Influence of Microbiota on Intestinal Immune System in Ulcerative Colitis and Its Intervention

Abstract

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with chronic and recurrent characteristics caused by multiple reasons. Although the pathogenic factors have not been clarified yet, recent studies have demonstrated that intestinal microbiota plays a major role in UC, especially in the immune system. This review focuses on the description of several major microbiota communities that affect UC and their interactions with the host. In this review, eight kinds of microbiota that are highly related to IBD, including Faecalibacterium prausnitzii, Clostridium clusters IV and XIVa, Bacteroides, Roseburia species, Eubacterium rectale, Escherichia coli, Fusobacterium, and Candida albicans are demonstrated on the changes in amount and roles in the onset and progression of IBD. In addition, potential therapeutic targets for UC involved in the regulation of microbiota, including NLRPs, vitamin D receptor as well as secreted proteins, are discussed in this review.

Keywords: epithelial cells; host immune response; intestinal microbiota; therapeutic targets; ulcerative colitis.

Figure 1

Role of the gut microbiota in the pathogenesis of UC. The picture describes the changes in the major intestinal microbiota in the UC and its influence on gastrointestinal. This illustration contains 11 types of intestinal microbiota and their changes mentioned in this review. The mechanisms underlying the effects of certain microbiota on the gastrointestinal are described. It includes microbiota acting on DC cells by secreting substances such as PSA, butyrate and SCFAs. Then, DC cells further act on CD4⁺ T cells or regulatory T (Treg) cells to inhibit inflammation. There are also mechanisms by which AIEC destroys the gut barrier and further induces inflammation. The first four species of microbiota are painted in dark red, representing harmful microbiota. The other seven species of microbiota are painted in other colors, representing healthy microbiota. UC, ulcerative colitis; DC, dendritic cell; PSA, polysaccharide A; SCFA, short-chain fatty acid; AIEC, adherent-invasive Escherichia coli.

Figure 2

Possible mechanisms controlled by NLRPs, VDR, and Metrnl in regulation of intestinal homeostasis and ulcerative colitis. NLRP3 and NLRP6 inflammasomes regulate secretion of IL-1β and IL-18. IL-18 helps to maintain a non-pathogenic gut microflora, which promote a healthy gut environment. IL-18 is not produced in Nlrp3^−/− or Nlrp6^−/− mice, leading to the development of potentially pathogenic species. Nlrp12^−/− mice results in a more inflammatory environment caused by higher production of cytokines such as IL-1β and IL-6. ATG16L1 is decreased in Vdr^−/− mice, which leading to reduction of AMP. Furthermore, ATG16L1 decreasing can also inhibit IL-18 production through upregulating NLRP3 expression. In the intestinal epithelial cell-specific Metrnl knockout mice, reduction of AMP leading to microbiota imbalance. NLRP, NLR family, pyrin domain-containing; VDR, vitamin D receptor; AMP, antimicrobial peptide.