The role of Akkermansia muciniphila in inflammatory bowel disease: Current knowledge and perspectives

Abstract

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, is a chronic relapsing gastrointestinal inflammatory disease mediated by dysregulated immune responses to resident intestinal microbiota. Current conventional approaches including aminosalicylates, corticosteroids, immunosuppressive agents, and biological therapies are focused on reducing intestinal inflammation besides inducing and maintaining disease remission, and managing complications. However, these therapies are not curative and are associated with various limitations, such as drug resistance, low responsiveness and adverse events. Recent accumulated evidence has revealed the involvement of mucin-degrading bacterium Akkermansia muciniphila (A. muciniphila) in the regulation of host barrier function and immune response, and how reduced intestinal colonisation of probiotic A. muciniphila can contribute to the process and development of inflammatory bowel diseases, suggesting that it may be a potential target and promising strategy for the therapy of inflammatory bowel disease. In this review, we summarise the current knowledge of the role of A. muciniphila in IBD, especially focusing on the related mechanisms, as well as the strategies based on supplementation with A. muciniphila, probiotics and prebiotics, natural diets, drugs, and herbs to promote its colonisation in the gut, and holds promise for A. muciniphila-targeted and -based therapies in the treatment of inflammatory bowel disease.

Keywords: Akkermansia muciniphila; barrier function; gut microbiota; inflammatory bowel disease; mucosal immunity.

Figure 1

The role of A. muciniphila in inflammatory bowel disease. Supplement with A. muciniphila reduces the levels of colonic infiltrating macrophages and cytotoxic T lymphocytes (CTLs) and relieves intestinal inflammation. The protective effects of A. muciniphila on intestinal homeostasis are associated with increased numbers of goblet cells, enhanced mucus barrier and anti-microbial responses. A. muciniphila supplement partially attenuates gut dysbiosis and resist the colonisation against other pathogens. Moreover, A. muciniphila derived SCFAs promoted the conversion from Naïve T cells to Foxp3+Treg cells through GPRs signal pathway, which may be accompanied by reduced Th1/17 cell-mediated inflammatory response. Interestingly, both pasteurised A. muciniphila and Amuc_1100, a specific outer membrane protein of the bacterium also play a similar role as A. muciniphila itself in immune protection and inhibit the infiltration macrophages and CTLs. Furthermore, A. muciniphila-derived extracellular vesicles (AmEVs), a bilayer structure composed of lipid, protein, lipopolysaccharides as well as other molecules, and Amuc_1100 also regulate intestinal barrier permeability by altering tight junction protein expression through activating TLR2 pathway.

Figure 2

A proposed model illustrating the protective effect of A. muciniphila-targeted and -based therapies in the treatment of inflammatory bowel disease.