Weissella cibaria suppresses colitis-associated colorectal cancer by modulating the gut microbiota-bile acid-FXR axis

作者：Qiuyao Hao, Feifei Huang, Liangzheng Chang, Hongyuan Dai, Weiwei Chen, Yiran Yao, Yunhuan Zhen · 发表于：mSystems · 年份：2025 · DOI：10.1128/msystems.00288-25 · 被引用次数：7 · 研究领域：Gut microbiota and health、Drug Transport and Resistance Mechanisms、Helicobacter pylori-related gastroenterology studies

ABSTRACT Gut microbiota dysbiosis critically contributes to colitis-associated colorectal cancer (CAC) pathogenesis, positioning microbial modulation as a promising therapeutic strategy. Weissella cibaria ( W. cibaria ) is an emerging probiotic with potential cancer-inhibiting effects. This study investigates the anti-tumorigenic potential of W. cibaria in an azoxymethane/dextran sulfate sodium-induced CAC murine model. Mice were orally administered W. cibaria every 2 days from the beginning of the model construction until the end of the experiment. The study demonstrated significant changes in the gut microbiota of CAC mice, with a significant increase in the relative abundance of Lactobacillaceae . Supplementation with W. cibaria restored the intestinal barrier and significantly reduced the relative abundance of Lactobacillaceae in the gut microbiota. The changes in the gut microbiota reduced bile salt hydrolase activity and unconjugated bile acid (BA), reversing tumorigenesis in CAC mice. Changes in intestinal BA after W. cibaria supplementation upregulated farnesoid X receptor (FXR) expression in the intestine of CAC mice and inhibited the nuclear factor kappa-B pathway. Our findings establish that W. cibaria mitigates CAC progression through the gut microbiota-BA-FXR axis, providing mechanistic evidence for its probiotic application in CAC prevention and therapy. IMPORTANCE Chronic gut inflammation driven by microbiota dysbiosis is a pivotal contributor to colitis-associ...