expressed by pathogenic Escherichia coli strains associated with intestinal and extraintestinal infections in humans and animals. The recently demonstrated heterogeneity of these operons (L. Lalioui, M. Jouve, P. Gounon, and C. Le Bouguénec, Infect. Immun. 67:5048-5059, 1999) was used to develop a new PCR assay for detecting all the operons of the afa family with a single genetic tool. This PCR approach was validated by investigating three collections of human E. coli isolates originating from the stools of infants with diarrhea (88 strains), the urine of patients with pyelonephritis (97 strains), and the blood of cancer patients (115 strains). The results obtained with this single test and those previously obtained with several PCR assays were closely correlated. The AfaE adhesins encoded by the afa operons are variable, particularly with respect to the primary sequence encoded by the afaE gene. The receptor binding specificities have not been determined for all of these adhesins; some recognize the Dr blood group antigen (Afa/Dr(+) adhesins) on the human decay-accelerating factor (DAF) as a receptor, and others (Afa/Dr(-) adhesins) do not. Thus, the afa operons detected in this study were characterized by subtyping the afaE gene using specific PCRs. In addition, the DAF-binding capacities of as-yet-uncharacterized AfaE adhesins were tested by various cellular approaches. The afaE8 subtype (Afa/Dr(-) adhesin) was found to predominate in afa-positive isolates from sepsis patients (75%); it was frequent in afa-positive pyelonephritis E. coli (55.5%) and absent from diarrhea-associated strains. In contrast, Afa/Dr(+) strains (regardless of the afaE subtype) were associated with both diarrhea (100%) and extraintestinal infections (44 and 25% in afa-positive pyelonephritis and sepsis strains, respectively). These data suggest that there is an association between the subtype of AfaE adhesin and the physiological site of the infection

  14. Inflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair

    PubMed Central

    Luissint, Anny-Claude; Parkos, Charles A.; Nusrat, Asma

    2017-01-01

    The intestinal tract is lined by a single layer of columnar epithelial cells that forms a dynamic, permeable barrier allowing for selective absorption of nutrients, while restricting access to pathogens and food-borne antigens. Precise regulation of epithelial barrier function is therefore required for maintaining mucosal homeostasis and depends, in part, on barrier-forming elements within the epithelium and a balance between pro- and anti-inflammatory factors in the mucosa. Pathologic states, such as inflammatory bowel disease, are associated with a leaky epithelial barrier, resulting in excessive exposure to microbial antigens, recruitment of leukocytes, release of soluble mediators, and ultimately mucosal damage. An inflammatory microenvironment affects epithelial barrier properties and mucosal homeostasis by altering the structure and function of epithelial intercellular junctions through direct and indirect mechanisms. We review our current understanding of complex interactions between the intestinal epithelium and immune cells, with a focus on pathologic mucosal inflammation and mechanisms of epithelial repair. We discuss leukocyte–epithelial interactions, as well as inflammatory mediators that affect the epithelial barrier and mucosal repair. Increased knowledge of communication networks between the epithelium and immune system will lead to tissue-specific strategies for treating pathologic intestinal inflammation. PMID:27436072

  15. Colonization of porcine intestine by enterotoxigenic Escherichia coli: selection of piliated forms in vivo, adhesion of piliated forms to epithelial cells in vitro, and incidence of a pilus antigen among porcine enteropathogenic E. coli.

    PubMed Central

    Nagy, B; Moon, H W; Isaacson, R E

    1977-01-01

    In contrast to K88-positive porcine enterotoxigenic Escherichia coli (ETEC), K88-negative porcine ETEC strains did not adhere to isolated intestinal epithelial cells in vitro. However, they did adhere to intestinal epithelium in vivo. Growth of one such ETEC (strain 987) in pig small intestine consistently yielded a greater percentage of piliated cells than did growth in vitro. This increase was demonstrable by electron microscopy, by change in colonial morphology, and by agglutination in specific antisera against the pili of strain 987. In contrast to the stored stock culture (which contained very few piliated cells), richly piliated forms of strain 987 did adhere to isolated intestinal epithelial cells in vitro. A series of porcine E. coli strains was tested for agglutinability in antiserum against the pili of strain 987, and several K88-negative ETEC strains were agglutinated. These data are consistent with the hypothesis that pili facilitate intestinal adhesion and colonization by K88-negative ETEC strains. Images PMID:326676

  16. Colonization of porcine intestine by enterotoxigenic Escherichia coli: selection of piliated forms in vivo, adhesion of piliated forms to epithelial cells in vitro, and incidence of a pilus antigen among porcine enteropathogenic E. coli.

    PubMed

    Nagy, B; Moon, H W; Isaacson, R E

    1977-04-01

    In contrast to K88-positive porcine enterotoxigenic Escherichia coli (ETEC), K88-negative porcine ETEC strains did not adhere to isolated intestinal epithelial cells in vitro. However, they did adhere to intestinal epithelium in vivo. Growth of one such ETEC (strain 987) in pig small intestine consistently yielded a greater percentage of piliated cells than did growth in vitro. This increase was demonstrable by electron microscopy, by change in colonial morphology, and by agglutination in specific antisera against the pili of strain 987. In contrast to the stored stock culture (which contained very few piliated cells), richly piliated forms of strain 987 did adhere to isolated intestinal epithelial cells in vitro. A series of porcine E. coli strains was tested for agglutinability in antiserum against the pili of strain 987, and several K88-negative ETEC strains were agglutinated. These data are consistent with the hypothesis that pili facilitate intestinal adhesion and colonization by K88-negative ETEC strains.

  17. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon

    PubMed Central

    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation. PMID

  18. Antigenic variation in Giardia lamblia.

    PubMed

    Prucca, Cesar G; Lujan, Hugo D

    2009-12-01

    Giardia lamblia undergoes antigenic variation, both in vitro and within the intestines of infected individuals. Variant-specific surface proteins (VSPs) cover the entire surface of the trophozoites and are the main antigens recognized by the host. Only 1 of about 200 VSP genes encoded by the Giardia genome is expressed on the surface of individual Giardia cells at any time; however, VSP antigen switching occurs spontaneously. In the recent year, significant advances in the knowledge of the antigen switching process have been achieved, which strongly suggests that antigenic variation in Giardia is regulated at the post-transcriptional level by a mechanism similar to RNA interference (RNAi). Several enzymes of the RNAi pathway are directly involved in VSP mRNA silencing and/or translational repression. Although several questions remain regarding how individual VSP antigens are selected for expression on the parasite surface, it is clear that an epigenetic mechanism is involved. In this review, we summarize the characteristics of this fascinating mechanism, analyse conflicting information regarding the structure of VSPs as it relates to the host's immune response, and highlight the major issues that need to be resolved to fully understand antigenic variation in this important pathogen.

  19. Mass Spectrometry and Multiplex Antigen Assays to Assess Microbial Quality and Toxin Production of Staphylococcus aureus Strains Isolated from Clinical and Food Samples

    PubMed Central

    Attien, Paul; Sina, Haziz; Moussaoui, Wardi; Zimmermann-Meisse, Gaëlle; Dadié, Thomas; Keller, Daniel; Riegel, Philippe; Edoh, Vincent; Kotchoni, Simeon O.; Djè, Marcellin; Prévost, Gilles

    2014-01-01

    The aim of our study was to investigate the microbial quality of meat products and on some clinical samples in Abidjan focused on Staphylococcus genus and the toxin production profile of Staphylococcus aureus (S. aureus) isolated. Bacteria were collected from 240 samples of three meat products sold in Abidjan and 180 samples issued from clinical infections. The strains were identified by both microbiological and MALDI-TOF-MS methods. The susceptibility to antibiotics was determined by the disc diffusion method. The production of Panton-Valentine Leukocidin, LukE/D, and epidermolysins was screened using radial gel immunodiffusion. The production of staphylococcal enterotoxins and TSST-1 was screened by a Bio-Plex Assay. We observed that 96/240 of meat samples and 32/180 of clinical samples were contaminated by Staphylococcus. Eleven species were isolated from meats and 4 from clinical samples. Forty-two S. aureus strains were isolated from ours samples. Variability of resistance was observed for most of the tested antibiotics but none of the strains displays a resistance to imipenem and quinolones. We observed that 89% of clinical S. aureus were resistant to methicillin against 58% for those issued from meat products. All S. aureus isolates issued from meat products produce epidermolysins whereas none of the clinical strains produced these toxins. The enterotoxins were variably produced by both clinical and meat product samples. PMID:24987686

  20. Fermented and extruded wheat bran in piglet diets: impact on performance, intestinal morphology, microbial metabolites in chyme and blood lipid radicals.

    PubMed

    Kraler, Manuel; Schedle, Karl; Schwarz, Christiane; Domig, Konrad J; Pichler, Martin; Oppeneder, Alexander; Wetscherek, Wolfgang; Prückler, Michael; Pignitter, Marc; Pirker, Katharina F; Somoza, Veronika; Heine, Daniel; Kneifel, Wolfgang

    2015-01-01

    The aim of the present study was to evaluate the influence of native, fermented and extruded wheat bran on the performance and intestinal morphology of piglets. Additionally, short-chain fatty acids (SCFA), biogenic amines, ammonia, lactic acid, pH as well as E. coli and lactic acid bacterial counts were analysed in digesta samples from three gut sections. Furthermore, the antioxidant potential in blood samples was evaluated based on the lipid radicals formed. For this purpose, 48 newly weaned piglets (28 d old) were allocated to one of the four different dietary treatment groups: no wheat bran (Control), native wheat bran, fermented wheat bran as well as extruded wheat bran. Wheat bran variants were included at 150 g/kg into the diets. All diets were mixed to reach the calculated isonitrogenic nutrient contents. Gut tissue and digesta samples were collected from the proximal jejunum, the terminal ileum and the colon ascendens, blood samples directly at slaughter. Although none of the dietary interventions had an impact on performance parameters, the amount of goblet cells in the ileum was increased upon feeding native and extruded wheat bran, compared to fermented bran (p < 0.05). The E. coli counts in colonic chyme were significantly lower (p < 0.05) in the Control group compared to the groups fed with wheat bran. The concentration of SCFA showed differences for minor compounds (p < 0.05), while linear contrast analyses revealed a reduced concentration of total SCFA in the colon following the feeding of modified wheat bran compared to native wheat bran. This may suggest that several compounds are more easily digested already in the ileum, resulting in a reduced nutrient flow into the large intestine and therefore less unexploited digesta is available as substrate for the microorganisms there. Fermentation also resulted in a significant decrease of methylamine in the colon (p < 0.05), while other biogenic amines in the ileum and colon showed no

  1. Intestinal Parasitoses.

    ERIC Educational Resources Information Center

    Lagardere, Bernard; Dumburgier, Elisabeth

    1994-01-01

    Intestinal parasites have become a serious public health problem in tropical countries because of the climate and the difficulty of achieving efficient hygiene. The objectives of this journal issue are to increase awareness of the individual and collective repercussions of intestinal parasites, describe the current conditions of contamination and…

  2. Effectiveness of Phytogenic Feed Additive as Alternative to Bacitracin Methylene Disalicylate on Hematological Parameters, Intestinal Histomorphology and Microbial Population and Production Performance of Japanese Quails

    PubMed Central

    Manafi, M.; Hedayati, M.; Khalaji, S.

    2016-01-01

    This study was conducted to evaluate the effects of phytogenic additive and antibiotic growth promoter in laying Japanese quails. One hundred and sixty five quails were divided into three groups of 5 replicates and 11 quails (8 females and 3 males) in each replicate. Treatment 1 was fed control diet, treatment 2 was fed control diet supplemented with 0.05% bacitracin methylene disalicylate as antibiotic growth promoter and treatment 3 was fed control diet supplemented with 0.1% phytogenic feed additive (PFA) for two periods of 3 weeks each from 37 to 42 weeks of age. Results showed that egg production, eggshell strength, eggshell weight, villus height and villus height to crypt depth ratio were significantly (p≤0.05) increased and feed consumption, feed conversion ratio, albumen, Haugh unit, cholesterol, low-density lipoprotein, alanine transaminase, gamma glutamyltransferase, alkaline phosphatase, high-density lipoprotein, triglyceride, number of goblet cell, crypt depth and intestinal bacterial population of Coliforms, Salmonella and E. coli were significantly (p≤0.05) decreased in PFA fed group. It is concluded that addition of PFA containing phytomolecules and organic acids as main ingredients could significantly improve the production parameters and the general health of laying quails as an alternative to antibiotic growth promoters. PMID:27189636

  3. The Intestinal Microbiome and Health

    PubMed Central

    Tuddenham, Susan; Sears, Cynthia L.

    2015-01-01

    Purpose of Review A diverse array of microbes colonizes the human intestine. In this review we seek to outline the current state of knowledge on what characterizes a “healthy” or “normal” intestinal microbiome, what factors modify the intestinal microbiome in the healthy state and how the intestinal microbiome affects normal host physiology Recent Findings What constitutes a “normal” or “healthy” intestinal microbiome is an area of active research, but key characteristics may include diversity, richness and a microbial community’s resilience and ability to resist change. A number of factors, including age, the host immune system, host genetics, diet and antibiotic use appear to modify the intestinal microbiome in the normal state. New research shows that the microbiome likely plays a critical role in the healthy human immune system and metabolism. Summary It is clear that there is a complicated bi-directional relationship between the intestinal microbiota and host which is vital to health. An enhanced understanding of this relationship will be critical not only to maximize and maintain human health but also to shape our understanding of disease and to foster new therapeutic approaches. PMID:26237547

  4. Regulation of intestinal blood flow.

    PubMed

    Matheson, P J; Wilson, M A; Garrison, R N

    2000-09-01

    The gastrointestinal system anatomically is positioned to perform two distinct functions: to digest and absorb ingested nutrients and to sustain barrier function to prevent transepithelial migration of bacteria and antigens. Alterations in these basic functions contribute to a variety of clinical scenarios. These primary functions intrinsically require splanchnic blood flow at both the macrovascular and microvascular levels of perfusion. Therefore, a greater understanding of the mechanisms that regulate intestinal vascular perfusion in the normal state and during pathophysiological conditions would be beneficial. The purpose of this review is to summarize the current understanding regarding the regulatory mechanisms of intestinal blood flow in fasted and fed conditions and during pathological stress.

  5. Effects of pomegranate chemical constituents/intestinal microbial metabolites on CYP1B1 in 22Rv1 prostate cancer cells.

    PubMed

    Kasimsetty, Sashi G; Bialonska, Dobroslawa; Reddy, Muntha K; Thornton, Cammi; Willett, Kristine L; Ferreira, Daneel

    2009-11-25

    The cytochrome P450 enzyme, CYP1B1, is an established target in prostate cancer chemoprevention. Compounds inhibiting CYP1B1 activity are contemplated to exert beneficial effects at three stages of prostate cancer development, that is, initiation, progression, and development of drug resistance. Pomegranate ellagitannins/microbial metabolites were examined for their CYP1B1 inhibitory activity in a recombinant CYP1B1-mediated ethoxyresorufin-O-deethylase (EROD) assay. Urolithin A, a microbial metabolite, was the most potent uncompetitive inhibitor of CYP1B1-mediated EROD activity, exhibiting 2-fold selectivity over CYP1A1, while urolithin B was a noncompetitive inhibitor with 3-fold selectivity. The punicalins and punicalagins exhibited potent CYP1A1 inhibition with 5-10-fold selectivity over CYP1B1. Urolithins, punicalins, and punicalagins were tested for their 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced CYP1 inhibitory activity in the 22Rv1 prostate cancer cell line. Urolithins A and B showed a decrease in their CYP1-mediated EROD inhibitory IC50 values upon increasing their treatment times from 30 min to 24 h. Urolithin C, 8-O-methylurolithin A, and 8,9-di-O-methylurolithin C caused a potent CYP1-mediated EROD inhibition in 22Rv1 cells upon 24 h of incubation. Neutral red uptake assay results indicated that urolithin C, 8-O-methylurolithin A, and 8,9-di-O-methylurolithin C induced profound cytotoxicity in the proximity of their CYP1 inhibitory IC50 values. Urolithins A and B were studied for their cellular uptake and inhibition of TCDD-induced CYP1B1 expression. Cellular uptake experiments demonstrated a 5-fold increase in urolithin uptake by 22Rv1 cells. Western blots of the CYP1B1 protein indicated that the urolithins interfered with the expression of CYP1B1 protein. Thus, urolithins were found to display a dual mode mechanism by decreasing CYP1B1 activity and expression.

  6. Short communication: Modulation of the small intestinal microbial community composition over short-term or long-term administration with Lactobacillus plantarum ZDY2013.

    PubMed

    Xie, Qiong; Pan, Mingfang; Huang, Renhui; Tian, Ximei; Tao, Xueying; Shah, Nagendra P; Wei, Hua; Wan, Cuixiang

    2016-09-01

    The small intestinal (SI) microbiota has an essential role in the maintenance of human health. However, data about the indigenous bacteria in SI as affected by probiotics are limited. In our study, the short-term and long-term effects of a probiotic candidate, Lactobacillus plantarum ZDY2013, on the SI microbiota of C57BL/6J mice were investigated by the Illumina HiSeq (Novogene Bioinformatics Technology Co., Ltd., Tianjin, China) platform targeting the V4 region of the 16S rDNA. A total of 858,011 sequences in 15 samples were read. The α diversity analysis revealed that oral administration with L. plantarum ZDY2013 for 3 wk led to a significant increase in the richness and diversity of the SI bacterial community. Principal coordinate analysis and unweighted pair-group method with arithmetic means analysis showed a clear alteration in the SI microbiota composition after 3 wk of L. plantarum ZDY2013 treatment, although these changes were not found 6 wk after ceasing L. plantarum ZDY2013 administration. Species annotation showed that the dominant phyla in SI microbiota were Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia. Interestingly, operational taxonomic unit cluster analysis showed that administration with L. plantarum ZDY2013 for 3 wk significantly increased the abundance of Proteobacteria, but decreased that of Bacteroidetes. Linear discriminant analysis coupled with effect size identified 18 bacterial taxa (e.g., Ruminococcus spp. and Clostridium spp.) that overgrew in the SI microbiota of the mice administered with L. plantarum ZDY2013 for 3 wk, and most of them belonged to the phyla Bacteroidetes and Proteobacteria. However, only one bacterial taxon (e.g., Nocardioides spp.) was over-represented in the SI microbiota of mice 6 wk after L. plantarum ZDY2013 administration. Overall, this study shows that oral administration with probiotic results in an important but transient alteration in the microbiota of SI.

  7. Intestinal Capillariasis

    DTIC Science & Technology

    1987-12-01

    bhIll inenais, the tiny nematode causing Intestinal capillariasis In humans, Is a Iunique parasite. It is one of the newest parasites that has been...Capillariaphilippinensis, the tiny nematode causing intestinal capillariasis in humans, is a unique parasite. It is one of the newest parasites that has been shown to...stichocytes surrounding the oesophagus. The posterior half of the nematode is wider than the anterior half and contains the digestive tract and the

  8. The Extracellular Calcium-Sensing Receptor in the Intestine: Evidence for Regulation of Colonic Absorption, Secretion, Motility, and Immunity

    PubMed Central

    Tang, Lieqi; Cheng, Catherine Y.; Sun, Xiangrong; Pedicone, Alexandra J.; Mohamadzadeh, Mansour; Cheng, Sam X.

    2016-01-01

    Different from other epithelia, the intestinal epithelium has the complex task of providing a barrier impeding the entry of toxins, food antigens, and microbes, while at the same time allowing for the transfer of nutrients, electrolytes, water, and microbial metabolites. These molecules/organisms are transported either transcellularly, crossing the apical and basolateral membranes of enterocytes, or paracellularly, passing through the space between enterocytes. Accordingly, the intestinal epithelium can affect energy metabolism, fluid balance, as well as immune response and tolerance. To help accomplish these complex tasks, the intestinal epithelium has evolved many sensing receptor mechanisms. Yet, their roles and functions are only now beginning to be elucidated. This article explores one such sensing receptor mechanism, carried out by the extracellular calcium-sensing receptor (CaSR). In addition to its established function as a nutrient sensor, coordinating food digestion, nutrient absorption, and regulating energy metabolism, we present evidence for the emerging role of CaSR in the control of intestinal fluid homeostasis and immune balance. An additional role in the modulation of the enteric nerve activity and motility is also discussed. Clearly, CaSR has profound effects on many aspects of intestinal function. Nevertheless, more work is needed to fully understand all functions of CaSR in the intestine, including detailed mechanisms of action and specific pathways involved. Considering the essential roles CaSR plays in gastrointestinal physiology and immunology, research may lead to a translational opportunity for the development of novel therapies that are based on CaSR's unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators. It is possible that, through targeting of intestinal CaSR with a combination of specific nutrients, oral solutions that are both inexpensive and practical may be

  9. The Forminalized Rat: A Convenient Microbial Ecosystem.

    ERIC Educational Resources Information Center

    Lee, Adrian

    1984-01-01

    Presents a series of experiments built around the bacteria found in the intestinal tract of formalinized rats as a model for discussing microbial ecology. Describes methods of examination of intestinal content, student tasks, and discussion questions; also gives a challenge problem to solve.

  10. Autoimmunity and the microbiome: T-cell receptor mimicry of "self" and microbial antigens mediates self tolerance in holobionts: The concepts of "holoimmunity" (TcR-mediated tolerance for the holobiont) and "holoautoimmunity" (loss of tolerance for the holobiont) are introduced.

    PubMed

    Root-Bernstein, Robert

    2016-11-01

    I propose a T-cell receptor (TcR)-based mechanism by which immunity mediates both "genetic self" and "microbial self" thereby, connecting microbiome disease with autoimmunity. The hypothesis is based on simple principles. First, TcR are selected to avoid strong cross-reactivity with "self," resulting in selection for a TcR repertoire mimicking "genetic self." Second, evolution has selected for a "microbial self" that mimics "genetic self" so as to share tolerance. In consequence, our TcR repertoire also mimics microbiome antigenicity, providing a novel mechanism for modulating tolerance to it. Also, the microbiome mimics the TcR repertoire, acting as a secondary immune system. I call this TcR-microbiome mimicry "holoimmunity" to denote immune tolerance to the "holobiont self." Logically, microbiome-host mimicry means that autoimmunity directed at host antigens will also attack components of the microbiome, and conversely, an immunological attack on the microbiome may cross-react with host antigens producing "holoautoimmunity."

  11. Natural selection promotes antigenic evolvability.

    PubMed

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  12. Glycoprotein biosynthesis in small intestine

    PubMed Central

    Kim, Young S.; Perdomo, Jose

    1972-01-01

    Rat small intestinal mucosa was examined for ability to produce mucins with human blood group A, B, and H activity. Blood group activity of the mucins was compared to antigenic activity of red blood cells in individual rats and the enzymatic basis for differences was investigated. Red cells in all the rats examined contained human blood group A and B antigens. All rats synthesized intestinal mucins having B and H antigenic activity but 57% failed to produce mucins with blood group A activity (A-); the remaining 43% (A+) produced A substance. The activities of five glycosyltransferases including α(1→2) fucosyltransferase, the determinant of human secretor status, were measured in the intestine of A+ and A- rats. Four enzymes were the same in both groups, while the fifth, N-acetylgalactosaminyltransferase, was present only in A+ rats. The specificity of this latter enzyme, as found in the rat, appeared similar to that in humans, since it catalyzed addition of N-acetyl-D-galactosamine only to acceptors which had the H determinant structure. In the presence of the enzyme, A- mucin could be converted to A+ mucin; this was shown both by hemagglutination inhibition and immunoprecipitin studies of the products of incubation of A- mucin with UDP-N-acetyl-D-galactosamine and the enzyme. These studies indicate that the difference between A+ and A- rats is due to the apparent absence of N-acetylgalactosaminyltransferase in the intestinal mucosa of A- rats. These rats may provide experimental models for studies on the effect of ABO and secretor status on susceptibility to ulceration and carcinogenesis. Images PMID:4112001

  13. Helminths and Intestinal Flora Team Up to Improve Gut Health.

    PubMed

    Giacomin, Paul; Agha, Zainab; Loukas, Alex

    2016-09-01

    Inflammatory bowel diseases (IBD) are associated with impaired intestinal barrier function, chronic inflammation, and microbial dysbiosis. In a recent publication in Science, Ramanan et al. used murine and human studies to demonstrate that infections with gastrointestinal helminths can protect against IBD by provoking immune responses that alter the balance of commensal and pathogenic bacteria in the intestine.

  14. Immunophenotype analysis of malignant histiocytosis of the intestine.

    PubMed Central

    Salter, D M; Krajewski, A S; Dewar, A E

    1986-01-01

    Five cases of malignant histiocytosis of the intestine and one case of true histiocytic lymphoma were studied using immunohistological techniques. In paraffin sections tumour cells in all cases were shown to contain alpha-1-antitrypsin and to express the leucocyte common antigen. Four of the five cases of malignant histiocytosis of the intestine and the case of histiocytic lymphoma expressed the epithelial membrane antigen. Cryostat sections in four cases of malignant histiocytosis of the intestine showed that most tumour cells reacted with anti-T cell monoclonal antibodies. Only a minority expressed a typical monocyte macrophage phenotype. Images PMID:3512610

  15. [Malaria and intestinal protozoa].

    PubMed

    Rojo-Marcos, Gerardo; Cuadros-González, Juan

    2016-03-01

    Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately.

  16. [Intestinal microbiota].

    PubMed

    Debré, Patrice; Le Gall, Jean-Yves

    2014-12-01

    The human body normally lives in symbiosis with a considerable microscopic environment present on all interfaces with the external environment; it hosts ten times more microbes (microbiota) that it has somatic or germ cells, representing a gene diversity (microbiome) 100-150 times higher than the human genome. These germs are located mainly in the gut, where they represent a mass of about one kilogram. The primary colonization of the gastrointestinal tract depends on the delivery route, the bacterial flora rewarding then depending on the environment, food hygiene, medical treatments. The intestinal microbiota plays an important role in the maturation of the immune system and in different physiological functions: digestion of polysaccharides, glycosaminoglycans and glycoproteins, vitamins biosynthesis, bile salt metabolism of some amino acids and xenobiotics. Quantitative and qualitative changes in the microbiota are observed in a wide range of diseases: obesity, colorectal cancer, liver cancer, inflammatory bowel disease, autoimmune diseases, allergies... pharmacobiotics aim to modify the intestinal microbiota in a therapeutic goal and this by various means: prebiotics, probiotics, antibiotics or fecal transplants. Intestinal flora also plays a direct role in the metabolism of certain drugs and the microbiota should be considered as a predictive parameter of response to some chemotherapies.

  17. Intestinal microbiota and obesity.

    PubMed

    Blaut, Michael; Klaus, Susanne

    2012-01-01

    The human gut harbors a highly diverse microbial ecosystem of approximately 400 different species, which is characterized by a high interindividual variability. The intestinal microbiota has recently been suggested to contribute to the development of obesity and the metabolic syndrome. Transplantation of gut microbiota from obese mice to nonobese, germ-free mice resulted in transfer of metabolic syndrome-associated features from the donor to the recipient. Proposed mechanisms for the role of gut microbiota include the provision of additional energy by the conversion of dietary fiber to short-chain fatty acids, effects on gut-hormone production, and increased intestinal permeability causing elevated systemic levels of lipopolysaccharides (LPS). This metabolic endotoxemia is suggested to contribute to low-grade inflammation, a characteristic trait of obesity and the metabolic syndrome. Finally, activation of the endocannabinoid system by LPS and/or high-fat diets is discussed as another causal factor. In conclusion, there is ample evidence for a role of gut microbiota in the development of obesity in rodents. However, the magnitude of its contribution to human obesity is still unknown.

  18. The Circadian Clock Mutation Promotes Intestinal Dysbiosis

    PubMed Central

    Voigt, Robin M.; Summa, Keith C.; Forsyth, Christopher B.; Green, Stefan J.; Engen, Phillip; Naqib, Ankur; Vitaterna, Martha H.; Turek, Fred W; Keshavarzian, Ali

    2016-01-01

    Background Circadian rhythm disruption is a prevalent feature of modern day society that is associated with an increase in pro-inflammatory diseases and there is a clear need for a better understanding of the mechanism(s) underlying this phenomenon. We have previously demonstrated that both environmental and genetic circadian rhythm disruption causes intestinal hyperpermeability and exacerbates alcohol-induced intestinal hyperpermeability and liver pathology. The intestinal microbiota can influence intestinal barrier integrity and impact immune system function; thus, in the current study, we sought to determine if genetic alteration of the core circadian clock gene, Clock, altered the intestinal microbiota community. Methods Male ClockΔ19 mutant mice (mice homozygous for a dominant-negative mutant allele) or littermate wild-type mice were fed one of three experimental diets: (1) a standard chow diet, (2) an alcohol-containing diet, or (3) an alcohol-control diet in which the alcohol calories were replaced with dextrose. Stool microbiota was assessed with 16S ribosomal RNA gene amplicon sequencing. Results The fecal microbial community of Clock mutant mice had lower taxonomic diversity, relative to wild type mice and the ClockΔ19 mutation was associated with intestinal dysbiosis when mice were fed either the alcohol-containing or the control diet. We found that alcohol consumption significantly altered the intestinal microbiota in both wild type and Clock mutant mice. Conclusion Our data support a model by which circadian rhythm disruption by the ClockΔ19 mutation perturbs normal intestinal microbial communities and this trend was exacerbated in the context of a secondary dietary intestinal stressor. PMID:26842252

  19. Immunohistochemical detection of disease-associated prion protein in the intestine of cattle naturally affected with bovine spongiform encephalopathy by using an alkaline-based chemical antigen retrieval method.

    PubMed

    Okada, Hiroyuki; Iwamaru, Yoshihumi; Imamura, Morikazu; Masujin, Kentaro; Yokoyama, Takashi; Mohri, Shirou

    2010-11-01

    An alkaline-based chemical antigen retrieval pretreatment step was used to enhance immunolabeling of disease-associated prion protein (PrP(Sc)) in formalin-fixed and paraffin-embedded tissue sections from cattle naturally affected with bovine spongiform encephalopathy (BSE). The modified chemical method used in this study amplified the PrP(Sc) signal by unmasking PrP(Sc) compared with the normal cellular prion protein. In addition, this method reduced nonspecific background immunolabeling that resulted from the destruction of the residual normal cellular form of prion protein, and reduced the treatment time compared with the usual autoclave pretreatment step. Immunolabeled PrP(Sc) was thereby clearly detected in the myenteric plexus of the ileum in naturally occurring BSE cattle.

  20. Intestinal capillariasis.

    PubMed Central

    Cross, J H

    1992-01-01

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt, and Taiwan, but most infections occur in the Philippines and Thailand. As established experimentally, the life cycle involves freshwater fish as intermediate hosts and fish-eating birds as definitive hosts. Embryonated eggs from feces fed to fish hatch and grow as larvae in the fish intestines. Infective larvae fed to monkeys, Mongolian gerbils, and fish-eating birds develop into adults. Larvae become adults in 10 to 11 days, and the first-generation females produce larvae. These larvae develop into males and egg-producing female worms. Eggs pass with the feces, reach water, embryonate, and infect fish. Autoinfection is part of the life cycle and leads to hyperinfection. Humans acquire the infection by eating small freshwater fish raw. The parasite multiplies, and symptoms of diarrhea, borborygmus, abdominal pain, and edema develop. Chronic infections lead to malabsorption and hence to protein and electrolyte loss, and death results from irreversible effects of the infection. Treatment consists of electrolyte replacement and administration of an antidiarrheal agent and mebendazole or albendazole. Capillariasis philippinensis is considered a zoonotic disease of migratory fish-eating birds. The eggs are disseminated along flyways and infect the fish, and when fish are eaten raw, the disease develops. Images PMID:1576584

  1. Intestinal capillariasis.

    PubMed

    Cross, J H

    1992-04-01

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt, and Taiwan, but most infections occur in the Philippines and Thailand. As established experimentally, the life cycle involves freshwater fish as intermediate hosts and fish-eating birds as definitive hosts. Embryonated eggs from feces fed to fish hatch and grow as larvae in the fish intestines. Infective larvae fed to monkeys, Mongolian gerbils, and fish-eating birds develop into adults. Larvae become adults in 10 to 11 days, and the first-generation females produce larvae. These larvae develop into males and egg-producing female worms. Eggs pass with the feces, reach water, embryonate, and infect fish. Autoinfection is part of the life cycle and leads to hyperinfection. Humans acquire the infection by eating small freshwater fish raw. The parasite multiplies, and symptoms of diarrhea, borborygmus, abdominal pain, and edema develop. Chronic infections lead to malabsorption and hence to protein and electrolyte loss, and death results from irreversible effects of the infection. Treatment consists of electrolyte replacement and administration of an antidiarrheal agent and mebendazole or albendazole. Capillariasis philippinensis is considered a zoonotic disease of migratory fish-eating birds. The eggs are disseminated along flyways and infect the fish, and when fish are eaten raw, the disease develops.

  2. A method for high purity intestinal epithelial cell culture from adult human and murine tissues for the investigation of innate immune function.

    PubMed

    Graves, Christina L; Harden, Scott W; LaPato, Melissa; Nelson, Michael; Amador, Byron; Sorenson, Heather; Frazier, Charles J; Wallet, Shannon M

    2014-12-01

    Intestinal epithelial cells (IECs) serve as an important physiologic barrier between environmental antigens and the host intestinal immune system. Thus, IECs serve as a first line of defense and may act as sentinel cells during inflammatory insults. Despite recent renewed interest in IEC contributions to host immune function, the study of primary IEC has been hindered by lack of a robust culture technique, particularly for small intestinal and adult tissues. Here, a novel adaptation for culture of primary IEC is described for human duodenal organ donor tissue as well as duodenum and colon of adult mice. These epithelial cell cultures display characteristic phenotypes and are of high purity. In addition, the innate immune function of human primary IEC, specifically with regard to Toll-like receptor (TLR) expression and microbial ligand responsiveness, is contrasted with a commonly used intestinal epithelial cell line (HT-29). Specifically, TLR expression at the mRNA level and production of cytokine (IFNγ and TNFα) in response to TLR agonist stimulation is assessed. Differential expression of TLRs as well as innate immune responses to ligand stimulation is observed in human-derived cultures compared to that of HT-29. Thus, use of this adapted method to culture primary epithelial cells from adult human donors and from adult mice will allow for more appropriate studies of IECs as innate immune effectors.

  3. Administration of a Polyphenol-Enriched Feed to Farmed Sea Bass (Dicentrarchus labrax L.) Modulates Intestinal and Spleen Immune Responses

    PubMed Central

    Magrone, Thea; Fontana, Sergio; Laforgia, Flavia; Dragone, Teresa; Jirillo, Emilio; Passantino, Letizia

    2016-01-01

    Farmed fish are exposed to a continuous antigenic pressure by microbial and environmental agents, which may lead to a condition of chronic inflammation. In view of the notion that polyphenols, largely contained in fruits and vegetables, are endowed with antioxidant and anti-inflammatory activities, farmed sea bass (Dicentrarchus labrax L.) have been administered with red grape polyphenol-enriched feed. Polyphenols were extracted from the seeds of Canosina Nero di Troia Vitis vinifera and mixed with conventional feed at two different concentrations (100 and 200 mg/kg, resp.). Fish samples collected at days 223 and 273, respectively, were evaluated for intestinal and spleen cytokine release as well as for spleen macrophage (MØ) and melanomacrophage center (MMC) areas and distribution. Data will show that in treated fish decrease of intestinal interleukin- (IL-) 1β and IL-6 and increase of splenic interferon- (IFN-) γ occur. On the other hand, in the spleen reduction of MØ number seems to parallel increase in MMCs. Collectively, these data suggest that polyphenol-administered sea bass generate lower levels of intestinal proinflammatory cytokines, while producing larger amounts of spleen IFN-γ, as an expression of a robust and protective adaptive immune response. Increase of MMCs corroborates the evidence for a protective spleen response induced by feed enriched with polyphenols. PMID:26779301

  4. Study Bacteria-Host Interactions Using Intestinal Organoids.

    PubMed

    Zhang, Yong-Guo; Sun, Jun

    2016-08-19

    The intestinal epithelial cells function to gain nutrients, retain water and electrolytes, and form an efficient barrier against foreign microbes and antigens. Researchers employed cell culture lines derived from human or animal cancer cells as experimental models in vitro for understanding of intestinal infections. However, most in vitro models used to investigate interactions between bacteria and intestinal epithelial cells fail to recreate the differentiated tissue components and structure observed in the normal intestine. The in vitro analysis of host-bacteria interactions in the intestine has been hampered by a lack of suitable intestinal epithelium culture systems. Here, we present a new experimental model using an organoid culture system to study bacterial infection.

  5. Intestinal protozoa.

    PubMed

    Juckett, G

    1996-06-01

    Giardia is the best known cause of protozoal gastrointestinal disease in North America, producing significant but not life-threatening gastrointestinal distress and diarrhea. Although diagnosis of giardiasis may be challenging, treatment is usually successful. Entamoeba histolytica poses a rarer but far more difficult clinical challenge. Dysentery caused by E. histolytica may be the most feared intestinal protozoal infection, although Cryptosporidium parvum, Balantidium coli, Isospora belli, Sarcocystis species and other newly described protozoa also may cause diarrhea in healthy individuals and may result in intractable, life-threatening illness in patients with acquired immunodeficiency syndrome or other immunosuppressive diseases. Certain protozoa once considered relatively unimportant, such as Cryptosporidium, are now recognized as significant causes of morbidity even in the United States, since transmission readily occurs through contaminated water.

  6. Regulation of intestinal immune system by dendritic cells.

    PubMed

    Ko, Hyun-Jeong; Chang, Sun-Young

    2015-02-01

    Innate immune cells survey antigenic materials beneath our body surfaces and provide a front-line response to internal and external danger signals. Dendritic cells (DCs), a subset of innate immune cells, are critical sentinels that perform multiple roles in immune responses, from acting as principal modulators to priming an adaptive immune response through antigen-specific signaling. In the gut, DCs meet exogenous, non-harmful food antigens as well as vast commensal microbes under steady-state conditions. In other instances, they must combat pathogenic microbes to prevent infections. In this review, we focus on the function of intestinal DCs in maintaining intestinal immune homeostasis. Specifically, we describe how intestinal DCs affect IgA production from B cells and influence the generation of unique subsets of T cell.

  7. Microbial Glycan Microarrays Define Key Features of Host-Microbial Interactions

    PubMed Central

    Stowell, Sean R.; Arthur, Connie M.; McBride, Ryan; Berger, Oren; Razi, Nahid; Heimburg-Molinaro, Jamie; Rodrigues, Lilian C.; Gourdine, Jean-Philippe; Noll, Alexander J.; von Gunten, Stephan; Smith, David F.; Knirel, Yuriy A.; Paulson, James C.; Cummings, Richard D.

    2014-01-01

    Genomic approaches continue to provide unprecedented insight into the microbiome, yet host immune interactions with diverse microbiota can be difficult to study. We therefore generated a microbial microarray containing defined antigens isolated from a broad range of microbial flora to examine adaptive and innate immunity. Serological studies with this microarray show that immunoglobulins from multiple mammalian species exhibit unique patterns of reactivity, while exposure of animals to distinct microbes induces specific serological recognition. While adaptive immunity exhibited plasticity toward microbial antigens, immunological tolerance limits reactivity toward self. We discovered that several innate immune galectins exhibit specific recognition of microbes that express self-like antigens, leading to direct killing of a broad range of gram negative and positive microbes. Thus, host protection against microbes appears to represent a balance between adaptive and innate immunity to defend against evolving antigenic determinants while protecting against molecular mimicry. PMID:24814672

  8. Gut-liver axis at the frontier of host-microbial interactions.

    PubMed

    Brandl, Katharina; Kumar, Vipin; Eckmann, Lars

    2017-02-23

    Liver and intestine are tightly linked through the venous system of the portal circulation. Consequently, the liver is the primary recipient of gut-derived products, most prominently dietary nutrients and microbial components. It functions as a secondary "firewall" and protects the body from intestinal pathogens and other microbial products that have crossed the primary barrier of the intestinal tract. Disruption of the intestinal barrier enhances microbial exposure of the liver, which can have detrimental or beneficial effects in the organ depending on the specific circumstances. Conversely, the liver also exerts influence over intestinal microbial communities via secretion of bile acids and IgA antibodies. This Mini-Review highlights key findings and concepts in the area of host-microbial interactions as pertinent to the bilateral communication between liver and gut, and the concept of the gut-liver axis.

  9. Immunostimulatory complexes containing Eimeria tenella antigens and low toxicity plant saponins induce antibody response and provide protection from challenge in broiler chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunostimulating complexes (ISCOMs) are unique multimolecular structures formed by encapsulating antigens, lipids and triterpene saponins and are one of the most successful antigen delivery systems for microbial antigens. In the current study, both the route of administration and the antigen conce...

  10. Requirement for capsular antigen KX105 and fimbrial antigen CS1541 in the pathogenicity of porcine enterotoxigenic Escherichia coli O8:KX105 strains.

    PubMed Central

    Broes, A; Fairbrother, J M; Jacques, M; Larivière, S

    1989-01-01

    The requirement for capsular antigen KX105 and fimbrial antigen CS1541 in the pathogenicity of porcine enterotoxigenic Escherichia coli O8:KX105 strains lacking the colonization factor antigens K88, K99, 987P and F41 was investigated using two encapsulated strains and their acapsular variants, one of which produced the fimbrial antigen CS1541 in vitro. None of the strains adhered in vitro to enterocytes isolated from newborn colostrum-deprived piglets. All of the strains caused diarrhea in orally infected, hysterotomy-derived, colostrum-deprived piglets although a great variability in the clinical response of the piglets was observed. Colonization of the small intestine of infected piglets by these strains was only moderate and no differences in the ability to colonize the small intestine was noted between the strains. All of the strains reacted in the indirect fluorescent antibody test with both CS1541 and 987P antisera when applied to organisms in the intestines of infected piglets. A control strain expressing the 987P fimbrial adhesin also reacted with the CS1541 antiserum applied to organisms in the intestines of an infected piglet. It was concluded that capsular antigen KX105 was not essential for intestinal colonization and production of diarrhea in hysterotomy-derived colostrum-deprived pigs, and that fimbrial antigen CS1541 does not promote in vitro adherence to enterocyte brush borders but could be important in bacterial colonization in vivo. Images Fig. 1. Fig. 2. Fig. 3. PMID:2563336

  11. Intestinal microbiota and overweight.

    PubMed

    Lyra, A; Lahtinen, S; Tiihonen, K; Ouwehand, A C

    2010-11-01

    The microbes in our gut can influence our weight by providing us with energy through the degradation of nondigestable carbohydrates and by affecting the cellular energy status of liver and muscle cells and the accumulation of lipids in adipose tissue. Thus, it is not surprising that in several studies the gastrointestinal microbiota of overweight and obese subjects has been found to differ from that of lean subjects. The initial findings linked obesity with proportionally decreased levels of the phylum Bacteroidetes and increased levels of the phylum Firmicutes. Later, several studies have assessed the association between overweight or obesity and the gastrointestinal microbiota, applying an array of molecular methods targeting the microbiota as a whole or specific bacterial groups or species within. However, at present it is difficult to draw conclusions on which of the observed microbiota alterations are relevant; essentially all of the bacterial groups that have been studied in more than one trial have given contradictory results in regard to their association with weight. Some of these discrepancies can result from methodological issues and some from the nature of the gastrointestinal microbiota, which is an extremely complex and dynamic microbial ecosystem with high subject specificity. In addition, selecting subjects purely based on weight may result in a largely heterogeneous group with several potentially confounding factors. While it may be premature to conclude which specific groups of bacteria are prominent in the intestinal tract of overweight and obese subjects, it appears clear that microbes contribute to weight gain and related health issues, such as the metabolic syndrome and type II diabetes. Therefore, it is important to continue to search for common microbial markers and predictors of obesity, and to study how these may be modulated with probiotics and prebiotics to promote health.

  12. [Intestinal microbiota].

    PubMed

    Perez, Horacio Joaquín; Menezes, Maria Elisabeth; d'Acâmpora, Armando José

    2014-01-01

    There is accumulative evidence on the multiple functions of the intestinal microflora in relation to the homeostasis of the host. At first considered as a simple mutualism, today this relationship proves to be essential to the health and to pathologic processes, particularly metabolic (eg, obesity) and gastrointestinal (eg, inflammatory bowel disease and functional disorders). The first studies were conducted on the microbiota from fecal material cultured anaerobically. With the advent of molecular biology, it has become possible to determine qualitative and quantitatively the dominant, subdominant and transients species. In recent years, there were advances in the understanding of the relationship betwen the microbiota and the host, as well as among the microorganisms in their respective niches. These advances result from translational integration of microbiology with specialities such as molecular biology, cell phisiology, immunology and ecology. There are few studies on the spatial distribution of the microflora in the gut. Unravelling the topography of the microflora in mammals is a way to validate new animal models for the study of microflora.

  13. Influence of Endogenous and Exogenous Estrogenic Endocrine on Intestinal Microbiota in Zebrafish

    PubMed Central

    Liu, Yukun; Yao, Yayun; Li, Huan; Qiao, Fang; Wu, Junlin; Du, Zhen-yu; Zhang, Meiling

    2016-01-01

    Gender is one of the factors influencing the intestinal microbial composition in mammals, but whether fish also have gender-specific intestinal microbial patterns remains unknown. In this decade, endocrine disrupting chemicals in surface and ground water of many areas and increasing observation of freshwater male fish displaying female sexual characteristics have been reported. Here we identified the difference in intestinal microbiota between male and female zebrafish, and revealed the influence of endocrine disrupting chemicals on zebrafish intestinal microbiota by using high-throughput sequencing. The results indicated that Fusobacteria, Bacteroidetes and Proteobacteria were dominant in the gut of zebrafish and there were no obvious gender-specific intestinal microbial patterns. Two endocrine disrupting chemicals, Estradiol (E2) and Bisphenol A (BPA), were selected to treat male zebrafish for 5 weeks. E2 and BPA increased vitellogenin expression in the liver of male zebrafish and altered the intestinal microbial composition with the abundance of the phylum CKC4 increased significantly. Our results suggested that because of the developmental character and living environment, gender did not influence the assembly of intestinal microbiota in zebrafish as it does in mammals, but exposure extra to endocrine disrupting chemicals disturbed the intestinal microbial composition, which may be related to changes in host physiological metabolism. PMID:27701432

  14. Interactions Between the Intestinal Microbiome and Liver Diseases

    PubMed Central

    Schnabl, Bernd; Brenner, David A.

    2014-01-01

    The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease. PMID:24440671

  15. Microbial hydrolysis of steviol glycosides.

    PubMed

    Renwick, A G; Tarka, S M

    2008-07-01

    A review of the role of gut microbiota in the metabolism of the steviol glycosides, stevioside and rebaudioside A, indicates that they are not absorbed intact but undergo hydrolysis by the intestinal microflora to steviol. Steviol is not metabolized by the intestinal flora and is absorbed from the intestine. The rate of hydrolysis for stevioside is greater than for rebaudioside A. Recent studies using mass spectrometry have shown that steviol-16,17-epoxide is not a microbial metabolite of steviol glycosides. Bacteroides species are primarily responsible for hydrolysis via their beta-glucosidase activity. Fecal incubation studies with both human and animal mixed flora provide similar results, and this indicates that the rat is an appropriate model for studies on steviol glycosides. Given the similarity in the microbial metabolism of stevioside and rebaudioside A with the formation of steviol as the single hydrolysis product that is absorbed from the intestinal tract, the toxicological data on stevioside are relevant to the risk assessment of rebaudioside A.

  16. Specific Microbiota-Induced Intestinal Th17 Differentiation Requires MHC II but not GALT and Mesenteric Lymph Nodes

    PubMed Central

    Geem, Duke; Medina-Contreras, Oscar; McBride, Michelle; Newberry, Rodney D.; Koni, Pandelakis A.; Denning, Timothy L.

    2014-01-01

    Interleukin (IL)-17 expressing CD4+ T lymphocytes (Th17 cells) naturally reside in the intestine where specific cytokines and microbiota, such as segmented filamentous bacteria (SFB), promote their differentiation. Intestinal Th17 cells are believed to initially differentiate in the GALT and/or mesenteric lymph nodes (mLN) upon antigen encounter and subsequently home to the lamina propria (LP) where they mediate effector functions. However, whether GALT and/or mLN are required for intestinal Th17 differentiation, and how microbiota containing SFB regulate antigen-specific intestinal Th17 cells remain poorly defined. Here we observed that naïve CD4+ T cells were abundant in the intestinal LP prior to weaning and that the accumulation of Th17 cells in response to microbiota containing SFB occurred in the absence of lymphotoxin (LT)-dependent lymphoid structures and the spleen. Furthermore, the differentiation of intestinal Th17 cells in the presence of microbiota containing SFB was dependent on MHC II expression by CD11c+ cells. Lastly, the differentiation of antigen-specific Th17 cells required both the presence of cognate antigen and microbiota containing SFB. These findings suggest that microbiota containing SFB create an intestinal milieu that may induce antigen-specific Th17 differentiation against food and/or bacterial antigens directly in the intestinal LP. PMID:24899505

  17. [Enterobacterial antigen in human peripheral blood lymphocytes].

    PubMed

    Faure-Fontenla, M A; García-Tamayo, F

    1989-11-01

    The following study has as prior history the research reports which have shown the existence of an antigenic tissue deposit in gram-negative enterobacteria. The antigens of the enterobacteria have also been found in the lymphocytic membranes and cytoplasm. Since intestinal lymphoid tissue cells can recirculate by means of the thoracic duct to the peripheral venous system, it was proposed that the circulating lymphocytes in healthy people could also contain small amounts of a common enterobacterial antigen. The study was carried out in 15 human venous blood samples, of which the lymphocytic population was separated to later be used in the preparation of 15 alcohol soluble extracts. This material was used for inhibiting the immuno-hemolysis assay in three occasions in order to show the presence of antigens shared by different enterobacterias, using as reference a fraction separated from the LPS of Escherichia coli 08. The results showed that the human lymphocytes also had antigenic determinants common to gram-negative bacteria.

  18. Tipping elements in the human intestinal ecosystem

    PubMed Central

    Lahti, Leo; Salojärvi, Jarkko; Salonen, Anne; Scheffer, Marten; de Vos, Willem M.

    2014-01-01

    The microbial communities living in the human intestine can have profound impact on our well-being and health. However, we have limited understanding of the mechanisms that control this complex ecosystem. Here, based on a deep phylogenetic analysis of the intestinal microbiota in a thousand western adults, we identify groups of bacteria that exhibit robust bistable abundance distributions. These bacteria are either abundant or nearly absent in most individuals, and exhibit decreased temporal stability at the intermediate abundance range. The abundances of these bimodally distributed bacteria vary independently, and their abundance distributions are not affected by short-term dietary interventions. However, their contrasting alternative states are associated with host factors such as ageing and overweight. We propose that the bistable groups reflect tipping elements of the intestinal microbiota, whose critical transitions may have profound health implications and diagnostic potential. PMID:25003530

  19. Tipping elements in the human intestinal ecosystem.

    PubMed

    Lahti, Leo; Salojärvi, Jarkko; Salonen, Anne; Scheffer, Marten; de Vos, Willem M

    2014-07-08

    The microbial communities living in the human intestine can have profound impact on our well-being and health. However, we have limited understanding of the mechanisms that control this complex ecosystem. Here, based on a deep phylogenetic analysis of the intestinal microbiota in a thousand western adults, we identify groups of bacteria that exhibit robust bistable abundance distributions. These bacteria are either abundant or nearly absent in most individuals, and exhibit decreased temporal stability at the intermediate abundance range. The abundances of these bimodally distributed bacteria vary independently, and their abundance distributions are not affected by short-term dietary interventions. However, their contrasting alternative states are associated with host factors such as ageing and overweight. We propose that the bistable groups reflect tipping elements of the intestinal microbiota, whose critical transitions may have profound health implications and diagnostic potential.

  20. From gut microflora imbalance to mycobacteria infection: is there a relationship with chronic intestinal inflammatory diseases?

    PubMed

    Tomasello, Giovanni; Bellavia, Maurizio; Palumbo, Vincenzo Davide; Gioviale, Maria Concetta; Damiani, Provvidenza; Lo Monte, Attilio Ignazio

    2011-01-01

    The gut of a healthy adult harbours a myriad of different microbial species. It is estimated that approximately 10 14 are present in total bacterial colony forming units (CFU). Each colony colonizes a specific intestinal tract. In healthy adult, the main control of intestinal bacterial colonization occurs through gastric acidity but also other factors can influence the intestinal microenvironment such as pH, temperature, competition among different bacterial strains, peristalsis, drugs, radiotherapy and much more. Impaired microbial homeostasis leads to an alteration of the permeability of tissue, together with the activation of the intestinal immune system MALT (mucosal associated lymphoid tissue). In this regard we discuss the increasing experimental evidences of the role of commensal microbiota in the activation of specific intestinal immunocompetent cells. The aforementioned micro-environmental changes provide the substrate for the etiopathogenetic outbreak of numerous pathologies of gastro-intestinal tract, such as intestinal chronic inflammation (Crohn's disease and Ulcerative Colitis), together with a miscellany of extra intestinal disorders. This article is an overview of the latest scientific findings about the close causal relationship between intestinal microbial flora and inflammatory bowel diseases or other extra-intestinal diseases; it is also mentioned the possible relationship between mycobacteria and Chron's disease. Finally we analyse the beneficial role of probiotics.

  1. Siglec-F is a novel intestinal M cell marker.

    PubMed

    Gicheva, Nadezhda; Macauley, Matthew S; Arlian, Britni M; Paulson, James C; Kawasaki, Norihito

    2016-10-07

    Intestinal microfold (M) cells are epithelial cells primarily present on Peyer's patches (PPs) in the small intestine. The ability of M cells to shuttle antigens into the PP for appropriate immune responses makes M cells a target for next-generation oral vaccine delivery. In this regard, discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery of cargo to M cells. Here, using a monoclonal antibody we generated to the Sialic acid-binding immunoglobulin-like lectin F (Siglec-F), we show that Siglec-F is expressed on mouse M cells in the small intestine. Immunohistochemical analysis of the PP tissue sections shows that Siglec-F is expressed on the surface of the M cell membrane exposed to the intestinal lumen. Anti-Siglec-F antibody injected into the mouse small intestine bound to M cells, demonstrating the potential to target M cells via Siglec-F.

  2. Obesity, fatty liver disease and intestinal microbiota

    PubMed Central

    Arslan, Nur

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations. PMID:25469013

  3. Dysfunction of the Intestinal Microbiome in Inflammatory Bowel Disease and Treatment

    DTIC Science & Technology

    2012-01-01

    However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of...gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by...dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool

  4. Small Intestine Disorders

    MedlinePlus

    Your small intestine is the longest part of your digestive system - about twenty feet long! It connects your stomach to ... many times to fit inside your abdomen. Your small intestine does most of the digesting of the foods ...

  5. Small intestine (image)

    MedlinePlus

    The small intestine is the portion of the digestive system most responsible for absorption of nutrients from food into the ... the duodenum. This short first portion of the small intestine is followed by the jejunum and the ileum. ...

  6. F41 pili as protective antigens of enterotoxigenic Escherichia coli that produce F41, K99, or both pilus antigens.

    PubMed Central

    Runnels, P L; Moseley, S L; Moon, H W

    1987-01-01

    Pigs suckling dams that have been vaccinated with pilus antigen are protected against challenge with enterotoxigenic Escherichia coli (ETEC) strains that express the same pilus antigen. However, some ETEC strains express more than one pilus antigen. Pregnant swine were vaccinated either with E. coli HB101 that harbored a recombinant plasmid coding for F41 expression (F41+) or with the HB101 parent strain that carries the pHC79 vector (F41-). Suckling pigs born to vaccinated dams were challenged with ETEC that expressed either K99, F41, or both pilus antigens. Production of F41 in vivo was demonstrated by immunofluorescence assay of sections of ileum and by seroconversion against F41 antigen by pigs challenged with F41+ and K99+ F41+ ETEC strains. The F41+ vaccine protected against challenge with an F41+ ETEC strain. In contrast, F41+ vaccination did not protect against challenge with K99+ or K99+ F41+ ETEC strains. The F41- vaccine did not protect against challenge with any strain used. The results indicate that K99+ F41+ ETEC strains produce F41 antigen in the small intestine during disease and that F41+ vaccination can be a protective antigen if the challenge strain expresses only F41 antigen, but that F41+ vaccination may not protect against strains that produce both K99 and F41 antigens. PMID:2880807

  7. Mouse models of intestinal inflammation and cancer.

    PubMed

    Westbrook, Aya M; Szakmary, Akos; Schiestl, Robert H

    2016-09-01

    Chronic inflammation is strongly associated with approximately one-fifth of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here, we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With

  8. Effect of the microbial lactase (EC 3.2.1.23) activity in yoghurt on the intestinal absorption of lactose: an in vivo study in lactase-deficient humans.

    PubMed

    Marteau, P; Flourie, B; Pochart, P; Chastang, C; Desjeux, J F; Rambaud, J C

    1990-07-01

    Breath hydrogen excretion was measured in eight lactase (EC 3.2.1.108)-deficient volunteers ingesting 18 g lactose in the form of milk, yoghurt and heated yoghurt. Total excess hydrogen excretion (area under curve) was significantly lower after yoghurt and heated yoghurt, than after milk: 103 (SE 29), 191 (SE 32), and 439 (SE 69) respectively (P less than 0.001). The oro-caecal transit time of fermentable components from yoghurt and heated yoghurt (mainly lactose) was longer than that from milk: 165 (SE 17), 206 (SE 19), v. 103 (SE 19) min (P less than 0.01). An intestinal perfusion technique was used in the same subjects after ingestion on two consecutive days of 18 g lactose in yoghurt and heated yoghurt. Significantly less lactose was recovered from the terminal ileum after yoghurt than after heated yoghurt meals: 1740 (SE 260) v. 2825 (SE 461) mg (P less than 0.05), and approximately one-fifth of the lactase activity contained in yoghurt reached the terminal ileum. These findings indicate that more than 90% of the lactose in yoghurt is digested in the small intestine of lactase-deficient subjects and suggest that both the lactase activity contained in the viable starter culture and a slow oro-caecal transit time are responsible for this excellent absorption.

  9. Glutamine-Induced Secretion of Intestinal Secretory Immunoglobulin A: A Mechanistic Perspective

    PubMed Central

    Ren, Wenkai; Wang, Kai; Yin, Jie; Chen, Shuai; Liu, Gang; Tan, Bie; Wu, Guoyao; Bazer, Fuller W.; Peng, Yuanyi; Yin, Yulong

    2016-01-01

    Secretory immunoglobulin A (SIgA) is one important line of defense in the intestinal mucosal surface to protect the intestinal epithelium from enteric toxins and pathogenic microorganisms. Multiple factors, such as intestinal microbiota, intestinal cytokines, and nutrients are highly involved in production of SIgA in the intestine. Recently, glutamine has been shown to affect intestinal SIgA production; however, the underlying mechanism by which glutamine stimulates secretion of intestinal SIgA is unknown. Here, we review current knowledge regarding glutamine in intestinal immunity and show that glutamine-enhanced secretion of SIgA in the intestine may involve intestinal microbiota, intestinal antigen sampling and presentation, induction pathways for SIgA production by plasma cells (both T-dependent and T-independent pathway), and even transport of SIgA. Altogether, the glutamine-intestinal SIgA axis has broad therapeutic implications for intestinal SIgA-associated diseases, such as celiac disease, allergies, and inflammatory bowel disease. PMID:27933057

  10. Establishment of Intestinal Bacteriology

    PubMed Central

    MITSUOKA, Tomotari

    2014-01-01

    Research on intestinal bacteria began around the end of the 19th century. During the last 5 decades of the 20th century, research on the intestinal microbiota made rapid progress. At first, in my work, I first developed a method of comprehensive analysis of the intestinal microbiota, and then I established classification and identification methods for intestinal anaerobes. Using these methods I discovered a number of ecological rules governing the intestinal microbiota and the role of the intestinl microbiota in health and disease. Moreover, using germfree animals, it was proven that the intestinal microbiota has a role in carcinogenesis and aging in the host. Thus, a new interdisciplinary field, “intestinal bacteriology” was established. PMID:25032084

  11. Early intestinal growth and development in poultry.

    PubMed

    Lilburn, M S; Loeffler, S

    2015-07-01

    While there are many accepted "facts" within the field of poultry science that are in truth still open for discussion, there is little debate with respect to the tremendous genetic progress that has been made with commercial broilers and turkeys (Havenstein et al., 2003, 2007). When one considers the changes in carcass development in poultry meat strains, these genetic "improvements" have not always been accompanied by correlated changes in other physiological systems and this can predispose some birds to developmental anomalies (i.e. ascites; Pavlidis et al., 2007; Wideman et al., 2013). Over the last decade, there has been increased interest in intestinal growth/health as poultry nutritionists have attempted to adopt new approaches to deal with the broader changes in the overall nutrition landscape. This landscape includes not only the aforementioned genetic changes but also a raft of governmental policies that have focused attention on the environment (phosphorus and nitrogen excretion), consumer pressure on the use of antibiotics, and renewable biofuels with its consequent effects on ingredient costs. Intestinal morphology has become a common research tool for assessing nutritional effects on the intestine but it is only one metric among many that can be used and histological results can often be interpreted in a variety of ways. This study will address the broader body of research on intestinal growth and development in commercial poultry and will attempt to integrate the topics of the intestinal: microbial interface and the role of the intestine as an immune tissue under the broad umbrella of intestinal physiology.

  12. Dysbiosis-induced intestinal inflammation activates TNFRI and mediates alcoholic liver disease in mice

    PubMed Central

    Chen, Peng; Stärkel, Peter; Turner, Jerrold R.; Ho, Samuel B.; Schnabl, Bernd

    2014-01-01

    Intestinal barrier dysfunction is an important contributor to alcoholic liver disease. Translocated microbial products trigger an inflammatory response in the liver and contribute to steatohepatitis. Our aim was to investigate mechanisms of barrier disruption following chronic alcohol feeding. A Lieber-DeCarli model was used to induce intestinal dysbiosis, increased intestinal permeability and liver disease in mice. Alcohol feeding for 8 weeks induced intestinal inflammation in the jejunum, which is characterized by an increased number of TNFα producing monocytes and macrophages. These findings were confirmed in duodenal biopsies from patients with chronic alcohol abuse. Intestinal decontamination with non-absorbable antibiotics restored eubiosis, decreased intestinal inflammation and permeability, and reduced alcoholic liver disease in mice. TNF-receptor I (TNFRI) mutant mice were protected from intestinal barrier dysfunction and alcoholic liver disease. To investigate whether TNFRI on intestinal epithelial cells mediates intestinal barrier dysfunction and alcoholic liver disease, we used TNFRI mutant mice carrying a conditional gain-of-function allele for this receptor. Reactivation of TNFRI on intestinal epithelial cells resulted in increased intestinal permeability and liver disease that is similar to wild type mice after alcohol feeding, suggesting that enteric TNFRI promotes intestinal barrier dysfunction. Myosin light chain kinase (MLCK) is a downstream target of TNFα and was phosphorylated in intestinal epithelial cells following alcohol administration. Using MLCK deficient mice, we further demonstrate a partial contribution of MLCK to intestinal barrier dysfunction and liver disease following chronic alcohol feeding. In conclusion, dysbiosis-induced intestinal inflammation and TNFRI signaling on intestinal epithelial cells are mediating a disruption of the intestinal barrier. Therefore, intestinal TNFRI is a crucial mediator of alcoholic liver disease

  13. The Intestinal Microbiota in the Irritable Bowel Syndrome.

    PubMed

    Collins, S M

    2016-01-01

    The irritable bowel syndrome (IBS) is a chronic abdominal symptom complex occurring in a bowel devoid of discernible relevant pathology. There is growing interest in the role of the intestinal microbiota as a basis for the intestinal and possibly behavioral manifestations of this condition. Molecular-based microbial profiling has revealed compositional changes in the microbiota of at least a subset of IBS patients but the data are often conflicting and no microbial signature for this condition has yet been defined. Animal studies in which a previously stable intestinal microbiota is perturbed, by antibiotics or dietary change, results in alterations in intestinal function reminiscent of that seen in IBS patients. These include visceral sensitivity to painful stimuli, altered motility and intestinal barrier function as well as immune activation, and low-grade inflammation. More recent studies have shown that perturbation of the microbial composition of the gut alters brain chemistry and behavior. In a step toward establishing a causal link between an altar microbiota and gut-brain manifestations of IBS, colonization of germ-free mice with microbiota from IBS patients results in an IBS-like phenotype, including alterations and behavior if the donor exhibited psychiatric comorbidity, such as high levels of anxiety. This model provides an opportunity for exploring the mechanisms underlying host-microbe interactions relevant to the pathogenesis of IBS and for developing novel therapeutic targets.

  14. Early cytokine responses during intestinal parasitic infections.

    PubMed Central

    Ishikawa, N; Goyal, P K; Mahida, Y R; Li, K F; Wakelin, D

    1998-01-01

    Infections with gastro-intestinal nematodes elicit immune and inflammatory responses mediated by cytokines released from T-helper type-2 (Th2) cells. In vitro assays of cells from the mesenteric lymph nodes (MLN) of experimentally infected rodents confirm that, after about 1 week, the dominant cytokine responses to mitogens and antigens are those associated with this Th-cell subset. Polarization of the Th response in this way implies an initial local cytokine environment that favours Th2 development. However, experimental infections with Trichinella spiralis and Nippostrongylus brasiliensis show that, within 2 days of worms reaching the intestine, MLN cells (MLNC) respond with a Th1 rather than a Th2 response [i.e. there is an increase in mRNA for the type 1 cytokine interferon-gamma (IFN-gamma), and mitogen-stimulated MLNC release IFN-gamma rather than interleukin-5 (IL-5)]. Antigen stimulation at this time does not elicit IFN-gamma release and the MLNC cannot adoptively transfer immunity. Within a few days the MLNC phenotype changes. There is a Th2 response (IL-5 release) to both mitogen and antigen stimulation and MLNC can adoptively transfer immunity. Early release of IFN-gamma is T-cell dependent, with CD4+ T cells playing the major role. The data are discussed in relation to factors regulating the mucosal response to invasion by parasites. PMID:9616376

  15. Immune and genetic gardening of the intestinal microbiome

    PubMed Central

    Jacobs, Jonathan P.; Braun, Jonathan

    2014-01-01

    The mucosal immune system – consisting of adaptive and innate immune cells as well as the epithelium – is profoundly influenced by its microbial environment. There is now growing evidence that the converse is also true, that the immune system shapes the composition of the intestinal microbiome. During conditions of health, this bidirectional interaction achieves a homeostasis in which inappropriate immune responses to nonpathogenic microbes are averted and immune activity suppresses blooms of potentially pathogenic microbes (pathobionts). Genetic alteration in immune/epithelial function can affect host gardening of the intestinal microbiome, contributing to the diversity of intestinal microbiota within a population and in some cases allowing for unfavorable microbial ecologies (dysbiosis) that confer disease susceptibility. PMID:24613921

  16. Transcutaneous antigen delivery system

    PubMed Central

    Lee, Mi-Young; Shin, Meong-Cheol; Yang, Victor C.

    2013-01-01

    Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy. [BMB Reports 2013; 46(1): 17-24] PMID:23351379

  17. The nonfermentable dietary fiber hydroxypropyl methylcellulose modulates intestinal microbiota.

    PubMed

    Cox, Laura M; Cho, Ilseung; Young, Scott A; Anderson, W H Kerr; Waters, Bartholomew J; Hung, Shao-Ching; Gao, Zhan; Mahana, Douglas; Bihan, Monika; Alekseyenko, Alexander V; Methé, Barbara A; Blaser, Martin J

    2013-02-01

    Diet influences host metabolism and intestinal microbiota; however, detailed understanding of this tripartite interaction is limited. To determine whether the nonfermentable fiber hydroxypropyl methylcellulose (HPMC) could alter the intestinal microbiota and whether such changes correlated with metabolic improvements, C57B/L6 mice were normalized to a high-fat diet (HFD), then either maintained on HFD (control), or switched to HFD supplemented with 10% HPMC, or a low-fat diet (LFD). Compared to control treatment, both LFD and HPMC reduced weight gain (11.8 and 5.7 g, respectively), plasma cholesterol (23.1 and 19.6%), and liver triglycerides (73.1 and 44.6%), and, as revealed by 454-pyrosequencing of the microbial 16S rRNA gene, decreased microbial α-diversity and differentially altered intestinal microbiota. Both LFD and HPMC increased intestinal Erysipelotrichaceae (7.3- and 12.4-fold) and decreased Lachnospiraceae (2.0- and 2.7-fold), while only HPMC increased Peptostreptococcaceae (3.4-fold) and decreased Ruminococcaceae (2.7-fold). Specific microorganisms were directly linked with weight change and metabolic parameters in HPMC and HFD mice, but not in LFD mice, indicating that the intestinal microbiota may play differing roles during the two dietary modulations. This work indicates that HPMC is a potential prebiotic fiber that influences intestinal microbiota and improves host metabolism.

  18. Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity.

    PubMed

    Estaki, Mehrbod; DeCoffe, Daniella; Gibson, Deanna L

    2014-11-14

    Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP's role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP's ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP's ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP's ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium.

  19. Diet and the intestinal microbiome: associations, functions, and implications for health and disease.

    PubMed

    Albenberg, Lindsey G; Wu, Gary D

    2014-05-01

    The mutual relationship between the intestinal microbiota and its mammalian host is influenced by diet. Consumption of various nutrients affects the structure of the microbial community and provides substrates for microbial metabolism. The microbiota can produce small molecules that are absorbed by the host and affect many important physiological processes. Age-dependent and societal differences in the intestinal microbiota could result from differences in diet. Examples include differences in the intestinal microbiota of breastfed vs formula-fed infants or differences in microbial richness in people who consume an agrarian plant-based vs a Western diet, which is high in meat and fat. We review how diet affects the structure and metabolome of the human intestinal microbiome and may contribute to health or the pathogenesis of disorders such as coronary vascular disease and inflammatory bowel disease.

  20. Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease

    PubMed Central

    Albenberg, Lindsey G.; Wu, Gary D.

    2014-01-01

    The mutual relationship between the intestinal microbiota and its mammalian host is influenced by diet. Consumption of various nutrients affects the structure of the microbial community and provides substrates for microbial metabolism. The microbiota can produce small molecules that are absorbed by the host and affect many important physiological processes. Age-dependent and societal differences in the intestinal microbiota could result from differences in diet. Examples include differences in the intestinal microbiota of breast- vs formula-fed infants, or differences in microbial richness in individuals consuming an agrarian plant-based vs a Western diet, which is high in meat and fat. We review how diet affects the structure and metabolome of the human intestinal microbiome, and may contribute to health or pathogenesis of disorders such as coronary vascular disease and inflammatory bowel diseases. PMID:24503132

  1. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation

    PubMed Central

    Hemarajata, Peera

    2013-01-01

    Recent explorations of the human gut microbiota suggest that perturbations of microbial communities may increase predisposition to different disease phenotypes. Dietary nutrients may be converted into metabolites by intestinal microbes that serve as biologically active molecules affecting regulatory functions in the host. Probiotics may restore the composition of the gut microbiome and introduce beneficial functions to gut microbial communities, resulting in amelioration or prevention of gut inflammation and other intestinal or systemic disease phenotypes. This review describes how diet and intestinal luminal conversion by gut microbes play a role in shaping the structure and function of intestinal microbial communities. Proposed mechanisms of probiosis include alterations of composition and function of the human gut microbiome, and corresponding effects on immunity and neurobiology. PMID:23320049

  2. [Saccharomyces boulardii modulates dendritic cell properties and intestinal microbiota disruption after antibiotic treatment].

    PubMed

    Collignon, A; Sandré, C; Barc, M-C

    2010-09-01

    Saccharomyces boulardii is a non-pathogenic yeast with biotherapeutic properties that has been used successfully to prevent and to treat various infectious and antibiotic-associated diarrheas. The intestinal microbiota is responsible for colonization resistance and immune response to pathogens but can be disrupted by antibiotics and lose its barrier effect. Dendritic cells (DCs) are professional antigen-presenting cells of the immune system with the ability to initiate a primary immune response or immune tolerance. In a human microbiota-associated mouse model, we evaluated the influence of S. boulardii on the composition of the microbiota and on the properties of dendritic cells in normal homeostatic conditions and after antibiotic-induced stress. The DCs were derived from splenic precursors. Membrane antigen expression and phagocytosis of FITC-latex beads by DCs were evaluated by flow cytometry. The molecular analysis of the microbiota was performed with fluorescence in situ hybridization (FISH) combined with flow cytometry or confocal microscopy using group specific 16S rRNA targeted probes. This evaluation was conducted during and after a 7-day oral treatment with amoxicillin-clavulanic acid alone and in combination with the administration of the yeast. The antibiotic treatment increased the phagocytic activity of DCs. Their antigen presenting function (MHC class II antigen and CD 86 costimulatory molecule membrane expression) was up-regulated. This reflects a functional activation of DCs. In the presence of S. boulardii, the modification of membrane antigen expression was down regulated. To correlate these modifications to the microbiota disruption, we analyzed in parallel the composition of the intestinal microbiota. As previously shown, the amoxicillin-clavulanic acid treatment, both alone and with S. boulardii, did not quantitatively alter the total microbiota. In contrast, after one day of the antibiotic treatment the Clostridium coccoides group decreased

  3. Engineering of Isogenic Cells Deficient for MR1 with a CRISPR/Cas9 Lentiviral System: Tools To Study Microbial Antigen Processing and Presentation to Human MR1-Restricted T Cells

    PubMed Central

    Lloyd, Angharad; Meermeier, Erin W.; Crowther, Michael D.; Connor, Thomas R.; Dolton, Garry; Miles, John J.; Burrows, Scott R.; Gold, Marielle C.; Lewinsohn, David M.

    2016-01-01

    The nonclassical HLA molecule MHC-related protein 1 (MR1) presents metabolites of the vitamin B synthesis pathways to mucosal-associated invariant T (MAIT) cells and other MR1-restricted T cells. This new class of Ags represents a variation on the classical paradigm of self/non-self discrimination because these T cells are activated through their TCR by small organic compounds generated during microbial vitamin B2 synthesis. Beyond the fundamental significance, the invariant nature of MR1 across the human population is a tantalizing feature for the potential development of universal immune therapeutic and diagnostic tools. However, many aspects of MR1 Ag presentation and MR1-restricted T cell biology remain unknown, and the ubiquitous expression of MR1 across tissues and cell lines can be a confounding factor for experimental purposes. In this study, we report the development of a novel CRISPR/Cas9 genome editing lentiviral system and its use to efficiently disrupt MR1 expression in A459, THP-1, and K562 cell lines. We generated isogenic MR1−/− clonal derivatives of the A549 lung carcinoma and THP-1 monocytic cell lines and used these to study T cell responses to intracellular pathogens. We confirmed that MAIT cell clones were unable to respond to MR1−/− clones infected with bacteria whereas Ag presentation by classical and other nonclassical HLAs was unaffected. This system represents a robust and efficient method to disrupt the expression of MR1 and should facilitate investigations into the processing and presentation of MR1 Ags as well as into the biology of MAIT cells. PMID:27307560

  4. Intestinal lymphangiectasia in children

    PubMed Central

    Isa, Hasan M.; Al-Arayedh, Ghadeer G.; Mohamed, Afaf M.

    2016-01-01

    Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification. PMID:26837404

  5. Intestinal transplantation: a review.

    PubMed

    Desai, Chirag Sureshchandra; Khan, Khalid Mahmood; Girlanda, Raffaele; Fishbein, Thomas M

    2012-09-01

    Parenteral nutrition is a life-saving therapy for patients with intestinal failure. Intestinal transplantation is now recognized as a treatment for patients who develop complications of parenteral nutrition and in whom attempts at intestinal rehabilitation have failed. Patients with parenteral nutrition related liver disease will require a liver graft typically part of a multivisceral transplant. Isolated intestinal transplants are more commonly performed in adults while multivisceral transplants are most commonly performed in infants. Isolated intestinal transplants have the best short-term outcome, with over 80 % survival at 1 year. Patients requiring multivisceral transplants have a high rate of attrition with a 1 year survival less than 70 %. Prognostic factors for a poor outcome include patient hospitalization at the time of transplant and donor age greater than 40 years while systemic sepsis and acute rejection are the major determinant of early postoperative outcome. For patients surviving the first year the outcome of transplantation of the liver in addition to intestine affords some survival advantage though long-term outcome does not yet match other abdominal organs. Outcomes for intestinal retransplantation are poor as a result of immunology and patient debility. Overall intestinal transplantation continues to develop and is a clear indication with cost and quality of life advantages in patients with intestinal failure that do not remain stable on parenteral nutrition.

  6. Linking intestinal homeostasis and liver disease

    PubMed Central

    Schnabl, Bernd

    2014-01-01

    Purpose of review Interactions of the gut microbiome with the host are important in health and disease. Microbial translocation releases bacterial products that play a key role in progression of chronic liver disease by promoting hepatic injury and inflammation. Although this has long been recognized, we are just beginning to understand the circumstances under which the gut becomes leaky and to discover bacterial metabolites that promote liver disease. In this review we will summarize recent findings from the last two years. Recent findings Chronic liver disease is associated with an altered microbiome with both qualitative (dysbiosis) and quantitative (overgrowth) differences. This can be viewed as a loss of the symbiotic relationship between the microflora and the host. An imbalanced intestinal homeostasis results in a breach of the gut barrier and subsequent microbial translocation. However, the contribution of the intestinal microflora is beyond simple microbial translocation as pathogenic factor. Bacterial metabolites resulting from an imbalanced homeostasis and dysbiosis play also a crucial role in liver disease. Summary A combination between an initiating liver insult and a disturbance of the gut – host symbiosis synergize in progression of liver disease. PMID:23493073

  7. Drosophila as a model for intestinal dysbiosis and chronic inflammatory diseases.

    PubMed

    Lee, Kyung-Ah; Lee, Won-Jae

    2014-01-01

    The association between deregulated intestinal microbial consortia and host diseases has been recognized since the birth of microbiology over a century ago. Intestinal dysbiosis refers to a state where living metazoans harbor harmful intestinal microflora. However, there is still an issue of whether causality arises from the host or the microbe because it is unclear whether deregulation of the gut microbiota community is the consequence or cause of the host disease. Recent studies using Drosophila and its simple microbiota have provided a valuable model system for dissecting the molecular mechanisms of intestinal dysbiosis. In this review, we examine recent exciting observations in Drosophila gut-microbiota interactions, particularly the links among the host immune genotype, the microbial community structure, and the host inflammatory phenotype. Future genetic analyses using Drosophila model system will provide a valuable outcome for understanding the evolutionarily conserved mechanisms that underlie intestinal dysbiosis and chronic inflammatory diseases.

  8. Oral administration of synthetic porcine beta-defensin-2 improves growth performance and cecal microbial flora and down-regulates the expression of intestinal toll-like receptor-4 and inflammatory cytokines in weaned piglets challenged with enterotoxigenic Escherichia coli.

    PubMed

    Tang, Zhiru; Xu, Ling; Shi, Baoshi; Deng, Huang; Lai, Xin; Liu, Jingyan; Sun, Zhihong

    2016-10-01

    Synthetic porcine beta-defensin-2 (pBD-2) was tested as an alternative to antimicrobial growth-promoters in pig production. Thirty 21-day weaned piglets were challenged with enterotoxigenic Escherichia coli, and orally dosed with either sterile water (CON), pBD-2 (BD) or neomycin sulphate (NS) twice daily for 21 days. pBD-2 and NS led to higher growth performance, jejunum villus height and increased expression of insulin-like growth factor-I compared with the CON group (P < 0.05). Hemolytic E. coli scores from rectal swabs, and copy numbers of E. coli, Bacteroides fragilis and Streptococcus in the cecal digesta of the BD- or NS-treated piglets were lower than those in the CON group (P < 0.05). Messenger RNA levels of toll-like receptor 4, tumor necrosis factor-α, interleukin (IL)-1β, and IL-8 in the jejunum mucosa of the BD and NS groups were lower than those in the CON group (P < 0.05). Copy numbers of Lactobacilli and Bifidobacteria in the cecal digesta of the BD group were higher than those of the CON and NS groups (P < 0.05). Therefore, pBD-2 has antimicrobial activity in piglets, and it can improve growth performance, reduce inflammatory cytokine expression and affect intestinal morphological indices in the same way as probiotics. © 2015 Japanese Society of Animal Science.

  9. [Quantitative and qualitative characteristics of representatives of the enterobacteriaceae family in postradiation intestinal dysbacteriosis].

    PubMed

    Pinegin, B V; Korshunov, V M; Ikonnikova, T B; Kissina, E V

    1980-08-01

    The irradiation of CBA mice with gamma quanta in a dose of 700 C/kg resulted in the development of postradiation intestinal dysbacteriosis in the animals. The dysbacteriosis was characterized by a considerable increase in the number of Escherichia and Proteus mirabilis in the large intestine and by the insemination of the small intestine with these microbial associations. Pr. vulgaris, Pr. morganii, Ent. aerogenes, Ent. cloacae, Citrobacter appeared in great numbers in the intestinal tract of the irradiated mice, while none of these organisms were found in the intact mice.

  10. IPNV Antigen Uptake and Distribution in Atlantic Salmon Following Oral Administration.

    PubMed

    Chen, Lihan; Evensen, Øystein; Mutoloki, Stephen

    2015-05-21

    One impediment to the successful oral vaccination in fish is the hostile stomach environment that antigens must cross. Furthermore, uptake of antigens from the gut to systemic distribution is required for induction of systemic immunity, the dynamics of which are poorly understood. In the present study, groups of Atlantic salmon parr were intubated with live or inactivated infectious pancreatic necrosis virus (IPNV), either orally or anally. At 1, 24 and 72 h post infection (p.i.), the fish were sacrificed. Serum was used for assessing IPNV by ELISA, while formalin-fixed head-kidney, spleen, liver and intestine tissues were used for the demonstration of antigens by immunohistochemistry. Both live and inactivated IPNV antigens were observed in enterocytes of the intestines and in immune cells of the head-kidneys and spleens of all groups. In the liver, no antigens were observed in any of the groups. Significantly higher serum antigen OD values (p < 0.04) were observed in orally- compared to anally-intubated fish. By contrast, no difference (p = 0.05) was observed in tissue antigens between these groups by immunohistochemistry. No significant difference (p = 0.05) in serum antigens was observed between groups intubated with live and inactivated IPNV, while in tissues, significantly more antigens (p < 0.03) were observe in the latter compared to the former. These findings demonstrate that both live and inactivated IPNV are taken up by enterocytes in the intestines of Atlantic salmon, likely by receptor-mediated mechanisms. Higher IPNV uptake by the oral compared to anal route suggests that both the anterior and posterior intestines are important for the uptake of the virus and that IPNV is resistant to gastric degradation of the Atlantic salmon stomach.

  11. Intestinal or bowel obstruction - discharge

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000150.htm Intestinal or bowel obstruction - discharge To use the sharing features on this ... your bowel (intestine). This condition is called an intestinal obstruction . The blockage may be partial or total (complete). ...

  12. Potentially conflicting selective forces that shape the vls antigenic variation system in Borrelia burgdorferi.

    PubMed

    Zhou, Wei; Brisson, Dustin

    2014-10-01

    Changing environmental conditions present an evolutionary challenge for all organisms. The environment of microbial pathogens, including the adaptive immune responses of the infected host, changes rapidly and is lethal to the pathogen lineages that cannot quickly adapt. The dynamic immune environment creates strong selective pressures favoring microbial pathogen lineages with antigenic variation systems that maximize the antigenic divergence among expressed antigenic variants. However, divergence among expressed antigens may be constrained by other molecular features such as the efficient expression of functional proteins. We computationally examined potential conflicting selection pressures on antigenic variation systems using the vls antigenic variation system in Borrelia burgdorferi as a model system. The vls system alters the sequence of the expressed antigen by recombining gene fragments from unexpressed but divergent 'cassettes' into the expression site, vlsE. The in silico analysis of natural and altered cassettes from seven lineages in the B. burgdorferi sensu lato species complex revealed that sites that are polymorphic among unexpressed cassettes, as well as the insertion/deletion mutations, are organized to maximize divergence among the expressed antigens within the constraints of translational ability and high translational efficiency. This study provides empirical evidence that conflicting selection pressures on antigenic variation systems can limit the potential antigenic divergence in order to maintain proper molecular function.

  13. Intestinal transport and metabolism of bile acids

    PubMed Central

    Dawson, Paul A.; Karpen, Saul J.

    2015-01-01

    In addition to their classical roles as detergents to aid in the process of digestion, bile acids have been identified as important signaling molecules that function through various nuclear and G protein-coupled receptors to regulate a myriad of cellular and molecular functions across both metabolic and nonmetabolic pathways. Signaling via these pathways will vary depending on the tissue and the concentration and chemical structure of the bile acid species. Important determinants of the size and composition of the bile acid pool are their efficient enterohepatic recirculation, their host and microbial metabolism, and the homeostatic feedback mechanisms connecting hepatocytes, enterocytes, and the luminal microbiota. This review focuses on the mammalian intestine, discussing the physiology of bile acid transport, the metabolism of bile acids in the gut, and new developments in our understanding of how intestinal metabolism, particularly by the gut microbiota, affects bile acid signaling. PMID:25210150

  14. The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation.

    PubMed

    Majka, Grzegorz; Więcek, Grażyna; Śróttek, Małgorzata; Śpiewak, Klaudyna; Brindell, Małgorzata; Koziel, Joanna; Marcinkiewicz, Janusz; Strus, Magdalena

    2016-12-01

    Translocation of bacteria, primarily Gram-negative pathogenic flora, from the intestinal lumen into the circulatory system leads to sepsis. In newborns, and especially very low birth weight infants, sepsis is a major cause of morbidity and mortality. The results of recently conducted clinical trials suggest that lactoferrin, an iron-binding protein that is abundant in mammalian colostrum and milk, may be an effective agent in preventing sepsis in newborns. However, despite numerous basic studies on lactoferrin, very little is known about how metal saturation of this protein affects a host's health. Therefore, the main objective of this study was to elucidate how iron-depleted, iron-saturated, and manganese-saturated forms of lactoferrin regulate intestinal barrier function via interactions with epithelial cells and macrophages. For these studies, a human intestinal epithelial cell line, Caco-2, was used. In this model, none of the tested lactoferrin forms induced higher levels of apoptosis or necrosis. There was also no change in the production of tight junction proteins regardless of lactoferrin metal saturation status. None of the tested forms induced a pro-inflammatory response in Caco-2 cells or in macrophages either. However, the various lactoferrin forms did effectively inhibit the pro-inflammatory response in macrophages that were activated with lipopolysaccharide with the most potent effect observed for apolactoferrin. Lactoferrin that was not bound to its cognate receptor was able to bind and neutralize lipopolysaccharide. Lactoferrin was also able to neutralize microbial-derived antigens, thereby potentially reducing their pro-inflammatory effect. Therefore, we hypothesize that lactoferrin supplementation is a relevant strategy for preventing sepsis.

  15. Intestinal obstruction repair - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100116.htm Intestinal obstruction repair - series—Normal anatomy To use the sharing ... M. Editorial team. Related MedlinePlus Health Topics Adhesions Intestinal Obstruction A.D.A.M., Inc. is accredited by ...

  16. Intestinal obstruction (pediatric) - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100165.htm Intestinal obstruction (pediatric) - series—Normal anatomy To use the sharing ... A.M. Editorial team. Related MedlinePlus Health Topics Intestinal Obstruction A.D.A.M., Inc. is accredited by ...

  17. Antigen injection (image)

    MedlinePlus

    Leprosy is caused by the organism Mycobacterium leprae . The leprosy test involves injection of an antigen just under ... if your body has a current or recent leprosy infection. The injection site is labeled and examined ...

  18. Suppression by Trypanosoma brucei of anaphylaxis-mediated ion transport in the small intestine of rats.

    PubMed Central

    Gould, S S; Castro, G A

    1994-01-01

    The hypothesis that failure of hosts infected with Trypanosoma brucei to express type 1 hypersensitivity is related to this parasite's ability to down-regulate IgE production, and not to an innate lack of allergenicity of T. brucei antigens, was tested by studying anaphylaxis-induced changes in net epithelial ion transport in rats. Transport changes were quantified electrophysiologically in vitro, as a change in transmural short-circuit current when sensitized intestine was challenged with homologous antigen. Rats injected parenterally with trypanosome antigen elicited intestinal anaphylaxis in response to antigenic challenge, whereas the intestine of rats infected with T. brucei failed to respond. Infection with T. brucei also suppressed the anaphylactic response in rats sensitized to and challenged with ovalbumin and T. spiralis-derived antigens. In these cases suppression was related to the ability of T. brucei to block production of IgE, and not to the physiological failure of the epithelial response. However, in rats sensitized by infection with T. spiralis, neither the anaphylactic response nor IgE production were inhibited by T. brucei. Furthermore, intestinal mastocytosis normally associated with trichinosis was unaffected by the trypanosome infection. Results support the conclusion that the failure to express anaphylaxis in T. brucei-infected rats is due to the inhibition of IgE production and not to the lack of allergenicity of trypanosome antigens. PMID:8206518

  19. Ecology, Microbial

    SciTech Connect

    Konopka, Allan

    2009-03-19

    Microbial ecology is a relatively young discipline within the field of microbiology. Its modern history spans just the past 60 years, and the field is defined by its emphasis on understanding the interactions of microbes with their environment, rather than their behavior under artificial laboratory conditions. Because microbes are ubiquitous, microbial ecologists study a broad diversity of habitats that range from aquatic to terrestrial to plant- or animal-associated. This has made it a challenge to identify unifying principles within the field. One approach is to recognize that although the activity of microbes in nature have effects at the macroscale, they interact with their physical, chemical and biological milieu at a scale of micrometers. At this scale, several different microbial ecosystems can be defined, based upon association with particles, the presence of environmental gradients and the continuous availability of water. Principles applicable to microbial ecology reflect not only their population ecology and physiological ecology, but also their broad versatility and quantitative importance in the biosphere as biogeochemical catalysts and capacity for rapid physiological and evolutionary responses.

  20. Ecology, Microbial

    SciTech Connect

    Konopka, Allan

    2009-05-15

    Microbial ecology is a relatively young discipline within the field of microbiology. Its modern history spans just the past 60 years, and the field is defined by its emphasis on understanding the interactions of microbes with their environment, rather than their behavior under artificial laboratory conditions. Because microbes are ubiquitous, microbial ecologists study a broad diversity of habitats that range from aquatic to terrestrial to plant- or animal-associated. This has made it a challenge to identify unifying principles within the field. One approach is to recognize that although the activity of microbes in nature have effects at the macroscale, they interact with their physical, chemical and biological milieu at a scale of micrometers. At this scale, several different microbial ecosystems can be defined, based upon association with particles, the presence of environmental gradients and the continuous availability of water. Principles applicable to microbial ecology reflect not only their population ecology and physiological ecology, but also their broad versatility and quantitative importance in the biosphere as biogeochemical catalysts and capacity for rapid physiological and evolutionary responses.

  1. Controlling Salmonella infection in weanling pigs through water delivery of direct-fed microbials or organic acids; Part I. Effects on growth performance, microbial populations and immune status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pigs (n=88) weaned at 19 ± 2 d of age were used in a 14 d study to evaluate the effects of water-delivered direct-fed microbials (DFM) or organic acids on immune status, Salmonella infection and shedding, and intestinal microbial populations following a Salmonella Typhimurium challenge. Pigs were ch...

  2. Intestinal Barrier and Behavior.

    PubMed

    Julio-Pieper, M; Bravo, J A

    2016-01-01

    The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses.

  3. Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

    PubMed Central

    Coats, Stephen R.; Hashim, Ahmed; Paramonov, Nikolay A.; Curtis, Michael A.

    2016-01-01

    ABSTRACT Intestinal homeostasis mechanisms must protect the host intestinal tissue from endogenous lipopolysaccharides (LPSs) produced by the intestinal microbiota. In this report, we demonstrate that murine intestinal fecal lipids effectively block Toll-like receptor 4 (TLR4) responses to naturally occurring Bacteroidetes sp. LPS. Cardiolipin (CL) represents a significant proportion of the total intestinal and fecal lipids and, furthermore, potently antagonizes TLR4 activation by reducing LPS binding at the lipopolysaccharide binding protein (LBP), CD14, and MD-2 steps of the TLR4 signaling pathway. It is further demonstrated that intestinal lipids and CL are less effective at neutralizing more potent Enterobacteriaceae-type LPS, which is enriched in feces obtained from mice with dextran sodium sulfate (DSS)-treated inflammatory bowel disease. The selective inhibition of naturally occurring LPS structures by intestinal lipids may represent a novel homeostasis mechanism that blocks LPS activation in response to symbiotic but not dysbiotic microbial communities. IMPORTANCE The guts of animals harbor a variety of Gram-negative bacteria associated with both states of intestinal health and states of disease. Environmental factors, such as dietary habits, can drive the microbial composition of the host animal's intestinal bacterial community toward a more pathogenic state. Both beneficial and harmful Gram-negative bacteria are capable of eliciting potentially damaging inflammatory responses from the host intestinal tissues via a lipopolysaccharide (LPS)-dependent pathway. Physical mucosal barriers and antibodies produced by the intestinal immune system protect against the undesired inflammatory effects of LPS, although it is unknown why some bacteria are more effective at overcoming the protective barriers than others. This report describes the discovery of a lipid-type protective barrier in the intestine that reduces the deleterious effects of LPSs from beneficial

  4. Mixing and pumping functions of the intestine of zebrafish larvae.

    PubMed

    Yang, Jinyou; Shimogonya, Yuji; Ishikawa, Takuji

    2017-02-07

    Due to its transparency, the intestine of zebrafish larvae has been widely used in studies of gastrointestinal diseases and the microbial flora of the gut. However, transport phenomena in the intestine of zebrafish larvae have not been fully clarified. In this study, therefore, transport caused by peristaltic motion in the intestine of zebrafish larvae was investigated by numerical simulation. An anatomically realistic three-dimensional geometric model of the intestine at various times after feeding was constructed based on the experimental data of Field et al. (2009). The flow of digested chyme was analyzed using the governing equations of fluid mechanics, together with peristaltic motion and long-term contraction of the intestinal wall. The results showed that retrograde peristaltic motion was the main contributor to the mixing function. The dispersion caused by peristalsis over 30min was in the order of 10(-12)m(2)/s, which is greater than the Brownian diffusion of a sphere of 0.4µm diameter. In contrast, anterograde peristaltic motion contributed mainly to the pumping function. The pressure decrease due to peristalsis was in the order of millipascals, which may reduce the activation and maintenance heat of intestinal muscle. These findings enhance our understanding of the mixing and pumping functions of the intestine of zebrafish larvae.

  5. The surface rhamnopolysaccharide epa of Enterococcus faecalis is a key determinant of intestinal colonization.

    PubMed

    Rigottier-Gois, Lionel; Madec, Clément; Navickas, Albertas; Matos, Renata C; Akary-Lepage, Elodie; Mistou, Michel-Yves; Serror, Pascale

    2015-01-01

    Enterococcus faecalis is a commensal bacterium of the human intestine and a major opportunistic pathogen in immunocompromised and elderly patients. The pathogenesis of E. faecalis infection relies in part on its capacity to colonize the gut. Following disruption of intestinal homeostasis, E. faecalis can overgrow, cross the intestinal barrier, and enter the lymph and bloodstream. To identify and characterize E. faecalis genes that are key to intestinal colonization, our strategy consisted in screening mutants for the following phenotypes related to intestinal lifestyle: antibiotic resistance, overgrowth, and competition against microbiota. From the identified colonization genes, epaX encodes a glycosyltransferase located in a variable region of the enterococcal polysaccharide antigen (epa) locus. We demonstrated that EpaX acts on sugar composition, promoting resistance to bile salts and cell wall integrity. Given that EpaX is enriched in hospital-adapted isolates, this study points to the importance of the epa variability as a key determinant for enterococcal intestinal colonization.

  6. Intestinal permeability, leaky gut, and intestinal disorders.

    PubMed

    Hollander, D

    1999-10-01

    A major task of the intestine is to form a defensive barrier to prevent absorption of damaging substances from the external environment. This protective function of the intestinal mucosa is called permeability. Clinicians can use inert, nonmetabolized sugars such as mannitol, rhamnose, or lactulose to measure the permeability barrier or the degree of leakiness of the intestinal mucosa. Ample evidence indicates that permeability is increased in most patients with Crohn's disease and in 10% to 20% of their clinically healthy relatives. The abnormal leakiness of the mucosa in Crohn's patients and their relatives can be greatly amplified by aspirin preadministration. Permeability measurements in Crohn's patients reflect the activity, extent, and distribution of the disease and may allow us to predict the likelihood of recurrence after surgery or medically induced remission. Permeability is also increased in celiac disease and by trauma, burns, and nonsteroidal anti-inflammatory drugs. The major determinant of the rate of intestinal permeability is the opening or closure of the tight junctions between enterocytes in the paracellular space. As we broaden our understanding of the mechanisms and agents that control the degree of leakiness of the tight junctions, we will be increasingly able to use permeability measurements to study the etiology and pathogenesis of various disorders and to design or monitor therapies for their management.

  7. Recognition of Microbial Glycolipids by Natural Killer T Cells

    PubMed Central

    Zajonc, Dirk M.; Girardi, Enrico

    2015-01-01

    T cells can recognize microbial antigens when presented by dedicated antigen-presenting molecules. While peptides are presented by classical members of the major histocompatibility complex (MHC) family (MHC I and II), lipids, glycolipids, and lipopeptides can be presented by the non-classical MHC member, CD1. The best studied subset of lipid-reactive T cells are type I natural killer T (iNKT) cells that recognize a variety of different antigens when presented by the non-classical MHCI homolog CD1d. iNKT cells have been shown to be important for the protection against various microbial pathogens, including B. burgdorferi, the causative agents of Lyme disease, and S. pneumoniae, which causes pneumococcal meningitis and community-acquired pneumonia. Both pathogens carry microbial glycolipids that can trigger the T cell antigen receptor (TCR), leading to iNKT cell activation. iNKT cells have an evolutionary conserved TCR alpha chain, yet retain the ability to recognize structurally diverse glycolipids. They do so using a conserved recognition mode, in which the TCR enforces a conserved binding orientation on CD1d. TCR binding is accompanied by structural changes within the TCR binding site of CD1d, as well as the glycolipid antigen itself. In addition to direct recognition of microbial antigens, iNKT cells can also be activated by a combination of cytokines (IL-12/IL-18) and TCR stimulation. Many microbes carry TLR antigens, and microbial infections can lead to TLR activation. The subsequent cytokine response in turn lower the threshold of TCR-mediated iNKT cell activation, especially when weak microbial or even self-antigens are presented during the cause of the infection. In summary, iNKT cells can be directly activated through TCR triggering of strong antigens, while cytokines produced by the innate immune response may be necessary for TCR triggering and iNKT cell activation in the presence of weak antigens. Here, we will review the molecular basis of iNKT cell

  8. Microbial translocation and microbiome dsybiosis in HIV-associated immune activation

    PubMed Central

    Zevin, Alexander S.; McKinnon, Lyle; Burgener, Adam; Klatt, Nichole R.

    2016-01-01

    Purpose of Review To describe the mechanisms and consequences of both microbial translocation and microbial dysbiosis in HIV infection. Recent Findings Microbes in HIV are likely playing a large role in contributing to HIV pathogenesis, morbidities and mortality. Two major disruptions to microbial systems in HIV infection include microbial translocation and microbiome dysbiosis. Microbial translocation occurs when the bacteria (or bacterial products) that should be in the lumen of the intestine translocate across the tight epithelial barrier into systemic circulation, where they contribute to inflammation and pathogenesis. This is associated with poorer health outcomes in HIV infected individuals. In addition, microbial populations in the GI tract are also altered after HIV infection, resulting in microbiome dysbiosis, which further exacerbates microbial translocation, epithelial barrier disruption, inflammation, and mucosal immune functioning. Summary Altered microbial regulation in HIV infection can lead to poor health outcomes, and understanding the mechanisms underlying microbial dysbiosis and translocation may result in novel pathways for therapeutic interventions. PMID:26679414

  9. Disrupted Intestinal Microbiota and Intestinal Inflammation in Children with Cystic Fibrosis and Its Restoration with Lactobacillus GG: A Randomised Clinical Trial

    PubMed Central

    Bruzzese, Eugenia; Callegari, Maria Luisa; Raia, Valeria; Viscovo, Sara; Scotto, Riccardo; Ferrari, Susanna; Morelli, Lorenzo; Buccigrossi, Vittoria; Lo Vecchio, Andrea; Ruberto, Eliana; Guarino, Alfredo

    2014-01-01

    Background & Aims Intestinal inflammation is a hallmark of cystic fibrosis (CF). Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations. We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation. We also investigated the microflora structure before and after Lactobacillus GG (LGG) administration in children with CF with and without antibiotic treatment. Methods The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE), real-time polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH). Intestinal inflammation was assessed by measuring fecal calprotectin (CLP) and rectal nitric oxide (rNO) production in children with CF as compared with healthy controls. We then carried out a small double-blind randomized clinical trial with LGG. Results Twenty-two children with CF children were enrolled in the study (median age, 7 years; range, 2–9 years). Fecal CLP and rNO levels were higher in children with CF than in healthy controls (184±146 µg/g vs. 52±46 µg/g; 18±15 vs. 2.6±1.2 µmol/L NO2−, respectively; P<0.01). Compared with healthy controls, children with CF had significantly different intestinal microbial core structures. The levels of Eubacterium rectale, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Faecalibacterium prausnitzii were reduced in children with CF. A similar but more extreme pattern was observed in children with CF who were taking antibiotics. LGG administration reduced fecal CLP and partially restored intestinal microbiota. There was a significant correlation between reduced microbial richness and intestinal inflammation. Conclusions CF causes qualitative and quantitative changes in intestinal microbiota, which may represent a novel therapeutic target in the treatment of CF. Administration of

  10. Biochemistry of intestinal development.

    PubMed Central

    Henning, S J

    1979-01-01

    In biochemical terms, the rat small intestine is relatively immature at birth and for the first two postnatal weeks. Then during the third week a dramatic array of enzymic changes begins, and by the end of the fourth week the intestine has the digestive and absorptive properties of the adult. Selective examples of these changes are discussed with emphasis on their implications for toxicological studies. The review also includes a detailed consideration of the roles of the dietary change of weaning and of glucocorticoid and thyroid hormones in the regulation of intestinal development. PMID:575507

  11. Immunomodulatory roles of the carcinoembryonic antigen family of glycoproteins.

    PubMed

    Shao, Ling; Allez, Matthieu; Park, Mee-Sook; Mayer, Lloyd

    2006-08-01

    One of the most remarkable aspects of the immune system is its ability to fashion an immune response most appropriate to the activating stimulus. Although the immune system possesses a number of adaptations to accomplish this, an important theme is local immune regulation by site-specific expression of receptors and ligands. One family of molecules that is gaining attention as modulators of the immune system is the carcinoembryonic antigen cell-adhesion molecule family (CEACAM). Functionally, the carcinoembryonic antigen family can mediate cell-cell contact, host-pathogen interactions, and immune regulation. For example, biliary glycoprotein (CEACAM1) can have direct activity on T cells, leading to the inhibition of helper or cytotoxic T cell function. The expression of carcinoembryonic antigen (CEACAM5) on intestinal epithelial cells is involved in the activation of populations of regulatory CD8(+) T cells, while a distinct subset of regulatory CD8+ T cells is activated by nonspecific cross-reacting antigen (CEACAM6) on placental trophoblasts. Interestingly, the function and phenotype of these cells depend upon the specific member of the carcinoembryonic antigen family expressed, as well as the antigen-presenting molecule with which it associates. Thus, these glycoproteins comprise a family of molecules whose functions can depend on their nature and context.

  12. Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation.

    PubMed

    Luettig, J; Rosenthal, R; Barmeyer, C; Schulzke, J D

    2015-01-01

    The epithelial tight junction determines the paracellular water and ion movement in the intestine and also prevents uptake of larger molecules, including antigens, in an uncontrolled manner. Claudin-2, one of the 27 mammalian claudins regulating that barrier function, forms a paracellular channel for small cations and water. It is typically expressed in leaky epithelia like proximal nephron and small intestine and provides a major pathway for the paracellular transport of sodium, potassium, and fluid. In intestinal inflammation (Crohn's disease, ulcerative colitis), immune-mediated diseases (celiac disease), and infections (HIV enteropathy), claudin-2 is upregulated in small and large intestine and contributes to diarrhea via a leak flux mechanism. In parallel to that upregulation, other epithelial and tight junctional features are altered and the luminal uptake of antigenic macromolecules is enhanced, for which claudin-2 may be partially responsible through induction of tight junction strand discontinuities.

  13. Disruption of antigenic variation is crucial for effective parasite vaccine.

    PubMed

    Rivero, Fernando D; Saura, Alicia; Prucca, Cesar G; Carranza, Pedro G; Torri, Alessandro; Lujan, Hugo D

    2010-05-01

    Giardia lamblia is a human intestinal pathogen. Like many protozoan microorganisms, Giardia undergoes antigenic variation, a mechanism assumed to allow parasites to evade the host's immune response, producing chronic and/or recurrent infections. Recently, we found that the mechanism controlling variant-specific surface protein (VSP) switching in Giardia involves components of the RNA interference machinery and that disruption of this pathway generates trophozoites simultaneously expressing many VSPs. Here we use these altered trophozoites to determine the role of antigenic variation in a gerbil model of giardiasis. Our results show that either primary infection with trophozoites simultaneously expressing many VSPs or immunization with purified VSPs from the transgenic cells protects gerbils from subsequent Giardia infections. These results constitute, to our knowledge, the first experimental evidence that antigenic variation is essential for parasite survival within hosts and that artificial disruption of this mechanism might be useful in generating vaccines against major pathogens that show similar behavior.

  14. Mechanisms of adaptation in the intestinal parasite Giardia lamblia.

    PubMed

    Lujan, Hugo D

    2011-01-01

    Giardia lamblia, a parasite of humans, is a major source of waterborne diarrhoeal disease. Giardia is also an excellent system to study basic biochemical processes because it is a single-celled eukaryote with a small genome and its entire life cycle can be replicated in vitro. Giardia trophozoites undergo fundamental changes to survive outside the intestine of their host by differentiating into infective cysts. Encystation entails the synthesis, processing, transport, secretion and extracellular assembly of cyst wall components. To survive within the intestine, Giardia undergoes antigenic variation, a process by which the parasite continuously switches its major surface molecules, allowing the parasite to evade the host's immune response and produce chronic and recurrent infections. The objective of the present chapter is to provide a better understanding of the molecular mechanisms involved in adaptation and differentiation in Giardia, with a particular focus on the process of encystation and antigenic variation of this interesting micro-organism.

  15. EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance

    PubMed Central

    Jiang, Lingling; Shen, Yingying; Guo, Danfeng; Yang, Diya; Liu, Jiajun; Fei, Xuefeng; Yang, Yunshan; Zhang, Buyi; Lin, Zhendong; Yang, Fei; Wang, Xiaojian; Wang, Keyi; Wang, Jianli; Cai, Zhijian

    2016-01-01

    How the intestinal tract develops a tolerance to foreign antigens is still largely unknown. Here we report that extracellular vesicles (EVs) with TGF-β1-dependent immunosuppressive activity are produced by intestinal epithelial cells (IECs) under physiological conditions. Transfer of these EVs into inflammatory bowel disease (IBD) mice induced by dextran sulfate sodium salt decreases IBD severity by inducing regulatory T cells and immunosuppressive dendritic cells. In contrast, decreased endogenous EV production promotes IBD development. IECs produce EVs with increased levels of TGF-β1 upon IBD development in an ERK-dependent manner. Furthermore, these EVs tend to localize in the intestinal tract associated with epithelial cell adhesion molecule (EpCAM). Knockdown of EpCAM in vivo increases the severity of murine IBD, and the protective effect of EVs from IECs with decreased EpCAM on murine IBD is blunted. Therefore, our study indicates that EVs from IECs participate in maintaining the intestinal tract immune balance. PMID:27721471

  16. Intestinal Complications of IBD

    MedlinePlus

    ... that only affects the colon). LOCAL COMPLICATIONS OF CROHN’S DISEASE INTESTINAL OBSTRUCTION The most common complication of Crohn’s disease, obstruction may arise from swelling and the formation ...

  17. Intestinal pseudo-obstruction

    MedlinePlus

    ... Taking drugs that slow intestinal movements. These include narcotic (pain) medicines and drugs used when you are ... that may have caused the problem (such as narcotic drugs) may help. In severe cases, surgery may ...

  18. Diagnostic Antigens of Leishmania.

    DTIC Science & Technology

    1994-01-31

    braziliensis (MHOM/BR/75/M2903), L. chagasi (MJOM/BR/82/BA-2,C 1), L. donovani (MHOMiEt/67iHU3), Leishmania guyanensis (MIHOMJBR/75/M4147), L. infantum (IPT-1...comparative test to a variety of other recombinant Leishmania antigens including L. chagasi hsp70, L. braziliensis hsp83/90, L. braziliensis eIF4A, L...34 4. AD CONTRACT NO: DAMD17-92-C-2082 EC•£ 2 j 994 ’i, L TITLE: DIAGNOSTIC ANTIGENS OF LEISHMANIA L PRINCIPAL INVESTIGATOR: Steven G. Reed, Ph.D

  19. Intestinal parasitic infection.

    PubMed

    Park, Mi-Suk; Kim, Ki Whang; Ha, Hyun Kwon; Lee, Dong Ho

    2008-01-01

    In general, gastrointestinal tract is the primary involvement site of parasites during their life cycle. In this article, we will describe amebiasis, ascariasis, and anisakiasis among the many common intestinal parasitic diseases. We will review the epidemiology, life cycles, clinical manifestations and complications, and illustrate detailed imaging findings of intestinal parasites. Recognizing features of parasitic infection is important to establish an early diagnosis that leads to prompt treatment and helps avoid unnecessary surgery.

  20. Intestinal adaptation following resection.

    PubMed

    Tappenden, Kelly A

    2014-05-01

    Intestinal adaptation is a natural compensatory process that occurs following extensive intestinal resection, whereby structural and functional changes in the intestine improve nutrient and fluid absorption in the remnant bowel. In animal studies, postresection structural adaptations include bowel lengthening and thickening and increases in villus height and crypt depth. Functional changes include increased nutrient transporter expression, accelerated crypt cell differentiation, and slowed transit time. In adult humans, data regarding adaptive changes are sparse, and the mechanisms underlying intestinal adaptation remain to be fully elucidated. Several factors influence the degree of intestinal adaptation that occurs post resection, including site and extent of resection, luminal stimulation with enteral nutrients, and intestinotrophic factors. Two intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide and recombinant growth hormone (somatropin), are now approved for clinical use in patients with short bowel syndrome (SBS). Both agents enhance fluid absorption and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid. Intestinal adaptation has been thought to be limited to the first 1-2 years following resection in humans. However, recent data suggest that a significant proportion of adult patients with SBS can achieve enteral autonomy, even after many years of PN dependence, particularly with trophic stimulation.

  1. Claudins in intestines

    PubMed Central

    Lu, Zhe; Ding, Lei; Lu, Qun; Chen, Yan-Hua

    2013-01-01

    Intestines are organs that not only digest food and absorb nutrients, but also provide a defense barrier against pathogens and noxious agents ingested. Tight junctions (TJs) are the most apical component of the junctional complex, providing one form of cell-cell adhesion in enterocytes and playing a critical role in regulating paracellular barrier permeability. Alteration of TJs leads to a number of pathophysiological diseases causing malabsorption of nutrition and intestinal structure disruption, which may even contribute to systemic organ failure. Claudins are the major structural and functional components of TJs with at least 24 members in mammals. Claudins have distinct charge-selectivity, either by tightening the paracellular pathway or functioning as paracellular channels, regulating ions and small molecules passing through the paracellular pathway. In this review, we have discussed the functions of claudin family members, their distribution and localization in the intestinal tract of mammals, their alterations in intestine-related diseases and chemicals/agents that regulate the expression and localization of claudins as well as the intestinal permeability, which provide a therapeutic view for treating intestinal diseases. PMID:24478939

  2. Autism spectrum disorders and intestinal microbiota.

    PubMed

    De Angelis, Maria; Francavilla, Ruggiero; Piccolo, Maria; De Giacomo, Andrea; Gobbetti, Marco

    2015-01-01

    Through extensive microbial-mammalian co-metabolism, the intestinal microbiota have evolved to exert a marked influence on health and disease via gut-brain-microbiota interactions. In this addendum, we summarize the findings of our recent study on the fecal microbiota and metabolomes of children with pervasive developmental disorder-not otherwise specified (PDD-NOS) or autism (AD) compared with healthy children (HC). Children with PDD-NOS or AD have altered fecal microbiota and metabolomes (including neurotransmitter molecules). We hypothesize that the degree of microbial alteration correlates with the severity of the disease since fecal microbiota and metabolomes alterations were higher in children with PDD-NOS and, especially, AD compared to HC. Our study indicates that the levels of free amino acids (FAA) and volatile organic compounds (VOC) differ in AD subjects compared to children with PDD-NOS, who are more similar to HC. Finally, we propose a new perspective on the implications for the interaction between intestinal microbiota and AD.

  3. Autism spectrum disorders and intestinal microbiota

    PubMed Central

    De Angelis, Maria; Francavilla, Ruggiero; Piccolo, Maria; De Giacomo, Andrea; Gobbetti, Marco

    2015-01-01

    Through extensive microbial-mammalian co-metabolism, the intestinal microbiota have evolved to exert a marked influence on health and disease via gut-brain-microbiota interactions. In this addendum, we summarize the findings of our recent study on the fecal microbiota and metabolomes of children with pervasive developmental disorder–not otherwise specified (PDD-NOS) or autism (AD) compared with healthy children (HC). Children with PDD-NOS or AD have altered fecal microbiota and metabolomes (including neurotransmitter molecules). We hypothesize that the degree of microbial alteration correlates with the severity of the disease since fecal microbiota and metabolomes alterations were higher in children with PDD-NOS and, especially, AD compared to HC. Our study indicates that the levels of free amino acids (FAA) and volatile organic compounds (VOC) differ in AD subjects compared to children with PDD-NOS, who are more similar to HC. Finally, we propose a new perspective on the implications for the interaction between intestinal microbiota and AD. PMID:25835343

  4. Prior stimulation of antigen-presenting cells with Lactobacillus regulates excessive antigen-specific cytokine responses in vitro when compared with Bacteroides

    PubMed Central

    Tsuda, Masato; Yanagibashi, Tsutomu; Hachimura, Satoshi; Hirayama, Kazuhiro; Itoh, Kikuji; Takahashi, Kyoko; Kaminogawa, Shuichi

    2007-01-01

    The development of allergy is related to differences in the intestinal microbiota. Therefore, it is suggested that the immune responses induced by different genera of bacteria might be regulated through adaptive as well as innate immunity. In this study, we examined whether antigen-specific immune responses were affected by stimulation with the different genera of intestinal bacteria in vitro. Mesenteric lymph node (MLN) cells isolated from germ-free ovalbumin (OVA)-specific T cell receptor transgenic (OVA-Tg) mice were stimulated with OVA and intestinal bacteria. Cecal contents from conventional mice but not germ-free mice could induce OVA-specific cytokine production. Among the murine intestinal bacteria, Bacteroides acidofaciens (BA) enhanced OVA-specific IFN-γ and IL-10 production while Lactobacillusjohnsonii (LA) increased OVA-specific IL-10 production only. The expression of cell surface molecules and cytokine production by antigen-presenting cells (APCs) from germ-free Balb/c mice were analyzed. BA increased the expression of MHC II and co-stimulatory molecules on APCs compared with LA. BA increased IL-6 and IL-10 production but induced less IL-12p40 than LA. To examine the effects of prior stimulation of APCs by intestinal bacteria on the induction of antigen-specific immune responses, cytokine production was determined following co-culture with OVA, CD4+ T cells from OVA-Tg mice, and APCs which were pre-stimulated with the bacteria or not. APCs pre-stimulated with LA did not enhance OVA-specific cytokine production while BA stimulated OVA-specific IL-10 production. These results suggest that the prior stimulation of intestinal immunocytes by Lactobacillus might regulate excessive antigen-specific cytokine responses via APCs when compared with prior stimulation by Bacteroides. PMID:19002998

  5. Hepatic and Intestinal Schistosomiasis: Review

    PubMed Central

    Elbaz, Tamer; Esmat, Gamal

    2013-01-01

    Schistosomiasis is an endemic disease in Egypt caused by the trematode Schistosoma which has different species. Hepatic schistosomiasis represents the best known form of chronic disease with a wide range of clinical manifestations. The pathogenesis of schistosomiasis is related to the host cellular immune response. This leads to granuloma formation and neo angiogenesis with subsequent periportal fibrosis manifested as portal hypertension, splenomegaly and esophageal varices. Intestinal schistosomiasis is another well identified form of chronic schistosomal affection. Egg deposition and granuloma formation eventually leads to acute then chronic schistosomal colitis and is commonly associated with polyp formation. It frequently presents as abdominal pain, diarrhea, tenesmus and anal pain. Definite diagnosis of schistosomiasis disease depends on microscopy and egg identification. Marked progress regarding serologic diagnosis occurred with development of recent PCR techniques that can confirm schistosomal affection at any stage. Many antischistosomal drugs have been described for treatment, praziquantel being the most safe and efficient drug. Still ongoing studies try to develop effective vaccines with identification of many target antigens. Preventive programs are highly needed to control the disease morbidity and to break the cycle of transmission. PMID:25685451

  6. Hetero-organic thymus antigens.

    PubMed

    Beletskaya, L V; Gnezditskaya, E V

    1985-01-01

    The use of sera containing antibodies to tissue-specific antigens of highly specialized organs (skeletal muscles, heart, skin, excretory glands) enabled us to detect, by immunofluorescence, cells capable of synthesizing analogous antigens (i.e. hetero-organic thymus antigens) in human and animal thymus. Detection of hetero-organic antigens in the thymus is the basis for the hypothesis that natural immunological tolerance to tissue self antigens is formed within the thymus in the course of T-lymphocyte maturation, with thymus antigens taking part in the process.

  7. Interferon Tau Affects Mouse Intestinal Microbiota and Expression of IL-17

    PubMed Central

    Ren, Wenkai; Chen, Shuai; Zhang, Liwen; Liu, Gang; Hussain, Tarique; Hao, Xiao; Yin, Jie; Duan, Jielin; Wu, Guoyao; Bazer, Fuller W.

    2016-01-01

    This study was conducted to explore the effects of interferon tau (IFNT) on the intestinal microbiota and expression of interleukin 17 (IL-17) in the intestine of mice. IFNT supplementation increased microbial diversity in the jejunum and ileum but decreased microbial diversity in the feces. IFNT supplementation influenced the composition of the intestinal microbiota as follows: (1) decreasing the percentage of Firmicutes and increasing Bacteroidetes in the jejunum and ileum; (2) enhancing the percentage of Firmicutes but decreasing Bacteroidetes in the colon and feces; (3) decreasing Lactobacillus in the jejunum and ileum; (4) increasing the percentage of Blautia, Bacteroides, Alloprevotella, and Lactobacillus in the colon; and (5) increasing the percentage of Lactobacillus, Bacteroides, and Allobaculum, while decreasing Blautia in the feces. Also, IFNT supplementation decreased the expression of IL-17 in the intestines of normal mice and of an intestinal pathogen infected mice. In conclusion, IFNT supplementation modulates the intestinal microbiota and intestinal IL-17 expression, indicating the applicability of IFNT to treat the intestinal diseases involving IL-17 expression and microbiota. PMID:27610003

  8. Gut microbiome derived metabolites modulate intestinal epithelial cell damage and mitigate Graft-versus-Host Disease

    PubMed Central

    Toubai, Tomomi; Oravecz-Wilson, Katherine; Wu, Shin-Rong; Sun, Yaping; Rossi, Corinne; Fujiwara, Hideaki; Byun, Jaeman; Shono, Yusuke; Lindemans, Caroline; Calafiore, Marco; Schmidt, Thomas C.; Honda, Kenya; Reddy, Pavan

    2016-01-01

    The impact of alterations in intestinal microbiota on microbial metabolites and on disease processes, such as graft-versus-host disease (GVHD), is not known. Here we performed unbiased analysis to identify novel alterations in gastrointestinal microbiota-derived short chain fatty acids (SCFA) after allogeneic bone marrow transplant (allo-BMT). Alterations in the amounts of only one SCFA, butyrate, were observed only within the intestinal tissue. The reduced butyrate in CD326+ intestinal epithelial cells (IECs) after allo-BMT resulted in decreased histone acetylation, which was restored upon local administration of exogenous butyrate. Butyrate restoration improved IEC junctional integrity, decreased apoptosis, and mitigated GVHD. Furthermore, alteration of the indigenous microbiota with 17 rationally selected strains of high butyrate producing Clostridia also decreased GVHD. These data demonstrate a heretofore unrecognized role of microbial metabolites and suggest that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and can mitigate its severity. PMID:26998764

  9. The enteric nervous system promotes intestinal health by constraining microbiota composition

    PubMed Central

    Mittge, Erika K.; Ganz, Julia; Troll, Josh V.; Melancon, Ellie; Wiles, Travis J.; Alligood, Kristin; Stephens, W. Zac; Eisen, Judith S.; Guillemin, Karen

    2017-01-01

    Sustaining a balanced intestinal microbial community is critical for maintaining intestinal health and preventing chronic inflammation. The gut is a highly dynamic environment, subject to periodic waves of peristaltic activity. We hypothesized that this dynamic environment is a prerequisite for a balanced microbial community and that the enteric nervous system (ENS), a chief regulator of physiological processes within the gut, profoundly influences gut microbiota composition. We found that zebrafish lacking an ENS due to a mutation in the Hirschsprung disease gene, sox10, develop microbiota-dependent inflammation that is transmissible between hosts. Profiling microbial communities across a spectrum of inflammatory phenotypes revealed that increased levels of inflammation were linked to an overabundance of pro-inflammatory bacterial lineages and a lack of anti-inflammatory bacterial lineages. Moreover, either administering a representative anti-inflammatory strain or restoring ENS function corrected the pathology. Thus, we demonstrate that the ENS modulates gut microbiota community membership to maintain intestinal health. PMID:28207737

  10. The enteric nervous system promotes intestinal health by constraining microbiota composition.

    PubMed

    Rolig, Annah S; Mittge, Erika K; Ganz, Julia; Troll, Josh V; Melancon, Ellie; Wiles, Travis J; Alligood, Kristin; Stephens, W Zac; Eisen, Judith S; Guillemin, Karen

    2017-02-01

    Sustaining a balanced intestinal microbial community is critical for maintaining intestinal health and preventing chronic inflammation. The gut is a highly dynamic environment, subject to periodic waves of peristaltic activity. We hypothesized that this dynamic environment is a prerequisite for a balanced microbial community and that the enteric nervous system (ENS), a chief regulator of physiological processes within the gut, profoundly influences gut microbiota composition. We found that zebrafish lacking an ENS due to a mutation in the Hirschsprung disease gene, sox10, develop microbiota-dependent inflammation that is transmissible between hosts. Profiling microbial communities across a spectrum of inflammatory phenotypes revealed that increased levels of inflammation were linked to an overabundance of pro-inflammatory bacterial lineages and a lack of anti-inflammatory bacterial lineages. Moreover, either administering a representative anti-inflammatory strain or restoring ENS function corrected the pathology. Thus, we demonstrate that the ENS modulates gut microbiota community membership to maintain intestinal health.

  11. Microbial Metalloproteomics

    PubMed Central

    Hagedoorn, Peter-Leon

    2015-01-01

    Metalloproteomics is a rapidly developing field of science that involves the comprehensive analysis of all metal-containing or metal-binding proteins in a biological sample. The purpose of this review is to offer a comprehensive overview of the research involving approaches that can be categorized as inductively coupled plasma (ICP)-MS based methods, X-ray absorption/fluorescence, radionuclide based methods and bioinformatics. Important discoveries in microbial proteomics will be reviewed, as well as the outlook to new emerging approaches and research areas. PMID:28248278

  12. Microbial Metabolomics

    PubMed Central

    Tang, Jane

    2011-01-01

    Microbial metabolomics constitutes an integrated component of systems biology. By studying the complete set of metabolites within a microorganism and monitoring the global outcome of interactions between its development processes and the environment, metabolomics can potentially provide a more accurate snap shot of the actual physiological state of the cell. Recent advancement of technologies and post-genomic developments enable the study and analysis of metabolome. This unique contribution resulted in many scientific disciplines incorporating metabolomics as one of their “omics” platforms. This review focuses on metabolomics in microorganisms and utilizes selected topics to illustrate its impact on the understanding of systems microbiology. PMID:22379393

  13. Suppression of intestinal immunity through silencing of TCTP by RNAi in transgenic silkworm, Bombyx mori.

    PubMed

    Hu, Cuimei; Wang, Fei; Ma, Sanyuan; Li, Xianyang; Song, Liang; Hua, Xiaoting; Xia, Qingyou

    2015-12-10

    Intestinal immune response is a front line of host defense. The host factors that participate in intestinal immunity response remain largely unknown. We recently reported that Translationally Controlled Tumor Protein (BmTCTP) was obtained by constructing a phage display cDNA library of the silkworm midgut and carrying out high throughput screening of pathogen binding molecules. To further address the function of BmTCTP in silkworm intestinal immunity, transgenic RNAi silkworms were constructed by microinjection piggBac plasmid to Dazao embryos. The antimicrobial capacity of transgenic silkworm decreased since the expression of gut antimicrobial peptide from transgenic silkworm was not sufficiently induced during oral microbial challenge. Moreover, dynamic ERK phosphorylation from transgenic silkworm midgut was disrupted. Taken together, the innate immunity of intestinal was suppressed through disruption of dynamic ERK phosphorylation after oral microbial infection as a result of RNAi-mediated knockdown of midgut TCTP in transgenic silkworm.

  14. Intestinal lymphangiectasia in adults.

    PubMed

    Freeman, Hugh James; Nimmo, Michael

    2011-02-15

    Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial

  15. Antigen detection systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious agents or their constituent parts (antigens or nucleic acids) can be detected in fresh, frozen, or fixed tissues or other specimens, using a variety of direct or indirect assays. The assays can be modified to yield the greatest sensitivity and specificity but in most cases a particular m...

  16. Human liver nucleolar antigens.

    PubMed

    Busch, R K; Busch, H

    1981-10-01

    In an extension of previous studies on the antigens in rat liver nucleoli (R. K. Busch, R. C. Reddy, D. H. Henning, and H. Busch, Proc. Soc. Exp. Biol. Med. 160, 185 (1979); R. K. Busch and H. Busch, Tumori 63, 347 (1977); F. M. Davis, R. K. Busch, L. C. Yeoman, and H. Busch, Cancer Res. 38, 1906 (1978), rabbit antibodies were elicited to human liver nucleoli isolated by the sucrose--Mg2+ method (10). Fluorescent nucleoli were found in liver cryostat sections treated with rabbit anti-human liver nucleolar antibodies followed by fluorescein-conjugated goat anti-rabbit antibodies. In HeLa cells, fluorescence was distributed throughout the nucleus and in a nuclear network but was not localized to the nucleolus. In placental cryostat sections, an overall nuclear fluorescence was observed with some localization to nucleoli. Immunodiffusion analysis revealed two immunoprecipitin bands which appeared to be liver specific. Other immunoprecipitin bands were common to liver, placenta, and HeLa nuclear extracts. Rocket immunoelectrophoresis revealed two liver-specific antigens, one migrating to the cathode and the other to the anode Other rockets exhibited identity to antigens of other nuclear extracts. These results demonstrate the presence of human liver nucleolar-specific antigens which were not found in the HeLa and placental cells.

  17. Antigen smuggling in tuberculosis.

    PubMed

    Hudrisier, Denis; Neyrolles, Olivier

    2014-06-11

    The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well established; however, how dendritic cells activate T cells in vivo remains obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report a mechanism of antigen transfer for efficient activation of antimycobacterial T cells.

  18. Antigen detection systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious agents or their constituent parts (antigens or nucleic acids) can be detected in fresh, frozen, or fixed tissue using a variety of direct or indirect assays. The assays can be modified to yield the greatest sensitivity and specificity but in most cases a particular methodology is chosen ...

  19. Differential Salmonella survival against communities of intestinal amoebae.

    PubMed

    Wildschutte, Hans; Lawrence, Jeffrey G

    2007-06-01

    Predation from intestinal amoebae may provide selective pressure for the maintenance of high genetic diversity at the Salmonella enterica rfb locus, whereby serovars better escape predators in particular environments depending on the O-antigens they express. Here, the hypothesis that amoebae from a particular intestinal environment collectively prefer one serovar over another is tested. Collections of Acanthamoeba, Tetramitus, Naegleria and Hartmannella were isolated from the intestinal tracts of several vertebrate hosts, including bullfrog tadpoles, goldfish, turtles and bearded dragons, and their feeding preferences were determined. Congeneric amoebae from the same environment had significantly similar feeding preferences. Strikingly, even unrelated amoebae - such as Naegleria and Tetramitus from goldfish - also had significantly similar feeding preferences. Yet amoebae isolated from different environments showed no similarity in prey choice. Thus, feeding preferences of amoebae appear to reflect their environment, not their taxonomic relationships. A mechanism mediating this phenotypic convergence is discussed.

  20. Microbial Ecology: Where are we now?

    PubMed Central

    2016-01-01

    Conventional microbiological methods have been readily taken over by newer molecular techniques due to the ease of use, reproducibility, sensitivity and speed of working with nucleic acids. These tools allow high throughput analysis of complex and diverse microbial communities, such as those in soil, freshwater, saltwater, or the microbiota living in collaboration with a host organism (plant, mouse, human, etc). For instance, these methods have been robustly used for characterizing the plant (rhizosphere), animal and human microbiome specifically the complex intestinal microbiota. The human body has been referred to as the Superorganism since microbial genes are more numerous than the number of human genes and are essential to the health of the host. In this review we provide an overview of the Next Generation tools currently available to study microbial ecology, along with their limitations and advantages. PMID:27975077

  1. Bioactivation of Phytoestrogens: Intestinal Bacteria and Health.

    PubMed

    Landete, J M; Arqués, J; Medina, M; Gaya, P; de Las Rivas, B; Muñoz, R

    2016-08-17

    Phytoestrogens are polyphenols similar to human estrogens found in plants or derived from plant precursors. Phytoestrogens are found in high concentration in soya, flaxseed and other seeds, fruits, vegetables, cereals, tea, chocolate, etc. They comprise several classes of chemical compounds (stilbenes, coumestans, isoflavones, ellagitannins, and lignans) which are structurally similar to endogenous estrogens but which can have both estrogenic and antiestrogenic effects. Although epidemiological and experimental evidence indicates that intake of phytoestrogens in foods may be protective against certain chronic diseases, discrepancies have been observed between in vivo and in vitro experiments. The microbial transformations have not been reported so far in stilbenes and coumestans. However, isoflavones, ellagitanins, and lignans are metabolized by intestinal bacteria to produce equol, urolithins, and enterolignans, respectively. Equol, urolithin, and enterolignans are more bioavailable, and have more estrogenic/antiestrogenic and antioxidant activity than their precursors. Moreover, equol, urolithins and enterolignans have anti-inflammatory effects and induce antiproliferative and apoptosis-inducing activities. The transformation of isoflavones, ellagitanins, and lignans by intestinal microbiota is essential to be protective against certain chronic diseases, as cancer, cardiovascular disease, osteoporosis, and menopausal symptoms. Bioavailability, bioactivity, and health effects of dietary phytoestrogens are strongly determined by the intestinal bacteria of each individual.

  2. The Intestinal Microbiota in Metabolic Disease

    PubMed Central

    Woting, Anni; Blaut, Michael

    2016-01-01

    Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet–host–microbe interactions. PMID:27058556

  3. Intestinal inflammation targets cancer-inducing activity of the microbiota

    PubMed Central

    Arthur, Janelle C.; Perez-Chanona, Ernesto; Mühlbauer, Marcus; Tomkovich, Sarah; Uronis, Joshua M.; Fan, Ting-Jia; Campbell, Barry J.; Abujamel, Turki; Dogan, Belgin; Rogers, Arlin B.; Rhodes, Jonathan M.; Stintzi, Alain; Simpson, Kenneth W.; Hansen, Jonathan J.; Keku, Temitope O.; Fodor, Anthony A.; Jobin, Christian

    2013-01-01

    Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here we identify the intestinal microbiota as a target of inflammation that impacts the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10-deficient (Il10−/−) mice. Monocolonization with the commensal Escherichia coli NC101 promoted invasive carcinoma in azoxymethane (AOM)-treated Il10−/− mice. Deletion of the polyketide synthase (pks) genotoxic island from E. coli NC101 decreased tumor multiplicity and invasion in AOM/Il10−/− mice, without altering intestinal inflammation. Mucosa-associated pks+ E. coli were found in a significantly high percentage of inflammatory bowel disease (IBD) and CRC patients. This suggests that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities. PMID:22903521

  4. The intestine is a blender

    NASA Astrophysics Data System (ADS)

    Yang, Patricia; Lamarca, Morgan; Kravets, Victoria; Hu, David

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines Contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  5. The intestine is a blender

    NASA Astrophysics Data System (ADS)

    Yang, Patricia; Lamarca, Morgan; Hu, David

    2015-11-01

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  6. Intestinal morphology of the wild Atlantic salmon (Salmo salar).

    PubMed

    Løkka, Guro; Austbø, Lars; Falk, Knut; Bjerkås, Inge; Koppang, Erling Olaf

    2013-08-01

    The worldwide-industrialized production of Atlantic salmon (Salmo salar) has increased dramatically during the last decades, followed by diseases related to the on-going domestication process as a growing concern. Even though the gastrointestinal tract seems to be a target for different disorders in farmed fish, a description of the normal intestinal status in healthy, wild salmon is warranted. Here, we provide such information in addition to suggesting a referable anatomical standardization for the intestine. In this study, two groups of wild Atlantic salmon were investigated, consisting of post smolts on feed caught in the sea and of sexually mature, starved individuals sampled from a river. The two groups represent different stages in the anadromous salmon life cycle, which also are part of the production cycle of farmed salmon. Selected regions of gastrointestinal tract were subjected to morphological investigations including immunohistochemical, scanning electron microscopic, and morphometric analyses. A morphology-based nomenclature was established, defining the cardiac part of the stomach and five different regions of the Atlantic salmon intestine, including pyloric caeca, first segment of the mid-intestine with pyloric caeca, first segment of the mid-intestine posterior to pyloric caeca, second segment of the mid-intestine and posterior intestinal segment. In each of the above described regions, for both groups of fish, morphometrical measurements and regional histological investigations were performed with regards to magnitude and direction of mucosal folding as well as the composition of the intestinal wall. Additionally, immunohistochemistry showing cells positive for cytokeratins, α-actin and proliferating cell nuclear antigen, in addition to alkaline phosphatase reactivity in the segments is presented.

  7. Intestinal and multivisceral transplantation

    PubMed Central

    Meira, Sérgio Paiva; Guardia, Bianca Della; Evangelista, Andréia Silva; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; de Almeida, Marcio Dias; Epstein, Marina Gabrielle; Pedroso, Pamella Tung; Salvalaggio, Paolo; Meirelles, Roberto Ferreira; Rocco, Rodrigo Andrey; de Almeida, Samira Scalso; de Rezende, Marcelo Bruno

    2015-01-01

    Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run. PMID:25993080

  8. Intestinal Microbiota and Its Relationship with Necrotizing Enterocolitis

    PubMed Central

    Patel, Ravi Mangal; Denning, Patricia W.

    2015-01-01

    Necrotizing enterocolitis is a leading cause of morbidity and mortality in infants born prematurely. After birth, the neonatal gut must acquire a healthy complement of commensal bacteria. Disruption or delay of this critical process, leading to deficient or abnormal microbial colonization of the gut, has been implicated as key risk factor in the pathogenesis of NEC. Conversely, a beneficial complement of commensal intestinal microbiota may protect the immature gut from inflammation and injury. Interventions aimed at providing or restoring a healthy complement of commensal bacteria, such as probiotic therapy, are currently the most promising treatment to prevent NEC. Shifting the balance of intestinal microbiota from a pathogenic to protective complement of bacteria can protect the gut from inflammation and subsequent injury that leads to NEC. Herein, we review the relationship of intestinal microbiota and NEC in preterm infants. PMID:25992911

  9. Immune Responses to Intestinal Microbes in Inflammatory Bowel Diseases.

    PubMed

    Hansen, Jonathan J

    2015-10-01

    Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are characterized by chronic, T-cell-mediated inflammation of the gastrointestinal tract that can cause significant, lifelong morbidity. Data from both human and animal studies indicate that IBDs are likely caused by dysregulated immune responses to resident intestinal microbes. Certain products from mycobacteria, fungi, and Clostridia stimulate increased effector T cell responses during intestinal inflammation, whereas other bacterial products from Clostridia and Bacteroides promote anti-inflammatory regulatory T cell responses. Antibody responses to bacterial and fungal components may help predict the severity of IBDs. While most currently approved treatments for IBDs generally suppress the patient's immune system, our growing understanding of microbial influences in IBDs will likely lead to the development of new diagnostic tools and therapies that target the intestinal microbiota.

  10. 3-D Intestinal Scaffolds for Evaluating the Therapeutic Potential of Probiotics

    PubMed Central

    2015-01-01

    Biomimetic in vitro intestinal models are becoming useful tools for studying host–microbial interactions. In the past, these models have typically been limited to simple cultures on 2-D scaffolds or Transwell inserts, but it is widely understood that epithelial cells cultured in 3-D environments exhibit different phenotypes that are more reflective of native tissue, and that different microbial species will preferentially adhere to select locations along the intestinal villi. We used a synthetic 3-D tissue scaffold with villous features that could support the coculture of epithelial cell types with select bacterial populations. Our end goal was to establish microbial niches along the crypt–villus axis in order to mimic the natural microenvironment of the small intestine, which could potentially provide new insights into microbe-induced intestinal disorders, as well as enabling targeted probiotic therapies. We recreated the surface topography of the small intestine by fabricating a biodegradable and biocompatible villous scaffold using poly lactic-glycolic acid to enable the culture of Caco-2 with differentiation along the crypt–villus axis in a similar manner to native intestines. This was then used as a platform to mimic the adhesion and invasion profiles of both Salmonella and Pseudomonas, and assess the therapeutic potential of Lactobacillus and commensal Escherichia coli in a 3-D setting. We found that, in a 3-D environment, Lactobacillus is more successful at displacing pathogens, whereas Nissle is more effective at inhibiting pathogen adhesion. PMID:24798584

  11. Involvement of Reduced Microbial Diversity in Inflammatory Bowel Disease

    PubMed Central

    Gong, Xiaojie; Wang, Lili; Yu, Xinjuan

    2016-01-01

    A considerable number of studies have been conducted to study the microbial profiles in inflammatory conditions. A common phenomenon in inflammatory bowel disease (IBD) is the reduction of the diversity of microbiota, which demonstrates that microbial diversity negatively correlates with disease severity in IBD. Increased microbial diversity is known to occur in disease remission. Species diversity plays an important role in maintaining the stability of the intestinal ecosystem as well as normal ecological function. A reduction in microbial diversity corresponds to a decrease in the stability of the ecosystem and can impair ecological function. Fecal microbiota transplantation (FMT), probiotics, and prebiotics, which aim to modulate the microbiota and restore its normal diversity, have been shown to be clinically efficacious. In this study, we hypothesized that a reduction in microbial diversity could play a role in the development of IBD. PMID:28074093

  12. Intestinal anisakidosis (anisakiosis).

    PubMed

    Takei, Hidehiro; Powell, Suzanne Z

    2007-10-01

    A case of intestinal anisakidosis in a 42-year-old man in Japan is presented. His chief complaint was an acute onset of severe abdominal pain. Approximately 12 hours before the onset of this symptom, he had eaten sliced raw mackerel ("sashimi"). Upper endoscopy was unremarkable. At exploratory laparotomy, an edematous, diffusely thickened segment of jejunum was observed, which was resected. The postoperative course was uneventful. The segment of small intestine showed a granular indurated area on the mucosal surface, and microscopically, a helminthic larva penetrating the intestinal wall, which was surrounded by a cuff of numerous neutrophils and eosinophils, as well as diffuse acute serositis. A cross section of the larva revealed the internal structures, pathognomonic of Anisakis simplex. Although anisakidosis is rare in the United States, with the increasing popularity of Japanese cuisine, the incidence is expected to increase, and pathologists should be familiar with this disease.

  13. Phenotypic and functional profiles of CRIg (Z39Ig)-expressing macrophages in the large intestine.

    PubMed

    Tanaka, Masashi; Nagai, Taku; Usami, Makoto; Hasui, Kazuhisa; Takao, Sonshin; Matsuyama, Takami

    2012-04-01

    Intestinal macrophages (Mφ) play significant roles in maintaining homeostasis by the efficient elimination of foreign particles in the large intestine. However, functional complement receptors have not been fully identified. In this study, we showed that a complement receptor of the Ig superfamily (CRIg, also known as Z39Ig), a receptor for complement fragments (C3b and iC3b), was expressed on a subset of intestinal M in murine and human large intestine. When abilities of uptake of antigens of murine CRIg(+) Mφ were examined, intestinal CRIg(+) Mφ displayed less endocytic and similar phagocytic abilities compared to resident peritoneal F4/80(+)CRIg(-) Mφ and F4/80(+)CRIg(+) Mφ. Additionally, we found that a significant portion of C3b-dependent phagocytosis by large intestinal M involves CRIg, emphasizing the importance of efficient mechanisms to eliminate foreign particles in the large intestine. On the other hand, intestinal Mφ from 2,4,6-trinitrobenzene sulfonic acid-treated mice had decreased CRIg expression but increased CD11b expression, implying some contribution to the removal of immune complexes. This study will shed new light on opsonization and phagocytosis by large intestinal Mφ.

  14. Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens

    PubMed Central

    Awad, Wageha A.; Hess, Claudia; Hess, Michael

    2017-01-01

    Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs) are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction’s molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as “leaky gut”. A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins) via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis, because some pathogens

  15. Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens.

    PubMed

    Awad, Wageha A; Hess, Claudia; Hess, Michael

    2017-02-10

    Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird's health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs) are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction's molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as "leaky gut". A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins) via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis, because some pathogens can

  16. Intestinal microbiota and ulcerative colitis.

    PubMed

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota.

  17. Small intestine contrast injection (image)

    MedlinePlus

    ... and throat, through the stomach into the small intestine. When in place, contrast dye is introduced and ... means of demonstrating whether or not the small intestine is normal when abnormality is suspected.

  18. Intestinal Failure (Short Bowel Syndrome)

    MedlinePlus

    ... N Vitamin deficiencies as a result of poor absorption in the intestine N Electrolyte and mineral deficiencies ... N Kidney stones or gallstones due to poor absorption of calcium or bile How is intestinal failure ...

  19. Small intestine aspirate and culture

    MedlinePlus

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  20. [Intestinal microbiocenosis in children with intestinal enzymopathy].

    PubMed

    Kamilova, A T; Akhmedov, N N; Pulatova, D B; Nurmatov, B A

    2001-01-01

    141 children with different kinds of intestinal enzymopathy were examined; of these, 33 had celiac disease, 39--the syndrome of celiac disease, 12--congenital lactase deficiency and 57--the syndrome of disaccharidase insufficiency. In these patients a significant decrease in the average characteristics of the main protective flora and the growth of hemolytic and lactose-negative enterobacteria were established. In all groups of patients increased amounts of Proteus were detected, which was indicative of profound dysbiosis. The content of bifidobacteria was found to be decreased in 89.5-97% of the patients and the content of lactic acid bacteria, in 15.8-33.3%. The decreased content of Escherichia coli with normal enzymatic activity (less than 10(7) colony-forming units) was noted in one-third of the patients with the syndrome of celiac disease and congenital lactase deficiency, in about a half of the patients with the syndrome of disaccharidase insufficiency and least of all in patients with celiac disease (9.1%). The association of opportunistic microbes was detected in 15.6% of the patients, more often in those with celiac disease, the syndrome of celiac disease and congenital lactase deficiency. The severity of disturbances in intestinal eubiosis was found to depend on the gravity of the patients' state.

  1. [Effect of lactobacillus and bifidobacteria preparations on the intestinal microflora of mice irradiated with gamma quanta].

    PubMed

    Korshunov, V M; Kissina, E V; Ikonnikova, T B; Mal'tsev, V N; Goncharova, G I

    1980-06-01

    Lactobacilli (strain B12G) and bifidobacteria (strain 75-41), administered orally in a dose of 5 x 10 cells to CBA mice on days 1, 3, 5 and 10 after irradiation with gamma quanta in a dose of 700 rad, restored the "eubiosis" of the intestinal tract, specifically suppressing opportunistic bacteria and facilitating the normalization of the quantitative and qualitative correlation between microbial associations constituting the obligatory intestinal flora. For one thing, the preparations of lactobacilli and bifidobacteria, used for treatment, restored the amount of lactobacilli in the intestinal tract of the irradiated animals to the level, characteristic of the intact animals; for another, these preparations prevented the dissemination of Escherichia, Proteus, Enterococcus in the small intestine and considerably decreased the amount of these microorganisms, as well as Clostridium, in the large intestine.

  2. SEROLOGICAL INTERRELATIONSHIPS BETWEEN THE PLAGUE MICROBE AND BACTERIA OF THE INTESTINAL GROUP

    DTIC Science & Technology

    31 cases (8.9%). Plague serum agglutinated 46 cultures of enterobacteria from various species out of 165 checked (27.8%). In the tests of the cross...microbe and enterobacteria . The presence in strains of P. pestis of antigens which are inherent to bacteria of the intestinal group was not connected with

  3. Stability and activity of an Enterobacter aerogenes-specific bacteriophage under simulated gastro-intestinal conditions.

    PubMed

    Verthé, K; Possemiers, S; Boon, N; Vaneechoutte, M; Verstraete, W

    2004-09-01

    A bacteriophage, designated UZ1 and showing lytic activity against a clinically important strain (BE1) of Enterobacter aerogenes was isolated from hospital sewage. The stability and lytic activity against this strain under simulated gastro-intestinal conditions was evaluated. After addition of bacteriophage UZ1 to a liquid feed at gastric pH 2, the phage was immediately inactivated and could not be recovered. However, by use of an antacid to neutralize stomach acidity, no significant changes in phage titer were observed after 2 h incubation at 37 degrees C. After supplementing pancreatic juice and further incubation for 4 h, the phage titer remained stable. The persistence of UZ1 in a mixed microbial ecosystem that was representative for the large intestine was monitored using an in vitro simulation of the human intestinal microbial ecosystem. A pulse administration of bacteriophage UZ1 at a concentration of 10(5) plaque-forming units (PFU)/ml to reactor 3 (which simulates the ascending colon) showed that, in the absence of the host, bacteriophage UZ1 persisted for 13 days in the simulated colon, while the theoretical washout was calculated at 16 days. To assess its lytic activity in an intestinal microbial ecosystem, a green fluorescent protein (gfp)-labeled E. aerogenes BE1 strain was constructed and gfp-specific primers were designed in order to quantify the host strain using real-time PCR. It was observed that bacteriophage UZ1 was able to replicate and showed lytic activity against E. aerogenes BE1/ gfp in an intestinal microbial ecosystem. Indeed, after 17 h a 2 log unit reduction of E. aerogenes BE1/ gfp was measured as compared with the assay without bacteriophage UZ1, while the phage titer increased by 2 log units at an initial multiplicity of infection of 0.07 PFU/colony-forming unit. This is the first report of an in vitro model to study bacteriophage activity in the complex intestinal microbial community.

  4. Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity

    PubMed Central

    Chng, Song Hui; Kundu, Parag; Dominguez-Brauer, Carmen; Teo, Wei Ling; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki; Mak, Tak Wah; Pettersson, Sven

    2016-01-01

    Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity. PMID:27068235

  5. Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity.

    PubMed

    Chng, Song Hui; Kundu, Parag; Dominguez-Brauer, Carmen; Teo, Wei Ling; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki; Mak, Tak Wah; Pettersson, Sven

    2016-04-12

    Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity.

  6. The Neuromodulation of the Intestinal Immune System and Its Relevance in Inflammatory Bowel Disease

    PubMed Central

    Di Giovangiulio, Martina; Verheijden, Simon; Bosmans, Goele; Stakenborg, Nathalie; Boeckxstaens, Guy E.; Matteoli, Gianluca

    2015-01-01

    One of the main tasks of the immune system is to discriminate and appropriately react to “danger” or “non-danger” signals. This is crucial in the gastrointestinal tract, where the immune system is confronted with a myriad of food antigens and symbiotic microflora that are in constant contact with the mucosa, in addition to any potential pathogens. This large number of antigens and commensal microflora, which are essential for providing vital nutrients, must be tolerated by the intestinal immune system to prevent aberrant inflammation. Hence, the balance between immune activation versus tolerance should be tightly regulated to maintain intestinal homeostasis and to prevent immune activation indiscriminately against all luminal antigens. Loss of this delicate equilibrium can lead to chronic activation of the intestinal immune response resulting in intestinal disorders, such as inflammatory bowel diseases (IBD). In order to maintain homeostasis, the immune system has evolved diverse regulatory strategies including additional non-immunological actors able to control the immune response. Accumulating evidence strongly indicates a bidirectional link between the two systems in which the brain modulates the immune response via the detection of circulating cytokines and via direct afferent input from sensory fibers and from enteric neurons. In the current review, we will highlight the most recent findings regarding the cross-talk between the nervous system and the mucosal immune system and will discuss the potential use of these neuronal circuits and neuromediators as novel therapeutic tools to reestablish immune tolerance and treat intestinal chronic inflammation. PMID:26635804

  7. The Neuromodulation of the Intestinal Immune System and Its Relevance in Inflammatory Bowel Disease.

    PubMed

    Di Giovangiulio, Martina; Verheijden, Simon; Bosmans, Goele; Stakenborg, Nathalie; Boeckxstaens, Guy E; Matteoli, Gianluca

    2015-01-01

    One of the main tasks of the immune system is to discriminate and appropriately react to "danger" or "non-danger" signals. This is crucial in the gastrointestinal tract, where the immune system is confronted with a myriad of food antigens and symbiotic microflora that are in constant contact with the mucosa, in addition to any potential pathogens. This large number of antigens and commensal microflora, which are essential for providing vital nutrients, must be tolerated by the intestinal immune system to prevent aberrant inflammation. Hence, the balance between immune activation versus tolerance should be tightly regulated to maintain intestinal homeostasis and to prevent immune activation indiscriminately against all luminal antigens. Loss of this delicate equilibrium can lead to chronic activation of the intestinal immune response resulting in intestinal disorders, such as inflammatory bowel diseases (IBD). In order to maintain homeostasis, the immune system has evolved diverse regulatory strategies including additional non-immunological actors able to control the immune response. Accumulating evidence strongly indicates a bidirectional link between the two systems in which the brain modulates the immune response via the detection of circulating cytokines and via direct afferent input from sensory fibers and from enteric neurons. In the current review, we will highlight the most recent findings regarding the cross-talk between the nervous system and the mucosal immune system and will discuss the potential use of these neuronal circuits and neuromediators as novel therapeutic tools to reestablish immune tolerance and treat intestinal chronic inflammation.

  8. Leukocyte Trafficking to the Small Intestine and Colon.

    PubMed

    Habtezion, Aida; Nguyen, Linh P; Hadeiba, Husein; Butcher, Eugene C

    2016-02-01

    Leukocyte trafficking to the small and large intestines is tightly controlled to maintain intestinal immune homeostasis, mediate immune responses, and regulate inflammation. A wide array of chemoattractants, chemoattractant receptors, and adhesion molecules expressed by leukocytes, mucosal endothelium, epithelium, and stromal cells controls leukocyte recruitment and microenvironmental localization in intestine and in the gut-associated lymphoid tissues (GALTs). Naive lymphocytes traffic to the gut-draining mesenteric lymph nodes where they undergo antigen-induced activation and priming; these processes determine their memory/effector phenotypes and imprint them with the capacity to migrate via the lymph and blood to the intestines. Mechanisms of T-cell recruitment to GALT and of T cells and plasmablasts to the small intestine are well described. Recent advances include the discovery of an unexpected role for lectin CD22 as a B-cell homing receptor GALT, and identification of the orphan G-protein-coupled receptor 15 (GPR15) as a T-cell chemoattractant/trafficking receptor for the colon. GPR15 decorates distinct subsets of T cells in mice and humans, a difference in species that could affect translation of the results of mouse colitis models to humans. Clinical studies with antibodies to integrin α4β7 and its vascular ligand mucosal vascular addressin cell adhesion molecule 1 are proving the value of lymphocyte trafficking mechanisms as therapeutic targets for inflammatory bowel diseases. In contrast to lymphocytes, cells of the innate immune system express adhesion and chemoattractant receptors that allow them to migrate directly to effector tissue sites during inflammation. We review the mechanisms for innate and adaptive leukocyte localization to the intestinal tract and GALT, and discuss their relevance to human intestinal homeostasis and inflammation.

  9. Glycan complexity dictates microbial resource allocation in the large intestine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The structure of the human gut microbiota, which impacts on the health of the host, is controlled by complex dietary carbohydrates and members of the Bacteroidetes phylum are the major contributors to the degradation of complex dietary carbohydrates. The extent to which complex dietary carbohydrates...

  10. Glycan complexity dictates microbial resource allocation in the large intestine

    PubMed Central

    Rogowski, Artur; Briggs, Jonathon A.; Mortimer, Jennifer C.; Tryfona, Theodora; Terrapon, Nicolas; Lowe, Elisabeth C.; Baslé, Arnaud; Morland, Carl; Day, Alison M.; Zheng, Hongjun; Rogers, Theresa E.; Thompson, Paul; Hawkins, Alastair R.; Yadav, Madhav P.; Henrissat, Bernard; Martens, Eric C.; Dupree, Paul; Gilbert, Harry J.; Bolam, David N.

    2015-01-01

    The structure of the human gut microbiota is controlled primarily through the degradation of complex dietary carbohydrates, but the extent to which carbohydrate breakdown products are shared between members of the microbiota is unclear. We show here, using xylan as a model, that sharing the breakdown products of complex carbohydrates by key members of the microbiota, such as Bacteroides ovatus, is dependent on the complexity of the target glycan. Characterization of the extensive xylan degrading apparatus expressed by B. ovatus reveals that the breakdown of the polysaccharide by the human gut microbiota is significantly more complex than previous models suggested, which were based on the deconstruction of xylans containing limited monosaccharide side chains. Our report presents a highly complex and dynamic xylan degrading apparatus that is fine-tuned to recognize the different forms of the polysaccharide presented to the human gut microbiota. PMID:26112186

  11. Photoaffinity antigens for human γδ T cells1

    PubMed Central

    Sarikonda, Ghanashyam; Wang, Hong; Puan, Kia-Joo; Liu, Xiao-hui; Lee, Hoi K.; Song, Yongcheng; Distefano, Mark D.; Oldfield, Eric; Prestwich, Glenn D.; Morita, Craig T.

    2009-01-01

    Vγ2Vδ2 T cells comprise the major subset of peripheral blood γ δ T cells in humans and expand during infections by recognizing small, nonpeptide prenyl pyrophosphates. These molecules include (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMBPP), a microbial isoprenoid intermediate, and isopentenyl pyrophosphate (IPP), an endogenous isoprenoid intermediate. Recognition of these nonpeptide antigens is mediated by the Vγ2Vδ2 T cell antigen receptor (TCR). Several findings suggest that prenyl pyrophosphates are presented by an antigen presenting molecule: contact between T cells and APCs is required; the antigens do not bind the Vγ2Vδ2 TCR directly; and antigen recognition is abrogated by TCR mutations in CDRs distant from the putative antigen recognition site. Identification of the putative antigen presenting molecule, however, has been hindered by the inability to achieve stable association of nonpeptide prenyl pyrophosphate antigens with the presenting molecule. In this study, we show that photoaffinity analogs of HMBPP, meta/para-benzophenone-(methylene)-prenyl pyrophosphates (m/p-BZ-(C)-C5-OPP), can cross-link to the surface of tumor cell lines and be presented as antigens to γ δ T cells. Mutant tumor cell lines lacking MHC class I, MHC class II, β2-microglobulin, and CD1, as well as tumor cell lines from a variety of tissues and individuals, will all crosslink to and present m-BZ-C5-OPP. Finally, pulsing of BZ-(C)-C5-OPP is inhibited by IPP and an inactive analog, suggesting that they bind to the same molecule. Taken together, these results suggest that nonpeptide antigens are presented by a novel antigen presenting molecule that is widely distributed, non-polymorphic, but not classical MHC class I, MHC class II, or CD1. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript

  12. Murine intestinal antibody response to heterologous rotavirus infection.

    PubMed Central

    Merchant, A A; Groene, W S; Cheng, E H; Shaw, R D

    1991-01-01

    Rotavirus is the most important worldwide cause of severe gastroenteritis. Extensive efforts have been devoted to the design of a vaccine that will prevent disease, but development of a more effective vaccine strategy may require progress in the understanding of the mucosal immune response to replicating viral antigens. In this article, we report the characterization of the intestinal antibody response of a murine model to heterologous infection with the rhesus rotavirus vaccine strain. We have adapted the enzyme-linked immunospot assay to measure this response without the difficulties associated with measurement of antibodies in intestinal contents or the artifacts associated with culturing of lymphocytes. The predominant response in terms of antibody-secreting cells (ASC) is seen in the small intestine lamina propria, which can be measured within 4 days of infection, peaks 3 weeks after infection, and remains near that level for longer than 8 weeks. The magnitude of the immunoglobulin A (IgA) cell response is approximately 10 times greater than the intestinal IgG cell response, and IgM cells are rare. Virus-specific ASC constitute approximately 50% of all ASC in the gut at the peak of the virus-specific response. This response is considerably greater than responses to nonreplicating mucosal antigens measured by similar techniques. Enteral infection engenders minimal virus-specific ASC response in the spleen. Rhesus rotavirus-specific enzyme-linked immunosorbent assay and neutralization assays of serum and intestinal contents did not correlate with virus-specific ASC response. Images PMID:1761691

  13. RNAi screen for kinases and phosphatases that play a role in antigen presentation by dendritic cells.

    PubMed

    Moita, Catarina F; Chora, Ângelo; Hacohen, Nir; Moita, Luis F

    2012-07-01

    Effective CD8(+) T-cell responses against tumor or microbial antigens that are not directly expressed in antigen-presenting cells (APCs) depend on the cross-presentation of these antigens on MHC class I in APCs. To identify signaling molecules that regulate cross-presentation, we used lentiviral-based RNA interference to test the roles of hundreds of kinases and phosphatases in this process. Our study uncovered eight previously unknown genes, consisting of one positive and seven negative regulators of antigen cross-presentation. Depletion of Acvr1c, a type I receptor for TGF-β family of signaling molecules, led to an increase in CD80 and CD86 co-stimulator surface expression and secreted IL-12 in mouse bone marrow-derived DCs, as well as antigen-specific T-cell proliferation.

  14. Anaerobic respiration of Escherichia coli in the mouse intestine.

    PubMed

    Jones, Shari A; Gibson, Terri; Maltby, Rosalie C; Chowdhury, Fatema Z; Stewart, Valley; Cohen, Paul S; Conway, Tyrrell

    2011-10-01

    The intestine is inhabited by a large microbial community consisting primarily of anaerobes and, to a lesser extent, facultative anaerobes, such as Escherichia coli, which we have shown requires aerobic respiration to compete successfully in the mouse intestine (S. A. Jones et al., Infect. Immun. 75:4891-4899, 2007). If facultative anaerobes efficiently lower oxygen availability in the intestine, then their sustained growth must also depend on anaerobic metabolism. In support of this idea, mutants lacking nitrate reductase or fumarate reductase have extreme colonization defects. Here, we further explore the role of anaerobic respiration in colonization using the streptomycin-treated mouse model. We found that respiratory electron flow is primarily via the naphthoquinones, which pass electrons to cytochrome bd oxidase and the anaerobic terminal reductases. We found that E. coli uses nitrate and fumarate in the intestine, but not nitrite, dimethyl sulfoxide, or trimethylamine N-oxide. Competitive colonizations revealed that cytochrome bd oxidase is more advantageous than nitrate reductase or fumarate reductase. Strains lacking nitrate reductase outcompeted fumarate reductase mutants once the nitrate concentration in cecal mucus reached submillimolar levels, indicating that fumarate is the more important anaerobic electron acceptor in the intestine because nitrate is limiting. Since nitrate is highest in the absence of E. coli, we conclude that E. coli is the only bacterium in the streptomycin-treated mouse large intestine that respires nitrate. Lastly, we demonstrated that a mutant lacking the NarXL regulator (activator of the NarG system), but not a mutant lacking the NarP-NarQ regulator, has a colonization defect, consistent with the advantage provided by NarG. The emerging picture is one in which gene regulation is tuned to balance expression of the terminal reductases that E. coli uses to maximize its competitiveness and achieve the highest possible population in

  15. Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation

    PubMed Central

    Kato, Karin; Nagao, Miki; Miyamoto, Kentaro; Oka, Kentaro; Takahashi, Motomichi; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Uemoto, Shinji; Ichiyama, Satoshi

    2017-01-01

    Background Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. Methods We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. Results Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. Conclusions The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.

  16. Metagenomic insights into tetracycline effects on microbial community and antibiotic resistance of mouse gut.

    PubMed

    Yin, Jinbao; Zhang, Xu-Xiang; Wu, Bing; Xian, Qiming

    2015-12-01

    Antibiotics have been widely used for disease prevention and treatment of the human and animals, and for growth promotion in animal husbandry. Antibiotics can disturb the intestinal microbial community, which play a fundamental role in animals' health. Misuse or overuse of antibiotics can result in increase and spread of microbial antibiotic resistance, threatening human health and ecological safety. In this study, we used Illumina Hiseq sequencing, (1)H nuclear magnetic resonance spectroscopy and metagenomics approaches to investigate intestinal microbial community shift and antibiotic resistance alteration of the mice drinking the water containing tetracycline hydrochloride (TET). Two-week TET administration caused reduction of gut microbial diversity (from 194 to 89 genera), increase in Firmicutes abundance (from 24.9 to 39.8%) and decrease in Bacteroidetes abundance (from 69.8 to 51.2%). Metagenomic analysis showed that TET treatment affected the intestinal microbial functions of carbohydrate, ribosomal, cell wall/membrane/envelope and signal transduction, which is evidenced by the alteration in the metabolites of mouse serum. Meanwhile, in the mouse intestinal microbiota, TET treatment enhanced the abundance of antibiotic resistance genes (ARGs) (from 307.3 to 1492.7 ppm), plasmids (from 425.4 to 3235.1 ppm) and integrons (from 0.8 to 179.6 ppm) in mouse gut. Our results indicated that TET administration can disturb gut microbial community and physiological metabolism of mice, and increase the opportunity of ARGs and mobile genetic elements entering into the environment with feces discharge.

  17. Immune recognition of protein antigens

    SciTech Connect

    Laver, W.G.; Air, G.M.

    1985-01-01

    This book contains 33 papers. Some of the titles are: Antigenic Structure of Influenze Virus Hemagglutinin; Germ-line and Somatic Diversity in the Antibody Response to the Influenza Virus A/PR/8/34 Hemagglutinin; Recognition of Cloned Influenza A Virus Gene Products by Cytotoxic T Lymphocytes; Antigenic Structure of the Influenza Virus N2 Neuraminidase; and The Molecular and Genetic Basis of Antigenic Variation in Gonococcal Pillin.

  18. Chemically induced mouse models of intestinal inflammation.

    PubMed

    Wirtz, Stefan; Neufert, Clemens; Weigmann, Benno; Neurath, Markus F

    2007-01-01

    Animal models of intestinal inflammation are indispensable for our understanding of the pathogenesis of Crohn disease and ulcerative colitis, the two major forms of inflammatory bowel disease in humans. Here, we provide protocols for establishing murine 2,4,6-trinitro benzene sulfonic acid (TNBS)-, oxazolone- and both acute and chronic dextran sodium sulfate (DSS) colitis, the most widely used chemically induced models of intestinal inflammation. In the former two models, colitis is induced by intrarectal administration of the covalently reactive reagents TNBS/oxazolone, which are believed to induce a T-cell-mediated response against hapten-modified autologous proteins/luminal antigens. In the DSS model, mice are subjected several days to drinking water supplemented with DSS, which seems to be directly toxic to colonic epithelial cells of the basal crypts. The procedures for the hapten models of colitis and acute DSS colitis can be accomplished in about 2 weeks but the protocol for chronic DSS colitis takes about 2 months.

  19. Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease.

    PubMed

    Wang, Zi-Kai; Yang, Yun-Sheng; Chen, Ye; Yuan, Jing; Sun, Gang; Peng, Li-Hua

    2014-10-28

    The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.

  20. Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease

    PubMed Central

    Wang, Zi-Kai; Yang, Yun-Sheng; Chen, Ye; Yuan, Jing; Sun, Gang; Peng, Li-Hua

    2014-01-01

    The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models. PMID:25356041

  1. Probiotic Bacillus pumilus SE5 shapes the intestinal microbiota and mucosal immunity in grouper Epinephelus coioides.

    PubMed

    Yang, Hong-Ling; Xia, Han-Qin; Ye, Yi-Dan; Zou, Wen-Chao; Sun, Yun-Zhang

    2014-09-30

    The health benefits of probiotics are thought to occur, at least in part, through an improved intestinal microbial balance in fish, although the molecular mechanisms whereby probiotics modulate the intestinal microbiota by means of activation of mucosal immunity are rarely explored. In this study, the effects of viable and heat-inactivated probiotic Bacillus pumilus SE5 on the intestinal dominant microbial community and mucosal immune gene expression were evaluated. The fish were fed for 60 d with 3 different diets: control (without probiotic), and diets T1 and T2 supplemented with 1.0 × 10⁸ cells g⁻¹ viable and heat-inactivated B. pumilus SE5, respectively. Upregulated expression of TLR1, TLR2 and IL-8, but not MyD88 was observed in fish fed the viable probiotic, while elevated expression of TLR2, IL-8 and TGF-β1, but not MyD88 was observed in fish fed the heat-inactivated B. pumilus SE5. The induced activation of intestinal mucosal immunity, especially the enhanced expression of antibacterial epinecidin-1, was consistent with the microbial data showing that several potentially pathogenic bacterial species such as Psychroserpens burtonensis and Pantoea agglomerans were suppressed by both the viable and heat-inactivated probiotic B. pumilus SE5. These results lay the foundation for future studies on the molecular interactions between probiotics, intestinal microbiota and mucosal immunity in fish.

  2. A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

    PubMed Central

    Murata, Makoto; Warren, Edus H.; Riddell, Stanley R.

    2003-01-01

    Minor histocompatibility antigens (minor H antigens) are targets of graft-versus-host disease and graft-versus-leukemia responses after allogeneic human leukocyte antigen identical hematopoietic stem cell transplantation. Only a few human minor H antigens have been molecularly characterized and in all cases, amino acid differences between homologous donor and recipient proteins due to nucleotide polymorphisms in the respective genes were responsible for immunogenicity. Here, we have used cDNA expression cloning to identify a novel human minor H antigen encoded by UGT2B17, an autosomal gene in the multigene UDP-glycosyltransferase 2 family that is selectively expressed in liver, intestine, and antigen-presenting cells. In contrast to previously defined human minor H antigens, UGT2B17 is immunogenic because of differential expression of the protein in donor and recipient cells as a consequence of a homozygous gene deletion in the donor. Deletion of individual members of large gene families is a common form of genetic variation in the population and our results provide the first evidence that differential protein expression as a consequence of gene deletion is a mechanism for generating minor H antigens in humans. PMID:12743171

  3. PARSING THE ALLOCHTHONOUS FROM THE AUTOCHTHONOUS FUNGAL BIOTA IN THE POULTRY INTESTINE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Examination of intestinal microbial communities is complicated by the presence of both autochthonous (natively colonizing) and allochthonous (transient) taxa. To examine community dynamics in poultry ceca an experiment was performed in which day-old turkeys were housed in isolators on raised wire f...

  4. Unusual intestinal talcosis.

    PubMed

    Anani, P A; Ribaux, C; Gardiol, D

    1987-11-01

    A case of intestinal talcosis in a 46-year-old man is reported. At the age of 27, the patient was treated for pulmonary tuberculosis with tablets containing talc (183 g talc per 2,670 g total drug intake) over a period of 28 months. Eighteen years later, the patient was hospitalized for abdominal pain that remained refractory to antacids; he subsequently underwent a right hemicolectomy. Light-microscopic examination revealed a prominent fibrosis of the intestinal wall in which birefringent particles were demonstrated by polarized light. Using energy-dispersive spectroscopy, an analysis of these particles showed that they were predominantly composed of silicon and magnesium as well as small amounts of phosphorus, sulphur, calcium, and iron--the spectrum typically associated with talc. We believe that the source of this talc is the tablets ingested by the patient during prior antituberculosis therapy.

  5. Membrane Lipid Interactions in Intestinal Ischemia/reperfusion-induced Injury

    PubMed Central

    Slone, Emily Archer; Fleming, Sherry D.

    2014-01-01

    Ischemia, lack of blood flow, and reperfusion, return of blood flow, is a common phenomenon affecting millions of Americans each year. Roughly 30,000 Americans per year experience intestinal ischemia-reperfusion (IR), which is associated with a high mortality rate. Previous studies of the intestine established a role for neutrophils, eicosanoids, the complement system and naturally occurring antibodies in IR-induced pathology. Furthermore, data indicate involvement of a lipid or lipid-like moiety in mediating IR-induced damage. It has been proposed that exposure of neo-antigens are recognized by antibodies, triggering action of the complement cascade. While it is evident that the pathophysiology of IR-induced injury is complex and multi-factorial, we focus this review on the involvement of eicosanoids, phospholipids and neo-antigens in the early pathogenesis. Lipid changes occurring in response to IR, neo-antigens exposed and the role of a phospholipid transporter, phospholipid scramblase 1 will be discussed. PMID:24814240

  6. Elenoside increases intestinal motility

    PubMed Central

    Navarro, E; Alonso, SJ; Navarro, R; Trujillo, J; Jorge, E

    2006-01-01

    AIM: To study the effects of elenoside, an arylnaph-thalene lignan from Justicia hyssopifolia, on gastro-intestinal motility in vivo and in vitro in rats. METHODS: Routine in vivo experimental assessments were catharsis index, water percentage of boluses, intestinal transit, and codeine antagonism. The groups included were vehicle control (propylene glycol-ethanol-plant oil-tween 80), elenoside (i.p. 25 and 50 mg/kg), cisapride (i.p. 10 mg/kg), and codeine phosphate (intragastric route, 50 mg/kg). In vitro approaches used isolated rat intestinal tissues (duodenum, jejunum, and ileum). The effects of elenoside at concentrations of 3.2 x 10-4, 6.4 x 10-4 and 1.2 x 10-3 mol/L, and cisapride at 10-6 mol/L were investigated. RESULTS: Elenoside in vivo produced an increase in the catharsis index and water percentage of boluses and in the percentage of distance traveled by a suspension of activated charcoal. Codeine phosphate antagonized the effect of 25 mg/kg of elenoside. In vitro, elenoside in duodenum, jejunum and ileum produced an initial decrease in the contraction force followed by an increase. Elenoside resulted in decreased intestinal frequency in duodenum, jejunum, and ileum. The in vitro and in vivo effects of elenoside were similar to those produced by cisapride. CONCLUSION: Elenoside is a lignan with an action similar to that of purgative and prokinetics drugs. Elenoside, could be an alternative to cisapride in treatment of gastrointestinal diseases as well as a preventive therapy for the undesirable gastrointestinal effects produced by opioids used for mild to moderate pain. PMID:17131476

  7. The antigenic repertoire of premalignant and high-risk lesions.

    PubMed

    Marquez, Juan Pablo; Stanton, Sasha E; Disis, Mary L

    2015-04-01

    Prophylactic vaccines have been a major advance in preventing the development of infections after exposure to pathogens. When contemplating an effective approach to cancer prevention, vaccines offer unique advantages over other more standard approaches: First, once appropriately stimulated, antigen-specific T cells will travel to all sites of disease and eradicate cells bearing the proteins to which the T cells have been primed by vaccination. Second, successful immunization will further result in the development of immunologic memory, providing lifelong immunologic surveillance. There is evidence of an adaptive tumor immune infiltrate even at the earliest stages of breast and colon cancer development. Furthermore, there is measurable immunity to lesion-associated antigens present in patients who will eventually develop malignancy even before cancer is clinically evident. Recent studies are beginning to unmask the preinvasive antigenic repertoire for these two malignancies. Preliminary experiments in transgenic mouse models of mammary and intestinal tumors suggest that immunization against antigens expressed in preinvasive and high-risk lesions may be effective in preventing the development of invasive malignancy.

  8. The allometry of rodent intestines.

    PubMed

    Lovegrove, Barry G

    2010-06-01

    This study examined the allometry of the small intestine, caecum, colon and large intestine of rodents (n = 51) using a phylogenetically informed approach. Strong phylogenetic signal was detected in the data for the caecum, colon and large intestine, but not for the small intestine. Most of the phylogenetic signal could be attributed to clade effects associated with herbivorous versus omnivorous rodents. The herbivorous rodents have longer caecums, colons and large intestines, but their small intestines, with the exception of the desert otomyine rodents, are no different to those of omnivorous rodents. Desert otomyine rodents have significantly shorter small intestines than all other rodents, reflecting a possible habitat effect and providing a partial explanation for the low basal metabolic rates of small desert mammals. However, the desert otomyines do not have shorter colons or large intestines, challenging claims for adaptation to water retention in arid environments. Data for the Arvicolidae revealed significantly larger caecums and colons, and hence longer large intestines, with no compensatory reduction in the length of the small intestine, which may explain how the smallest mammalian herbivores manage to meet the demands of a very high mass-specific metabolic rate. This study provides phylogenetically corrected allometries suitable for future prediction testing.

  9. Alcohol and the Intestine

    PubMed Central

    Patel, Sheena; Behara, Rama; Swanson, Garth R.; Forsyth, Christopher B.; Voigt, Robin M.; Keshavarzian, Ali

    2015-01-01

    Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches. PMID:26501334

  10. Dysbiosis in intestinal inflammation: Cause or consequence.

    PubMed

    Buttó, Ludovica F; Haller, Dirk

    2016-08-01

    The intestinal microbiota encompasses hundreds of bacterial species that constitute a relatively stable ecosystem. Alteration in the microbiota composition may arise from infections, immune defects, metabolic alterations, diet or antibiotic treatment. Dysbiosis is considered as an alteration in microbiota community structure and/or function, capable of causing/driving a detrimental distortion of microbe-host homeostasis. A variety of pathologies are associated with changes in the community structure and function of the gut microbiota, suggesting a link between dysbiosis and disease etiology. With an emphasis in this review on inflammatory bowel diseases (IBD), the non-trivial question is whether dysbiosis is the cause or consequence of inflammation. It is important to understand whether changes in microbial ecosystems are causally linked to the pathology and to what extend disease risk is predicable based on characteristic changes in community structure and/or function. Local changes in tissue integrity associated with focal areas of inflammation may result in the selection of a dysbiotic bacterial community associated with the propagation of a disease phenotype. This review outlines the role of dysbiosis in intestinal inflammation with particular focus on IBD-relevant gnotobiotic mouse models, the factors implicated in the development of dysbiosis and the means available to investigate dysbiosis in the context of human diseases.

  11. Translocation of gliadin into HLA-DR antigen containing lysosomes in coeliac disease enterocytes.

    PubMed Central

    Zimmer, K P; Poremba, C; Weber, P; Ciclitira, P J; Harms, E

    1995-01-01

    Coeliac disease is triggered by ingestion of wheat gliadin and is probably immune mediated. There is evidence by light microscopy that expression of class II major histocompatibility complex (MHC) molecules is increased in the small intestinal epithelium of patients with untreated coeliac disease and that gliadin can be taken up by small intestinal enterocytes. The pathway by which gliadin is transported to class II MHC proteins has not been demonstrated. Using an immunogold technique and thin frozen sections of jejunal biopsy specimens, gliadin, HLA-DR antigens, and IgA were localised at an ultrastructural level in the jejunal epithelium of patients with both untreated and treated coeliac disease and controls. Cathepsin D was used as a marker for late endosomes or lysosomes. The results show that gliadin is translocated into vacuoles positive for HLA-DR antigens as well as cathepsin D in jejunal enterocytes of patients with untreated coeliac disease. Secretory IgA may have a role in this translocation of gliadin, which is a specific event that occurred only in jejunal enterocytes from patients with untreated coeliac disease but not in a patient maintained on a gluten free diet or in controls. These results support a central role for epithelial cells of the human intestinal mucosa in the transport of gliadin to an HLA-DR positive compartment which precedes antigen presentation of gliadin to antigen sensitive T lymphocytes. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7797120

  12. Effects of Bacillus subtilis-based direct-fed microbials on growth performance, immune characteristics and resistance against experimental coccidiosis in broiler chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present experiment was conducted to study the effects of dietary Bacillus-based direct-fed microbials (DFMs) on cytokine expression patterns, intestinal intraepithelial lymphocyte (IEL) subpopulation, splenocyte proliferation, macrophage functions and resistance against experimental coccidiosis ...

  13. Gut Microbial Metabolites Fuel Host Antibody Responses.

    PubMed

    Kim, Myunghoo; Qie, Yaqing; Park, Jeongho; Kim, Chang H

    2016-08-10

    Antibody production is a metabolically demanding process that is regulated by gut microbiota, but the microbial products supporting B cell responses remain incompletely identified. We report that short-chain fatty acids (SCFAs), produced by gut microbiota as fermentation products of dietary fiber, support host antibody responses. In B cells, SCFAs increase acetyl-CoA and regulate metabolic sensors to increase oxidative phosphorylation, glycolysis, and fatty acid synthesis, which produce energy and building blocks supporting antibody production. In parallel, SCFAs control gene expression to express molecules necessary for plasma B cell differentiation. Mice with low SCFA production due to reduced dietary fiber consumption or microbial insufficiency are defective in homeostatic and pathogen-specific antibody responses, resulting in greater pathogen susceptibility. However, SCFA or dietary fiber intake restores this immune deficiency. This B cell-helping function of SCFAs is detected from the intestines to systemic tissues and conserved among mouse and human B cells, highlighting its importance.

  14. Composition, Diversity, and Origin of the Bacterial Community in Grass Carp Intestine

    PubMed Central

    Wu, Shangong; Wang, Guitang; Angert, Esther R.; Wang, Weiwei; Li, Wenxiang; Zou, Hong

    2012-01-01

    Gut microbiota has become an integral component of the host, and received increasing attention. However, for many domestic animals, information on the microbiota is insufficient and more effort should be exerted to manage the gastrointestinal bacterial community. Understanding the factors that influence the composition of microbial community in the host alimentary canal is essential to manage or improve the microbial community composition. In the present study, 16S rRNA gene sequence-based comparisons of the bacterial communities in the grass carp (Ctenopharyngodon idellus) intestinal contents and fish culture-associated environments are performed. The results show that the fish intestinal microbiota harbors many cellulose-decomposing bacteria, including sequences related to Anoxybacillus, Leuconostoc, Clostridium, Actinomyces, and Citrobacter. The most abundant bacterial operational taxonomic units (OTUs) in the grass carp intestinal content are those related to feed digestion. In addition, the potential pathogens and probiotics are important members of the intestinal microbiota. Further analyses show that grass carp intestine holds a core microbiota composed of Proteobacteria, Firmicutes, and Actinobacteria. The comparison analyses reveal that the bacterial community in the intestinal contents is most similar to those from the culture water and sediment. However, feed also plays significant influence on the composition of gut microbiota. PMID:22363439

  15. GLP-1R Agonists Modulate Enteric Immune Responses Through the Intestinal Intraepithelial Lymphocyte GLP-1R.

    PubMed

    Yusta, Bernardo; Baggio, Laurie L; Koehler, Jacqueline; Holland, Dianne; Cao, Xiemin; Pinnell, Lee J; Johnson-Henry, Kathene C; Yeung, William; Surette, Michael G; Bang, K W Annie; Sherman, Philip M; Drucker, Daniel J

    2015-07-01

    Obesity and diabetes are characterized by increased inflammation reflecting disordered control of innate immunity. We reveal a local intestinal intraepithelial lymphocyte (IEL)-GLP-1 receptor (GLP-1R) signaling network that controls mucosal immune responses. Glp1r expression was enriched in intestinal IEL preparations and copurified with markers of Tαβ and Tγδ IELs, the two main subsets of intestinal IELs. Exendin-4 increased cAMP accumulation in purified IELs and reduced the production of cytokines from activated IELs but not from splenocytes ex vivo. These actions were mimicked by forskolin, absent in IELs from Glp1r(-/-) mice, and attenuated by the GLP-1R agonist exendin (9-39) consistent with a GLP-1R-dependent mechanism of action. Furthermore, Glp1r(-/-) mice exhibited dysregulated intestinal gene expression, an abnormal representation of microbial species in feces, and enhanced sensitivity to intestinal injury following administration of dextran sodium sulfate. Bone marrow transplantation using wild-type C57BL/6 donors normalized expression of multiple genes regulating immune function and epithelial integrity in Glp1r(-/-) recipient mice, whereas acute exendin-4 administration robustly induced the expression of genes encoding cytokines and chemokines in normal and injured intestine. Taken together, these findings define a local enteroendocrine-IEL axis linking energy availability, host microbial responses, and mucosal integrity to the control of innate immunity.

  16. The human milk oligosaccharide 2′-fucosyllactose augments the adaptive response to extensive intestinal

    PubMed Central

    Hawkins, Jennifer A.; Ollberding, Nicholas J.; Karns, Rebekah; Morrow, Ardythe L.; Helmrath, Michael A.

    2015-01-01

    Intestinal resection resulting in short bowel syndrome (SBS) carries a heavy burden of long-term morbidity, mortality, and cost of care, which can be attenuated with strategies that improve intestinal adaptation. SBS infants fed human milk, compared with formula, have more rapid intestinal adaptation. We tested the hypothesis that the major noncaloric human milk oligosaccharide 2′-fucosyllactose (2′-FL) contributes to the adaptive response after intestinal resection. Using a previously described murine model of intestinal adaptation, we demonstrated increased weight gain from 21 to 56 days (P < 0.001) and crypt depth at 56 days (P < 0.0095) with 2′-FL supplementation after ileocecal resection. Furthermore, 2′-FL increased small bowel luminal content microbial alpha diversity following resection (P < 0.005) and stimulated a bloom in organisms of the genus Parabacteroides (log2-fold = 4.1, P = 0.035). Finally, transcriptional analysis of the intestine revealed enriched ontologies and pathways related to antimicrobial peptides, metabolism, and energy processing. We conclude that 2′-FL supplementation following ileocecal resection increases weight gain, energy availability through microbial community modulation, and histological changes consistent with improved adaptation. PMID:26702137

  17. Novel antigen delivery systems

    PubMed Central

    Trovato, Maria; Berardinis, Piergiuseppe De

    2015-01-01

    Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the “E2 scaffold” of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID:26279977

  18. Health relevance of intestinal protein fermentation in young pigs.

    PubMed

    Pieper, R; Villodre Tudela, C; Taciak, M; Bindelle, J; Pérez, J F; Zentek, J

    2016-12-01

    The physiological role of the gastrointestinal microbiota has become an important subject of nutrition research in pigs in the past years, and the importance of intestinal microbial activity in the etiology of disease is doubtless. This review summarizes the recent knowledge related to the microbial ecology of protein fermentation and the appearance of protein-derived metabolites along the pig intestine. The amount of fermentable protein depends on factors such as dietary protein concentration, protein digestibility due to secondary or tertiary structure, the interaction with dietary compounds or anti-nutritional factors, and the secretion of endogenous proteins into the gut lumen. High protein diets increase the luminal concentrations and epithelial exposure to putatively toxic metabolites and increase the risk for post-weaning diarrhea, but the mechanisms are not yet clarified. Although the use of fermentable carbohydrates to reduce harmful protein-derived metabolites in pigs is well-established, recent studies suggest that the inclusion of fermentable carbohydrates into diets with low protein digestibility or high dietary protein level may not ameliorate all negative effects with regard to epithelial response. Based on the current knowledge, the use of diets with low levels of high-quality protein may help to reduce the risk for intestinal disease in young pigs.

  19. Intestinal Microbiota in Animal Models of Inflammatory Diseases.

    PubMed

    Hörmannsperger, G; Schaubeck, M; Haller, D

    2015-01-01

    The intestinal microbiota has long been known to play an important role in the maintenance of health. In addition, alterations of the intestinal microbiota have recently been associated with a range of immune-mediated and metabolic disorders. Characterizing the composition and functionality of the intestinal microbiota, unravelling relevant microbe-host interactions, and identifying disease-relevant microbes are therefore currently of major interest in scientific and medical communities. Experimental animal models for the respective diseases of interest are pivotal in order to address functional questions on microbe-host interaction and to clarify the clinical relevance of microbiome alterations associated with disease initiation and development. This review presents an overview of the outcomes of highly sophisticated experimental studies on microbe-host interaction in animal models of inflammatory diseases, with a focus on inflammatory bowel disease (IBD). We will address the advantages and drawbacks of analyzing microbe-host interaction in complex colonized animal models compared with gnotobiotic animal models using monoassociation, simplified microbial consortia (SMC), or microbial humanization.

  20. Stool Test: H. Pylori Antigen

    MedlinePlus

    ... Your 1- to 2-Year-Old Stool Test: H. Pylori Antigen KidsHealth > For Parents > Stool Test: H. Pylori Antigen A A A What's in this article? ... en español Muestra de materia fecal: antígeno de H. pylori What It Is Helicobacter pylori ( H. pylori ) bacteria ...

  1. Oral PEG 15-20 protects the intestine against radiation : role of lipid rafts.

    SciTech Connect

    Valuckaite, V.; Zaborina, O.; Long, J.; Hauer-Jensen, M.; Wang, J.; Holbrook, C.; Zaborin, A.; Drabik, K.; Katdare, M.; Mauceri, H.; Weichselbaum, R.; Firestone, M. A.; Lee, K. Y.; Chang, E. B.; Matthews, J.; Alverdy, J. C.; Materials Science Division; Univ. of Chicago; Univ. of Arkansas

    2009-12-01

    Intestinal injury following abdominal radiation therapy or accidental exposure remains a significant clinical problem that can result in varying degrees of mucosal destruction such as ulceration, vascular sclerosis, intestinal wall fibrosis, loss of barrier function, and even lethal gut-derived sepsis. We determined the ability of a high-molecular-weight polyethylene glycol-based copolymer, PEG 15-20, to protect the intestine against the early and late effects of radiation in mice and rats and to determine its mechanism of action by examining cultured rat intestinal epithelia. Rats were exposed to fractionated radiation in an established model of intestinal injury, whereby an intestinal segment is surgically placed into the scrotum and radiated daily. Radiation injury score was decreased in a dose-dependent manner in rats gavaged with 0.5 or 2.0 g/kg per day of PEG 15-20 (n = 9-13/group, P < 0.005). Complementary studies were performed in a novel mouse model of abdominal radiation followed by intestinal inoculation with Pseudomonas aeruginosa (P. aeruginosa), a common pathogen that causes lethal gut-derived sepsis following radiation. Mice mortality was decreased by 40% in mice drinking 1% PEG 15-20 (n = 10/group, P < 0.001). Parallel studies were performed in cultured rat intestinal epithelial cells treated with PEG 15-20 before radiation. Results demonstrated that PEG 15-20 prevented radiation-induced intestinal injury in rats, prevented apoptosis and lethal sepsis attributable to P. aeruginosa in mice, and protected cultured intestinal epithelial cells from apoptosis and microbial adherence and possible invasion. PEG 15-20 appeared to exert its protective effect via its binding to lipid rafts by preventing their coalescence, a hallmark feature in intestinal epithelial cells exposed to radiation.

  2. Radioimmunoassays of hidden viral antigens

    SciTech Connect

    Neurath, A.R.; Strick, N.; Baker, L.; Krugman, S.

    1982-07-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.

  3. Radioimmunoassays of hidden viral antigens.

    PubMed Central

    Neurath, A R; Strick, N; Baker, L; Krugman, S

    1982-01-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bond adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure. Images PMID:6956871

  4. Intestinal epithelial barrier function and tight junction proteins with heat and exercise.

    PubMed

    Dokladny, Karol; Zuhl, Micah N; Moseley, Pope L

    2016-03-15

    A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or "leaky" intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise.

  5. Intestinal epithelial barrier function and tight junction proteins with heat and exercise

    PubMed Central

    Zuhl, Micah N.; Moseley, Pope L.

    2015-01-01

    A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or “leaky” intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise. PMID:26359485

  6. Immunohistochemical characterization of cellular proliferation in small intestinal hyperplasia of rats with hepatic Strobilocercus fasciolaris infection.

    PubMed

    Lagapa, J T; Oku, Y; Kamiya, M

    2008-07-01

    Rats infected with the larvae of Taenia taeniaeformis harbour the intermediate stage of the parasite Strobilocercus fasciolaris within the liver. Affected animals also develop gastric and intestinal hyperplasia. The pathogenesis of the gastric hyperplasia has been extensively investigated, but few studies have addressed the nature of the intestinal changes. This study characterizes the proliferation of small intestinal epithelial cells by immunohistochemical labelling for proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) uptake. At 6 weeks post-infection (wpi) there was an increase in villous length but crypt depth was normal. At 9 wpi there was evidence of epithelial hyperplasia, increased villous length and crypt depth, and expansion of zones of epithelial proliferation. Immunohistochemical labelling indicated that an increase in the number of proliferating cells produced a greater number of progeny cells. Intestinal hyperplasia during experimental infection with T. taeniaeformis larvae is likely to be related to the associated gastropathy, although the mechanisms underlying both changes remain undefined.

  7. Extra-intestinal detection of canine kobuvirus in a puppy from Southern Brazil.

    PubMed

    Ribeiro, Juliane; Headley, Selwyn Arlington; Diniz, Jaqueline Assumpção; Pereira, Alfredo Hajime Tanaka; Lorenzetti, Elis; Alfieri, Amauri Alcindo; Alfieri, Alice Fernandes

    2017-03-01

    This study presents the pathological, immunohistochemical, and molecular findings associated with the extra-intestinal detection of canine kobuvirus (CaKV) in a 5-month-old Chihuahua puppy, that had a clinical history of bloody-tinged feces. Principal pathological findings were interstitial pneumonia, necrotizing bronchitis, and parvovirus-induced enteritis. Molecular diagnostic methods identified CaKV within the cerebellum, cerebrum, lung, tonsil, and liver. CaKV and rotavirus were not identified within the feces and intestine. Immunohistochemistry (IHC) assays detected antigens of CDV and CAdV-1 in the lungs. These results confirmed the extra-intestinal detection of CaKV in this puppy and represent the first extra-intestinal detection of CaKV in a dog.

  8. Microfluidics and microbial engineering.

    PubMed

    Kou, Songzi; Cheng, Danhui; Sun, Fei; Hsing, I-Ming

    2016-02-07

    The combination of microbial engineering and microfluidics is synergistic in nature. For example, microfluidics is benefiting from the outcome of microbial engineering and many reported point-of-care microfluidic devices employ engineered microbes as functional parts for the microsystems. In addition, microbial engineering is facilitated by various microfluidic techniques, due to their inherent strength in high-throughput screening and miniaturization. In this review article, we firstly examine the applications of engineered microbes for toxicity detection, biosensing, and motion generation in microfluidic platforms. Secondly, we look into how microfluidic technologies facilitate the upstream and downstream processes of microbial engineering, including DNA recombination, transformation, target microbe selection, mutant characterization, and microbial function analysis. Thirdly, we highlight an emerging concept in microbial engineering, namely, microbial consortium engineering, where the behavior of a multicultural microbial community rather than that of a single cell/species is delineated. Integrating the disciplines of microfluidics and microbial engineering opens up many new opportunities, for example in diagnostics, engineering of microbial motors, development of portable devices for genetics, high throughput characterization of genetic mutants, isolation and identification of rare/unculturable microbial species, single-cell analysis with high spatio-temporal resolution, and exploration of natural microbial communities.

  9. How to make an intestine

    PubMed Central

    Wells, James M.; Spence, Jason R.

    2014-01-01

    With the high prevalence of gastrointestinal disorders, there is great interest in establishing in vitro models of human intestinal disease and in developing drug-screening platforms that more accurately represent the complex physiology of the intestine. We will review how recent advances in developmental and stem cell biology have made it possible to generate complex, three-dimensional, human intestinal tissues in vitro through directed differentiation of human pluripotent stem cells. These are currently being used to study human development, genetic forms of disease, intestinal pathogens, metabolic disease and cancer. PMID:24496613

  10. PROSTATE SPECIFIC MEMBRANE ANTIGEN-BASED IMAGING

    PubMed Central

    Osborne, Joseph R.; Akhtar, Naveed H.; Vallabhajosula, Shankar; Anand, Alok; Deh, Kofi; Tagawa, Scott T.

    2012-01-01

    SUMMARY Prostate cancer (PC) is the most common non-cutaneous malignancy affecting men in North America. Despite significant efforts, conventional imaging of PC does not contribute to patient management as much as imaging performed for other common cancers. Given the lack of specificity in conventional imaging techniques, one possible solution is to screen for PC specific antigenic targets and generate agents able to specifically bind. Prostate specific membrane antigen (PSMA) is over-expressed in PC tissue, with low levels of expression in the small intestine, renal tubular cells and salivary gland. The first clinical agent for targeting PSMA was 111In-capromab, involving an antibody recognizing the internal domain of PSMA. The second- and third-generation humanized PSMA binding antibodies have the potential to overcome some of the limitations inherent to capromab pendetide i.e. inability to bind to live PC cells. One example is the humanized monoclonal antibody J591 (Hu mAb J591) that was developed primarily for therapeutic purposes but also has interesting imaging characteristics including the identification of bone metastases in PC. The major disadvantage of use of mAb for imaging is slow target recognition and background clearance in an appropriate timeframe for diagnostic imaging. Urea-based compounds such as small molecule inhibitors may also present promising agents for PC imaging with SPECT and PET. Two such small-molecule inhibitors targeting PSMA, MIP-1072 and MIP-1095, have exhibited high affinity for PSMA. The uptake of 123I-MIP-1072 and 123I-MIP-1095 in PC xenografts have imaged successfully with favorable properties amenable to human trials. While advances in conventional imaging will continue, Ab and small molecule imaging exemplified by PSMA targeting have the greatest potential to improve diagnostic sensitivity and specificity. PMID:22658884

  11. Homing of immune cells: role in homeostasis and intestinal inflammation.

    PubMed

    Hart, Ailsa L; Ng, Siew C; Mann, Elizabeth; Al-Hassi, Hafid Omar; Bernardo, David; Knight, Stella C

    2010-11-01

    Rather like a satellite navigation system directing a vehicle to a particular destination defined by post-code, immune cells have homing molecules or "immune post-codes" enabling them to be recruited to specific organs, such as the intestine or skin. An efficient system would be designed such that the site of entry of an antigen influences the homing of effector T cells back to the appropriate organ. For example, to mount an immune response against an intestinal pathogen, T cells with a propensity to home to the gut to clear the infection would be induced. In health, there is such a sophisticated and finely tuned system in operation, enabling an appropriate balance of immune activity in different anatomical compartments. In disease states such as inflammatory bowel disease (IBD), which is characterized by intestinal inflammation and often an inflammatory process involving other organs such as skin, joints, liver, and eye, there is accumulating evidence that there is malfunction of this immune cell trafficking system. The clinical importance of dysregulated immune cell trafficking in IBD is reflected in recently proven efficacious therapies that target trafficking pathways such as natalizumab, an α4 integrin antibody, and Traficet-EN, a chemokine receptor-9 (CCR9) antagonist. Here we review the mechanisms involved in the homing of immune cells to different tissues, in particular the intestine, and focus on alterations in immune cell homing pathways in IBD. Unraveling the mechanisms underlying the immune post-code system would assist in achieving the goal of tissue-specific immunotherapy.

  12. Giant primary angiosarcoma of the small intestine showing severe sepsis.

    PubMed

    Takahashi, Mizuna; Ohara, Masanori; Kimura, Noriko; Domen, Hiromitsu; Yamabuki, Takumi; Komuro, Kazuteru; Tsuchikawa, Takahiro; Hirano, Satoshi; Iwashiro, Nozomu

    2014-11-21

    Primary malignant tumors of the small intestine are rare, comprising less than 2% of all gastrointestinal tumors. An 85-year-old woman was admitted with fever of 40 °C and marked abdominal distension. Her medical history was unremarkable, but blood examination showed elevated inflammatory markers. Abdominal computed tomography showed a giant tumor with central necrosis, extending from the epigastrium to the pelvic cavity. Giant gastrointestinal stromal tumor of the small intestine communicating with the gastrointestinal tract or with superimposed infection was suspected. Because no improvement occurred in response to antibiotics, surgery was performed. Laparotomy revealed giant hemorrhagic tumor adherent to the small intestine and occupying the peritoneal cavity. The giant tumor was a solid tumor weighing 3490 g, measuring 24 cm × 17.5 cm × 18 cm and showing marked necrosis. Histologically, the tumor comprised spindle-shaped cells with anaplastic large nuclei. Immunohistochemical studies showed tumor cells positive for vimentin, CD31, and factor VIII-related antigen, but negative for c-kit and CD34. Angiosarcoma was diagnosed. Although no postoperative complications occurred, the patient experienced enlargement of multiple metastatic tumors in the abdominal cavity and died 42 d postoperatively. The prognosis of small intestinal angiosarcoma is very poor, even after volume-reducing palliative surgery.

  13. Regulation of intestinal permeability: The role of proteases

    PubMed Central

    Van Spaendonk, Hanne; Ceuleers, Hannah; Witters, Leonie; Patteet, Eveline; Joossens, Jurgen; Augustyns, Koen; Lambeir, Anne-Marie; De Meester, Ingrid; De Man, Joris G; De Winter, Benedicte Y

    2017-01-01

    The gastrointestinal barrier is - with approximately 400 m2 - the human body’s largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extra-intestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases.

  14. Intestinal Microbiota And Diet in IBS: Causes, Consequences, or Epiphenomena?

    PubMed Central

    Rajilić-Stojanović, Mirjana; Jonkers, Daisy M; Salonen, Anne; Hanevik, Kurt; Raes, Jeroen; Jalanka, Jonna; de Vos, Willem M; Manichanh, Chaysavanh; Golic, Natasa; Enck, Paul; Philippou, Elena; Iraqi, Fuad A; Clarke, Gerard; Spiller, Robin C; Penders, John

    2015-01-01

    Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS. PMID:25623659

  15. Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena?

    PubMed

    Rajilić-Stojanović, Mirjana; Jonkers, Daisy M; Salonen, Anne; Hanevik, Kurt; Raes, Jeroen; Jalanka, Jonna; de Vos, Willem M; Manichanh, Chaysavanh; Golic, Natasa; Enck, Paul; Philippou, Elena; Iraqi, Fuad A; Clarke, Gerard; Spiller, Robin C; Penders, John

    2015-02-01

    Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS.

  16. [Progress in the knowledge of the intestinal human microbiota].

    PubMed

    Robles-Alonso, Virginia; Guarner, Francisco

    2013-01-01

    New sequencing technologies together with the development of bio-informatics allow a description of the full spectrum of the microbial communities that inhabit the human intestinal tract, as well as their functional contributions to host health. Most community members belong to the domain Bacteria, but Archaea, Eukaryotes (yeasts and protists), and Viruses are also present. Only 7 to 9 of the 55 known divisions or phyla of the domain Bacteria are detected in faecal or mucosal samples from the human gut. Most taxa belong to just two divisions: Bacteroidetes and Firmicutes, and the other divisions that have been consistently found are Proteobacteria, Actinobacteria, Fusobacteria, and Verrucomicrobia. Bacteroides, Faecalibacterium and Bifidobacterium are the most abundant genera but their relative proportion is highly variable across individuals. Full metagenomic analysis has identified more than 5 million non-redundant microbial genes encoding up to 20,000 biological functions related with life in the intestinal habitat. The overall structure of predominant genera in the human gut can be assigned into three robust clusters, which are known as "enterotypes". Each of the three enterotypes is identifiable by the levels of one of three genera: Bacteroides (enterotype 1), Prevotella (enterotype 2) and Ruminococcus (enterotype 3). This suggests that microbiota variations across individuals are stratified, not continuous. Next steps include the identification of changes that may play a role in certain disease states. A better knowledge of the contributions of microbial symbionts to host health will help in the design of interventions to improve symbiosis and combat disease.

  17. Immunization using GroEL decreases Clostridium difficile intestinal colonization.

    PubMed

    Péchiné, Séverine; Hennequin, Claire; Boursier, Céline; Hoys, Sandra; Collignon, Anne

    2013-01-01

    Clostridium difficile is a pathogen which is responsible for diarrhea and colitis, particularly after treatment with antibiotics. Clinical signs are mainly due to two toxins, TcdA and TcdB. However, the first step of pathogenesis is the colonization process. We evaluated C. difficile surface proteins as vaccine antigens in the hamster model to prevent intestinal colonization. This vaccination induced a partial protection of hamsters against death after a C. difficile challenge. A proteomic analysis of animal sera allowed us to identify proteins which could be responsible for the protection observed. Among these proteins, we identified the GroEL heat shock protein. To confirm the role of the specific GroEL antibodies in the delayed C. difficile colonization of hamsters, we performed an immunization assay in a mouse model. After intranasal immunization with the recombinant protein GroEL, we observed a lower C. difficile intestinal colonization in the immunized group as compared to the control group.

  18. Microbial Biogeography and Core Microbiota of the Rat Digestive Tract

    PubMed Central

    Li, Dongyao; Chen, Haiqin; Mao, Bingyong; Yang, Qin; Zhao, Jianxin; Gu, Zhennan; Zhang, Hao; Chen, Yong Q.; Chen, Wei

    2017-01-01

    As a long-standing biomedical model, rats have been frequently used in studies exploring the correlations between gastrointestinal (GI) bacterial biota and diseases. In the present study, luminal and mucosal samples taken along the longitudinal axis of the rat digestive tract were subjected to 16S rRNA gene sequencing-based analysis to determine the baseline microbial composition. Results showed that the community diversity increased from the upper to lower GI segments and that the stratification of microbial communities as well as shift of microbial metabolites were driven by biogeographic location. A greater proportion of lactate-producing bacteria (such as Lactobacillus, Turicibacter and Streptococcus) were found in the stomach and small intestine, while anaerobic Lachnospiraceae and Ruminococcaceae, fermenting carbohydrates and plant aromatic compounds, constituted the bulk of the large-intestinal core microbiota where topologically distinct co-occurrence networks were constructed for the adjacent luminal and mucosal compartments. When comparing the GI microbiota from different hosts, we found that the rat microbial biogeography might represent a new reference, distinct from other murine animals. Our study provides the first comprehensive characterization of the rat GI microbiota landscape for the research community, laying the foundation for better understanding and predicting the disease-related alterations in microbial communities. PMID:28374781

  19. Intestinal microbiota and immune related genes in sea cucumber (Apostichopus japonicus) response to dietary β-glucan supplementation.

    PubMed

    Yang, Gang; Xu, Zhenjiang; Tian, Xiangli; Dong, Shuanglin; Peng, Mo

    2015-02-27

    β-glucan is a prebiotic well known for its beneficial outcomes on sea cucumber health through modifying the host intestinal microbiota. High-throughput sequencing techniques provide an opportunity for the identification and characterization of microbes. In this study, we investigated the intestinal microbial community composition, interaction among species, and intestinal immune genes in sea cucumber fed with diet supplemented with or without β-glucan supplementation. The results show that the intestinal dominant classes in the control group are Flavobacteriia, Gammaproteobacteria, and Alphaproteobacteria, whereas Alphaproteobacteria, Flavobacteriia, and Verrucomicrobiae are enriched in the β-glucan group. Dietary β-glucan supplementation promoted the proliferation of the family Rhodobacteraceae of the Alphaproteobacteria class and the family Verrucomicrobiaceae of the Verrucomicrobiae class and reduced the relative abundance of the family Flavobacteriaceae of Flavobacteria class. The ecological network analysis suggests that dietary β-glucan supplementation can alter the network interactions among different microbial functional groups by changing the microbial community composition and topological roles of the OTUs in the ecological network. Dietary β-glucan supplementation has a positive impact on immune responses of the intestine of sea cucumber by activating NF-κB signaling pathway, probably through modulating the balance of intestinal microbiota.

  20. Immunoglobulin in intestinal secretions.

    PubMed

    Cutropia de Guirao, C

    1977-12-01

    The objective of the present investigation is the study and interpretation of the role played by the immunoglobulins, especially IgA, during acute diarrhea in children. IgA, IGG and IgM values in serum and IgA in intestinal secretions were studied in a group of children (between 3 months and 5 years of age) during diarrhea, convalescence and in normals. The method of simple radial immunodiffusion according to Mancini was employed. IgA is the immunoglobulin which suffers the greastest alteration in acute diarrhea. The precipitation halos (the average values), were lower during the diarrhea than in convalescence and in normals.

  1. Oral administration of Lactobacillus fermentum I5007 favors intestinal development and alters the intestinal microbiota in formula-fed piglets.

    PubMed

    Liu, Hong; Zhang, Jiang; Zhang, Shihai; Yang, Fengjuan; Thacker, Phil A; Zhang, Guolong; Qiao, Shiyan; Ma, Xi

    2014-01-29

    The present study was conducted to evaluate the effects of early administration of Lactobacillus fermentum I5007 on intestinal development and microbial composition in the gastrointestinal tract using a neonatal piglet model. Full-term 4 day old piglets, fed with milk replacer, were divided into a control group (given placebo of 0.1% peptone water) and a L. fermentum I5007 group (dosed daily with 6 × 10(9) CFU/mL L. fermentum I5007). The experiment lasted 14 days. On day 14, a significant increase in the jejunum villous height (583 ± 33 vs 526 ± 18) and increases in the concentrations of butyrate (7.55 ± 0.55 vs 5.33 ± 0.39) and branched chain fatty acids in the colonic digesta were observed in piglets in the L. fermentum I5007 treatment (P < 0.05). mRNA expression of IL-1β (1.29 ± 0.29 vs. 0.62 ± 0.07) in the ileum were lower after 14 days of treatment with L. fermentum I5007. Denaturing gradient gel electrophoresis (DGGE) revealed that L. fermentum I5007 affected the colonic microbial communities on day 14 and, in particular, reduced numbers of Clostridium sp. L. fermentum I5007 play a positive role in gut development in neonatal piglets by modulating microbial composition, intestinal development, and immune status. L. fermentum I5007 may be useful as a probiotic for application in neonatal piglets.

  2. Benchtop Antigen Detection Technique using Nanofiltration and Fluorescent Dyes

    NASA Technical Reports Server (NTRS)

    Scardelletti, Maximilian C.; Varaljay, Vanessa

    2009-01-01

    The designed benchtop technique is primed to detect bacteria and viruses from antigenic surface marker proteins in solutions, initially water. This inclusive bio-immunoassay uniquely combines nanofiltration and near infrared (NIR) dyes conjugated to antibodies to isolate and distinguish microbial antigens, using laser excitation and spectrometric analysis. The project goals include detecting microorganisms aboard the International Space Station, space shuttle, Crew Exploration Vehicle (CEV), and human habitats on future Moon and Mars missions, ensuring astronaut safety. The technique is intended to improve and advance water contamination testing both commercially and environmentally as well. Lastly, this streamlined technique poses to greatly simplify and expedite testing of pathogens in complex matrices, such as blood, in hospital and laboratory clinics.

  3. Beneficial effects of milk oligosaccharides on gut permeability, microbial dysbiosis and the obese phenotype in high-fat diet-induced obesity in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Microbial dysbiosis and increased intestinal permeability is a target for prevention or reversal of weight gain in high-fat (HF) diet-induced obesity (DIO); however, it is not known whether decreased intestinal permeability is necessary or sufficient for weight loss. Prebiotic milk oligos...

  4. Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication.

    PubMed

    Kristoff, Jan; Haret-Richter, George; Ma, Dongzhu; Ribeiro, Ruy M; Xu, Cuiling; Cornell, Elaine; Stock, Jennifer L; He, Tianyu; Mobley, Adam D; Ross, Samantha; Trichel, Anita; Wilson, Cara; Tracy, Russell; Landay, Alan; Apetrei, Cristian; Pandrea, Ivona

    2014-06-01

    Damage to the intestinal mucosa results in the translocation of microbes from the intestinal lumen into the circulation. Microbial translocation has been proposed to trigger immune activation, inflammation, and coagulopathy, all of which are key factors that drive HIV disease progression and non-HIV comorbidities; however, direct proof of a causal link is still lacking. Here, we have demonstrated that treatment of acutely SIV-infected pigtailed macaques with the drug sevelamer, which binds microbial lipopolysaccharide in the gut, dramatically reduces immune activation and inflammation and slightly reduces viral replication. Furthermore, sevelamer administration reduced coagulation biomarkers, confirming the contribution of microbial translocation in the development of cardiovascular comorbidities in SIV-infected nonhuman primates. Together, our data suggest that early control of microbial translocation may improve the outcome of HIV infection and limit noninfectious comorbidities associated with AIDS.

  5. Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication

    PubMed Central

    Kristoff, Jan; Haret-Richter, George; Ma, Dongzhu; Ribeiro, Ruy M.; Xu, Cuiling; Cornell, Elaine; Stock, Jennifer L.; He, Tianyu; Mobley, Adam D.; Ross, Samantha; Trichel, Anita; Wilson, Cara; Tracy, Russell; Landay, Alan; Apetrei, Cristian; Pandrea, Ivona

    2014-01-01

    Damage to the intestinal mucosa results in the translocation of microbes from the intestinal lumen into the circulation. Microbial translocation has been proposed to trigger immune activation, inflammation, and coagulopathy, all of which are key factors that drive HIV disease progression and non-HIV comorbidities; however, direct proof of a causal link is still lacking. Here, we have demonstrated that treatment of acutely SIV-infected pigtailed macaques with the drug sevelamer, which binds microbial lipopolysaccharide in the gut, dramatically reduces immune activation and inflammation and slightly reduces viral replication. Furthermore, sevelamer administration reduced coagulation biomarkers, confirming the contribution of microbial translocation in the development of cardiovascular comorbidities in SIV-infected nonhuman primates. Together, our data suggest that early control of microbial translocation may improve the outcome of HIV infection and limit noninfectious comorbidities associated with AIDS. PMID:24837437

  6. Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine.

    PubMed

    Pfeiffer, Julie K; Virgin, Herbert W

    2016-01-15

    Viruses that infect the intestine include major human pathogens (retroviruses, noroviruses, rotaviruses, astroviruses, picornaviruses, adenoviruses, herpesviruses) that constitute a serious public health problem worldwide. These viral pathogens are members of a large, complex viral community inhabiting the intestine termed "the enteric virome." Enteric viruses have intimate functional and genetic relationships with both the host and other microbial constituents that inhabit the intestine, such as the bacterial microbiota, their associated phages, helminthes, and fungi, which together constitute the microbiome. Emerging data indicate that enteric viruses regulate, and are in turn regulated by, these other microbes through a series of processes termed "transkingdom interactions." This represents a changing paradigm in intestinal immunity to viral infection. Here we review recent advances in the field and propose new ways in which to conceptualize this important area.

  7. A deregulated intestinal cell cycle program disrupts tissue homeostasis without affecting longevity in Drosophila.

    PubMed

    Petkau, Kristina; Parsons, Brendon D; Duggal, Aashna; Foley, Edan

    2014-10-10

    Recent studies illuminate a complex relationship between the control of stem cell division and intestinal tissue organization in the model system Drosophila melanogaster. Host and microbial signals drive intestinal proliferation to maintain an effective epithelial barrier. Although it is widely assumed that proliferation induces dysplasia and shortens the life span of the host, the phenotypic consequences of deregulated intestinal proliferation for an otherwise healthy host remain unexplored. To address this question, we genetically isolated and manipulated the cell cycle programs of adult stem cells and enterocytes. Our studies revealed that cell cycle alterations led to extensive cell death and morphological disruptions. Despite the extensive tissue damage, we did not observe an impact on longevity, suggesting a remarkable degree of plasticity in intestinal function.

  8. Transkingdom control of viral infection and immunity in the mammalian intestine

    PubMed Central

    Pfeiffer, Julie K.; Virgin, Herbert W.

    2016-01-01

    Viruses that infect the intestine include major human pathogens (retroviruses, noroviruses, rotaviruses, astroviruses, picornaviruses, adenoviruses, herpesviruses) constituting a major public health problem worldwide. These viral pathogens are members of a large, complex viral community inhabiting the intestine termed the enteric virome. Enteric viruses have intimate functional and genetic relationships with both the host and other microbial constituents that inhabit the intestine, like the bacterial microbiota, their associated phages, helminthes and fungi which together constitute the microbiome. Emerging data indicate that enteric viruses regulate, and are in turn regulated by, these other microbes through a series of processes termed transkingdom interactions. This represents a changing paradigm in intestinal immunity to viral infection. Here we review recent advances in the field and propose new ways in which to conceptualize this important area. PMID:26816384

  9. Serospecific antigens of Legionella pneumophila.

    PubMed Central

    Otten, S; Iyer, S; Johnson, W; Montgomery, R

    1986-01-01

    Serospecific antigens isolated by EDTA extraction from four serogroups of Legionella pneumophila were analyzed for their chemical composition, molecular heterogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunological properties. The antigens were shown to be lipopolysaccharides and to differ from the lipopolysaccharides of other gram-negative bacteria. The serospecific antigens contained rhamnose, mannose, glucosamine, and two unidentified sugars together with 2-keto-3-deoxyoctonate, phosphate, and fatty acids. The fatty acid composition was predominantly branched-chain acids with smaller amounts of 3-hydroxymyristic acid. The antigens contain periodate-sensitive groups; mannosyl residues were completely cleaved by periodate oxidation. Hydrolysis of the total lipopolysaccharide by acetic acid resulted in the separation of a lipid A-like material that cross-reacted with the antiserum to lipid A from Salmonella minnesota but did not comigrate with it on sodium dodecyl sulfate gels. None of the four antigens contained heptose. All of the antigen preparations showed endotoxicity when tested by the Limulus amebocyte lysate assay. The results of this study indicate that the serogroup-specific antigens of L. pneumophila are lipopolysaccharides containing an unusual lipid A and core structure and different from those of other gram-negative bacteria. Images PMID:3017918

  10. The Role of Pattern Recognition Receptors in Intestinal Inflammation

    PubMed Central

    Fukata, Masayuki; Arditi, Moshe

    2013-01-01

    Recognition of microorganisms by pattern recognition receptors (PRRs) is the primary component of innate immunity that is responsible for the maintenance of host-microbial interactions in intestinal mucosa. Disregulation in host-commensal interactions has been implicated as the central pathogenesis of inflammatory bowel disease (IBD), which predisposes to developing colorectal cancer. Recent animal studies have begun to outline some unique physiology and pathology involving each PRR signaling in the intestine. The major roles played by PRRs in the gut appear to be regulation of the number and the composition of commensal bacteria, epithelial proliferation and mucosal permiability in response to epithelial injury. In addition, PRR signaling in lamina propria immune cells may be involved in induction of inflammation in response to invasion of pathogens. Because some PRR-deficient mice have shown variable susceptibility to colitis, the outcome of intestinal inflammation may be modified depending on PRR signaling in epithelial cells, immune cells, and the composition of commensal flora. Through recent findings in animal models of IBD, this review will discuss how abnormal PRR signaling may contribute to the pathogenesis of inflammation and inflammation-associated tumorigenesis in the intestine. PMID:23515136

  11. [Effect of antibiotics on intestinal microflora and production of metabolites].

    PubMed

    Tamm, A O; Siĭgur, U Kh; Mikel'saar, M E

    1989-06-01

    Methodical approaches to detection of relation between intestinal microflora and its metabolites are described. The microbial origin of certain compounds can be asserted by a decrease in their production after exposure to antibacterial drugs or the absence of their production in microbe-free animals. The authors consider that parallel investigation of intestinal microflora and its metabolites after exposure to various agents e.g. narrow spectrum antibiotics or specific substrates is the most accurate methodical approach to detection of their interrelations. Data on the effect of four drugs i.e. kanamycin, metronidazole, cefotaxime and bactrim on production of 10 bacterial metabolites: p-cresol, phenol, indican, acetic, propionic, butyric, isobutyric, valeric, isovaleric and caproic acids in rats are presented. Correlation between the metabolites and the intestinal microflora composition was revealed. It is concluded that detection of microorganisms responsible for production of definite metabolites requires at the maximum: (1) exposure to drugs of different spectra, (2) detection of changes in intestinal microflora by biotope++ and (3) investigation of mucosa microflora which more exactly characterizes metabolism of definite biotops.

  12. Antigen exposure shapes the ratio between antigen-specific Tregs and conventional T cells in human peripheral blood

    PubMed Central

    Su, Laura F.; del Alcazar, Daniel; Stelekati, Erietta; Wherry, E. John; Davis, Mark M.

    2016-01-01

    The T-cell receptor (TCR) is required for maturation and function of regulatory T cells (Tregs), but the ligand specificities of Tregs outside the context of transgenic TCRs are largely unknown. Using peptide–MHC tetramers, we isolated rare specific Foxp3+ cells directly ex vivo from adult peripheral blood and defined their frequency and phenotype. We find that a proportion of circulating Tregs recognize foreign antigens and the frequency of these cells are similar to that of self-reactive Tregs in the absence of cognate infection. In contrast, the frequencies of Tregs that recognize some common microbial antigens are significantly reduced in the blood of most adults. Exposure to peripheral antigens likely has a major influence on the balance between Tregs and conventional T-cell subsets because a larger proportion of flu-specific T cells has a regulatory cell phenotype in the cord blood. Consistent with this finding, we show that lymphocytic choriomeningitis virus infection can directly modulate the ratio of virus-specific effectors and Tregs in mice. The resulting change in the balance within an antigen-specific T-cell population further correlates with the magnitude of effector response and the chronicity of infection. Taken together, our data highlight the importance of antigen specificity in the functional dynamics of the T-cell repertoire. Each specific population of CD4+ T cells in human peripheral blood contains a subset of Tregs at birth, but the balance between regulatory and effector subsets changes in response to peripheral antigen exposure and this could impact the robustness of antipathogen immunity. PMID:27681619

  13. K99 surface antigen of Escherichia coli: antigenic characterization.

    PubMed Central

    Isaacson, R E

    1978-01-01

    K99 prepared by acid precipitation hemagglutinated guinea pig erythrocytes, whereas K99 prepared by chromatography on diethylaminoethyl-Sephadex did not. K99 purified by either procedure hemagglutinated horse erythrocytes. K99 prepared by acid precipitation contained a second antigen not presnet in the K99 prepared by chromatography on diethylaminoethyl-Sephadex. This antigen could be detected by immunoprecipitation with some, but not all, sera prepared against K99-positive Escherichia coli strains. It was assumed that this second antigen is not K99 and is responsible for the guinea pig erythrocyte hemagglutination reaction. Furthermore, the second antigen has an isoelectric point of 4.2, which has been reported by Morris and co-workers to be the isoelectric point of K99. Images PMID:83300

  14. Roles of the intestinal microbiota in pathogen protection

    PubMed Central

    Ubeda, Carles; Djukovic, Ana; Isaac, Sandrine

    2017-01-01

    Hundreds of commensal bacterial species inhabit the gastrointestinal tract. This diverse microbial ecosystem plays a crucial role in the prevention and resolution of infectious diseases. In this review we will describe the major mechanisms by which the intestinal microbiota confers protection against infections, focusing on those caused by intestinal bacterial pathogens. These mechanisms include both non-immune- and immune-cell-mediated pathways, notably through bacterial production of inhibitory molecules and nutrient deprivation by the former and innate lymphoid cell-, myeloid cell- or lymphocyte-dependent stimulation by the latter. Finally, we will discuss novel therapeutic approaches based on commensal microbes and their products, which could potentially be used to combat infections. PMID:28243438

  15. CDX2 increases SLC7A7 expression and proliferation of pig intestinal epithelial cells

    PubMed Central

    Li, Xiang-guang; Xu, Gao-feng; Zhai, Zhen-ya; Gao, Chun-qi; Yan, Hui-chao; Xi, Qian-yun; Guan, Wu-tai; Wang, Song-bo; Wang, Xiu-qi

    2016-01-01

    Nutrient absorption mediated by nutrient transporters expressed in the intestinal epithelium supplies substrates to support intestinal processes, including epithelial cell proliferation. We evaluated the role of Caudal type homeobox 2 (CDX2), an intestine-specific transcription factor, in the proliferation of pig intestinal epithelial cells (IPEC-1) and searched for novel intestinal nutrient transporter genes activated by CDX2. Our cloned pig CDX2 cDNA contains a “homeobox” DNA binding motif, suggesting it is a transcriptional activator. CDX2 overexpression in IPEC-1 cells increased cell proliferation, the percentage of cells in S/G2 phase, and the abundance of transcripts of the cell cycle-related genes Cyclin A2; Cyclin B; Cyclin D2; proliferating cell nuclear antigen; and cell cycle cyclin-dependent kinases 1, 2 and 4, as well as the predicted CDX2 target genes SLC1A1, SLC5A1 and SLC7A7. In addition, luciferase reporter and chromatin immunoprecipitation assays revealed that CDX2 binds directly to the SLC7A7 promoter. This is the first report of CDX2 function in pig intestinal epithelial cells and identifies SLC7A7 as a novel CDX2 target gene. Our findings show that nutrient transporters are activated during CDX2-induced proliferation of normal intestinal epithelial cells. PMID:27121315

  16. Gamma/delta intraepithelial lymphocytes in the mouse small intestine.

    PubMed

    Ogata, Masaki; Itoh, Tsunetoshi

    2016-09-01

    Although many studies of intraepithelial lymphocytes (IELs) have been reported, most of them have focused on αβ-IELs; little attention has been paid to γδ-IELs. The function of γδ-IELs remains largely unclear. In this article, we briefly review a number of reports on γδ-IELs, especially those in the small intestine, along with our recent studies. We found that γδ-IELs are the most abundant (comprising >70 % of the) IELs in the duodenum and the jejunum, implying that it is absolutely necessary to investigate the function(s) of γδ-IELs when attempting to delineate the in vivo defense system of the small intestine. Intraperitoneal injection of anti-CD3 mAb stimulated the γδ-IELs and caused rapid degranulation of them. Granzyme B released from their granules induced DNA fragmentation of duodenal and jejunal epithelial cells (paracrine) and of the IELs themselves (autocrine). However, perforin (Pfn) was not detected, and DNA fragmentation was induced even in Pfn-knockout mice; our system was therefore found to present a novel type of in vivo Pfn-independent DNA fragmentation. We can therefore consider γδ-IELs to be a novel type of large granular lymphocyte without Pfn. Fragmented DNA was repaired in the cells, indicating that DNA fragmentation alone cannot be regarded as an unambiguous marker of cell death or apoptosis. Finally, since the response was so rapid and achieved without the need for accessory cells, it seems that γδ-IELs respond readily to various stimuli, are activated only once, and die 2-3 days after activation in situ without leaving their site. Taken together, these results suggest that γδ-IELs are not involved in the recognition of specific antigen(s) and are not involved in the resulting specific killing or exclusion of the relevant antigen(s).

  17. Intronic Cis-Regulatory Modules Mediate Tissue-Specific and Microbial Control of angptl4/fiaf Transcription

    PubMed Central

    Camp, J. Gray; Jazwa, Amelia L.; Trent, Chad M.; Rawls, John F.

    2012-01-01

    The intestinal microbiota enhances dietary energy harvest leading to increased fat storage in adipose tissues. This effect is caused in part by the microbial suppression of intestinal epithelial expression of a circulating inhibitor of lipoprotein lipase called Angiopoietin-like 4 (Angptl4/Fiaf). To define the cis-regulatory mechanisms underlying intestine-specific and microbial control of Angptl4 transcription, we utilized the zebrafish system in which host regulatory DNA can be rapidly analyzed in a live, transparent, and gnotobiotic vertebrate. We found that zebrafish angptl4 is transcribed in multiple tissues including the liver, pancreatic islet, and intestinal epithelium, which is similar to its mammalian homologs. Zebrafish angptl4 is also specifically suppressed in the intestinal epithelium upon colonization with a microbiota. In vivo transgenic reporter assays identified discrete tissue-specific regulatory modules within angptl4 intron 3 sufficient to drive expression in the liver, pancreatic islet β-cells, or intestinal enterocytes. Comparative sequence analyses and heterologous functional assays of angptl4 intron 3 sequences from 12 teleost fish species revealed differential evolution of the islet and intestinal regulatory modules. High-resolution functional mapping and site-directed mutagenesis defined the minimal set of regulatory sequences required for intestinal activity. Strikingly, the microbiota suppressed the transcriptional activity of the intestine-specific regulatory module similar to the endogenous angptl4 gene. These results suggest that the microbiota might regulate host intestinal Angptl4 protein expression and peripheral fat storage by suppressing the activity of an intestine-specific transcriptional enhancer. This study provides a useful paradigm for understanding how microbial signals interact with tissue-specific regulatory networks to control the activity and evolution of host gene transcription. PMID:22479192

  18. TLR5 mediates CD172α(+) intestinal lamina propria dendritic cell induction of Th17 cells.

    PubMed

    Liu, Han; Chen, Feidi; Wu, Wei; Cao, Anthony T; Xue, Xiaochang; Yao, Suxia; Evans-Marin, Heather L; Li, Yan-Qing; Cong, Yingzi

    2016-02-24

    Multiple mechanisms exist in regulation of host responses to massive challenges from microbiota to maintain immune homeostasis in the intestines. Among these is the enriched Th17 cells in the intestines, which regulates intestinal homeostasis through induction of antimicrobial peptides and secretory IgA among others. However, the means by which Th17 cells develop in response to microbiota is still not completely understood. Although both TLR5 and CD172α(+) lamina propria dendritic cells (LPDC) have been shown to promote Th17 cell development, it is still unclear whether TLR5 mediates the CD172α(+)LPDC induction of Th17 cells. By using a microbiota antigen-specific T cell reporter mouse system, we demonstrated that microbiota antigen-specific T cells developed into Th17 cells in the intestinal LP, but not in the spleen when transferred into TCRβxδ(-/-) mice. LPDCs expressed high levels of TLR5, and most CD172α(+)LPDCs also co-expressed TLR5. LPDCs produced high levels of IL-23, IL-6 and TGFβ when stimulated with commensal flagellin and promoted Th17 cell development when cultured with full-length CBir1 flagellin but not CBir1 peptide. Wild-type CD172α(+), but not CD172α(-), LPDCs induced Th17 cells, whereas TLR5-deficient LPDC did not induce Th17 cells. Our data thereby demonstrated that TLR5 mediates CD172α(+)LPDC induction of Th17 cells in the intestines.

  19. Microbial Biotransformations of Bile Acids as Detected by Electrospray Mass Spectrometry123

    PubMed Central

    Hagey, Lee R.; Krasowski, Matthew D.

    2013-01-01

    Many current experiments investigating the effects of diet, dietary supplements, and pre- and probiotics on the intestinal environments do not take into consideration the potential for using bile salts as markers of environmental change. Intestinal bacteria in vertebrates can metabolize bile acids into a number of different structures, with deamidation, hydroxyl group oxidation, and hydroxyl group elimination. Fecal bile acids are readily available to sample and contain a considerable structural complexity that directly relates to intestinal morphology, bile acid residence time in the intestine, and the species of microbial forms in the intestinal tract. Here we offer a classification scheme that can serve as an initial guide to interpret the different bile acid patterns expressed in vertebrate feces. PMID:23319120

  20. [Clinical and diagnostic importance of the evaluation of the Ig proteases activity in children with intestinal dysbacteriosis].

    PubMed

    Zinkevich, O D; Bondarenko, V M; Tiurin, Iu A; Safina, N A; Anokhin, V A

    2004-01-01

    The specific activity of serine, metal dependent and thiolic Ig proteases in the coprofiltrates of children with manifestations of intestinal dysbacteriosis was determined by the enzyme immunoassay. 56 children with pronounced symptoms of intestinal disorders (37 children aged up to 1 year and 19 children over 1 year) were examined. A group of 25 clinically healthy children was used as control. Simultaneously with protease activity of coprofiltrates, there was detected the level of Ig-degrading activity of the opportunistic bacteria islolates of different taxonomic groups from feces of children with dysbacteriosis of different severity (as determined by the classical bacteriological method). The evaluation of the Ig-proteolytic activity of fecal supernatants, associated with the presence of serine, metal-dependent and thiolic proteases in the intestine, as well as detection of such proteases in microbial isolates, seems to be highly important for the diagnosis of intestinal disorders in children and is recommended for screening of intestinal dysbacteriosis.

  1. Interactions between parasites and microbial communities in the human gut

    PubMed Central

    Berrilli, Federica; Di Cave, David; Cavallero, Serena; D'Amelio, Stefano

    2012-01-01

    The interactions between intestinal microbiota, immune system, and pathogens describe the human gut as a complex ecosystem, where all components play a relevant role in modulating each other and in the maintenance of homeostasis. The balance among the gut microbiota and the human body appear to be crucial for health maintenance. Intestinal parasites, both protozoans and helminths, interact with the microbial community modifying the balance between host and commensal microbiota. On the other hand, gut microbiota represents a relevant factor that may strongly interfere with the pathophysiology of the infections. In addition to the function that gut commensal microbiota may have in the processes that determine the survival and the outcome of many parasitic infections, including the production of nutritive macromolecules, also probiotics can play an important role in reducing the pathogenicity of many parasites. On these bases, there is a growing interest in explaining the rationale on the possible interactions between the microbiota, immune response, inflammatory processes, and intestinal parasites. PMID:23162802

  2. Regenerative Inflammation: Lessons from Drosophila Intestinal Epithelium in Health and Disease

    PubMed Central

    Panayidou, Stavria; Apidianakis, Yiorgos

    2013-01-01

    Intestinal inflammation is widely recognized as a pivotal player in health and disease. Defined cytologically as the infiltration of leukocytes in the lamina propria layer of the intestine, it can damage the epithelium and, on a chronic basis, induce inflammatory bowel disease and potentially cancer. The current view thus dictates that blood cell infiltration is the instigator of intestinal inflammation and tumor-promoting inflammation. This is based partially on work in humans and mice showing that intestinal damage during microbially mediated inflammation activates phagocytic cells and lymphocytes that secrete inflammatory signals promoting tissue damage and tumorigenesis. Nevertheless, extensive parallel work in the Drosophila midgut shows that intestinal epithelium damage induces inflammatory signals and growth factors acting mainly in a paracrine manner to induce intestinal stem cell proliferation and tumor formation when genetically predisposed. This is accomplished without any apparent need to involve Drosophila hemocytes. Therefore, recent work on Drosophila host defense to infection by expanding its main focus on systemic immunity signaling pathways to include the study of organ homeostasis in health and disease shapes a new notion that epithelially emanating cytokines and growth factors can directly act on the intestinal stem cell niche to promote “regenerative inflammation” and potentially cancer. PMID:25437036

  3. The interplay between intestinal bacteria and host metabolism in health and disease: lessons from Drosophila melanogaster

    PubMed Central

    Wong, Adam C. N.; Vanhove, Audrey S.; Watnick, Paula I.

    2016-01-01

    ABSTRACT All higher organisms negotiate a truce with their commensal microbes and battle pathogenic microbes on a daily basis. Much attention has been given to the role of the innate immune system in controlling intestinal microbes and to the strategies used by intestinal microbes to overcome the host immune response. However, it is becoming increasingly clear that the metabolisms of intestinal microbes and their hosts are linked and that this interaction is equally important for host health and well-being. For instance, an individual's array of commensal microbes can influence their predisposition to chronic metabolic diseases such as diabetes and obesity. A better understanding of host–microbe metabolic interactions is important in defining the molecular bases of these disorders and could potentially lead to new therapeutic avenues. Key advances in this area have been made using Drosophila melanogaster. Here, we review studies that have explored the impact of both commensal and pathogenic intestinal microbes on Drosophila carbohydrate and lipid metabolism. These studies have helped to elucidate the metabolites produced by intestinal microbes, the intestinal receptors that sense these metabolites, and the signaling pathways through which these metabolites manipulate host metabolism. Furthermore, they suggest that targeting microbial metabolism could represent an effective therapeutic strategy for human metabolic diseases and intestinal infection. PMID:26935105

  4. High-throughput 16S rRNA gene sequencing reveals alterations of mouse intestinal microbiota after radiotherapy.

    PubMed

    Kim, Young Suk; Kim, Jinu; Park, Soo-Je

    2015-06-01

    The mammalian gastrointestinal tract harbors a highly complex microbial community that comprises hundreds of different types of bacterial cells. The gastrointestinal microbiota plays an important role in the function of the host intestine. Most cancer patients undergoing pelvic irradiation experience side effects such as diarrhea; however, little is currently known about the effects of irradiation on the microorganisms colonizing the mucosal surfaces of the gastrointestinal tract. The aim of this study was to investigate the effects of gamma irradiation on the compositions of the large and small intestinal microbiotas. The gut microbiotas in control mice and mice receiving irradiation treatment were characterized by high-throughput sequencing of the bacterial 16S rRNA gene. Irradiation treatment induced significant alterations in the bacterial compositions of the large and small intestines at the genus level. Unexpectedly, irradiation treatment increased the number of operational taxonomic units in the small intestine but not the large intestine. In particular, irradiation treatment increased the level of the genera Alistipes in the large intestine and increased the level of the genus Corynebacterium in the small intestine. By contrast, compared with that in the corresponding control group, the level of the genera Prevotella was lower in the irradiated large intestine, and the level of the genera Alistipes was lower in the irradiated small intestine. Overall, the data presented here reveal the potential microbiological effects of pelvic irradiation on the gastrointestinal tracts of cancer patients.

  5. Intestinal paragonimiasis with colonic ulcer and hematochezia in an elderly Taiwanese woman.

    PubMed

    Liu, Chung-Te; Chen, Yen-Cheng; Chen, Tso-Hsiao; Barghouth, Ursula; Fan, Chia-Kwung

    2012-12-01

    A 94-year-old female with end-stage renal disease presents with fever, fatigue, and hematochezia. She had previously resided in Hunan Province, China, and Myanmar, and she immigrated to Taiwan 30 years ago. Colonoscopy revealed a colonic ulcer. Biopsy of the colonic ulcer showed ulceration of the colonic mucosa, and many Paragonimus westermani-like eggs were noted. Serum IgG antibody levels showed strong reactivity with P. westermani excretory-secretory antigens by ELISA. Intestinal paragonimiasis was thus diagnosed according to the morphology of the eggs and serologic finding. After treatment with praziquantel, hematochezia resolved. The present case illustrates the extreme manifestations encountered in severe intestinal paragonimiasis.

  6. What Happens After Treatment for Small Intestine Adenocarcinoma?

    MedlinePlus

    ... After Treatment What Happens After Treatment for Small Intestine Adenocarcinoma? For some people with small intestine cancer, ... Small Intestine Adenocarcinoma Stops Working More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  7. B cell-helping functions of gut microbial metabolites.

    PubMed

    Kim, Chang H

    2016-09-23

    Commensal microflora profoundly affects the host immune system. It has long been observed that commensal bacteria enhance antibody production in the host by producing antigens for B cell receptors (BCR) and ligands for Toll-like receptors (TLR). We recently reported that the microbial metabolites short-chain fatty acids (SCFAs) regulate the metabolism and gene expression in B cells to promote antibody production (Kim et al. Gut Microbial Metabolites Fuel Host Antibody Responses. Cell Host & Microbe. 2016; 20(2):202-14). The B-cell helping function of SCFAs and its implication in the host immune system are discussed in this article.

  8. B cell-helping functions of gut microbial metabolites

    PubMed Central

    Kim, Chang H.

    2016-01-01

    Commensal microflora profoundly affects the host immune system. It has long been observed that commensal bacteria enhance antibody production in the host by producing antigens for B cell receptors (BCR) and ligands for Toll-like receptors (TLR). We recently reported that the microbial metabolites short-chain fatty acids (SCFAs) regulate the metabolism and gene expression in B cells to promote antibody production (Kim et al. Gut Microbial Metabolites Fuel Host Antibody Responses. Cell Host & Microbe. 2016; 20(2):202-14). The B-cell helping function of SCFAs and its implication in the host immune system are discussed in this article. PMID:28357321

  9. The brain-gut axis dysfunctions and hypersensitivity to food antigens in the etiopathogenesis of schizophrenia.

    PubMed

    Karakuła-Juchnowicz, Hanna; Dzikowski, Michał; Pelczarska, Agnieszka; Dzikowska, Izabela; Juchnowicz, Dariusz

    2016-01-01

    Despite over 100-year history of research on schizophrenia, its etiology is still not fully understood, which might be due to the significant heterogeneity in terms of both its course, as well as the etiopathogenesis. One of the best-proven mediating mechanisms in the development of schizophrenia is the immuno-inflammatory response, the sources of which are believed to be the dysfunctions of brain-gut axis and pathological processes occurring in the intestines. This paper is a review of the literature on this subject which presents factors both involved in the functioning of brain-gut axis and important for the development of schizophrenia, i.e. 1. intestinal microbiome (intestinal microbiota), 2. permeable intestine (leaky gut syndrome), 3. hypersensitivity to food antigens, including gluten and casein of cow's milk. Research results seem to be very promising and indicate the possibility of improved clinical outcomes in some patients with schizophrenia by modifying diet, use of probiotics, and the implementation of antibiotic therapy of specific treatment groups. However, further research is needed on links between the intestinal microbiome and intestinal function as factors mediating the activation of the immune system and the development and further course of schizophrenia.

  10. An Investigation of the Memory Response of the Local Immune System to Shigella Antigens

    DTIC Science & Technology

    1989-03-03

    of developing oral fense against viral infections of epithelial cells along vaccines to enteropathogens, toxins, and carcin- the gastrointestinal ...Ferguson A: Small intestinal cell epithelial kinet- 4. Altmann GG, LeBlond CP: Factors influencing villus size in the ics and protozoal infection in mice...are present within the epithelium overlying lymphoid structures throughout the gastrointestinal tract (8-10). Through these M cells, antigenic material

  11. Biotechnology approaches to produce potent, self-adjuvanting antigen-adjuvant fusion protein subunit vaccines.

    PubMed

    Moyle, Peter Michael

    Traditional vaccination approaches (e.g. live attenuated or killed microorganisms) are among the most effective means to prevent the spread of infectious diseases. These approaches, nevertheless, have failed to yield successful vaccines against many important pathogens. To overcome this problem, methods have been developed to identify microbial components, against which protective immune responses can be elicited. Subunit antigens identified by these approaches enable the production of defined vaccines, with improved safety profiles. However, they are generally poorly immunogenic, necessitating their administration with potent immunostimulatory adjuvants. Since few safe and effective adjuvants are currently used in vaccines approved for human use, with those available displaying poor potency, or an inability to stimulate the types of immune responses required for vaccines against specific diseases (e.g. cytotoxic lymphocytes (CTLs) to treat cancers), the development of new vaccines will be aided by the availability of characterized platforms of new adjuvants, improving our capacity to rationally select adjuvants for different applications. One such approach, involves the addition of microbial components (pathogen-associated molecular patterns; PAMPs), that can stimulate strong immune responses, into subunit vaccine formulations. The conjugation of PAMPs to subunit antigens provides a means to greatly increase vaccine potency, by targeting immunostimulation and antigen to the same antigen presenting cell. Thus, methods that enable the efficient, and inexpensive production of antigen-adjuvant fusions represent an exciting mean to improve immunity towards subunit antigens. Herein we review four protein-based adjuvants (flagellin, bacterial lipoproteins, the extra domain A of fibronectin (EDA), and heat shock proteins (Hsps)), which can be genetically fused to antigens to enable recombinant production of antigen-adjuvant fusion proteins, with a focus on their

  12. Alternative Protein Sources in the Diet Modulate Microbiota and Functionality in the Distal Intestine of Atlantic Salmon (Salmo salar)

    PubMed Central

    Jaramillo-Torres, Alexander; Kortner, Trond M.; Merrifield, Daniel L.; Tinsley, John; Bakke, Anne Marie; Krogdahl, Åshild

    2016-01-01

    ABSTRACT The present study aimed to investigate whether alternative dietary protein sources modulate the microbial communities in the distal intestine (DI) of Atlantic salmon, and whether alterations in microbiota profiles are reflected in modifications in host intestinal function and health status. A 48-day feeding trial was conducted, in which groups of fish received one of five diets: a reference diet in which fishmeal (diet FM) was the only protein source and four experimental diets with commercially relevant compositions containing alternative ingredients as partial replacements of fishmeal, i.e., poultry meal (diet PM), a mix of soybean meal and wheat gluten (diet SBMWG), a mix of soy protein concentrate and poultry meal (diet SPCPM), and guar meal and wheat gluten (diet GMWG). Samples were taken of DI digesta and mucosa for microbial profiling using high-throughput sequencing and from DI whole tissue for immunohistochemistry and expression profiling of marker genes for gut health. Regardless of diet, there were significant differences between the microbial populations in the digesta and the mucosa in the salmon DI. Microbial richness was higher in the digesta than the mucosa. The digesta-associated bacterial communities were more affected by the diet than the mucosa-associated microbiota. Interestingly, both legume-based diets (SBMWG and GMWG) presented high relative abundance of lactic acid bacteria in addition to alteration in the expression of a salmon gene related to cell proliferation (pcna). It was, however, not possible to ascertain the cause-effect relationship between changes in bacterial communities and the host's intestinal responses to the diets. IMPORTANCE The intestine of cultivated Atlantic salmon shows symptoms of compromised function, which are most likely caused by imbalances related to the use of new feed ingredients. Intestinal microbiota profiling may become in the future a valuable endpoint measurement in order to assess fish intestinal

  13. Alternative Protein Sources in the Diet Modulate Microbiota and Functionality in the Distal Intestine of Atlantic Salmon (Salmo salar).

    PubMed

    Gajardo, Karina; Jaramillo-Torres, Alexander; Kortner, Trond M; Merrifield, Daniel L; Tinsley, John; Bakke, Anne Marie; Krogdahl, Åshild

    2017-03-01

    The present study aimed to investigate whether alternative dietary protein sources modulate the microbial communities in the distal intestine (DI) of Atlantic salmon, and whether alterations in microbiota profiles are reflected in modifications in host intestinal function and health status. A 48-day feeding trial was conducted, in which groups of fish received one of five diets: a reference diet in which fishmeal (diet FM) was the only protein source and four experimental diets with commercially relevant compositions containing alternative ingredients as partial replacements of fishmeal, i.e., poultry meal (diet PM), a mix of soybean meal and wheat gluten (diet SBMWG), a mix of soy protein concentrate and poultry meal (diet SPCPM), and guar meal and wheat gluten (diet GMWG). Samples were taken of DI digesta and mucosa for microbial profiling using high-throughput sequencing and from DI whole tissue for immunohistochemistry and expression profiling of marker genes for gut health. Regardless of diet, there were significant differences between the microbial populations in the digesta and the mucosa in the salmon DI. Microbial richness was higher in the digesta than the mucosa. The digesta-associated bacterial communities were more affected by the diet than the mucosa-associated microbiota. Interestingly, both legume-based diets (SBMWG and GMWG) presented high relative abundance of lactic acid bacteria in addition to alteration in the expression of a salmon gene related to cell proliferation (pcna). It was, however, not possible to ascertain the cause-effect relationship between changes in bacterial communities and the host's intestinal responses to the diets.IMPORTANCE The intestine of cultivated Atlantic salmon shows symptoms of compromised function, which are most likely caused by imbalances related to the use of new feed ingredients. Intestinal microbiota profiling may become in the future a valuable endpoint measurement in order to assess fish intestinal health

  14. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

    PubMed

    Yu, Yueyue; Lu, Lei; Sun, Jun; Petrof, Elaine O; Claud, Erika C

    2016-09-01

    Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics.

  15. Antigenic variation in Giardia lamblia is regulated by RNA interference.

    PubMed

    Prucca, César G; Slavin, Ileana; Quiroga, Rodrigo; Elías, Eliana V; Rivero, Fernando D; Saura, Alicia; Carranza, Pedro G; Luján, Hugo D

    2008-12-11

    Giardia lamblia (also called Giardia intestinalis) is one of the most common intestinal parasites of humans. To evade the host's immune response, Giardia undergoes antigenic variation-a process that allows the parasite to develop chronic and recurrent infections. From a repertoire of approximately 190 variant-specific surface protein (VSP)-coding genes, Giardia expresses only one VSP on the surface of each parasite at a particular time, but spontaneously switches to a different VSP by unknown mechanisms. Here we show that regulation of VSP expression involves a system comprising RNA-dependent RNA polymerase, Dicer and Argonaute, known components of the RNA interference machinery. Clones expressing a single surface antigen efficiently transcribe several VSP genes but only accumulate transcripts encoding the VSP to be expressed. Detection of antisense RNAs corresponding to the silenced VSP genes and small RNAs from the silenced but not for the expressed vsp implicate the RNA interference pathway in antigenic variation. Remarkably, silencing of Dicer and RNA-dependent RNA polymerase leads to a change from single to multiple VSP expression in individual parasites.

  16. Microbial Properties Database Editor Tutorial

    EPA Science Inventory

    A Microbial Properties Database Editor (MPDBE) has been developed to help consolidate microbial-relevant data to populate a microbial database and support a database editor by which an authorized user can modify physico-microbial properties related to microbial indicators and pat...

  17. Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria: producer phenotyping and relation with intestinal community.

    PubMed

    Possemiers, Sam; Bolca, Selin; Eeckhaut, Ellen; Depypere, Herman; Verstraete, Willy

    2007-08-01

    Many studies have investigated the importance of the intestinal bacterial activation of individual phytoestrogens. However, human nutrition contains different phytoestrogens and the final exposure depends on the microbial potential to activate all different groups within each individual. In this work, interindividual variations in the bacterial activation of the different phytoestrogens were assessed. Incubation of feces from 100 individuals using SoyLife EXTRA, LinumLife EXTRA and isoxanthohumol suggested that individuals could be separated into high, moderate and low O-desmethylangolensin (O-DMA), equol, enterodiol (END), enterolactone (ENL) or 8-prenylnaringenin producers, but that the metabolism of isoflavones, lignans and prenylflavonoids follows separate, independent pathways. However, O-DMA and equol production correlated negatively, whereas a positive correlation was found between END and ENL production. In addition, END production correlated negatively with Clostridium coccoides-Eubacterium rectale counts. Furthermore, O-DMA production was correlated with the abundance of methanogens, whereas equol production correlated with sulfate-reducing bacteria, indicating that the metabolic fate of daidzein may be related to intestinal H(2) metabolism.

  18. Why Microbial Communities?

    ScienceCinema

    Fredrickson, Jim (PNNL)

    2016-07-12

    The Microbial Communities Initiative is a 5-year investment by Pacific Northwest National Laboratory that integrates biological/ecological experimentation, analytical chemistry, and simulation modeling. The objective is to create transforming technologies, elucidate mechanistic forces, and develop theoretical frameworks for the analysis and predictive understanding of microbial communities. Dr. Fredrickson introduces the symposium by defining microbial communities and describing their scientific relevance as they relate to solving problems in energy, climate, and sustainability.

  19. Intestinal flora, probiotics, and cirrhosis.

    PubMed

    Guerrero Hernández, Ignacio; Torre Delgadillo, Aldo; Vargas Vorackova, Florencia; Uribe, Misael

    2008-01-01

    Intestinal microflora constitutes a symbiotic ecosystem in permanent equilibrium, composed mainly of anaerobic bacteria. However, such equilibrium may be altered by daily conditions as drug use or pathologies interfering with intestinal physiology, generating an unfavorable environment for the organism. Besides, there are factors which may cause alterations in the intestinal wall, creating the conditions for translocation or permeation of substances or bacteria. In cirrhotic patients, there are many conditions that combine to alter the amount and populations of intestinal bacteria, as well as the functional capacity of the intestinal wall to prevent the permeation of substances and bacteria. Nowadays, numerous complications associated with cirrhosis have been identified, where such mechanisms could play an important role. There is evidence that some probiotic microorganisms could restore the microbiologic and immunologic equilibrium in the intestinal wall in cirrhotic patients and help in the treatment of complications due to cirrhosis. This article has the objective to review the interactions between intestinal flora, gut permeability, and the actual role of probiotics in the field of cirrhotic patients.

  20. Comparative Analysis of Gingival Tissue Antigen Presentation Pathways in Aging and Periodontitis

    PubMed Central

    Gonzalez, O.A.; Novak, M.J.; Kirakodu, S.; Orraca, L.; Chen, K.C.; Strom-berg, A.; Gonzalez-Martinez, J.; Ebersole, J. L.

    2014-01-01

    Aim Gingival tissues of periodontitis lesions contribute to local elevations in mediators, including both specific T cell and antibody immune responses to oral bacterial antigens. Thus, antigen processing and presentation activities must exist in these tissues to link antigen-presenting cells with adaptive immunity. We hypothesized that alterations in the transcriptome of antigen processing and presentation genes occur in aging gingival tissues and that periodontitis enhances these differences reflecting tissues less capable of immune resistance to oral pathogens. Materials and Methods Rhesus monkeys (n=34) from 3–23 years of age were examined. A buccal gingival sample from healthy or periodontitis sites were obtained, total RNA isolated, and microarray analysis was used to describe the transcriptome. Results The results demonstrated increased transcription of genes related to the MHC class II and negative regulation of NK cells with aging in healthy gingival tissues. In contrast, both adult and aging periodontitis tissues showed decreased transcription of genes for MHC class II antigens, coincident with up-regulation of MHC class I-associated genes. Conclusion These transcriptional changes suggest a response of healthy aging tissues through the class II pathway (i.e., endocytosed antigens) and altered responses in periodontitis that could reflect host-associated self-antigens or targeting cytosolic intra-cellular microbial pathogens. PMID:24304139

  1. Intestinal microbiota and immune related genes in sea cucumber (Apostichopus japonicus) response to dietary β-glucan supplementation

    SciTech Connect

    Yang, Gang; Xu, Zhenjiang; Tian, Xiangli; Dong, Shuanglin; Peng, Mo

    2015-02-27

    β-glucan is a prebiotic well known for its beneficial outcomes on sea cucumber health through modifying the host intestinal microbiota. High-throughput sequencing techniques provide an opportunity for the identification and characterization of microbes. In this study, we investigated the intestinal microbial community composition, interaction among species, and intestinal immune genes in sea cucumber fed with diet supplemented with or without β-glucan supplementation. The results show that the intestinal dominant classes in the control group are Flavobacteriia, Gammaproteobacteria, and Alphaproteobacteria, whereas Alphaproteobacteria, Flavobacteriia, and Verrucomicrobiae are enriched in the β-glucan group. Dietary β-glucan supplementation promoted the proliferation of the family Rhodobacteraceae of the Alphaproteobacteria class and the family Verrucomicrobiaceae of the Verrucomicrobiae class and reduced the relative abundance of the family Flavobacteriaceae of Flavobacteria class. The ecological network analysis suggests that dietary β-glucan supplementation can alter the network interactions among different microbial functional groups by changing the microbial community composition and topological roles of the OTUs in the ecological network. Dietary β-glucan supplementation has a positive impact on immune responses of the intestine of sea cucumber by activating NF-κB signaling pathway, probably through modulating the balance of intestinal microbiota. - Highlights: • Dietary β-glucan supplementation increases the abundance of Rhodobacteraceae and Verrucomicrobiaceae in the intestine. • Dietary β-glucan supplementation changes the topological roles of OTUs in the ecological network. • Dietary β-glucan supplementation has a positive impact on the immune response of intestine of sea cucumber.

  2. Epithelial Microvilli Establish an Electrostatic Barrier to Microbial Adhesion

    PubMed Central

    Bennett, Kaila M.; Walker, Sharon L.

    2014-01-01

    Microvilli are membrane extensions on the apical surface of polarized epithelia, such as intestinal enterocytes and tubule and duct epithelia. One notable exception in mucosal epithelia is M cells, which are specialized for capturing luminal microbial particles; M cells display a unique apical membrane lacking microvilli. Based on studies of M cell uptake under different ionic conditions, we hypothesized that microvilli may augment the mucosal barrier by providing an increased surface charge density from the increased membrane surface and associated glycoproteins. Thus, electrostatic charges may repel microbes from epithelial cells bearing microvilli, while M cells are more susceptible to microbial adhesion. To test the role of microvilli in bacterial adhesion and uptake, we developed polarized intestinal epithelial cells with reduced microvilli (“microvillus-minus,” or MVM) but retaining normal tight junctions. When tested for interactions with microbial particles in suspension, MVM cells showed greatly enhanced adhesion and uptake of particles compared to microvillus-positive cells. This preference showed a linear relationship to bacterial surface charge, suggesting that microvilli resist binding of microbes by using electrostatic repulsion. Moreover, this predicts that pathogen modification of electrostatic forces may contribute directly to virulence. Accordingly, the effacement effector protein Tir from enterohemorrhagic Escherichia coli O157:H7 expressed in epithelial cells induced a loss of microvilli with consequent enhanced microbial binding. These results provide a new context for microvillus function in the host-pathogen relationship, based on electrostatic interactions. PMID:24778113

  3. Common antigen structures of HL-A antigens

    PubMed Central

    Miyakawa, Y.; Tanigaki, N.; Yagi, Y.; Pressman, D.

    1973-01-01

    Antigenic determinants recognizable by rabbits were found to be present on the molecular fragments (48,000 Daltons) which were obtained by papain-solubilization of the membrane fractions of cultured human lymphoid cells and which carried the HL-A determinants. Results were obtained which suggest that these antigenic determinants are present in common on these molecular fragments carrying HL-A determinants regardless of their HL-A specificity and are restricted to the molecular fragments which carry HL-A determinants. The study was made by use of radioimmune methods involving the binding of radioiodine-labelled soluble HL-A antigen preparations by anti-HL-A alloantisera and by rabbit antisera raised against the membrane fractions of cultured human lymphoid cells. PMID:4119543

  4. Proteobacteria: microbial signature of dysbiosis in gut microbiota.

    PubMed

    Shin, Na-Ri; Whon, Tae Woong; Bae, Jin-Woo

    2015-09-01

    Recent advances in sequencing techniques, applied to the study of microbial communities, have provided compelling evidence that the mammalian intestinal tract harbors a complex microbial community whose composition is a critical determinant of host health in the context of metabolism and inflammation. Given that an imbalanced gut microbiota often arises from a sustained increase in abundance of the phylum Proteobacteria, the natural human gut flora normally contains only a minor proportion of this phylum. Here, we review studies that explored the association between an abnormal expansion of Proteobacteria and a compromised ability to maintain a balanced gut microbial community. We also propose that an increased prevalence of Proteobacteria is a potential diagnostic signature of dysbiosis and risk of disease.

  5. Microbial Communities in Pre-Columbian Coprolites

    PubMed Central

    Santiago-Rodriguez, Tasha M.; Narganes-Storde, Yvonne M.; Chanlatte, Luis; Crespo-Torres, Edwin; Toranzos, Gary A.; Jimenez-Flores, Rafael; Hamrick, Alice; Cano, Raul J.

    2013-01-01

    The study of coprolites from earlier cultures represents a great opportunity to study an “unaltered” composition of the intestinal microbiota. To test this, pre-Columbian coprolites from two cultures, the Huecoid and Saladoid, were evaluated for the presence of DNA, proteins and lipids by cytochemical staining, human and/or dog-specific Bacteroides spp. by PCR, as well as bacteria, fungi and archaea using Terminal Restriction Fragment analyses. DNA, proteins and lipids, and human-specific Bacteroides DNA were detected in all coprolites. Multidimensional scaling analyses resulted in spatial arrangements of microbial profiles by culture, further supported by cluster analysis and ANOSIM. Differences between the microbial communities were positively correlated with culture, and SIMPER analysis indicated 68.8% dissimilarity between the Huecoid and Saladoid. Proteobacteria, Bacteroidetes and methanogens were found in all coprolite samples. Propionebacteria, Shewanella and lactic acid bacteria dominated in the Huecoid samples, while Acidobacteria, and peptococci were dominant in Saladoid samples. Yeasts, including Candida albicans and Crypotococcus spp. were found in all samples. Basidiomycetes were the most notable fungi in Huecoid samples while Ascomycetes predominated in Saladoid samples, suggesting differences in dietary habits. Our study provides an approach for the study of the microbial communities of coprolite samples from various cultures. PMID:23755194

  6. How does antigen retrieval work?

    PubMed

    Leong, Trishe Y-M; Leong, Anthony S-Y

    2007-03-01

    The introduction of antigen retrieval has enabled immunohistology to become an integral component of morphologic diagnosis, routinely employed in cancer diagnosis, and for the identification of therapeutic and prognostic markers. The mechanism of antigen retrieval, however, remains speculative with the key to our understanding embedded in the actions of formaldehyde on proteins. One commonly held concept is that heat primarily breaks down protein cross-linkages that occur with aldehyde fixation, thus "unmasking" protein epitopes of interest. Enzymatic pretreatment is also thought to have a similar action whereas such "breakages" are the result of extremely rapid molecular movement induced by microwaves and ultrasound. The formation of rigid cagelike calcium complexes during formaldehyde fixation is another suggested mechanism of antigen masking requiring chelating agents for reversal. A more recent suggestion for the antigen retrieval phenomenon has evoked the Mannich reaction, which occurs with the cross-linking of some proteins. Such cross-linkages can be hydrolyzed by heat or alkalis so that the process of antigen retrieval may be the simple removal of such cross-linked proteins that are sterically interfering with the binding of antibodies to linear protein epitopes in the tissue section. We are clearly not yet in possession of all the answers to the problem.

  7. Analysis of gene–environment interactions in postnatal development of the mammalian intestine

    PubMed Central

    Rakoff-Nahoum, Seth; Kong, Yong; Kleinstein, Steven H.; Subramanian, Sathish; Ahern, Philip P.; Gordon, Jeffrey I.; Medzhitov, Ruslan

    2015-01-01

    Unlike mammalian embryogenesis, which takes place in the relatively predictable and stable environment of the uterus, postnatal development can be affected by a multitude of highly variable environmental factors, including diet, exposure to noxious substances, and microorganisms. Microbial colonization of the intestine is thought to play a particularly important role in postnatal development of the gastrointestinal, metabolic, and immune systems. Major changes in environmental exposure occur right after birth, upon weaning, and during pubertal maturation into adulthood. These transitions include dramatic changes in intestinal contents and require appropriate adaptations to meet changes in functional demands. Here, we attempt to both characterize and provide mechanistic insights into postnatal intestinal ontogeny. We investigated changes in global intestinal gene expression through postnatal developmental transitions. We report profound alterations in small and large intestinal transcriptional programs that accompany both weaning and puberty in WT mice. Using myeloid differentiation factor 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) double knockout littermates, we define the role of toll-like receptors (TLRs) and interleukin (IL)-1 receptor family member signaling in postnatal gene expression programs and select ontogeny-specific phenotypes, such as vascular and smooth muscle development and neonatal epithelial and mast cell homeostasis. Metaanalysis of the effect of the microbiota on intestinal gene expression allowed for mechanistic classification of developmentally regulated genes by TLR/IL-1R (TIR) signaling and/or indigenous microbes. We find that practically every aspect of intestinal physiology is affected by postnatal transitions. Developmental timing, microbial colonization, and TIR signaling seem to play distinct and specific roles in regulation of gene-expression programs throughout postnatal development. PMID:25691701

  8. Gut Adhesive Bacillus subtilis Spores as a Platform for Mucosal Delivery of Antigens

    PubMed Central

    Tavares Batista, Milene; Souza, Renata D.; Paccez, Juliano D.; Luiz, Wilson B.; Ferreira, Ewerton L.; Cavalcante, Rafael C. M.; Ferreira, Rita C. C.

    2014-01-01

    Bacillus subtilis spores have been used as safe and heat-resistant antigen delivery vectors. Nonetheless, the oral administration of spores typically induces weak immune responses to the passenger antigens, which may be attributed to the fast transit through the gastrointestinal tract. To overcome this limitation, we have developed B. subtilis spores capable of binding to the gut epithelium by means of expressing bacterial adhesins on the spore surface. The resulting spores bound to in vitro intestinal cells, showed a longer transit through the mouse intestinal tract, and interacted with Peyer's patch cells. The adhesive spores increased the systemic and secreted antibody responses to the Streptococcus mutans P1 protein, used as a model antigen, following oral, intranasal, and sublingual administration. Additionally, P1-specific antibodies efficiently inhibited the adhesion of the oral pathogen Streptococcus mutans to abiotic surfaces. These results support the use of gut-colonizing B. subtilis spores as a new platform for the mucosal delivery of vaccine antigens. PMID:24421038

  9. Effects of target antigen competition on distribution of monoclonal antibody to solid tumors.

    PubMed

    Kennel, S J

    1992-03-01

    Monoclonal antibody (MoAb) 11A and MoAb 13A recognize normal murine cell surface glycoproteins, which are also expressed in high concentrations on Line 1 lung carcinoma. Studies were initiated to examine the competition in vivo for radiolabeled MoAb between sites on the tumor versus sites on normal tissue. Quantitative 2-site assay of the alpha 6 beta 4 integrin recognized by MoAb 11A showed that major sites of expression are tumor, intestine, and skin. Microdistribution studies show that at doses of 125I-labeled MoAb 11A less than the total body antigen load, the MoAb bound to beta 4 endothelial cells with little extravasation to epithelial sites. As the MoAb dose was increased, and endothelial sites became saturated, deposition at epithelial sites including skin and tumor became apparent. Quantitative radioimmunoassay with MoAb 13A, recognizing CD44 (P100), demonstrated major sites of expression as tumor, intestine, liver and, to a lesser extent, spleen and skin. Microdistribution studies at low doses of 125I-labeled MoAb showed deposition mainly in the liver and spleen sinusoids, whereas higher doses were necessary to maximize MoAb accumulation in tumor. The rapid access of MoAb to target antigen is the most important parameter in efficient localization of MoAb. Access of antigen outside the vascular space is regulated at least in part by the permeability of the endothelial barrier. Of the organs studied, antigen accessibility increases in the following order: lung epithelium less than skin epithelium less than intestine and uterus epithelium less than epithelial tumors less than liver and spleen sinusoids less than intervascular sites. Antigens in easily accessible sites interact with MoAb first and must be saturated before MoAb will penetrate to less accessible areas. Thus, the extent of competition of antigen for available MoAb depends not only on the amount of antigen, but also on the site at which it is expressed. Doses that achieve maximum binding to tumor

  10. Exogenous lactobacilli mitigate microbial changes associated with grain fermentation in vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cereal grains are often included in equine diets. Sugars and starch in grains can be digested and absorbed in the small intestine, but a high proportion of grain in the diet can allow starch to reach the hindgut, disturbing the microbial ecology. Streptococci and lactobacilli both catabolize starch ...

  11. Chronic intestinal pseudo-obstruction.

    PubMed

    Antonucci, Alexandra; Fronzoni, Lucia; Cogliandro, Laura; Cogliandro, Rosanna-F; Caputo, Carla; De Giorgio, Roberto; Pallotti, Francesca; Barbara, Giovanni; Corinaldesi, Roberto; Stanghellini, Vincenzo

    2008-05-21

    Chronic intestinal pseudo-obstruction (CIPO) is a severe digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features intestinal pseudo-obstruction can be classified into three main categories: neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseudo-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases.

  12. Chronic intestinal pseudo-obstruction

    PubMed Central

    Antonucci, Alexandra; Fronzoni, Lucia; Cogliandro, Laura; Cogliandro, Rosanna F; Caputo, Carla; Giorgio, Roberto De; Pallotti, Francesca; Barbara, Giovanni; Corinaldesi, Roberto; Stanghellini, Vincenzo

    2008-01-01

    Chronic intestinal pseudo-obstruction (CIPO) is a severe digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features intestinal pseudo-obstruction can be classified into three main categories: neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseudo-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases. PMID:18494042

  13. Intestinal angioedema mimicking Crohn's disease.

    PubMed

    Malcolm, A; Prather, C M

    1999-10-18

    Angioedema usually presents as episodic attacks of swelling of the face, airway and extremities, but it may also involve visceral tissues. A 58-year-old woman with repeated episodes of abdominal pain, nausea and vomiting had two laparotomies and was treated for Crohn's disease for two years before a diagnosis of acquired intestinal angioedema was made. This case provides important insights into the presentation of intestinal angioedema.

  14. Biofilms: A microbial home

    PubMed Central

    Chandki, Rita; Banthia, Priyank; Banthia, Ruchi

    2011-01-01

    Microbial biofilms are mainly implicated in etiopathogenesis of caries and periodontal disease. Owing to its properties, these pose great challenges. Continuous and regular disruption of these biofilms is imperative for prevention and management of oral diseases. This essay provides a detailed insight into properties, mechanisms of etiopathogenesis, detection and removal of these microbial biofilms. PMID:21976832

  15. Inflight microbial analysis technology

    NASA Technical Reports Server (NTRS)

    Pierson, Duane L.; Brown, Harlan D.

    1987-01-01

    This paper provides an assessment of functional characteristics needed in the microbial water analysis system being developed for Space Station. Available technology is reviewed with respect to performing microbial monitoring, isolation, or identification functions. An integrated system composed of three different technologies is presented.

  16. Mensenchymal stem cells can delay radiation-induced crypt death: impact on intestinal CD44(+) fragments.

    PubMed

    Chang, Peng-Yu; Jin, Xing; Jiang, Yi-Yao; Wang, Li-Xian; Liu, Yong-Jun; Wang, Jin

    2016-05-01

    Intestinal stem cells are primitive cells found within the intestinal epithelium that play a central role in maintaining epithelial homeostasis through self-renewal and commitment into functional epithelial cells. Several markers are available to identify intestinal stem cells, such as Lgr5, CD24 and EphB2, which can be used to sort intestinal stem cells from mammalian gut. Here, we identify and isolate intestinal stem cells from C57BL/6 mice by using a cell surface antigen, CD44. In vitro, some CD44(+) crypt cells are capable of forming "villus-crypt"-like structures (organoids). A subset strongly positive for CD44 expresses high levels of intestinal stem-cell-related genes, including Lgr5, Bmi1, Hopx, Lrig1, Ascl2, Smoc2 and Rnf43. Cells from this subset are more capable of developing into organoids in vitro, compared with the subset weakly positive for CD44. However, the organoids are sensitive to ionizing irradiation. We investigate the specific roles of mesenchymal stem cells in protecting organoids against radiation-induced crypt death. When co-cultured with mesenchymal stem cells, the crypt domains of irradiated organoids possess more proliferative cells and fewer apoptotic cells than those not co-cultured with mesenchymal stem cells. Cd44v6 continues to be expressed in the crypt domains of irradiated organoids co-cultured with mesenchymal stem cells. Our results indicate specific roles of mesenchymal stem cells in delaying radiation-induced crypt death in vitro.

  17. Intestinal absorption and histomorphometry of Syrian hamsters (Mesocricetus auratus) experimentally infected with Lawsonia intracellularis.

    PubMed

    Vannucci, Fabio Augusto; Borges, Elizabeth Lage; de Oliveira, Juliana Saes Vilaça; Guedes, Roberto Mauricio Carvalho

    2010-10-26

    The objective of this study was to evaluate the intestinal absorption and histomorphometry of hamsters experimentally infected with Lawsonia intracellularis and correlate these parameters with severity of infection based on immunohistochemistry. Sixty hamsters were equally divided into control and inoculated groups which were orally infected with intestinal mucosa homogenate from pigs naturally infected with L. intracellularis. The intestinal absorption of glucose, sodium, potassium and chloride was evaluated in live animals (25 inoculated and 25 control) on day 26 after inoculation. In this procedure, a standard solution was infused into the cranial jejunum and collected at the terminal ileum. The experimental infection was confirmed by gross and histopathological examination and L. intracellularis antigen labeling by immunohistochemistry. Histomorphometry analysis demonstrated positive correlation between intestinal crypt depth and severity of infection based on immunohistochemistry. Infected animals had significantly lower intestinal absorption of glucose, potassium and chloride. These results indicate a lower intestinal absorption as an important mechanism of diarrhea in hamsters experimentally infected with L. intracellularis. Therefore, malabsorption should be considered as the main mechanism involved in the physiopathology of the diarrhea in L. intracellularis infected animals.

  18. Dendritic cell subsets in the intestinal lamina propria: ontogeny and function.

    PubMed

    Persson, Emma K; Scott, Charlotte L; Mowat, Allan McI; Agace, William W

    2013-12-01

    The intestinal mucosa is exposed to large amounts of foreign antigen (Ag) derived from commensal bacteria, dietary Ags, and intestinal pathogens. Dendritic cells (DCs) are believed to be involved in the induction of tolerance to harmless Ags and in mounting protective immune responses to pathogens and, as such, to play key roles in regulating intestinal immune homeostasis. The characterization of classical DCs (cDCs) in the intestinal lamina propria has been under intense investigation in recent years but the use of markers (including CD11c, CD11b, MHC class II), which are also expressed by intestinal MΦs, has led to some controversy regarding their definition. Here we review recent studies that help to distinguish cDCs subsets from monocyte-derived cells in the intestinal mucosa. We address the phenotype and ontogeny of these cDC subsets and highlight recent findings indicating that these subsets play distinct roles in the regulation of mucosal immune responses in vivo.

  19. Acute antibody-mediated rejection after intestinal transplantation

    PubMed Central

    Wu, Guo-Sheng; Cruz Jr, Ruy J; Cai, Jun-Chao

    2016-01-01

    AIM To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection (ABMR) after intestinal transplantation (ITx). METHODS A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody (DSA), acute tissue damage, C4d deposition, and allograft dysfunction. RESULTS Acute ABMR was identified in 18 (10.3%) out of 175 intestinal allografts with an average occurrence of 10 d (range, 4-162) after ITx. All acute ABMR cases were presensitized to donor human leukocyte antigens class I and/or II antigens with a detectable DSA. A positive cross-match was seen in 14 (77.8%) cases and twelve of 18 patients (66.7%) produced newly-formed DSA following ITx. Histological characteristics of acute ABMR include endothelial C4d deposits, interstitial hemorrhage, and severe congestion with focal fibrin thrombin in the lamina propria capillaries. Multivariate analysis identified a liver-free graft and high level of panel reactive antibody as a significant independent risk factor. Despite initial improvement after therapy, eleven recipients (61.1%) lost transplant secondary to rejection. Of those, 9 (50%) underwent graft removal and 4 (22.2%) received second transplantation following acute ABMR. At an average follow-up of 32.3 mo (range, 13.3-76.4), 8 (44.4%) recipients died. CONCLUSION Our results indicate that acute ABMR is an important cause of intestine graft dysfunction, particularly in a liver-exclusive graft and survivors are at an increased risk of developing refractory acute rejection and chronic rejection. More effective strategies to prevent and manage acute ABMR are needed to improve outcomes. PMID:28058223

  20. 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.

  1. Systemic follicular lymphoma with massive intestinal involvement with leukemic manifestation.

    PubMed

    Ono, Yuichiro; Aoki, Kazunari; Kato, Aiko; Arima, Hiroshi; Takiuchi, Yohko; Nagano, Seiji; Tabata, Sumie; Yanagita, Sohshi; Matsushita, Akiko; Maruoka, Hayato; Imai, Yukihiro; Ishikawa, Takayuki; Takahashi, Takayuki

    2011-01-01

    A 30-year-old man was referred to our hospital with leukocytosis and fecal occult blood. His white blood cell count was 30.2 × 10(9)/L with 79% small- to medium-sized lymphocytes. Surface antigen analysis revealed that these lymphocytes were positive for CD19, CD20, CD10, and CD23, but negative for CD5. The lymphocytes infiltrated the bone marrow. On endoscopic examination of the duodenum and jejunum, many small polypoid lesions were observed. A histologic picture of a biopsied lesion showed diffuse infiltration of small- to medium-sized lymphocytes in the submucosal region. On immunohistochemistry, these lymphocytes were positive for CD20, BCL2, and CD10 (weakly). Polymerase chain reaction analysis of cells from peripheral blood, bone marrow, and intestinal lesion showed a fusion product of BCL2 and immunoglobulin heavy chain (IGH) genes. The fused BCL2/IGH gene was also demonstrated by fluorescence in situ hybridization in the same cell sources. Computed tomography scanning showed marked wall thickening throughout the small intestine and enlarged mesenteric lymph nodes. A diagnosis of follicular lymphoma with massive intestinal involvement in a leukemic state was made. After 6 courses of rituximab-combined CHOP chemotherapy, complete remission was obtained.

  2. HLA antigens and Berger's disease.

    PubMed

    Bignon, J D; Houssin, A; Soulillou, J P; Denis, J; Guimbretiere, J; Guenel, J

    1980-07-01

    We have studied the frequencies of HLA-A, -B antigens in 73 Berger's disease patients, plus HLA-DR antigens in 35 of them, and compared the percentages of antigens frequencies with those of a local and national panel. This study does not confirm the positive associations with HLA-Bw35 or HLA-B12 which have been previously reported. The HLA-DR typing only showed increased frequency of blanks in the patients (P smaller than 0.01, but no significant corr.P). Patients with Berger's disease and renal failure have a higher (but still not significant) HLA-Bw35 frequency than those without renal failure. The reasons for the discrepancy between our group and others are analysed.

  3. Intestinal Microbiota Distinguish Gout Patients from Healthy Humans

    PubMed Central

    Guo, Zhuang; Zhang, Jiachao; Wang, Zhanli; Ang, Kay Ying; Huang, Shi; Hou, Qiangchuan; Su, Xiaoquan; Qiao, Jianmin; Zheng, Yi; Wang, Lifeng; Koh, Eileen; Danliang, Ho; Xu, Jian; Lee, Yuan Kun; Zhang, Heping

    2016-01-01

    Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota. PMID:26852926

  4. Intestinal Microbiota Distinguish Gout Patients from Healthy Humans.

    PubMed

    Guo, Zhuang; Zhang, Jiachao; Wang, Zhanli; Ang, Kay Ying; Huang, Shi; Hou, Qiangchuan; Su, Xiaoquan; Qiao, Jianmin; Zheng, Yi; Wang, Lifeng; Koh, Eileen; Danliang, Ho; Xu, Jian; Lee, Yuan Kun; Zhang, Heping

    2016-02-08

    Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota.

  5. Antimicrobial Proteins in Intestine and Inflammatory Bowel Diseases

    PubMed Central

    2014-01-01

    Mucosal surface of the intestinal tract is continuously exposed to a large number of microorganisms. To manage the substantial microbial exposure, epithelial surfaces produce a diverse arsenal of antimicrobial proteins (AMPs) that directly kill or inhibit the growth of microorganisms. Thus, AMPs are important components of innate immunity in the gut mucosa. They are frequently expressed in response to colonic inflammation and infection. Expression of many AMPs, including human β-defensin 2-4 and cathelicidin, is induced in response to invasion of pathogens or enteric microbiota into the mucosal barrier. In contrast, some AMPs, including human α-defensin 5-6 and human β-defensin 1, are constitutively expressed without microbial contact or invasion. In addition, specific AMPs are reported to be associated with inflammatory bowel disease (IBD) due to altered expression of AMPs or development of autoantibodies against AMPs. The advanced knowledge for AMPs expression in IBD can lead to its potential use as biomarkers for disease activity. Although the administration of exogenous AMPs as therapeutic strategies against IBD is still at an early stage of development, augmented induction of endogenous AMPs may be another interesting future research direction for the protective and therapeutic purposes. This review discusses new advances in our understanding of how intestinal AMPs protect against pathogens and contribute to pathophysiology of IBD. PMID:25349560

  6. Efficient Norovirus and Reovirus Replication in the Mouse Intestine Requires Microfold (M) Cells

    PubMed Central

    Gonzalez-Hernandez, Mariam B.; Liu, Thomas; Payne, Hilary C.; Stencel-Baerenwald, Jennifer E.; Ikizler, Mine; Yagita, Hideo; Dermody, Terence S.; Williams, Ifor R.

    2014-01-01

    ABSTRACT Microfold (M) cells are specialized intestinal epithelial cells that internalize particulate antigens and aid in the establishment of immune responses to enteric pathogens. M cells have also been suggested as a portal for pathogen entry into the host. While virus particles have been observed in M cells, it is not known whether viruses use M cells to initiate a productive infection. Noroviruses (NoVs) are single-stranded RNA viruses that infect host organisms via the fecal-oral route. Murine NoV (MNV) infects intestinal macrophages and dendritic cells and provides a tractable experimental system for understanding how an enteric virus overcomes the intestinal epithelial barrier to infect underlying target cells. We found that replication of two divergent MNV strains was reduced in mice depleted of M cells. Reoviruses are double-stranded RNA viruses that infect hosts via respiratory or enteric routes. In contrast to MNV, reovirus infects enterocytes in the intestine. Despite differences in cell tropism, reovirus infection was also reduced in M cell-depleted mice. These data demonstrate that M cells are required for the pathogenesis of two unrelated enteric viruses that replicate in different cell types within the intestine. IMPORTANCE To successfully infect their hosts, pathogens that infect via the gastrointestinal tract must overcome the multilayered system of host defenses. Microfold (M) cells are specialized intestinal epithelial cells that internalize particulate antigens and aid in the establishment of immune responses to enteric pathogens. Virus particles have been observed within M cells. However, it is not known whether viruses use M cells to initiate a productive infection. To address this question, we use MNV and reovirus, two enteric viruses that replicate in different cell types in the intestine, intestinal epithelial cells for reovirus and intestinal mononuclear phagocytes for MNV. Interestingly, MNV- and reovirus-infected mice depleted of M

  7. Protozoan predation, diversifying selection, and the evolution of antigenic diversity in Salmonella

    PubMed Central

    Wildschutte, Hans; Wolfe, David M.; Tamewitz, Aletheia; Lawrence, Jeffrey G.

    2004-01-01

    Extensive population-level genetic variability at the Salmonella rfb locus, which encodes enzymes responsible for synthesis of the O-antigen polysaccharide, is thought to have arisen through frequency-dependent selection (FDS) by means of exposure of this pathogen to host immune systems. The FDS hypothesis works well for pathogens such as Haemophilus influenzae and Neisseria meningitis, which alter the composition of their O-antigens during the course of bloodborne infections. In contrast, Salmonella remains resident in epithelial cells or macrophages during infection and does not have phase variability in its O-antigen. More importantly, Salmonella shows host–serovar specificity, whereby strains bearing certain O-antigens cause disease primarily in specific hosts; this behavior is inconsistent with FDS providing selection for the origin or maintenance of extensive polymorphism at the rfb locus. Alternatively, selective pressure may originate from the host intestinal environment itself, wherein diversifying selection mediated by protozoan predation allows for the continued existence of Salmonella able to avoid consumption by host-specific protozoa. This selective pressure would result in high population-level diversity at the Salmonella rfb locus without phase variation. We show here that intestinal protozoa recognize antigenically diverse Salmonella with different efficiencies and demonstrate that differences solely in the O-antigen are sufficient to allow for prey discrimination. Combined with observations of the differential distributions of both serotypes of bacterial species and their protozoan predators among environments, our data provides a framework for the evolution of high genetic diversity at the rfb locus and host-specific pathogenicity in Salmonella. PMID:15247413

  8. Microbiota of the Small Intestine Is Selectively Engulfed by Phagocytes of the Lamina Propria and Peyer’s Patches

    PubMed Central

    Morikawa, Masatoshi; Tsujibe, Satoshi; Kiyoshima-Shibata, Junko; Watanabe, Yohei; Kato-Nagaoka, Noriko; Shida, Kan; Matsumoto, Satoshi

    2016-01-01

    Phagocytes such as dendritic cells and macrophages, which are distributed in the small intestinal mucosa, play a crucial role in maintaining mucosal homeostasis by sampling the luminal gut microbiota. However, there is limited information regarding microbial uptake in a steady state. We investigated the composition of murine gut microbiota that is engulfed by phagocytes of specific subsets in the small intestinal lamina propria (SILP) and Peyer’s patches (PP). Analysis of bacterial 16S rRNA gene amplicon sequences revealed that: 1) all the phagocyte subsets in the SILP primarily engulfed Lactobacillus (the most abundant microbe in the small intestine), whereas CD11bhi and CD11bhiCD11chi cell subsets in PP mostly engulfed segmented filamentous bacteria (indigenous bacteria in rodents that are reported to adhere to intestinal epithelial cells); and 2) among the Lactobacillus species engulfed by the SILP cell subsets, L. murinus was engulfed more frequently than L. taiwanensis, although both these Lactobacillus species were abundant in the small intestine under physiological conditions. These results suggest that small intestinal microbiota is selectively engulfed by phagocytes that localize in the adjacent intestinal mucosa in a steady state. These observations may provide insight into the crucial role of phagocytes in immune surveillance of the small intestinal mucosa. PMID:27701454

  9. Role of fucosyltransferases in the association between apomucin and Lewis antigen expression in normal and malignant gastric epithelium

    PubMed Central

    Lopez-Ferrer, A; de Bolos, C; Barranco, C; Garrido, M; Isern, J; Carlstedt, I; Reis, C; Torrado, J; Real, F

    2000-01-01

    BACKGROUND—In normal gastric epithelium, MUC5AC is detected in superficial epithelium associated with Lewis type 1 antigens and MUC6 is detected in antral glands with Lewis type 2. Therefore, the stomach constitutes an excellent model to examine the role of glycosyltransferases in determining the specificity of apomucin glycosylation.
AIMS—To determine the molecular basis of this association and to examine changes in expression of gastric and intestinal apomucins and their association with Lewis antigens during the gastric carcinogenesis process.
METHODS—Fucosyltransferase (FUT1, FUT2, FUT3) and mucin (MUC5AC, MUC6) transcripts were detected using reverse transcription-polymerase chain reaction. Apomucin (MUC2, MUC4, MUC5AC, MUC6) and Lewis antigen (types 1 and 2) expression were analysed using single and double immunohistochemistry and in situ hybridisation.
RESULTS—In the normal stomach, FUT1 is exclusively detected associated with MUC6; FUT2 is only detected when MUC5AC is present. This co-regulation is lost in gastric tumours, as is differential expression of MUC5AC and MUC6 in normal gastric epithelial cells. In gastric tumours, especially those with the intestinal phenotype, MUC2 and MUC4 genes are upregulated, and gastric-type and intestinal-type mucins are coexpressed. These changes are early events in the gastric carcinogenesis process, as they are detected in intestinal metaplasia.
CONCLUSIONS—The glycosylation pattern found in normal gastric epithelium is dictated by the specific set of fucosyltranferases expressed by the cells rather than by the apomucin sequence. The development of intestinal metaplasia and gastric cancer is associated with the appearance of cellular phenotypes that are absent from normal epithelium.


Keywords: fucosyltransferases; gastric carcinogenesis; gastric mucins; Lewis antigens PMID:10940270

  10. Monoclonal antibody-based therapies for microbial diseases

    PubMed Central

    Saylor, Carolyn; Dadachova, Ekaterina; Casadevall, Arturo

    2009-01-01

    The monoclonal antibody (mAb) revolution that currently provides many new options for the treatment of neoplastic and inflammatory diseases has largely bypassed the field of infectious diseases. Only one mAb is licensed for use against an infectious disease, although there are many in various stages of development. This situation is peculiar given that serum therapy was one of the first effective treatments for microbial diseases and that specific antibodies have numerous antimicrobial properties. The underdevelopment and underutilization of mAb therapies for microbial diseases has various complex explanations that include the current availability of antimicrobial drugs, small markets, high costs and microbial antigenic variation. However, there are signs that the climate for mAb therapeutics in infectious diseases is changing given increasing antibiotic drug resistance, the emergence of new pathogenic microbes for which no therapy is available, and development of mAb cocktail formulations. Currently, the major hurdle for the widespread introduction of mAb therapies for microbial diseases is economic, given the high costs of immunoglobulin preparations and relatively small markets. Despite these obstacles there are numerous opportunities for mAb development against microbial diseases and the development of radioimmunotherapy provides new options for enhancing the magic bullet. Hence, there is cautious optimism that the years ahead will see more mAbs in clinical use against microbial diseases. PMID:20006139

  11. Understanding how commensal obligate anaerobic bacteria regulate immune functions in the large intestine.

    PubMed

    Maier, Eva; Anderson, Rachel C; Roy, Nicole C

    2014-12-24

    The human gastrointestinal tract is colonised by trillions of commensal bacteria, most of which are obligate anaerobes residing in the large intestine. Appropriate bacterial colonisation is generally known to be critical for human health. In particular, the development and function of the immune system depends on microbial colonisation, and a regulated cross-talk between commensal bacteria, intestinal epithelial cells and immune cells is required to maintain mucosal immune homeostasis. This homeostasis is disturbed in various inflammatory disorders, such as inflammatory bowel diseases. Several in vitro and in vivo studies indicate a role for Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Akkermansia muciniphila and segmented filamentous bacteria in maintaining intestinal immune homeostasis. These obligate anaerobes are abundant in the healthy intestine but reduced in several inflammatory diseases, suggesting an association with protective effects on human health. However, knowledge of the mechanisms underlying the effects of obligate anaerobic intestinal bacteria remains limited, in part due to the difficulty of co-culturing obligate anaerobes together with oxygen-requiring human epithelial cells. By using novel dual-environment co-culture models, it will be possible to investigate the effects of the unstudied majority of intestinal microorganisms on the human epithelia. This knowledge will provide opportunities for improving human health and reducing the risk of inflammatory diseases.

  12. Alteration of Intestinal Microbiota in Mice Orally Administered with Salmon Cartilage Proteoglycan, a Prophylactic Agent

    PubMed Central

    Asano, Krisana; Yoshimura, Sayuri; Nakane, Akio

    2013-01-01

    Proteoglycan (PG) extracted from salmon nasal cartilage has potential to be a prophylactic agent. Daily oral administration of the PG attenuates systemic inflammatory response in the experimental mouse models. In this study, we applied the culture-independent approach to investigate an alteration of intestinal microbiota composition in PG-administered mice. The results indicated that the population level of bacilli increased in the small and large intestine upon PG administration. On the other hand, the population level of clostridia decreased in the large intestine. The proportion of bacteria that are able to ferment saccharides and produce short-chain fatty acids increased in the small intestine and decreased in the large intestine. Importantly, population level of probiotic lactobacilli and bacteria exhibiting the immunomodulatory effect increased in the PG-administered mice. In addition, several disease-associated bacteria decreased upon PG administration. These results provided an understanding of the specific role of PG involved in host immune modulation and supported our hypothesis that daily oral administration of PG improves the overall balance in composition of the intestinal microbial community. PMID:24040376

  13. Understanding How Commensal Obligate Anaerobic Bacteria Regulate Immune Functions in the Large Intestine

    PubMed Central

    Maier, Eva; Anderson, Rachel C.; Roy, Nicole C.

    2014-01-01

    The human gastrointestinal tract is colonised by trillions of commensal bacteria, most of which are obligate anaerobes residing in the large intestine. Appropriate bacterial colonisation is generally known to be critical for human health. In particular, the development and function of the immune system depends on microbial colonisation, and a regulated cross-talk between commensal bacteria, intestinal epithelial cells and immune cells is required to maintain mucosal immune homeostasis. This homeostasis is disturbed in various inflammatory disorders, such as inflammatory bowel diseases. Several in vitro and in vivo studies indicate a role for Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Akkermansia muciniphila and segmented filamentous bacteria in maintaining intestinal immune homeostasis. These obligate anaerobes are abundant in the healthy intestine but reduced in several inflammatory diseases, suggesting an association with protective effects on human health. However, knowledge of the mechanisms underlying the effects of obligate anaerobic intestinal bacteria remains limited, in part due to the difficulty of co-culturing obligate anaerobes together with oxygen-requiring human epithelial cells. By using novel dual-environment co-culture models, it will be possible to investigate the effects of the unstudied majority of intestinal microorganisms on the human epithelia. This knowledge will provide opportunities for improving human health and reducing the risk of inflammatory diseases. PMID:25545102

  14. Transgenic milk containing recombinant human lactoferrin modulates the intestinal flora in piglets.

    PubMed

    Hu, Wenping; Zhao, Jie; Wang, Jianwu; Yu, Tian; Wang, Jing; Li, Ning

    2012-06-01

    Lactoferrin (LF) is a beneficial multifunctional protein in milk. The objective of this study was to determine whether bovine transgenic milk containing recombinant human lactoferrin (rhLF) can modulate intestinal flora in the neonatal pig as an animal model for the human infant. We fed 7-day-old piglets (i) ordinary whole milk (OM), (ii) a 1:1 mixture of OM and rhLF milk (MM), or (iii) rhLF milk (LFM). LFM provided better average daily mass gain than OM (P = 0.007). PCR-denaturing gradient gel electrophoresis and 16S rDNA sequencing analysis revealed that the LFM piglets exhibited more diversity of the intestinal flora than the OM group. Except for the colon in the LFM group, an increasing trend in microbial diversity occurred from the duodenum to the colon. Fecal flora was not different across different ages or different treatment groups, but a cluster analysis showed that the fecal flora of OM- and MM-fed piglets had a higher degree of similarity than that of LFM-fed piglets. Based on culture-based bacterial counts of intestinal content samples, concentrations of Salmonella spp. in the colon and of Escherichia coli throughout the intestine were reduced with LFM (P < 0.01). Concentrations of Bifidobacterium spp. in the ileum and of Lactobacillus spp. throughout the intestine were also increased with LFM (P ≤ 0.01). We suggest that rhLF can modulate the intestinal flora in piglets.

  15. Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing.

    PubMed

    Berry, David; Stecher, Bärbel; Schintlmeister, Arno; Reichert, Jochen; Brugiroux, Sandrine; Wild, Birgit; Wanek, Wolfgang; Richter, Andreas; Rauch, Isabella; Decker, Thomas; Loy, Alexander; Wagner, Michael

    2013-03-19

    The animal and human intestinal mucosa secretes an assortment of compounds to establish a physical barrier between the host tissue and intestinal contents, a separation that is vital for health. Some pathogenic microorganisms as well as members of the commensal intestinal microbiota have been shown to be able to break down these secreted compounds. Our understanding of host-compound degradation by the commensal microbiota has been limited to knowledge about simplified model systems because of the difficulty in studying the complex intestinal ecosystem in vivo. In this study, we introduce an approach that overcomes previous technical limitations and allows us to observe which microbial cells in the intestine use host-derived compounds. We added stable isotope-labeled threonine i.v. to mice and combined fluorescence in situ hybridization with high-resolution secondary ion mass spectrometry imaging to characterize utilization of host proteins by individual bacterial cells. We show that two bacterial species, Bacteroides acidifaciens and Akkermansia muciniphila, are important host-protein foragers in vivo. Using gnotobiotic mice we show that microbiota composition determines the magnitude and pattern of foraging by these organisms, demonstrating that a complex microbiota is necessary in order for this niche to be fully exploited. These results underscore the importance of in vivo studies of intestinal microbiota, and the approach presented in this study will be a powerful tool to address many other key questions in animal and human microbiome research.

  16. Neonatal Colonization of Mice with LGG Promotes Intestinal Development and Decreases Susceptibility to Colitis in Adulthood

    PubMed Central

    Yan, Fang; Liu, Liping; Cao, Hailong; Moore, Daniel J.; Washington, M. Kay; Wang, Bangmao; Peek, Richard M.; Acra, Sari A.; Polk, D. Brent

    2016-01-01

    Development of the intestinal microbiota during early life serves a key regulatory stage in establishing the host-microbial relationship. This symbiotic relationship contributes to developing host immunity and maintaining health throughout the life span. This study was to develop an approach to colonize conventionally raised mice with a model probiotic bacterium, Lactobacillus rhamnosus GG (LGG), and determine the effects of LGG colonization on intestinal development and prevention of colitis in adulthood. LGG colonization in conventionally raised was established by administering LGG to pregnant mice starting at gestational day 18 and pups at postnatal day 1 to day 5. LGG colonization promoted bodyweight gain and increased diversity and richness of the colonic mucosa-associated microbiota prior to weaning. Intestinal epithelial cell proliferation, differentiation, tight junction formation and mucosal IgA production were all significantly enhanced in LGG colonized mice. Adult mice colonized with LGG showed increased IgA production and decreased susceptibility to intestinal injury and inflammation induced in the dextran sodium sulphate model of colitis. Thus, neonatal colonization of mice with LGG enhances intestinal functional maturation and IgA production and confers life long health consequences on protection from intestinal injury and inflammation. This strategy might be applied for benefiting health in the host. PMID:27095077

  17. Effects of age, species difference, antibiotics and toxicants on intestinal enzyme activity and genotoxicity

    SciTech Connect

    Chadwick, R.W.; George, S.E.; Kohan, M.J.; Allison, J.C. . Health Effects Research Lab.); Chang, J.; Long, J.E.; Duffy, M.C. ); Dekker, J.P.; Forehand, L.R. )

    1993-08-01

    Altered intestinal enzyme activity significantly affects the biotransformation and toxicity of many xenobiotics. This article summarizes research, supported by the US Air Force Bioenvironmental Hazards Research Program, that employs a novel gas-liquid chromatographic assay to investigate the effects of age, species difference, antibiotics, and environmental chemicals on enzyme activity in various regions of the intestinal tract. Significant research findings include the following: (a) age-dependent alterations in enzyme activity in the gastrointestinal (GI) tract of the developing animal that suggest a changing susceptibility to toxicants during this period; (b) discovery of previously unreported mucosal enzymes in the small intestine that are present in germ-free rats and are not susceptible to antibiotics; (c) markedly greater intestinal nitroreductase activity and significantly higher bioactivation of the procarcinogen 2,6-dinitrotoluene (DNT) in CD-1 mice than in Fischer 344 rats; (d) significantly altered intestinal enzyme activity in rats pretreated with lindane, pentachlorophenol, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), or Aroclor 1254; (e) potentiated DNT genotoxicity by Aroclor 1254 and pentachlorophenol pretreatment; and (f) a transient antagonism of DNT genotoxicity by 2,4,5-T pretreatment. Enzyme activity in the small intestine may have greater toxicological importance than previously thought in the biotransformation of environmental chemicals and as an indicator of change in the microbial flora.

  18. [Bacterial community structure in intestine of the white shrimp, Litopenaeus vannamei].

    PubMed

    Li, Ke; Zheng, Tian-ling; Tian, Yun; Yuan, Jian-jun

    2007-08-01

    The composition of bacterial community in the intestine of the white shrimp, Litopenaeus vannamei under laboratory culture condition was determined using the 16S rDNA clone library. 16s rRNA gene was amplified and a library was constructed by using the genomic DNA extracted from the bacteria in the shrimp intestine as template. 12 different RFLP patterns of the clones were obtained by restriction fragment length polymorphism analysis using Afa I and Msp I. Compared with the published sequences in GenBank database, sequencing results of cloned 16S rDNA amplicons revealed a diverse community including gamma-proteobacteria and Firmicutes in the intestine of artificial diet-fed shrimp. Results showed that the Firmicutes group can be a dominant component (75.4%) in the shrimp intestinal microflora and other clones belong to gamma-proteobacteria (24.6%) which were identified as Shewanella sp., Pantoea sp., Aranicola sp., Pseudomonas sp. and Vibrio sp., respectively. These results provide the first comprehensive description of microbial diversity of the white shrimp intestine and suggest that most of the bacteria associated with shrimp intestine are uncultured and novel species.

  19. They Must Hold Tight: Junction Proteins, Microbiota And Immunity In Intestinal Mucosa.

    PubMed

    Castoldi, Angela; Favero de Aguiar, Cristhiane; Moraes-Vieira, Pedro Manoel; Olsen Saraiva Câmara, Niels

    2015-01-01

    Homeostasis of the immune system depends on several factors. The gastrointestinal tract plays an important role in maintaining our immune system. With this aim, the intestinal immune system interacts with epithelial barrier molecules, especially tight junction proteins, that are key molecules involved in controlling paracellular permeability to increase the protection barrier against external antigens or possibly to respond to commensal microorganisms. During intestinal inflammatory diseases, the expression of innate immune receptors in intestinal epithelial cells and infiltration of immune cells are related, but it is still unclear how the immune system induces modulation of paracellular permeability. In this review, we provide an overview of the understanding of how the immune system modulates the expression of tight junctions to maintain the mucosal immune system.

  20. Guardians of the Gut – Murine Intestinal Macrophages and Dendritic Cells

    PubMed Central

    Gross, Mor; Salame, Tomer-Meir; Jung, Steffen

    2015-01-01

    Intestinal mononuclear phagocytes find themselves in a unique environment, most prominently characterized by its constant exposure to commensal microbiota and food antigens. This anatomic setting has resulted in a number of specializations of the intestinal mononuclear phagocyte compartment that collectively contribute the unique steady state immune landscape of the healthy gut, including homeostatic innate lymphoid cells, B, and T cell compartments. As in other organs, macrophages and dendritic cells (DCs) orchestrate in addition the immune defense against pathogens, both in lymph nodes and mucosa-associated lymphoid tissue. Here, we will discuss origins and functions of intestinal DCs and macrophages and their respective subsets, focusing largely on the mouse and cells residing in the lamina propria. PMID:26082775

  1. Diversity of human small intestinal Streptococcus and Veillonella populations.

    PubMed

    van den Bogert, Bartholomeus; Erkus, Oylum; Boekhorst, Jos; de Goffau, Marcus; Smid, Eddy J; Zoetendal, Erwin G; Kleerebezem, Michiel

    2013-08-01

    Molecular and cultivation approaches were employed to study the phylogenetic richness and temporal dynamics of Streptococcus and Veillonella populations in the small intestine. Microbial profiling of human small intestinal samples collected from four ileostomy subjects at four time points displayed abundant populations of Streptococcus spp. most affiliated with S. salivarius, S. thermophilus, and S. parasanguinis, as well as Veillonella spp. affiliated with V. atypica, V. parvula, V. dispar, and V. rogosae. Relative abundances varied per subject and time of sampling. Streptococcus and Veillonella isolates were cultured using selective media from ileostoma effluent samples collected at two time points from a single subject. The richness of the Streptococcus and Veillonella isolates was assessed at species and strain level by 16S rRNA gene sequencing and genetic fingerprinting, respectively. A total of 160 Streptococcus and 37 Veillonella isolates were obtained. Genetic fingerprinting differentiated seven Streptococcus lineages from ileostoma effluent, illustrating the strain richness within this ecosystem. The Veillonella isolates were represented by a single phylotype. Our study demonstrated that the small intestinal Streptococcus populations displayed considerable changes over time at the genetic lineage level because only representative strains of a single Streptococcus lineage could be cultivated from ileostoma effluent at both time points.

  2. Evolution of Symbiotic Bacteria in the Distal Human Intestine

    PubMed Central

    Ley, Ruth E; Lozupone, Catherine A; Hamady, Micah; Martens, Eric C; Henrissat, Bernard; Coutinho, Pedro M; Minx, Patrick; Latreille, Philippe; Cordum, Holland; Van Brunt, Andrew; Kim, Kyung; Fulton, Robert S; Fulton, Lucinda A; Clifton, Sandra W; Wilson, Richard K; Knight, Robin D; Gordon, Jeffrey I

    2007-01-01

    The adult human intestine contains trillions of bacteria, representing hundreds of species and thousands of subspecies. Little is known about the selective pressures that have shaped and are shaping this community's component species, which are dominated by members of the Bacteroidetes and Firmicutes divisions. To examine how the intestinal environment affects microbial genome evolution, we have sequenced the genomes of two members of the normal distal human gut microbiota, Bacteroides vulgatus and Bacteroides distasonis, and by comparison with the few other sequenced gut and non-gut Bacteroidetes, analyzed their niche and habitat adaptations. The results show that lateral gene transfer, mobile elements, and gene amplification have played important roles in affecting the ability of gut-dwelling Bacteroidetes to vary their cell surface, sense their environment, and harvest nutrient resources present in the distal intestine. Our findings show that these processes have been a driving force in the adaptation of Bacteroidetes to the distal gut environment, and emphasize the importance of considering the evolution of humans from an additional perspective, namely the evolution of our microbiomes. PMID:17579514

  3. 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.

  4. The Effects of GH Transgenic Goats on the Microflora of the Intestine, Feces and Surrounding Soil.

    PubMed

    Bao, Zekun; Gao, Xue; Zhang, Qiang; Lin, Jian; Hu, Weiwei; Yu, Huiqing; Chen, Jianquan; Yang, Qian; Yu, Qinghua

    2015-01-01

    The development of genetically engineered animals has brought with it increasing concerns about biosafety issues. We therefore evaluated the risks of growth hormone from transgenic goats, including the probability of horizontal gene transfer and the impact on the microbial community of the goats' gastrointestinal tracts, feces and the surrounding soil. The results showed that neither the GH nor the neoR gene could be detected in the samples. Moreover, there was no significant change in the microbial community of the gastrointestinal tracts, feces and soil, as tested with PCR-denaturing gradient gel electrophoresis and 16S rDNA sequencing. Finally, phylogenetic analysis showed that the intestinal content, feces and soil samples all contained the same dominant group of bacteria. These results demonstrated that expression of goat growth hormone in the mammary of GH transgenic goat does not influence the microflora of the intestine, feces and surrounding soil.

  5. Can Attention to the Intestinal Microbiota Improve Understanding and Treatment of Anorexia Nervosa?

    PubMed Central

    Carr, Jacquelyn; Kleiman, Susan C.; Bulik, Cynthia M.; Bulik-Sullivan, Emily C.; Carroll, Ian M.

    2016-01-01

    Summary Anorexia nervosa (AN) is characterized by severe dietary restriction or other weight loss behaviors and exhibits the highest mortality rate of any psychiatric disorder. Therapeutic renourishment in AN is founded primarily on clinical opinion and guidelines, with a weak evidence base. Genetic factors do not fully account for the etiology of AN, and non-genetic factors that contribute to the onset and persistence of this disease warrant investigation. Compelling evidence that the intestinal microbiota regulates adiposity and metabolism, and more recently, anxiety behavior, provides a strong rationale for exploring the role of this complex microbial community in the onset, maintenance of, and recovery from AN. This review explores the relationship between the intestinal microbiota and AN and a potential role for this enteric microbial community as a therapy for this severe illness. PMID:27003627

  6. Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus.

    PubMed Central

    Salfeld, J; Pfaff, E; Noah, M; Schaller, H

    1989-01-01

    The precore/core gene of hepatitis B virus directs the synthesis of two polypeptides, the 21-kilodalton subunit (p21c) forming the viral nucleocapsid (serologically defined as core antigen [HBcAg]) and a secreted processed protein (p17e, serologically defined as HBe antigen [HBeAg]). Although most of their primary amino acid sequences are identical, HBcAg and HBeAg display different antigenic properties that are widely used in hepatitis B virus diagnosis. To locate and to characterize the corresponding determinants, segments of the core gene were expressed in Escherichia coli and probed with a panel of polyclonal or monoclonal antibodies in radioimmunoassays or enzyme-linked immunosorbent assays, Western blots, and competition assays. Three distinct major determinants were characterized. The single conformational determinant responsible for HBc antigenicity in the assembled core (HBc) and a linear HBe-related determinant (HBe1) were both mapped to an overlapping hydrophilic sequence around amino acid 80; a second HBe determinant (HBe2) was assigned to a location in the vicinity of amino acid 138 but found to require for its antigenicity the intramolecular participation of the extended sequence between amino acids 10 and 140. It is postulated that HBcAg and HBeAg share common basic three-dimensional structure exposing the common linear determinant HBe1 but that they differ in the presentation of two conformational determinants that are either introduced (HBc) or masked (HBe2) in the assembled core. The simultaneous presentation of HBe1 and HBc, two distinctly different antigenic determinants with overlapping amino acid sequences, is interpreted to indicate the presence of slightly differently folded, stable conformational states of p21c in the hepatitis B virus nucleocapsid. Images PMID:2463383

  7. Lack of Intestinal Epithelial Atg7 Affects Paneth Cell Granule Formation but Does Not Compromise Immune Homeostasis in the Gut

    PubMed Central

    Wittkopf, Nadine; Günther, Claudia; Martini, Eva; Waldner, Maximilian; Amann, Kerstin U.; Neurath, Markus F.; Becker, Christoph

    2012-01-01

    Genetic polymorphisms of autophagy-related genes have been associated with an increased risk to develop inflammatory bowel disease (IBD). Autophagy is an elementary process participating in several cellular events such as cellular clearance and nonapoptotic programmed cell death. Furthermore, autophagy may be involved in intestinal immune homeostasis due to its participation in the digestion of intracellular pathogens and in antigen presentation. In the present study, the role of autophagy in the intestinal epithelial layer was investigated. The intestinal epithelium is essential to maintain gut homeostasis, and defects within this barrier have been associated with the pathogenesis of IBD. Therefore, mice with intestinal epithelial deletion of Atg7 were generated and investigated in different mouse models. Knockout mice showed reduced size of granules and decreased levels of lysozyme in Paneth cells. However, this was dispensable for gut immune homeostasis and had no effect on susceptibility in mouse models of experimentally induced colitis. PMID:22291845

  8. Modulating the Gut Micro-Environment in the Treatment of Intestinal Parasites.

    PubMed

    Vitetta, Luis; Saltzman, Emma Tali; Nikov, Tessa; Ibrahim, Isabelle; Hall, Sean

    2016-11-16

    The interactions of micro-organisms cohabitating with Homo sapiens spans millennia, with microbial communities living in a symbiotic relationship with the host. Interacting to regulate and maintain physiological functions and immunological tolerance, the microbial community is able to exert an influence on host health. An example of micro-organisms contributing to an intestinal disease state is exhibited by a biodiverse range of protozoan and bacterial species that damage the intestinal epithelia and are therefore implicated in the symptoms of diarrhea. As a contentious exemplar, Blastocystis hominis is a ubiquitous enteric protist that can adversely affect the intestines. The symptoms experienced are a consequence of the responses of the innate immune system triggered by the disruption of the intestinal barrier. The infiltration of the intestinal epithelial barrier involves a host of immune receptors, including toll like receptors and IgM/IgG/IgA antibodies as well as CD8+ T cells, macrophages, and neutrophils. Whilst the mechanisms of interactions between the intestinal microbiome and protozoan parasites remain incompletely understood, it is acknowledged that the intestinal microbiota is a key factor in the pathophysiology of parasitic infections. Modulating the intestinal environment through the administration of probiotics has been postulated as a possible therapeutic agent to control the proliferation of intestinal microbes through their capacity to induce competition for occupation of a common biotype. The ultimate goal of this mechanism is to prevent infections of the like of giardiasis and eliminate its symptoms. The differing types of probiotics (i.e., bacteria and yeast) modulate immunity by stimulating the host immune system. Early animal studies support the potential benefits of probiotic administration to prevent intestinal infections, with human clinical studies showing probiotics can reduce the number of parasites and the severity of symptoms. The

  9. Modulating the Gut Micro-Environment in the Treatment of Intestinal Parasites

    PubMed Central

    Vitetta, Luis; Saltzman, Emma Tali; Nikov, Tessa; Ibrahim, Isabelle; Hall, Sean

    2016-01-01

    The interactions of micro-organisms cohabitating with Homo sapiens spans millennia, with microbial communities living in a symbiotic relationship with the host. Interacting to regulate and maintain physiological functions and immunological tolerance, the microbial community is able to exert an influence on host health. An example of micro-organisms contributing to an intestinal disease state is exhibited by a biodiverse range of protozoan and bacterial species that damage the intestinal epithelia and are therefore implicated in the symptoms of diarrhea. As a contentious exemplar, Blastocystis hominis is a ubiquitous enteric protist that can adversely affect the intestines. The symptoms experienced are a consequence of the responses of the innate immune system triggered by the disruption of the intestinal barrier. The infiltration of the intestinal epithelial barrier involves a host of immune receptors, including toll like receptors and IgM/IgG/IgA antibodies as well as CD8+ T cells, macrophages, and neutrophils. Whilst the mechanisms of interactions between the intestinal microbiome and protozoan parasites remain incompletely understood, it is acknowledged that the intestinal microbiota is a key factor in the pathophysiology of parasitic infections. Modulating the intestinal environment through the administration of probiotics has been postulated as a possible therapeutic agent to control the proliferation of intestinal microbes through their capacity to induce competition for occupation of a common biotype. The ultimate goal of this mechanism is to prevent infections of the like of giardiasis and eliminate its symptoms. The differing types of probiotics (i.e., bacteria and yeast) modulate immunity by stimulating the host immune system. Early animal studies support the potential benefits of probiotic administration to prevent intestinal infections, with human clinical studies showing probiotics can reduce the number of parasites and the severity of symptoms. The

  10. Interleukin (IL)-21 promotes intestinal IgA response to microbiota.

    PubMed

    Cao, A T; Yao, S; Gong, B; Nurieva, R I; Elson, C O; Cong, Y

    2015-09-01

    Commensal microbiota-specific T helper type 17 (Th17) cells are enriched in the intestines, which can convert into T follicular helper (Tfh) in Peyer's patches, and are crucial for production of intestinal immunoglobulin A (IgA) against microbiota; however, the role of Th17 and Tfh cytokines in regulating the mucosal IgA response to enteric microbiota is still not completely known. In this study, we found that intestinal IgA was impaired in mice deficient in interleukin (IL)-17 or IL-21 signaling. IL-21, but not IL-17, is able to augment B-cell differentiation to IgA(+) cells as mediated by transforming growth factor β1 (TGFβ1) and accelerate IgA class switch recombination (CSR). IL-21 and retinoic acid (RA) induce IgA(+) B-cell development and IgA production and drives autocrine TGFβ1 production to initiate IgA CSR. Repletion of T-cell-deficient TCRβxδ(-/-) mice with Th17 cells specific for commensal bacterial antigen increased the levels of IgA(+) B cells and IgA production in the intestine, which was blocked by neutralizing IL-21. Thus IL-21 functions to strongly augment IgA production under intestinal environment. Furthermore, IL-21 promotes intestinal B-cell homing through α4β7 expression, alone or with TGFβ and RA. Together, IL-21 from microbiota-specific Th17 and/or Tfh cells contributes to robust intestinal IgA levels by enhancing IgA(+) CSR, IgA production and B-cell trafficking into the intestine.

  11. Distinguishing Intestinal Lymphoma From Inflammatory Bowel Disease in Canine Duodenal Endoscopic Biopsy Samples.

    PubMed

    Carrasco, V; Rodríguez-Bertos, A; Rodríguez-Franco, F; Wise, A G; Maes, R; Mullaney, T; Kiupel, M

    2015-07-01

    Inflammatory bowel disease (IBD) and intestinal lymphoma are intestinal disorders in dogs, both causing similar chronic digestive signs, although with a different prognosis and different treatment requirements. Differentiation between these 2 conditions is based on histopathologic evaluation of intestinal biopsies. However, an accurate diagnosis is often difficult based on histology alone, especially when only endoscopic biopsies are available to differentiate IBD from enteropathy-associated T-cell lymphoma (EATL) type 2, a small cell lymphoma. The purpose of this study was to evaluate the utility of histopathology; immunohistochemistry (IHC) for CD3, CD20, and Ki-67; and polymerase chain reaction (PCR) for antigen receptor rearrangement (T-cell clonality) in the differential diagnosis of severe IBD vs intestinal lymphoma. Endoscopic biopsies from 32 dogs with severe IBD or intestinal lymphoma were evaluated. The original diagnosis was based on microscopic examination of hematoxylin and eosin (HE)-stained sections alone followed by a second evaluation using morphology in association with IHC for CD3 and CD20 and a third evaluation using PCR for clonality. Our results show that, in contrast to feline intestinal lymphomas, 6 of 8 canine small intestinal lymphomas were EATL type 1 (large cell) lymphomas. EATL type 2 was uncommon. Regardless, in dogs, intraepithelial lymphocytes were not an important diagnostic feature to differentiate IBD from EATL as confirmed by PCR. EATL type 1 had a significantly higher Ki-67 index than did EATL type 2 or IBD cases. Based on the results of this study, a stepwise diagnostic approach using histology as the first step, followed by immunophenotyping and determining the Ki67 index and finally PCR for clonality, improves the accuracy of distinguishing intestinal lymphoma from IBD in dogs.

  12. Alterations in microbiota and fermentation products in equine large intestine in response to dietary variation and intestinal disease.

    PubMed

    Daly, Kristian; Proudman, Christopher J; Duncan, Sylvia H; Flint, Harry J; Dyer, Jane; Shirazi-Beechey, Soraya P

    2012-04-01

    We aimed to determine the effects of variations in dietary composition on equine gut microbiota and their fermentation products, and proposed that dietary modifications profoundly affect microbial ecosystems and their metabolites. Bacterial communities within the large intestine of three groups of horses were compared using oligonucleotide-RNA hybridisation methodology. Each group consisting of six horses was maintained on (1) a grass-only diet, (2) a concentrate diet (i.e. supplemented with hydrolysable carbohydrates) and (3) a concentrate diet but horses were affected by simple colonic obstruction and distension (SCOD), a prevalent form of dietary-induced intestinal disease. We show that in response to dietary change and intestinal disease, there is a progressive and significant increase in Lachnospiraceae, the Bacteroidetes assemblage and the lactic acid-producing, Bacillus-Lactobacillus-Streptococcus (BLS) group. In contrast, there is a corresponding decrease in the proportion of obligate fibrolytic, acid-intolerant bacteria, Fibrobacter and Ruminococcaceae. Assessment of monocarboxylic acids indicated that there are significantly higher concentrations of lactic acid in the colonic contents of horses maintained on a concentrate diet and those suffering from SCOD, correlating with the observed increase in the population abundance of the BLS group. However, the population size of the Veillonellaceae (lactate utilisers) remained constant in each study group. The inability of this group to respond to increased lactic acid may be a contributory factor to the build-up of lactic acid observed in horses fed a concentrate diet and those suffering from SCOD.

  13. [Detection of T-antigen in colorectal adenocarcinoma and polyps].

    PubMed

    Xu, S; Lu, Y; Wang, Q

    1995-10-01

    Galactose oxidase method was employed to detect the beta-D-Gal (1-->3) -D-Gal NAc residue of T-antigen present in the large intestinal mucus of 156 subjects. The positive rates of the test were 84.4%, 29.1%, and 7.2% in the mucus samples obtained from 32 patients with colorectal adenocarcinomas, 55 with polyps and 69 controls respectively. Chi-square test demonstrated that there were significant differences between the group of carcinoma and control (P < 0.001) as well as between also polyp and control (P < 0.01). The test had a high sensitivity (84.4%) and specificity (92.8%) in the diagnosis of colorectal cancer and may be used as a practical mass screening test for colorectal neoplasms.

  14. Expansion of Microbial Forensics

    PubMed Central

    Schmedes, Sarah E.; Sajantila, Antti

    2016-01-01

    Microbial forensics has been defined as the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes. Over the past 15 years, technology, particularly massively parallel sequencing, and bioinformatics advances now allow the characterization of microorganisms for a variety of human forensic applications, such as human identification, body fluid characterization, postmortem interval estimation, and biocrimes involving tracking of infectious agents. Thus, microbial forensics should be more broadly described as the discipline of applying scientific methods to the analysis of microbial evidence in criminal and civil cases for investigative purposes. PMID:26912746

  15. A Mutant Library Approach to Identify Improved Meningococcal Factor H Binding Protein Vaccine Antigens

    PubMed Central

    Konar, Monica; Rossi, Raffaella; Walter, Helen; Pajon, Rolando; Beernink, Peter T.

    2015-01-01

    Factor H binding protein (FHbp) is a virulence factor used by meningococci to evade the host complement system. FHbp elicits bactericidal antibodies in humans and is part of two recently licensed vaccines. Using human complement Factor H (FH) transgenic mice, we previously showed that binding of FH decreased the protective antibody responses to FHbp vaccination. Therefore, in the present study we devised a library-based method to identify mutant FHbp antigens with very low binding of FH. Using an FHbp sequence variant in one of the two licensed vaccines, we displayed an error-prone PCR mutant FHbp library on the surface of Escherichia coli. We used fluorescence-activated cell sorting to isolate FHbp mutants with very low binding of human FH and preserved binding of control anti-FHbp monoclonal antibodies. We sequenced the gene encoding FHbp from selected clones and introduced the mutations into a soluble FHbp construct. Using this approach, we identified several new mutant FHbp vaccine antigens that had very low binding of FH as measured by ELISA and surface plasmon resonance. The new mutant FHbp antigens elicited protective antibody responses in human FH transgenic mice that were up to 20-fold higher than those elicited by the wild-type FHbp antigen. This approach offers the potential to discover mutant antigens that might not be predictable even with protein structural information and potentially can be applied to other microbial vaccine antigens that bind host proteins. PMID:26057742

  16. Small intestinal physiology and pathophysiology.

    PubMed

    Sarna, S K; Otterson, M F

    1989-06-01

    The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents to uniformly and evenly expose them to the mucosal surface, and to propel them distally at a rate that allows optimal absorption of food components, and reabsorption of bile. Most of these functions are performed by individual phasic contractions. In humans, the phasic contractions are largely disorganized in time and space. These contractions may cause mixing and agitation of luminal contents with slow distal propulsion. Occasionally, an individual contraction of large amplitude and long duration migrates over several centimeters and may rapidly propel the contents over this distance. In general, the spatial and temporal relationships of individual phasic contractions become less organized distally, resulting in a slower propulsion rate in the distal small intestine than in the proximal small intestine. The migrating clustered contractions generated after a meal may also be propulsive, but because of their unpredictable and irregular occurrence, their precise role in postprandial propulsion is incompletely understood. Rapidly migrating contractions may occur when the electrical control activity is obliterated by pharmacologic agents or during parasitic infections. Their effects on motility are not known yet. Between meals, when digestion is complete, the small intestine generates migrating motor complexes that help keep the small intestine clean by dislodging debris from the villi and dumping them into the colon. This may prevent decay of these materials in the small intestine and limit their contribution to bacterial overgrowth. Giant migrating contractions may perform a similar function in the distal small intestine as well as return any refluxed fecal

  17. Intestinal ischemia in neonates and children.

    PubMed

    Jeican, Ionuţ Isaia; Ichim, Gabriela; Gheban, Dan

    2016-01-01

    The article reviews the intestinal ischemia theme on newborn and children. The intestinal ischemia may be either acute - intestinal infarction (by vascular obstruction or by reduced mesenteric blood flow besides the occlusive mechanism), either chronic. In neonates, acute intestinal ischemia may be caused by aortic thrombosis, volvulus or hypoplastic left heart syndrome. In children, acute intestinal ischemia may be caused by fibromuscular dysplasia, volvulus, abdominal compartment syndrome, Burkitt lymphoma, dermatomyositis (by vascular obstruction) or familial dysautonomia, Addison's disease, situs inversus abdominus (intraoperative), burns, chemotherapy administration (by nonocclusive mesenteric ischemia). Chronic intestinal ischemia is a rare condition in pediatrics and can be seen in abdominal aortic coarctation or hypoplasia, idiopathic infantile arterial calcinosis.

  18. Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.

    PubMed

    Zhang, Lei; Zeng, Zhanzhuang; Hu, Chaohua; Bellis, Susan L; Yang, Wendi; Su, Yintao; Zhang, Xinyan; Wu, Yunkun

    2016-01-01

    Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(D,L-lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia, an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae, a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination.

  19. β-Glucan microparticles are good candidates for mucosal antigen delivery in oral vaccination.

    PubMed

    De Smet, Rebecca; Demoor, Tine; Verschuere, Stephanie; Dullaers, Melissa; Ostroff, Gary R; Leclercq, Georges; Allais, Liesbeth; Pilette, Charles; Dierendonck, Marijke; De Geest, Bruno G; Cuvelier, Claude A

    2013-12-28

    Continuously improving the developmental process and the efficacy of oral vaccines is essential in the fight against intestinal pathogens. A promising strategy for vaccination applying safe, biodegradable and non-replicating antigen delivery systems has gained increased interest for eliciting cellular and humoral immune responses. The current study evaluates the potential of β-glucan particles (GP) as an oral antigen delivery system and their adjuvant characteristics. GP are efficiently internalized by human intestinal epithelial cell lines (Caco-2 and HT-29 cells), without exerting negative effects on cell viability. GP triggered the expression of pro-inflammatory cytokines IL-23p19, IL-8 and the β-glucan receptors dectin-1 and TLR2 by activated Caco-2 cells, and CCL20 in HT-29 cells. In contrast, the expression level of TGF-β, an important mediator of oral tolerance, was significantly downregulated in HT-29 cells. Additionally, adoptive transfer experiments showed proliferating ovalbumin (OVA)-specific CD4(+) T cells mainly in the spleens of GP-OVA-fed mice. Furthermore, we detected a significantly increased IL-17 and a trend towards increased IFN-γ production in the spleen of GP-OVA-fed mice upon antigen restimulation. Oral administration of GP-OVA induced increased OVA-specific IgA, secretory-IgA (S-IgA) and secretory component (SC) production in intestinal fluids. Our data show that GP vehicles are able to deliver OVA via an oral route allowing efficient antigen presentation alongside adaptive immune activation, resulting in a Th17-biased response and the production of OVA-specific IgA, secretory-IgA and secretory component antibodies.

  20. The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis.

    PubMed

    Magrone, Thea; Jirillo, Emilio

    2013-01-01

    Gut immune system is daily exposed to a plethora of antigens contained in the environment as well as in food. Both secondary lymphoid tissue, such as Peyer's patches, and lymphoid follicles (tertiary lymphoid tissue) are able to respond to antigenic stimuli releasing cytokines or producing antibodies (secretory IgA). Intestinal epithelial cells are in close cooperation with intraepithelial lymphocytes and possess Toll-like receptors on their surface and Nod-like receptors (NLRs) which sense pathogens or pathogen-associated molecular patterns. Intestinal microbiota, mainly composed of Bacteroidetes and Firmicutes, generates tolerogenic response acting on gut dendritic cells and inhibiting the T helper (h)-17 cell anti-inflammatory pathway. This is the case of Bacteroides fragilis which leads to the production of interleukin-10, an anti-inflammatory cytokine, from both T regulatory cells and lamina propria macrophages. Conversely, segmented filamentous bacteria rather induce Th17 cells, thus promoting intestinal inflammation. Intestinal microbiota and its toxic components have been shown to act on both Nod1 and Nod2 receptors and their defective signaling accounts for the development of inflammatory bowel disease (IBD). In IBD a loss of normal tolerance to intestinal microbiota seems to be the main trigger of mucosal damage. In addition, intestinal microbiota thanks to its regulatory function of gut immune response can prevent or retard neoplastic growth. In fact, chronic exposure to environmental microorganisms seems to be associated with low frequency of cancer risk. Major nutraceuticals or functional foods employed in the modulation of intestinal microbiota are represented by prebiotics, probiotics, polyunsaturated fatty acids, amino acids and polyphenols. The cellular and molecular effects performed by these natural products in terms of modulation of the intestinal microbiota and mostly attenuation of the inflammatory pathway are described.

  1. Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health

    PubMed Central

    Ha, Connie WY; Lam, Yan Y; Holmes, Andrew J

    2014-01-01

    Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging. PMID:25469018

  2. [Chronic intestinal pseudo-obstruction].

    PubMed

    Muñoz, M T; Solís Herruzo, J A

    2007-02-01

    Chronic intestinal pseudo-obstruction (CIPO) is a syndrome characterized by the presence of recurrent episodes of clinical intestinal obstruction in the absence of obstructive lesions. Although this syndrome is rare, it causes a high morbidity. It is caused by a disturbance of the intestinal motility, that results in a failure of the progression of the intestinal content. Basically, the failure of the intestinal motility is a consequence of muscular disorder, neurological disorder or both. Usually, CIPO is secondary to other systemic disease; however, in the last years, many cases of primary CIPO have been described. The use of new manometric tecniques and specific histological procedures have allowed to clarify the pathogenesis of some of these entities including mitochondrial diseases and paraneoplasic syndromes. Clinical manifestations of CIPO are diverse, depending on the location and extension of the motility disorder. As the diagnosis of this disease is usually not an easy task, patients frecuently undergo unnecesary surgical interventions, are diagnosed of psyquiatric disorders, or the correct diagnosis is delayed several years after the first symptoms arise. The aims of the treatment are to maintain the nutritional condition and to improve symptoms using nutritional measures, drugs or, eventually, endoscopical or surgical procedures.

  3. Human intestinal capillariasis in Thailand

    PubMed Central

    Saichua, Prasert; Nithikathkul, Choosak; Kaewpitoon, Natthawut

    2008-01-01

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt and Taiwan; major outbreaks have occurred in the Philippines and Thailand. This article reviews the epidemiology, history and sources of C. philippinensis infection in Thailand. The annual epidemiological surveillance reports indicated that 82 accumulated cases of intestinal capillariasis were found in Thailand from 1994-2006. That made Thailand a Capillaria-prevalent area. Sisaket, in northeast Thailand, was the first province which has reported intestinal capillariasis. Moreover, Buri Ram presented a high prevalence of intestinal capillariasis, totaling 24 cases from 1994-2006. About half of all cases have consumed raw or undercooked fish. However, even if the numbers of the intestinal capillariasis cases in Thailand is reduced, C. philippinensis infection cases are still reported. The improvement of personal hygiene, specifically avoiding consumption of undercooked fish and promoting a health education campaign are required. These strategies may minimize or eliminate C. philippinensis infection in Thailand. PMID:18203280

  4. Intestinal Microbiota Metabolism and Atherosclerosis

    PubMed Central

    Liu, Tian-Xing; Niu, Hai-Tao; Zhang, Shu-Yang

    2015-01-01

    Objective: This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target. Data Sources: This study was based on data obtained from PubMed and EMBASE up to June 30, 2015. Articles were selected using the following search terms: “Intestinal microbiota”, “trimethylamine N-oxide (TMAO)”, “trimethylamine (TMA)”, “cardiovascular”, and “atherosclerosis”. Study Selection: Studies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included. Results: A new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear. Conclusions: Intestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management. PMID:26481750

  5. Intestinal circulation during inhalation anesthesia

    SciTech Connect

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-04-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of /sub 86/Rb and 9-microns spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO/sub 2/) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines.

  6. Prebiotics in Chronic Intestinal Inflammation

    PubMed Central

    Looijer–van Langen, Mirjam A.C.; Dieleman, Levinus A.

    2016-01-01

    Prebiotics are nondigestible fermentable fibers that are reported to have health benefits for the host. Older as well as more recent studies show beneficial effects in experimental colitis and lately also in human inflammatory bowel diseases (IBD), such as Crohn’s disease, ulcerative colitis, and chronic pouchitis. In this review we give an overview of the benefits of prebiotics in rodent IBD models and in IBD patients and discuss their possible protective mechanisms. Commensal intestinal bacteria induce and perpetuate chronic intestinal inflammation, whereas others are protective. However, most of the current medications are directed against the exaggerated proinflammatory immune response of the host, some of them toxic and costly. Feeding prebiotics changes the composition of the intestinal microflora toward more protective intestinal bacteria and alters systemic and mucosal immune responses of the host. Therapy for IBD targeting intestinal bacteria and their function is just emerging. Prebiotics have the promise to be relatively safe, inexpensive, and easy to administer. Unraveling their protective mechanisms will help to develop rational applications of prebiotics. However, the initial promising results with dietary prebiotics in preclinical trials as well as small studies in human IBD will need to be confirmed in large randomized controlled clinical trials. PMID:18831524

  7. Influenza Virus Affects Intestinal Microbiota and Secondary Salmonella Infection in the Gut through Type I Interferons.

    PubMed

    Deriu, Elisa; Boxx, Gayle M; He, Xuesong; Pan, Calvin; Benavidez, Sammy David; Cen, Lujia; Rozengurt, Nora; Shi, Wenyuan; Cheng, Genhong

    2016-05-01