A219 PROTECTIVE EFFECTS OF AKKERMANSIA MUCINIPHILA ON INTESTINAL BARRIER FUNCTION AND INFLAMMATION Journal Articles uri icon

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abstract

  • Abstract Background Akkermansia muciniphila, an anaerobic gram-negative bacteria, accounts for ~3% of human gut microbiota. Despite its mucolytic nature, A. muciniphila has been shown to stimulate mucin production, enhance anti-inflammatory regulatory T cell proliferation and improve gut barrier integrity. Interestingly, an inverse relationship has been established between A. muciniphila and several disease states including inflammatory bowel disease (IBD) suggesting it may have protective and anti-inflammatory effects. However, the precise role and mechanism of A. muciniphila in the pathogenesis of colitis remains unknown. Thus, we hypothesize that A. muciniphila may induce protective effects on intestinal inflammation by influencing host immune response and epithelial barrier integrity. Aims (1) To investigate the protective role of A. muciniphila in intestinal inflammation in a chemically induced model of IBD and (2) to investigate the protective role of A. muciniphila in intestinal inflammation and host defense in a model of enteric parasitic infection. Methods Colitis was induced in germ-free C57BL/6 mice with 2.5% dextran sulphate sodium (DSS) after treatment with either C57BL/6 wild-type (WT) cecal contents or WT cecal contents supplemented with A. muciniphila. Colitis severity was assessed by disease activity index (DAI), macroscopic and histological scores, myeloperoxidase (MPO) assay and cytokine expression. In addition, colitis was induced by Trichuris muris, an intestinal nematode, following treatment with A. muciniphila. Post-infection, the severity of intestinal inflammation was assessed by worm burden, goblet cell staining, cytokines analysis, MPO activity and Muc2 expression. Microbial composition was assessed by 16s rRNA gene sequencing. Results In preliminary studies, mice treated with A. muciniphila and administered DSS for 5 days yielded a significant decrease in DAI, macroscopic scoring, and MPO values compared with controls. IL-10 was also elevated in mice receiving A. muciniphila. Groups receiving A. muciniphila in the T. muris model trended toward decreased worm burden, IL-4, IL-13, as well as increased levels of IL-10, goblet cell expression, and Muc2 and Muc5ac expression. A significant decrease in MPO activity was also observed in the group receiving the A. muciniphila-supplemented gavage. Microbial analysis indicated that 3 weeks post-gavage Akkermansia levels were significantly elevated in groups receiving the A. muciniphila-supplemented WT cecal contents versus WT alone. This significance was maintained post-T. muris infection. Conclusions These findings suggest that A. muciniphila may have a protective role in the context of intestinal inflammation. This research has the potential to fuel the development of novel treatments by utilizing this protective role in IBD. Funding Agencies CIHR

publication date

  • February 26, 2020