PMID- 34612661 OWN - NLM STAT- MEDLINE DCOM- 20220131 LR - 20240226 IS - 2165-0497 (Electronic) IS - 2165-0497 (Linking) VI - 9 IP - 2 DP - 2021 Oct 31 TI - Akkermansia muciniphila Alleviates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by NLRP3 Activation. PG - e0073021 LID - 10.1128/Spectrum.00730-21 [doi] LID - e00730-21 AB - 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 A. muciniphila on the development of acute colitis and explore the underlying mechanism. We found that the fecal level of A. muciniphila was decreased in ulcerative colitis (UC) patients compared to the healthy people in the GMrepo database. Oral administration of A. muciniphila 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 A. muciniphila treatment. Furthermore, proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), 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-1beta p17 were upregulated in A. muciniphila-treated mice. Additionally, the colon tissues from high-A. muciniphila UC patients had a higher NLRP3 expression than that from low-A. muciniphila 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 A. muciniphila. To clarify whether the protective effect of A. muciniphila in colitis depends on NLRP3, we performed the NLRP3-deficient assay in NLRP3(-/-) mice in vivo. The evidence showed that NLRP3 deficiency eliminated the protective effects of A. muciniphila in acute colitis. In conclusion, A. muciniphila alleviates DSS-induced acute colitis by NLRP3 activation, which enriches the mechanism and provides a new prospect for the probiotic-based treatment of colitis. IMPORTANCE 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 A. muciniphila strain BAA-835 significantly ameliorated the symptoms of acute colitis. Mechanistically, the expression of NLRP3 was upregulated in the A. muciniphila group, and the protective effect of A. muciniphila 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 A. muciniphila and provide guidance for the treatment of human colitis in the future. FAU - Qu, Siwen AU - Qu S AD - Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. AD - Department of Gastroenterology, The Second Hospital of Jiaxing, Jiaxing, China. FAU - Fan, Lina AU - Fan L AD - Department of Gastroenterology, Second Affiliated Hospital, School of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. AD - Institute of Gastroenterology, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Qi, Yadong AU - Qi Y AD - Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. AD - Institute of Gastroenterology, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Xu, Chaochao AU - Xu C AD - Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. AD - Institute of Gastroenterology, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Hu, Yingying AU - Hu Y AD - Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Chen, Shujie AU - Chen S AD - Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. AD - Institute of Gastroenterology, Zhejiang Universitygrid.13402.34, Hangzhou, China. AD - Cancer Center, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Liu, Wei AU - Liu W AD - Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China. FAU - Liu, Weili AU - Liu W AD - Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. AD - Institute of Gastroenterology, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Si, Jianmin AU - Si J AUID- ORCID: 0000-0001-6257-2512 AD - Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. AD - Institute of Gastroenterology, Zhejiang Universitygrid.13402.34, Hangzhou, China. AD - Cancer Center, Zhejiang Universitygrid.13402.34, Hangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211006 PL - United States TA - Microbiol Spectr JT - Microbiology spectrum JID - 101634614 RN - 0 (IL1B protein, human) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (NLRP3 protein, human) RN - 0 (Nlrp3 protein, mouse) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9042-14-2 (Dextran Sulfate) RN - EC 3.4.22.36 (Caspase 1) RN - Akkermansia muciniphila SB - IM MH - Akkermansia MH - Animals MH - Bacteria/classification MH - Caspase 1/metabolism MH - Colitis/*chemically induced/*metabolism/*microbiology MH - Colitis, Ulcerative/chemically induced/metabolism/microbiology MH - Colon MH - Dextran Sulfate/*adverse effects MH - Gastrointestinal Microbiome MH - Goblet Cells/metabolism MH - Inflammasomes MH - Inflammatory Bowel Diseases MH - Interleukin-1beta MH - Macrophages/metabolism MH - Mice, Inbred C57BL MH - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*metabolism MH - Probiotics MH - Tumor Necrosis Factor-alpha/metabolism MH - Mice PMC - PMC8510245 OTO - NOTNLM OT - colitis OT - gut inflammation OT - inflammasome OT - inflammatory bowel disease OT - probiotics EDAT- 2021/10/07 06:00 MHDA- 2022/02/01 06:00 PMCR- 2021/10/06 CRDT- 2021/10/06 12:15 PHST- 2021/10/07 06:00 [pubmed] PHST- 2022/02/01 06:00 [medline] PHST- 2021/10/06 12:15 [entrez] PHST- 2021/10/06 00:00 [pmc-release] AID - 00730-21 [pii] AID - spectrum.00730-21 [pii] AID - 10.1128/Spectrum.00730-21 [doi] PST - ppublish SO - Microbiol Spectr. 2021 Oct 31;9(2):e0073021. doi: 10.1128/Spectrum.00730-21. Epub 2021 Oct 6.