与胆囊切除相关的肠道微生物群失生症加剧了结直肠瘤发生
Bo Tang1, Shengpeng Li1, Xin Li1
1Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China.
Nature communications
|August 16, 2025
概括
胆囊切除,胆囊切除,通过改变肠道细菌和胆酸,增加结直肠癌的风险,影响FXR信号传输. 调节这种肠道微生物群-胆酸-FXR轴可以预防癌症.
科学领域:
- 胃肠道学和瘤学
- 微生物组研究 微生物组研究
- 胆酸新陈代谢 胆酸新陈代谢
背景情况:
- 胆囊切除术是治疗胆囊问题的常见手术.
- 新出现的证据将胆囊切除术与结直肠癌 (CRC) 风险增加联系起来.
- 这种关联背后的机制尚未完全理解.
研究的目的:
- 研究胆囊切除术对结直肠瘤发生的影响.
- 阐明涉及肠道微生物群和胆酸代谢的潜在机制.
- 探索针对肠道微生物群-胆酸-FXR轴的潜在治疗策略.
主要方法:
- 使用AOM/DSS和APCmin/+大肠直肠癌小鼠模型.
- 执行了元基因组测序和目标代谢学.
- 进行了便微生物群移植,细菌殖民,胆酸补充,RNA测序和共免疫沉.
主要成果:
- 胆囊切除术在小鼠模型中加剧了结直肠瘤发生.
- 观察到肠道微生物群 (B. breve减少,R. gnavus增加) 和胆酸 (GUDCA/TUDCA增加) 的显著变化.
- 确定了FXR信号抑制和破坏的FXR/β-catenin相互作用作为关键机制.
- 用FXR激动剂obeticholic acid (OCA) 治疗可以预防胆囊切除术相关的瘤发生.
结论:
- 胆囊切除术诱导的肠道微生物群和胆酸变化促进结直肠瘤发生.
- 在这个过程中,肠道微生物群-胆酸-FXR信号通路至关重要.
- 针对这个轴,特别是使用FXR激动剂,为CRC后胆囊切除术提供了一个有前途的预防策略.
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