Akkermansia muciniphila Alleviates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by NLRP3 Activation.

Microbiol Spectr

Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China.

Published: October 2021

Akkermansia muciniphila has been proved to play a crucial role in the progression of colitis, but its underlying mechanism remains inconclusive. In this study, we aim to investigate the effect of on the development of acute colitis and explore the underlying mechanism. We found that the fecal level of was decreased in ulcerative colitis (UC) patients compared to the healthy people in the GMrepo database. Oral administration of strain BAA-835 significantly ameliorated the symptoms in dextran sulfate sodium (DSS)-induced acute colitis, evidenced by decreased body weight loss, colon length shortening, and colon histological inflammatory score. In addition, the number of goblet cells and the mucin family were enhanced after treatment. Furthermore, proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein 1 (MCP-1) had a downward trend. Mechanistically, the expression of NLRP3, caspase-1 p20, and IL-1β p17 were upregulated in -treated mice. Additionally, the colon tissues from high- UC patients had a higher NLRP3 expression than that from low- UC patients. Moreover, the upregulation of NLRP3 was observed in mouse macrophage Raw264.7 cells and bone marrow-derived macrophage (BMDM) cells after incubation with . To clarify whether the protective effect of in colitis depends on NLRP3, we performed the NLRP3-deficient assay in NLRP3 mice . The evidence showed that NLRP3 deficiency eliminated the protective effects of in acute colitis. In conclusion, alleviates DSS-induced acute colitis by NLRP3 activation, which enriches the mechanism and provides a new prospect for the probiotic-based treatment of colitis. The gut microbiota and host immune response interaction influences the progression of intestinal inflammatory disease. As a well-recognized next-generation probiotic, Akkermansia muciniphila has been proved to play a crucial role in the progression of colitis, but its underlying mechanism remains inconclusive. We found that oral administration of strain BAA-835 significantly ameliorated the symptoms of acute colitis. Mechanistically, the expression of NLRP3 was upregulated in the group, and the protective effect of in colitis depends on NLRP3 activation. This enriches the mechanism and provides a new prospect for the probiotic-based treatment of colitis, which would promote a deeper understanding of the complex characteristics of and provide guidance for the treatment of human colitis in the future.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510245PMC
http://dx.doi.org/10.1128/Spectrum.00730-21DOI Listing

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