Bacteroides dorei BDX-01 alleviates DSS-induced experimental colitis in mice by regulating intestinal bile salt hydrolase activity and the FXR-NLRP3 signaling pathway

作者：Xiaowei Sun, Zhenhui Chen, Lu Yu, Weisen Zeng, Boyuan Sun, Hongying Fan, Yang Bai · 发表于：Frontiers in Pharmacology · 年份：2023 · DOI：10.3389/fphar.2023.1205323 · 被引用次数：31 · 研究领域：Gut microbiota and health、Gastrointestinal motility and disorders、Helicobacter pylori-related gastroenterology studies

Background: The relationships among intestinal dysbiosis, bile acid (BA) metabolism disorders, and ulcerative colitis pathogenesis are now recognized. However, how specific strains regulate BA metabolism to alleviate colitis is still unclear. This study investigated the effects of Bacteroides dorei on the development of acute colitis and elucidated the underlying mechanisms. Methods: The safety of BDX-01 was evaluated in vitro and in vivo . 2.5% dextran sulfate sodium (DSS) induced colitis in C57BL/6 mice, Caco-2, and J774A.1 cells were used to evaluate the anti-inflammatory effect of BDX-01. qPCR and Western blotting were used to detect the expression of inflammatory pathways. Microbiota composition was analyzed by 16S rRNA gene sequencing. Enzyme activity analysis and targeted metabolomics were used to analyze fecal bile salt hydrolase (BSH) and BA levels. Antibiotic-induced pseudo-germ-free mice were used to investigate the role of gut microbiota in the alleviation of colitis by BDX-01. Results: We confirmed the safety of novel strain Bacteroides dorei BDX-01 in vitro and in vivo . Oral BDX-01 administration significantly ameliorated the symptoms and pathological damage of DSS-induced acute colitis. Moreoever, 16S rRNA sequencing and enzyme activity analysis showed that BDX-01 treatment increased intestinal BSH activity and the abundance of bacteria harboring this enzyme. Targeted metabolomics revealed that BDX-01 significantly increased intestinal BA excretion and deconju...