通过调节肠道微生物群-胆汁酸-FXR轴抑制结肠炎相关的结直肠癌。

Gut microbiota dysbiosis critically contributes to colitis-associated colorectal cancer (CAC) pathogenesis, positioning microbial modulation as a promising therapeutic strategy. () is an emerging probiotic with potential cancer-inhibiting effects. This study investigates the anti-tumorigenic potential of in an azoxymethane/dextran sulfate sodium-induced CAC murine model. Mice were orally administered 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 . Supplementation with restored the intestinal barrier and significantly reduced the relative abundance of 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 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 mitigates CAC progression through the gut microbiota-BA-FXR axis, providing mechanistic evidence for its probiotic application in CAC prevention and therapy.IMPORTANCEChronic gut inflammation driven by microbiota dysbiosis is a pivotal contributor to colitis-associated colorectal cancer (CAC) pathogenesis. Emerging evidence highlights ( as a promising anti-colorectal cancer agent (Y. Du, L. Liu, W. Yan, Y. Li, et al., Sci Rep 13:21117, 2023, https://doi.org/10.1038/s41598-023-47943-7; S. Ahmed, S. Singh, V. Singh, K. D. Roberts, et al., Microorganisms 10:2427, 2022, https://doi.org/10.3390/microorganisms10122427), yet its role in CAC remains unexplored. To address this gap, we investigated the inhibitory effects of on CAC development and elucidated its underlying mechanisms. Our results demonstrated that oral administration of significantly reshaped gut microbial communities and activated bile acid (BA)-related metabolic pathways. Subsequent mechanistic studies revealed that microbiota remodeling by altered intestinal BA composition, particularly activating the farnesoid X receptor (FXR). FXR activation mediated by these BA shifts was identified as a critical suppressor of tumorigenesis, establishing as a novel probiotic capable of attenuating CAC progression. Collectively, this study uncovers a protective axis linking -driven microbiota modulation, BA metabolism change, and FXR-dependent tumor suppression, providing experimental evidence for probiotic-based CAC intervention strategies.

肠道微生物群失调是结肠炎相关结直肠癌（CAC）发病机制的关键因素，这使得微生物调节成为一种有前景的治疗策略。（）是一种新兴的益生菌，具有潜在的癌症抑制作用。本研究在氧化偶氮甲烷/葡聚糖硫酸钠诱导的CAC小鼠模型中研究了（）的抗肿瘤潜力。从模型构建开始到实验结束，每2天给小鼠口服一次（）。研究表明，CAC小鼠的肠道微生物群发生了显著变化，（）的相对丰度显著增加。补充（）可恢复肠道屏障，并显著降低肠道微生物群中（）的相对丰度。肠道微生物群的变化降低了胆汁盐水解酶活性和未结合胆汁酸（BA），逆转了CAC小鼠的肿瘤发生。补充（）后肠道BA的变化上调了CAC小鼠肠道中法尼醇X受体（FXR）的表达，并抑制了核因子κB通路。我们的研究结果表明，（）通过肠道微生物群-BA-FXR轴减轻了CAC的进展，为其在CAC预防和治疗中的益生菌应用提供了机制证据。

重要性由微生物群失调驱动的慢性肠道炎症是结肠炎相关结直肠癌（CAC）发病机制的关键因素。新出现的证据表明（）是一种有前景的抗结直肠癌药物（Y. Du、L. Liu、W. Yan、Y. Li等人，《科学报告》13:21117，2023，https://doi.org/10.1038/s41598-023-47943-7；S. Ahmed、S. Singh、V. Singh、K. D. Roberts等人，《微生物》10:2427，2022，https://doi.org/10.3390/microorganisms10122427），但其在CAC中的作用仍未得到探索。为了填补这一空白，我们研究了（）对CAC发展的抑制作用，并阐明了其潜在机制。我们的结果表明，口服（）显著重塑了肠道微生物群落，并激活了与胆汁酸（BA）相关的代谢途径。随后的机制研究表明，（）引起的微生物群重塑改变了肠道BA组成，特别是激活了法尼醇X受体（FXR）。这些BA变化介导的FXR激活被确定为肿瘤发生的关键抑制因子，确立了（）作为一种能够减轻CAC进展的新型益生菌。总的来说，本研究揭示了一个保护性轴，将（）驱动的微生物群调节、BA代谢变化和FXR依赖性肿瘤抑制联系起来，为基于益生菌的CAC干预策略提供了实验证据。