丁酸盐调节肠道微生物组和上皮功能,减轻易诺特干诱导的肠道毒性
Research square
|September 5, 2025
概括
通过改善肠道屏障完整性和恢复健康的肠道微生物群,口服丁酸可防止化疗引起的胃肠道毒性. 这提供了一个潜在的治疗策略来控制像伊利诺特干这样的癌症治疗的副作用.
科学领域:
- 胃肠病学
- 癌症学
- 微生物组研究
背景情况:
- 化疗,特别是伊利诺特干,导致显著的胃肠道 (GI) 毒性,限制了癌症治疗的有效性.
- 肠道上皮屏障的破坏导致粘膜炎和腹,影响患者的生活质量.
- 酸盐是一种微生物代谢物,可维持上皮屏障的完整性.
研究的目的:
- 在小鼠模型中研究口服丁酸盐减轻肠道毒性的治疗潜力.
- 评估酸盐对治疗后肠道屏障功能,运动性和微生物组合的影响.
主要方法:
- 治疗小鼠以诱导肠道毒性,其中一些小鼠接受口服丁酸盐补充剂.
- 评估的参数包括体重,便中的水含量,大肠骨神经元活动,上皮膜透性和干细胞标记 (Lgr5,Muc2).
- 分析了便样本中的β- 葡萄糖酶活性和微生物群体结构 (β多样性).
主要成果:
- 口服丁酸盐改善了皮质透性,保持了Lgr5和Muc2的表达,并降低了便中的水含量.
- 丁酸盐减轻了因伊利诺特干诱导的肠道运动和β- 葡萄糖酶活性.
- 丁酸盐治疗抵消了因伊利诺特干诱导的肠道疾病,减少了有害细菌,如Akkermansia muciniphila和Desulfovibrio.
结论:
- 在小鼠中,口服的丁酸盐有效地减轻了因 irinotekan 引起的胃肠毒性.
- 丁酸盐的保护作用与上皮屏障功能改善和肠道微生物组平衡的恢复有关.
- 丁酸是治疗化疗相关胃肠道副作用的有前途的药物.
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