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

Abstract

<i>Akkermansia muciniphila</i> is a commensal bacterium of the gut mucus layer. Although both <i>in vitro</i> and <i>in vivo</i> data have shown that <i>A. muciniphila</i> 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 <i>A. muciniphila</i> strains (FSDLZ39M14, FSDLZ36M5 and FSDLZ20M4) and the <i>A. muciniphila</i> type strain ATCC BAA-835 to examine the effects of different <i>A. muciniphila</i> strains on dextran sulfate sodium-induced colitis. All of the <i>A. muciniphila</i> 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. <i>A. muciniphila</i> strains were orally administered to the mice at a dose of 1 × 10⁹ CFU. Only <i>A. muciniphila</i> 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, <i>A. muciniphila</i> FSDLZ20M4 showed a tendency to exacerbate inflammation according to several indicators. Gut microbiota sequencing showed that <i>A. muciniphila</i> 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 <i>A. muciniphila</i> 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 <i>A. muciniphila</i> in improving UC and provide gene targets for the efficient and rapid screening of <i>A. muciniphila</i> strains with UC-alleviating effects.