胆酸结合和水解活性之间的平衡可以改变肠道炎症的结果
Yousi Fu1, Douglas V Guzior1,2, Maxwell Okros1
1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Nature communications
|April 10, 2025
概括
结合胆酸 (BAs) 影响肠道炎症. 宿主结合的BA在小鼠中改善了结肠炎,但由胆盐酸酶 (BSH) 基因的微生物脱影响了炎症性肠病 (IBD) 的结果.
科学领域:
- 胃肠道学和微生物学
- 肠道微生物组和宿主-IA相互作用
- 胆酸新陈代谢 胆酸新陈代谢
背景情况:
- 结合胆汁酸 (BAs) 对胃肠功能至关重要,由胆汁酸-CoA:氨基酸N-转移酶 (BAAT) 等宿主酶和胆汁盐化酶 (BSH) 等微生物酶产生.
- 患有炎症性肠病 (IBD) 的患者表现出宿主和微生物结合BA (MCBA) 的水平发生变化,但它们在肠道炎症中的具体作用尚不清楚.
- 了解宿主和微生物BA代谢之间的相互作用对于破译它们对胃肠道健康和疾病的影响至关重要.
研究的目的:
- 在大肠炎的小鼠模型中研究宿主结合BA的作用.
- 在IBD的背景下,探索微生物胆汁盐化酶 (BSH) 活性对结合BA的影响.
- 为了确定BA结合和脱结合平衡对胃肠道炎症的影响.
主要方法:
- 使用胆汁酸-CoA:氨基酸N-转移酶 (BAAT) 淘汰小鼠模型来研究结肠炎.
- 给BAAT淘汰赛小鼠服用taurocholate (TCA) 补充剂,并评估大肠炎的严重程度,上皮屏障完整性和杯状细胞功能.
- 进行了代谢分析,以分析BA型号,并研究了用结合BA的各种肠道细菌的胆盐化酶 (BSH) 活性.
- 分析了人类IBD患者的元基因组数据,以确定富含的bsh基因,特别是在克罗恩病中.
主要成果:
- BAAT淘汰赛小鼠表现出严重的结肠炎表型,这些表型通过补充taurocholate (TCA) 来显著挽救.
- 在结肠炎模型中,TCA补充改善了上皮屏障完整性和杯状细胞功能.
- 代谢分析显示,补充TCA的大量代谢转化为二次BA.
- 多种肠道细菌在各种氨基酸结合BA上表现出广泛的胆汁盐酸酶 (BSH) 活性.
- 发现特定的bsh基因序列,特别是来自Ruminococcus gnavus的基因序列,在人类克罗恩病患者的元基因组数据中得到了丰富.
结论:
- 主体结合胆酸,以TCA为例,可以通过增强表皮屏障功能和杯状细胞活性来改善实验性结肠炎.
- 胆汁盐化酶 (BSH) 对胆汁酸的微生物脱是调节肠道内BA池的一个重要因素.
- 受到特定bsh基因的存在和活性影响的BA结合和解结合之间的平衡在宿主微生物群相互作用及其对炎症性肠病 (IBD) 的影响中发挥着关键作用.
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