Microbial Sensing by the Intestinal Epithelium in the Pathogenesis of Inflammatory Bowel Disease

Overview

Journal Int J Inflam

Publisher Wiley

Date 2010 Dec 29

PMID 21188218

Citations 10

Authors

Michael Scharl

Gerhard Rogler

Affiliations

Soon will be listed here.

Abstract

Recent years have raised evidence that the intestinal microbiota plays a crucial role in the pathogenesis of chronic inflammatory bowels diseases. This evidence comes from several observations. First, animals raised under germ-free conditions do not develop intestinal inflammation in several different model systems. Second, antibiotics are able to modulate the course of experimental colitis. Third, genetic polymorphisms in a variety of genes of the innate immune system have been associated with chronic intestinal inflammatory diseases. Dysfunction of these molecules results in an inappropriate response to bacterial and antigenic stimulation of the innate immune system in the gastrointestinal tract. Variants of pattern recognition receptors such as NOD2 or TLRs by which commensal and pathogenic bacteria can be detected have been shown to be involved in the pathogenesis of IBD. But not only pathways of microbial detection but also intracellular ways of bacterial processing such as autophagosome function are associated with the risk to develop Crohn's disease. Thus, the "environment concept" and the "genetic concept" of inflammatory bowel disease pathophysiology are converging via the intestinal microbiota and the recognition mechanisms for an invasion of members of the microbiota into the mucosa.

Citing Articles

The evidence for fungus in Crohn's disease pathogenesis.

Miyoshi J, Sofia M, Pierre J Clin J Gastroenterol. 2018; 11(6):449-456.

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The Impact of Cold Spells on the Incidence of Infectious Gastroenteritis and Relapse Rates of Inflammatory Bowel Disease: A Retrospective Controlled Observational Study.

Manser C, Kraus A, Frei T, Rogler G, Held L Inflamm Intest Dis. 2018; 2(2):124-130.

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Dysregulation of microRNA biogenesis in the small intestine after ethanol and burn injury.

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Microbiome-Linked Crosstalk in the Gastrointestinal Exposome towards Host Health and Disease.

Moon Y Pediatr Gastroenterol Hepatol Nutr. 2017; 19(4):221-228.

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References

Barnich N, Carvalho F, Glasser A, Darcha C, Jantscheff P, Allez M . CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J Clin Invest. 2007; 117(6):1566-74. PMC: 1868786. DOI: 10.1172/JCI30504. View

Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M . Mucosal flora in inflammatory bowel disease. Gastroenterology. 2002; 122(1):44-54. DOI: 10.1053/gast.2002.30294. View

Saitoh T, Fujita N, Jang M, Uematsu S, Yang B, Satoh T . Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008; 456(7219):264-8. DOI: 10.1038/nature07383. View

Hoeve J, Ibarra-Sanchez M, Fu Y, Zhu W, Tremblay M, David M . Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol. 2002; 22(16):5662-8. PMC: 133976. DOI: 10.1128/MCB.22.16.5662-5668.2002. View

Rosenstiel P, Fantini M, Brautigam K, Kuhbacher T, Waetzig G, Seegert D . TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Gastroenterology. 2003; 124(4):1001-9. DOI: 10.1053/gast.2003.50157. View

Baumgart M, Dogan B, Rishniw M, Weitzman G, Bosworth B, Yantiss R . Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum. ISME J. 2007; 1(5):403-18. DOI: 10.1038/ismej.2007.52. View

Gu Y, Kuida K, Tsutsui H, Ku G, Hsiao K, Fleming M . Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme. Science. 1997; 275(5297):206-9. DOI: 10.1126/science.275.5297.206. View

Sellon R, Tonkonogy S, Schultz M, Dieleman L, Grenther W, Balish E . Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998; 66(11):5224-31. PMC: 108652. DOI: 10.1128/IAI.66.11.5224-5231.1998. View

Hornung V, Bauernfeind F, Halle A, Samstad E, Kono H, Rock K . Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008; 9(8):847-56. PMC: 2834784. DOI: 10.1038/ni.1631. View

10.

Cai D, Yuan M, Frantz D, Melendez P, Hansen L, Lee J . Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005; 11(2):183-90. PMC: 1440292. DOI: 10.1038/nm1166. View

11.

Cadwell K, Liu J, Brown S, Miyoshi H, Loh J, Lennerz J . A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 2008; 456(7219):259-63. PMC: 2695978. DOI: 10.1038/nature07416. View

12.

Rath H, WILSON K, Sartor R . Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli. Infect Immun. 1999; 67(6):2969-74. PMC: 96608. DOI: 10.1128/IAI.67.6.2969-2974.1999. View

13.

Brant S, Panhuysen C, Nicolae D, Reddy D, Bonen D, Karaliukas R . MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Am J Hum Genet. 2003; 73(6):1282-92. PMC: 1180394. DOI: 10.1086/379927. View

14.

Jones D, Bevins C . Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem. 1992; 267(32):23216-25. View

15.

Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E, Schlee M . NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut. 2004; 53(11):1658-64. PMC: 1774270. DOI: 10.1136/gut.2003.032805. View

16.

Dupuis M, Ibarra-Sanchez M, Tremblay M, Duplay P . Gr-1+ myeloid cells lacking T cell protein tyrosine phosphatase inhibit lymphocyte proliferation by an IFN-gamma- and nitric oxide-dependent mechanism. J Immunol. 2003; 171(2):726-32. DOI: 10.4049/jimmunol.171.2.726. View

17.

Zhu W, Mustelin T, David M . Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase. J Biol Chem. 2002; 277(39):35787-90. DOI: 10.1074/jbc.C200346200. View

18.

Wehkamp J, Schmid M, Stange E . Defensins and other antimicrobial peptides in inflammatory bowel disease. Curr Opin Gastroenterol. 2007; 23(4):370-8. DOI: 10.1097/MOG.0b013e328136c580. View

19.

Franke A, Balschun T, Karlsen T, Hedderich J, May S, Lu T . Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet. 2008; 40(6):713-5. DOI: 10.1038/ng.148. View

20.

Rath H, Schultz M, Freitag R, Dieleman L, Li F, Linde H . Different subsets of enteric bacteria induce and perpetuate experimental colitis in rats and mice. Infect Immun. 2001; 69(4):2277-85. PMC: 98156. DOI: 10.1128/IAI.69.4.2277-2285.2001. View