MUC · The microbial degradation and utilization of mucin by Bacteroides in ulcerative colitis

The microbial degradation and utilization of mucin by Bacteroides in ulcerative colitis

The human gastrointestinal track is colonized by a diverse microbial community (microbiota) which as a significant impact in human health and disease. In the colon, the mucus layer provides a physical barrier that separates the microbiota and the intestinal epithelium preventing the close contact and inflammation (Figure 1A and B). This barrier is organized in a dense inner mucus layer that is almost devoid of bacteria and an outer mucus layer heavily colonized by the microbiota (Figure 1A). The major component of the mucus layer is MUC2, a mucin glycoprotein that is heavily O-glycosylated (Figure 1C). The combination of increased mucus degrading bacteria and the corresponding disruption of the mucus barrier have been proposed to promote inflammatory bowel diseases (IBD) (Figure 1B), a disease for which the incidence is rising in the Western society. Bacteroides thetaiotaomicron (B. theta), a dominant member of human microbiota, has numerous Polysaccharide Utilization Loci (PULs) encoding dozens of predicted mucin-degradation enzymes (glycoside hydrolases and sulfatases). B. theta was shown to induce ulcerative colitis (UC) in a susceptible animal model. Interestingly, this inflammatory process was dependent on B. theta sulfatases enzymes. Significantly, the enzymatic mechanisms of mucin degradation by this and other gut bacteria remain unclear. This project was designed to investigate the mechanisms of mucin utilization by the human microbiota and its impact on UC development. The main goals are 1) identification of key “early” steps in the depolymerization process, which can be used to block the downstream degradation of mucin glycans, and 2) disclose the mechanism of mucin degradation and utilization by B. theta. These findings will provide insights in the mechanism behind the mucin utilization by gut bacteria and UC development, allowing the development of future therapeutic strategies in IBD. Additionally, the understanding how members of microbiota can alter the mucins compositions present in mucus layer can, potentially, be deployed to ensure that the structure of this ecosystem maximizes human health. This project disclosed the first model of depolymerization of O-glycans by a single gut bacteria that requires at least 35 enzymes. Additionally, in this study we identified a key sulfatase and two fucosidases that are essential to the utilization of mucin O-glycans by B. theta.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз