Alcaligenes faecalis promotes colitis to colorectal cancer transition through IgA+ B cell suppression and vinculin acetylation

作者：Jing Zheng, Chishun Zhou, Zizheng Li, Xin Jin, Yihua Zou, Shasha Bai, Huilei Zheng, Weichao Ling, Yiru Zhao, Ying Wang, Rong Zhang, Zhongqiu Liu, Linlin Lu · 发表于：Gut Microbes · 年份：2025 · DOI：10.1080/19490976.2025.2473511 · 被引用次数：21 · 研究领域：Pancreatitis Pathology and Treatment、Pancreatic and Hepatic Oncology Research、Gut microbiota and health

Lymphoid tissue-resident commensal bacteria (LRC), a subtype of gut microbiota essential for inflammation-associated carcinogenesis, predominantly attribute to colorectal cancer(CRC), whereas its role was largely unknown. Herein, we found Alcaligenes faecalis (A. faecalis), the main LRC embedded in Peyer’s patches, was abundantly enriched in colitis, adenoma, and stage-dependently observed in CRC tissues. Interestingly, A. faecalis alone can not affect intestinal homeostasis, while during colitis, A. faecalis significantly translocated from Peyer’s patches to colon, remarkably attenuated immune response abilities of B cells, T cells, and DC cells in PPs, consequently impeded IgA+ B cells homing. Meanwhile, during colitis, the ectopia of A. faecalis in colon tissues, promoted vinculin acetylation by A. faecalis–derived metabolite acetic acid, which impeded intestinal barrier via hindering the binding of vinculin to β-catenin. Our study revealed A. faecalis not only suppress mucosal immune responses via reducing IgA+ B cells in Peyer’s patches but also disrupt intestinal barrier via increasing vinculin acetylation, ultimately promoting inflammation-to-cancer transition in CRC.