Akkermansia muciniphila and its culture supernatant ameliorate colitis in interleukin-10 knockout mice via gut barrier and immune modulation

MIingshan Jiang^1,2,3Jia Yongbin^1,2,3Chunxiang Ma^1,2,3Zhen Zeng^1,2,3Yan Li^1,2,3Lili Li^1,2,3Hao Lin^1,2,3Jiangmei Pang^1,2,3Jiaxin Li^1,2,3Jingjing Chen^1,2,3Xi Li^1,2,3Kexin Chen^1,2,3Hong Zhang^1,2,3Yu Gan⁴Zou Xiang⁵Linlin Chen^6*Hu Zhang^1,2,3*

• ¹Center for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
• ²Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
• ³Laboratory of Inflammatory Bowel Disease, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
• ⁴The First Department of the Digestive Disease Center, Suining Central Hospital, Chengdu, China
• ⁵Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hong Kong, China
• ⁶Department of Gastroenterology，Suining Central Hospital, Suining, Sichuan, China

Background: Akkermansia muciniphila (A. muciniphila) is a mucin-degrading commensal bacterium with established roles in maintaining intestinal homeostasis and modulating host immune responses. However, its therapeutic potential and mechanisms in chronic spontaneous colitis remain incompletely defined. Interleukin-10 knockout (IL-10⁻/⁻) mice are a well-established model of spontaneous colitis due to impaired anti-inflammatory cytokine signaling and disrupted immune regulation. In this study, we aimed to determine whether A. muciniphila and its culture-derived supernatant could ameliorate intestinal inflammation in IL-10⁻/⁻ mice. Methods: We administered A. muciniphila or its culture supernatant (A. muciniphila supernatant [A.m-SN]) to IL-10⁻/⁻ mice and monitored disease progression over 30 days. Clinical assessments included body weight, disease activity index (DAI), colon length, histopathology, and endoscopy. Tight junction proteins (zonula occludens-1 [ZO-1] and Occludin) and colonic messenger ribonucleic acid levels of pro- and anti-inflammatory cytokines were evaluated. Gut microbiota composition was assessed using 16S ribosomal deoxyribonucleic acid sequencing, and untargeted metabolomic profiling was performed on the culture medium to identify potential anti-inflammatory components.