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Infectious etiopathogenesis of Crohn's disease

World Journal of Gastroenterology 2014年第34期20卷 12102-12117页

作者： Jessica Carriere Arlette Darfeuille-Michaud Hang Thi Thu Nguyen Clermont Universite M2iSHUMR 1071 Inserm University of Auvergne 63001 Clermont-FerrandFrance INRA USC 2018 63000 Clermont-FerrandFrance Centre Hospitalier Universitaire 63000 Clermont-FerrandFrance

Important advances during the last decade have been made in understanding the complex etiopathogenesis of Crohn’s disease(CD).While many gaps in our knowledge still exist,it has been suggested that the etiology of CD is multifactorial including genetic,environmental and infectious *** most widely accepted theory states that CD is caused by an aggressive immune response to infectious agents in genetically predisposed *** rise of genome-wide association studies allowed the identification of loci and genetic variants in several components of host innate and adaptive immune responses to microorganisms in the gut,highlighting an implication of intestinal microbiota in CD ***,numerous independent studies reported a dysbiosis,i.e.,a modification of intestinal microbiota composition,with an imbalance between the abundance of beneficial and harmful *** microorganisms including viruses,yeasts,fungi and bacteria have been postulated as potential CD pathogens,based on epidemiological,clinicopathological,genetic and experimental evidence,their precise role in this disease is not clearly *** review summarizes the current knowledge of the infectious agents associated with an increased risk of developing *** approaches to modulate the intestinal dysbiosis and to target the putative CD-associated pathogens,as well as their potential mechanisms of action are also discussed.

关键词： Crohn's disease Intestinal microbiota Dysbiosis adherent-invasive escherichia coli Probiotics Antibiotics Fecal microbiota transplantation

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Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease

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World Journal of Gastroenterology 2014年第5期20卷 1127-1138页

作者： In-Ah Lee Alan Kamba Daren Low Emiko Mizoguchi Gastrointestinal Unit Department of Medicine Harvard Medical School Center for the Study of Inflammatory Bowel Disease Massachusetts General Hospital Harvard Medical School

Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1(CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease(IBD), bronchial asthma and several other inflammatory disorders. Based on the data from highthroughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-in-flammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivativemediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine,-based antiinflammatory therapeutics in the field of IBD and IBDassociated carcinogenesis.

关键词： adherent-invasive escherichia coli Chitinase 3-like 1 Chitinase inhibitors Intestinal epithelial cells Host-microbial interactions Inflammatory bowel disease

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Role of bacteria in the etiopathogenesis of inflammatory bowel disease

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World Journal of Gastroenterology 2007年第42期13卷 5571-5576页

作者： Nicolas Barnich Arlette Darfeuille-Michaud Pathogénie Bactérienne Intestinale Univ Clermont 1 USC INRA 2018 Clermont-Ferrand F-63001 and Institut Universitaire de Technologie en Génie Biologique Aubière F-63172 France

Increased numbers of mucosa-associated escherichia coli are observed in both of the major inflammatory bowel diseases,Crohn's disease(CD)and ulcerative colitis(UC).A potential pathophysiological link between the presence of pathogenic invasive bacteria and genetic host susceptibility of patients with ileal CD is *** CD patients,with increased ileal expression of the CEACAM6 molecule acting as a receptor recognized by type 1 pilus bacterial adhesin,and with the identification of mutations in the NOD2-encoding gene,the presence of pathogenic invasive bacteria could be the link between abnormal ileal bacterial colonization and innate immune responses to invasive *** a susceptible host,the sequential etiological steps of the disease induced by adherent-invasive ***(AIEC)are:(1)abnormal colonization via binding to the CEACAM6 receptor,which is overexpressed in the ileal mucosa of CD patients;(2)ability to adhere to and to invade intestinal epithelial cells,which allows bacteria to cross the mucosal barrier;(3)survival and replication within infected macrophages in the lamina propria;and(4)induction of tumor necrosis factor-α secretion and granuloma formation.

关键词： adherent-invasive escherichia coli Crohn's disease Inflammatory bowel disease Ulcerative colitis

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