AUTHOR=Liu Qing , Lu Wenwei , Tian Fengwei , Zhao Jianxin , Zhang Hao , Hong Kan , Yu Leilei 

TITLE=Akkermansia muciniphila Exerts Strain-Specific Effects on DSS-Induced Ulcerative Colitis in Mice

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.698914

DOI=10.3389/fcimb.2021.698914

ISSN=2235-2988

ABSTRACT=<p><italic>Akkermansia muciniphila</italic> is a commensal bacterium of the gut mucus layer. Although both <italic>in vitro</italic> and <italic>in vivo</italic> data have shown that <italic>A. muciniphila</italic> strains exhibit strain-specific modulation of gut functions, its ability to moderate immunity to ulcerative colitis have not been verified. We selected three isolated human <italic>A. muciniphila</italic> strains (FSDLZ39M14, FSDLZ36M5 and FSDLZ20M4) and the <italic>A. muciniphila</italic> type strain ATCC BAA-835 to examine the effects of different <italic>A. muciniphila</italic> strains on dextran sulfate sodium-induced colitis. All of the <italic>A. muciniphila</italic> strains were cultured anaerobically in brain heart infusion medium supplemented with 0.25% type II mucin from porcine stomach. To create animal models, colitis was established in C57BL/6 mice which randomly divided into six groups with 10 mice in each group by adding 3% dextran sulfate sodium to drinking water for 7 days. <italic>A. muciniphila</italic> strains were orally administered to the mice at a dose of 1 × 10<sup>9</sup> CFU. Only <italic>A. muciniphila</italic> FSDLZ36M5 exerted significant protection against ulcerative colitis (UC) by increasing the colon length, restoring body weight, decreasing gut permeability and promoting anti-inflammatory cytokine expression. However, the other strains (FSDLZ39M14, ATCC BAA-835 and FSDLZ20M4) failed to provide these effects. Notably, <italic>A. muciniphila</italic> FSDLZ20M4 showed a tendency to exacerbate inflammation according to several indicators. Gut microbiota sequencing showed that <italic>A. muciniphila</italic> FSDLZ36M5 supplementation recovered the gut microbiota of mice to a similar state to that of the control group. A comparative genomic analysis demonstrated that the positive effects of <italic>A. muciniphila</italic> FSDLZ36M5 compared with the FSDLZ20M4 strain may be associated with specific functional genes that are involved in immune defense mechanisms and protein synthesis. Our results verify the efficacy of <italic>A. muciniphila</italic> in improving UC and provide gene targets for the efficient and rapid screening of <italic>A. muciniphila</italic> strains with UC-alleviating effects.</p>