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https://www.readbyqxmd.com/read/28943327/a-two-component-system-regulates-bacteroides-fragilis-toxin-to-maintain-intestinal-homeostasis-and-prevent-lethal-disease
#1
Aaron L Hecht, Benjamin W Casterline, Vivian M Choi, Juliane Bubeck Wardenburg
Intestinal microbes are recognized for their role in human disease. Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in inflammatory bowel disease and colorectal cancer; however, colonization alone is insufficient to cause these illnesses. We hypothesized that homeostasis in healthy carriers is maintained by colonic mucus, the major constituent of which is the glycoprotein Muc2. We found that Muc2-deficient mice succumb to lethal disease from ETBF colonization in a B. fragilis toxin (BFT)-dependent manner...
October 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28904372/butyrate-producing-bacteria-supplemented-in-vitro-to-crohn-s-disease-patient-microbiota-increased-butyrate-production-and-enhanced-intestinal-epithelial-barrier-integrity
#2
Annelies Geirnaert, Marta Calatayud, Charlotte Grootaert, Debby Laukens, Sarah Devriese, Guy Smagghe, Martine De Vos, Nico Boon, Tom Van de Wiele
The management of the dysbiosed gut microbiota in inflammatory bowel diseases (IBD) is gaining more attention as a novel target to control this disease. Probiotic treatment with butyrate-producing bacteria has therapeutic potential since these bacteria are depleted in IBD patients and butyrate has beneficial effects on epithelial barrier function and overall gut health. However, studies assessing the effect of probiotic supplementation on microbe-microbe and host-microbe interactions are rare. In this study, butyrate-producing bacteria (three mono-species and one multispecies mix) were supplemented to the fecal microbial communities of ten Crohn's disease (CD) patients in an in vitro system simulating the mucus- and lumen-associated microbiota...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28707083/layered-defense-how-mucus-and-tight-junctions-seal-the-intestinal-barrier
#3
REVIEW
Christopher T Capaldo, Domonica N Powell, Daniel Kalman
The colonic mucosa provides a vital defensive barrier separating the body from the microbial populations residing in the intestinal lumen. Indeed, growing evidence shows that loss of this barrier may cause disease or exacerbate disease progression. The loss of barrier integrity increases the translocation of bacterial antigens and stimulates inflammation in the intestinal mucosa, which is the central pathological feature of inflammatory bowel diseases (IBDs). This review focuses on how intestinal mucus and intercellular tight junctions (TJs) act together to maintain the integrity of the colonic barrier and how barrier integrity is dysregulated in IBD...
July 13, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28649593/colonic-microbiota-encroachment-correlates-with-dysglycemia-in-humans
#4
Benoit Chassaing, Shreya M Raja, James D Lewis, Shanthi Srinivasan, Andrew T Gewirtz
BACKGROUND AND AIMS: Mucoid structures that coat the epithelium play an essential role in keeping the intestinal microbiota at a safe distance from host cells. Encroachment of bacteria into the normally almost-sterile inner mucus layer has been observed in inflammatory bowel disease and in mouse models of colitis. Moreover, such microbiota encroachment has also been observed in mouse models of metabolic syndrome, which are associated low-grade intestinal inflammation. Hence, we investigated if microbiota encroachment might correlate with indices of metabolic syndrome in humans...
September 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28147355/improvement-of-a-leaky-intestinal-barrier
#5
REVIEW
Eduard F Stange
In Crohn's disease, the mucus layer appears to be defective in terms of low defensin levels and lack of antibacterial activity. These deficiencies actually explain the Montreal phenotypes and the stable localization of disease in the terminal ileum with low α-defensins from Paneth cells and/or low β-defensins in colonic disease, respectively. Conversely, in ulcerative colitis (UC) the defensin production is normal or even induced, but the mucus layer is thinner and patchy, more in the liquid form and also chemically altered so that antibacterial peptides are not retained and lost into the luminal bacterial bulk...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/27930307/cosmc-is-an-x-linked-inflammatory-bowel-disease-risk-gene-that-spatially-regulates-gut-microbiota-and-contributes-to-sex-specific-risk
#6
Matthew R Kudelka, Benjamin H Hinrichs, Trevor Darby, Carlos S Moreno, Hikaru Nishio, Christopher E Cutler, Jianmei Wang, Huixia Wu, Junwei Zeng, Yingchun Wang, Tongzhong Ju, Sean R Stowell, Asma Nusrat, Rheinallt M Jones, Andrew S Neish, Richard D Cummings
Inflammatory bowel disease (IBD) results from aberrant immune stimulation against a dysbiotic mucosal but relatively preserved luminal microbiota and preferentially affects males in early onset disease. However, factors contributing to sex-specific risk and the pattern of dysbiosis are largely unexplored. Core 1 β3GalT-specific molecular chaperone (Cosmc), which encodes an X-linked chaperone important for glycocalyx formation, was recently identified as an IBD risk factor by genome-wide association study. We deleted Cosmc in mouse intestinal epithelial cells (IECs) and found marked reduction of microbiota diversity in progression from the proximal to the distal gut mucosa, but not in the overlying lumen, as seen in IBD...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26926038/identification-of-commensal-species-positively-correlated-with-early-stress-responses-to-a-compromised-mucus-barrier
#7
Bruno Sovran, Peng Lu, Linda M P Loonen, Floor Hugenholtz, Clara Belzer, Ellen H Stolte, Mark V Boekschoten, Peter van Baarlen, Hauke Smidt, Michiel Kleerebezem, Paul de Vos, Ingrid B Renes, Jerry M Wells, Jan Dekker
BACKGROUND: Our aims were (1) to correlate changes in the microbiota to intestinal gene expression before and during the development of colitis in Muc2 mice and (2) to investigate whether the heterozygote Muc2 mouse would reveal host markers of gut barrier stress. METHODS: Colon histology, transcriptomics, and microbiota profiling of faecal samples was performed on wild type, Muc2, and Muc2 mice at 2, 4, and 8 weeks of age. RESULTS: Muc2 mice develop colitis in proximal colon after weaning, resulting in inflammatory and adaptive immune responses, and expression of genes associated with human inflammatory bowel disease...
April 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/26840462/alterations-of-the-ileal-and-colonic-mucosal-microbiota-in-canine-chronic-enteropathies
#8
Eric Cassmann, Robin White, Todd Atherly, Chong Wang, Yaxuan Sun, Samir Khoda, Curtis Mosher, Mark Ackermann, Albert Jergens
BACKGROUND: The intestinal microbiota is increasingly linked to the pathogenesis of chronic enteropathies (CE) in dogs. While imbalances in duodenal and fecal microbial communities have been associated with mucosal inflammation, relatively little is known about alterations in mucosal bacteria seen with CE involving the ileum and colon. AIM: To investigate the composition and spatial organization of mucosal microbiota in dogs with CE and controls. METHODS: Tissue sections from endoscopic biopsies of the ileum and colon from 19 dogs with inflammatory bowel disease (IBD), 6 dogs with granulomatous colitis (GC), 12 dogs with intestinal neoplasia, and 15 controls were studied by fluorescence in situ hybridization (FISH) on a quantifiable basis...
2016: PloS One
https://www.readbyqxmd.com/read/26149685/autophagy-protects-against-colitis-by-the-maintenance-of-normal-gut-microflora-and-secretion-of-mucus
#9
Koichiro Tsuboi, Mayo Nishitani, Atsushi Takakura, Yasuyuki Imai, Masaaki Komatsu, Hiroto Kawashima
Genome-wide association studies of inflammatory bowel diseases identified susceptible loci containing an autophagy-related gene. However, the role of autophagy in the colon, a major affected area in inflammatory bowel diseases, is not clear. Here, we show that colonic epithelial cell-specific autophagy-related gene 7 (Atg7) conditional knock-out (cKO) mice showed exacerbation of experimental colitis with more abundant bacterial invasion into the colonic epithelium. Quantitative PCR analysis revealed that cKO mice had abnormal microflora with an increase of some genera...
August 14, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26067254/surface-associated-lipoproteins-link-enterococcus-faecalis-virulence-to-colitogenic-activity-in-il-10-deficient-mice-independent-of-their-expression-levels
#10
Soeren Ocvirk, Irina G Sava, Isabella Lengfelder, Ilias Lagkouvardos, Natalie Steck, Jung H Roh, Sandrine Tchaptchet, Yinyin Bao, Jonathan J Hansen, Johannes Huebner, Ian M Carroll, Barbara E Murray, R Balfour Sartor, Dirk Haller
The commensal Enterococcus faecalis is among the most common causes of nosocomial infections. Recent findings regarding increased abundance of enterococci in the intestinal microbiota of patients with inflammatory bowel diseases and induction of colitis in IL-10-deficient (IL-10-/-) mice put a new perspective on the contribution of E. faecalis to chronic intestinal inflammation. Based on the expression of virulence-related genes in the inflammatory milieu of IL-10-/- mice using RNA-sequencing analysis, we characterized the colitogenic role of two bacterial structures that substantially impact on E...
June 2015: PLoS Pathogens
https://www.readbyqxmd.com/read/26033517/chronic-cigarette-smoke-exposure-induces-microbial-and-inflammatory-shifts-and-mucin-changes-in-the-murine-gut
#11
Liesbeth Allais, Frederiek-Maarten Kerckhof, Stephanie Verschuere, Ken R Bracke, Rebecca De Smet, Debby Laukens, Pieter Van den Abbeele, Martine De Vos, Nico Boon, Guy G Brusselle, Claude A Cuvelier, Tom Van de Wiele
Inflammatory bowel diseases (IBD) are complex multifactorial diseases characterized by an inappropriate host response to an altered commensal microbiome and dysfunctional mucus barrier. Cigarette smoking is the best known environmental risk factor in IBD. Here, we studied the influence of chronic smoke exposure on the gut microbiome, mucus layer composition and immune factors in conventional mice. We compared smoke-exposed with air-exposed mice (n = 12) after a smoke exposure of 24 weeks. Both Illumina sequencing (n = 6) and denaturing gradient gel electrophoresis (n = 12) showed that bacterial activity and community structure were significantly altered in the colon due to smoke exposure...
May 2016: Environmental Microbiology
https://www.readbyqxmd.com/read/25974250/delivery-of-a-mucin-domain-enriched-in-cysteine-residues-strengthens-the-intestinal-mucous-barrier
#12
Valérie Gouyer, Laurent Dubuquoy, Catherine Robbe-Masselot, Christel Neut, Elisabeth Singer, Ségolène Plet, Karel Geboes, Pierre Desreumaux, Frédéric Gottrand, Jean-Luc Desseyn
A weakening of the gut mucous barrier permits an increase in the access of intestinal luminal contents to the epithelial cells, which will trigger the inflammatory response. In inflammatory bowel diseases, there is an inappropriate and ongoing activation of the immune system, possibly because the intestinal mucus is less protective against the endogenous microflora. General strategies aimed at improving the protection of the intestinal epithelium are still missing. We generated a transgenic mouse that secreted a molecule consisting of 12 consecutive copies of a mucin domain into its intestinal mucus, which is believed to modify the mucus layer by establishing reversible interactions...
2015: Scientific Reports
https://www.readbyqxmd.com/read/25914114/keeping-bugs-in-check-the-mucus-layer-as-a-critical-component-in-maintaining-intestinal-homeostasis
#13
REVIEW
Martin Faderl, Mario Noti, Nadia Corazza, Christoph Mueller
In the mammalian gastrointestinal tract the close vicinity of abundant immune effector cells and trillions of commensal microbes requires sophisticated barrier and regulatory mechanisms to maintain vital host-microbial interactions and tissue homeostasis. During co-evolution of the host and its intestinal microbiota a protective multilayered barrier system was established to segregate the luminal microbes from the intestinal mucosa with its potent immune effector cells, limit bacterial translocation into host tissues to prevent tissue damage, while ensuring the vital functions of the intestinal mucosa and the luminal gut microbiota...
April 2015: IUBMB Life
https://www.readbyqxmd.com/read/25855934/the-therapeutic-management-of-gut-barrier-leaking-the-emerging-role-for-mucosal-barrier-protectors
#14
REVIEW
L R Lopetuso, F Scaldaferri, G Bruno, V Petito, F Franceschi, A Gasbarrini
OBJECTIVE: Gut barrier is a functional unit organized as a multi-layer system and its multiple functions are crucial for maintaining gut homeostasis. Numerous scientific evidences showed a significant association between gut barrier leaking and gastro-intestinal/extra-intestinal diseases. MATERIALS AND METHODS: In this review we focus on the relationship between gut barrier leaking and human health. At the same time we speculate on the possible new role of gut barrier protectors in enhancing and restoring gut barrier physiology with the final goal of promoting gut health...
2015: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/25731162/dietary-emulsifiers-impact-the-mouse-gut-microbiota-promoting-colitis-and-metabolic-syndrome
#15
Benoit Chassaing, Omry Koren, Julia K Goodrich, Angela C Poole, Shanthi Srinivasan, Ruth E Ley, Andrew T Gewirtz
The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine...
March 5, 2015: Nature
https://www.readbyqxmd.com/read/25666708/mucosal-immune-development-in-early-life-setting-the-stage
#16
REVIEW
Sylvia Brugman, Olaf Perdijk, R J Joost van Neerven, Huub F J Savelkoul
Our environment poses a constant threat to our health. To survive, all organisms must be able to discriminate between good (food ingredients and microbes that help digest our food) and bad (pathogenic microbes, viruses and toxins). In vertebrates, discrimination between beneficial and harmful antigens mainly occurs at the mucosal surfaces of the respiratory, digestive, urinary and genital tract. Here, an extensive network of cells and organs form the basis of what we have come to know as the mucosal immune system...
August 2015: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/25561781/dismicrobism-in-inflammatory-bowel-disease-and-colorectal-cancer-changes-in-response-of-colocytes
#17
REVIEW
Giovanni Tomasello, Pietro Tralongo, Provvidenza Damiani, Emanuele Sinagra, Benedetto Di Trapani, Marie Noelle Zeenny, Inaya Hajj Hussein, Abdo Jurjus, Angelo Leone
Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health...
December 28, 2014: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/25222662/intestinal-inflammation-and-mucosal-barrier-function
#18
REVIEW
Fermín Sánchez de Medina, Isabel Romero-Calvo, Cristina Mascaraque, Olga Martínez-Augustin
Intestinal mucosal barrier function is the capacity of the intestine to provide adequate containment of luminal microorganisms and molecules while preserving the ability to absorb nutrients. The central element is the epithelial layer, which physically separates the lumen and the internal milieu and is in charge of vectorial transport of ions, nutrients, and other substances. The secretion of mucus-forming mucins, sIgA, and antimicrobial peptides reinforces the mucosal barrier on the extraepithelial side, while a variety of immune cells contributes to mucosal defense in the inner side...
December 2014: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/25215613/ibd-candidate-genes-and-intestinal-barrier-regulation
#19
Declan F McCole
Technological advances in the large scale analysis of human genetics have generated profound insights into possible genetic contributions to chronic diseases including the inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis. To date, 163 distinct genetic risk loci have been associated with either Crohn's disease or ulcerative colitis, with a substantial degree of genetic overlap between these 2 conditions. Although many risk variants show a reproducible correlation with disease, individual gene associations only affect a subset of patients, and the functional contribution(s) of these risk variants to the onset of IBD is largely undetermined...
October 2014: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/25071341/ulcerative-colitis-as-a-polymicrobial-infection-characterized-by-sustained-broken-mucus-barrier
#20
REVIEW
Shui-Jiao Chen, Xiao-Wei Liu, Jian-Ping Liu, Xi-Yan Yang, Fang-Gen Lu
To reduce medication for patients with ulcerative colitis (UC), we need to establish the etiology of UC. The intestinal microbiota of patients with inflammatory bowel disease (IBD) has been shown to differ from that of healthy controls and abundant data indicate that it changes in both composition and localization. Small intestinal bacterial overgrowth is significantly higher in IBD patients compared with controls. Probiotics have been investigated for their capacity to reduce the severity of UC. The luminal surfaces of the gastrointestinal tract are covered by a mucus layer...
July 28, 2014: World Journal of Gastroenterology: WJG
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