Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases

Abstract

Background-Abnormal host-microbe interactions are implicated in the pathogenesis of inflammatory bowel diseases. Previous 16S rRNA sequence analysis of intestinal tissues demonstrated that a subset of Crohn's disease (CD) and ulcerative colitis (UC) samples exhibited altered intestinal associated microbial compositions characterized by depletion of Bacteroidetes and Firmicutes (particularly Clostridium taxa). We hypothesize that NOD2 and ATG16L1 risk

Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease

“…Previous studies have shown that the gut microbial community of IBD patients is characterized by reduced diversity and decreased abundance of the phylum Firmicutes, and a concomitant increase in the phylum Proteobacteria [6,7,31]. Several studies have found that the reduced diversity of the gut microbiota in IBD patients is primarily associated with the lower abundance of the phylum Firmicutes, particularly in the Clostridium cluster IV of anaerobic bacteria [4].…”

“…The dysbiosis of IBD is characterized by a decrease in bacterial diversity and a decrease in members of the phylum Firmicutes, and concomitant expansion of the phylum Proteobacteria [6][7][8]. A reduced abundance of certain Clostridium subsets, such as cluster IV and subcluster XIVa, contributes to the decreased abundance of the phylum Firmicutes [9,10], and an increase in the phylum Proteobacteria is represented by the expansion of Enterobacteriaceae, including E. coli.…”

ATG16L1: A multifunctional susceptibility factor in Crohn disease

“…98 In another study on T300A Crohn disease patients, a significantly increased presence of AIEC was observed in Paneth cells. 99 Therefore, as a result of this deficiency in bacterial clearance, the ATG16L1 risk variant has been associated with shifts in the microbial compositions of the intestine 100 and, additionally, has been related to the presence of bacterial DNA and an increased formation of antibacterial antibodies in patients with Crohn disease. 101,102 Of interest, bacterial DNA has been correlated with higher disease activity/flares and elevated levels of TNF.…”

Intestinal Microbes in Inflammatory Bowel Diseases

“…Defects in genes involved in innate immunity, such as nucleotide oligomerization domain-2 (NOD2, an intracellular pattern recognition receptor) have been shown to result in defective α -defensin production and reduced clearance of intracellular bacteria ( 27,28 ). Recently, NOD2 polymorphisms were associated with dysbiosis in Crohn ' s disease patients ( 29 ). Similarly, mutations in the Crohn ' s disease -related genes ATG16L1 (a component of the autophagy apparatus related to abnormal Paneth cell morphology and function) ( 30 ), NCF4 ( a cytosolic regulatory component of the superoxide-producing phagocyte NADPH oxidase) ( 3,30,31 ), and IRGM (which is an autophagy-related protein involved in interferon-γ -induced killing of phagocytosed bacteria and associated with altered Paneth cell morphology) ( 32 ) would all be expected to reduce luminal and intracellular bacterial killing, potentially resulting in the dysbiosis that is characteristic of IBD.…”