The Gut Microbiota in Inflammatory Bowel Disease

Abstract

Epidemiological surveys indicate that the incidence of inflammatory bowel disease (IBD) is increasing rapidly with the continuous growth of the economy. A large number of studies have investigated the relationship between the genetic factors related to the susceptibility to IBD and the gut microbiota of patients by using high-throughput sequencing. IBD is considered the outcome of the interaction between host and microorganisms, including intestinal microbial factors, abnormal immune response, and a damaged intestinal mucosal barrier. The imbalance of microbial homeostasis leads to the colonization and invasion of opportunistic pathogens in the gut, which increases the risk of the host immune response and promotes the development of IBD. It is critical to identify the specific pathogens related to the pathogenesis of IBD. An in-depth understanding of various pathogenic factors is of great significance for the early detection of IBD. This review highlights the role of gut microbiota in the pathogenesis of IBD and provides a theoretical basis for the personalized approaches that modulate the gut microbiota to treat IBD.

Keywords: IBD; gut microbiota; inflammatory bowel disease; metabolite; treatment.

Figure 1

Evidence of the gut microbiota enriched in UC and CD playing a vital role in pathogenesis. Circos plots showing the correlation of bacteria with pathogenesis in IBD. The red ribbons represent the higher production of bacteria enriched in IBD development. The blue ribbons represent the lower production of bacteria enriched in IBD. The causality of the microbiota in IBD has not yet been fully elucidated. Different taxa are divided into six groups and colored by the phylum.

Figure 2

Diagram summarizing the pathogenic interaction between the gut microbiome and intestinal epithelial barrier in IBD. NLRX1 boosts the dysbiosis to induce the ileac inflammation via SIRT1 signaling pathway with enrichment of Veillonella and Clostridium. SCFAs produced by microbiota induce the activation of NLRP3 through GPR43 and GPR109A and protect colitis through IL-18. A. parvulum produce H2S to induce ileac inflammation by mitochondrial damage. NLRP6 is a key regulator to facilitate the colonization of A. muciniphila via IL-18 and IL-10 to promote IBD onset. AIEC penetrate the mucus layer and adhere to intestinal epithelial cells through FimH and ceacam6. Enterotoxin secreted by E. coli induce IBD by the NF-κB pathway. SIRT1 participates in the inflammation by stimulating Paneth cell to reflect the bile acids metabolism via the NF-κB signaling pathway. Klebsiella pneumoniae invades intestinal epithelial cells and promotes the secretion of IL-1β and TNF by interacting with macrophages. Fusobacterium nucleatum upregulates CARD3 via NOD2 in colonic epithelial cells to activate the IL-17F/NF-κB signaling pathway. Faecalibacterium prausnitzii produce butyrate to inhibit the IL-6/STAT3/IL-17 pathway to activate Foxp3.The soluble factors released by apoptotic intestinal epithelial cells through caspase3/7 facilitate the colonization of Enterobacteriaceae by driving the pyruvate formate-lyase-encoding pflB gene.

Figure 3

Diagram summarizing the interaction between immune cells and the microbiota in IBD. Necrotic intestinal mucosal cells activate macrophages to produce IL-6 and TGF-β through STAT3 and RORγt, which induce the differentiation of Th17 cells. IL-6 and low levels of TGF-β can stimulate T cells to differentiate into Th 17. High-levels of TGF-β can inhibit the production of Th 17 cells and promote the production of Treg cells. SFB can induce Th17 cells to secrete IL-17 and IL-22 and promote intestinal inflammation. The Clostridium spp. resulted in the production of Tregs. B. fragilis induced Tregs by the IBD-related genes Atg16L1 and NOD2. B. thetaiotaomicron recapitulate the effects of gut microbiota and induce Tregs to influence the immune system in IBD. Klebsiella pneumoniae improve the induction of Th1 cell to induce the occurrence of inflammation.