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Mucus , ibd,bacterial

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
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
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
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
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
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
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
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
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
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
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
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
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
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
Malin E V Johansson
The intestinal epithelium is covered with mucus with the main structural building block being the densely O-glycosylated MUC2 mucin. The intestinal epithelium is exposed to ingested material, our digestive machinery, and large amounts of microorganisms. Mucus is the first line of defense and aids to limit exposure to all these threats to the epithelium. In the small intestine, mucus acts as a matrix, which contains antimicrobial products, such as defensins and immunoglobulin A that limit epithelial exposure to the luminal bacteria...
November 2014: Inflammatory Bowel Diseases
Yvette Merga, Barry J Campbell, Jonathan M Rhodes
The mucosal barrier has three major components, the mucus layer, the epithelial glycocalyx and the surface epithelium itself, whose integrity largely depends on tight junction function. In health, there is relatively little direct interaction between the luminal microbiota and the epithelium - the continuous mucus layer in the colon keeps the surface epithelium out of contact with bacteria and the ileo-caecal valve ensures that the distal small intestine is relatively microbe free. Most interaction takes place at the Peyer's patches in the distal ileum and their smaller colonic equivalents, the lymphoid follicles...
2014: Digestive Diseases
Evropi Theodoratou, Harry Campbell, Nicholas T Ventham, Daniel Kolarich, Maja Pučić-Baković, Vlatka Zoldoš, Daryl Fernandes, Iain K Pemberton, Igor Rudan, Nicholas A Kennedy, Manfred Wuhrer, Elaine Nimmo, Vito Annese, Dermot P B McGovern, Jack Satsangi, Gordan Lauc
A number of genetic and immunological studies give impetus for investigating the role of glycosylation in IBD. Experimental mouse models have helped to delineate the role of glycosylation in intestinal mucins and to explore the putative pathogenic role of glycosylation in colitis. These experiments have been extended to human studies investigating the glycosylation patterns of intestinal mucins as well as levels of glycans of serum glycoproteins and expression of glycan receptors. These early human studies have generated interesting hypotheses regarding the pathogenic role of glycans in IBD, but have generally been restricted to fairly small underpowered studies...
October 2014: Nature Reviews. Gastroenterology & Hepatology
Melinda A Engevik, Annelies Hickerson, Gary E Shull, Roger T Worrell
BACKGROUND: The mechanisms bacteria use to proliferate and alter the normal bacterial composition remain unknown. The ability to link changes in the intestinal micro-environment, such as ion composition and pH, to bacterial proliferation is clinically advantageous for diseases that involve an altered gut microbiota, such as Inflammatory Bowel Disease, obesity and diabetes. In human and mouse intestine, the apical Na(+)/H(+) exchangers NHE2 and NHE3 affect luminal Na(+), water, and pH...
2013: Cellular Physiology and Biochemistry
Bhanu Priya Ganesh, Robert Klopfleisch, Gunnar Loh, Michael Blaut
Excessive mucin degradation by intestinal bacteria may contribute to inflammatory bowel diseases because access of luminal antigens to the intestinal immune system is facilitated. This study investigated how the presence of a mucin degrading commensal bacterium affects the severity of an intestinal Salmonella enterica Typhimurium-induced gut inflammation. Using a gnotobiotic C3H mouse model with a background microbiota of eight bacterial species (SIHUMI) the impact of the mucin-degrading commensal bacterium Akkermansia muciniphila (SIHUMI-A) on inflammatory and infectious symptoms caused by S...
2013: PloS One
Xiaofa Qin
It has been a big puzzle as why the inflammation of ulcerative colitis (UC) is limited to the mucosa, while in Crohn's disease (CD) the inflammation is transmural and can be seen in all layers of the gut. Here, I give a tentative explanation extended from the unified hypothesis I proposed on the etiology of inflammatory bowel disease. This hypothesis suggested that both UC and CD are caused by weakening of the gut barrier due to damage of the protective mucus layer and the underlying tissue by the poorly inactivated digestive proteases resulting from a reduction of gut bacteria by dietary chemicals like saccharin and sucralose...
August 15, 2013: World Journal of Gastrointestinal Pathophysiology
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