胆汁微生物群及其二次胆汁酸调节乳山羊对非酒精性胆汁肝炎的敏感性
Yue Wang1,2,3, Xiaodong Chen1,4,3, Sharon A Huws5
1College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Microbiome
|November 23, 2024
概括
动物非酒精性脂肪肝炎 (NASH) 的易感性与胆汁酸 (BA) 的代谢有关. 来自肠道细菌的特定BA,如UDCA,isoDCA和isoLCA,可以通过调节免疫细胞来改善NASH,为肝脏健康提供潜在的后生物治疗方法.
科学领域:
- 兽医肝病学 兽医肝病学
- 动物肠道微生物组研究
- 胆汁酸的新陈代谢 胆汁酸的新陈代谢
背景情况:
- 非酒精性脂肪肝炎 (NASH) 在反动物中构成重大健康挑战,对易感性机制的理解不充分.
- 肠肝轴,特别是胆酸 (BA) 循环,在肝脏疾病调节中至关重要.
- 皮质BA再吸收影响肝脏健康,使其成为NASH病变发生的关键焦点.
研究的目的:
- 为了研究以叶叶微生物BA代谢如何影响不同NASH易感性山羊的肝脏代谢和免疫力.
- 揭示乳山羊中差异性NASH病原体背后的机制.
- 在小鼠模型中验证发现.
主要方法:
- 在NASH耐药和易受性山羊中,分析了叶元基因组,代谢组,肝脏和血清代谢组以及肝脏单核转录组.
- 使用高脂肪饮食诱导的NASH小鼠模型进行验证.
- 研究了特定细菌BA在调节免疫细胞群中的作用 (Treg和TH17).
主要成果:
- 纳什山羊的肝/血清胆固醇,甘油三,初级BA增加,二级BA减少,促进脂肪积累.
- 大肠杆菌,Erysipelotrichaceae) 和透性增加有助于NASH山羊的肝炎.
- 耐NASH的山羊增加了与特定细菌和基因相关的叶二次BA (UDCA,isoDCA,isoLCA),并改变了Treg/TH17细胞平衡.
结论:
- 皮质微生物组和二次BA在NASH的弹性和易感性中发挥着关键作用,通过影响肝脏Treg和TH17细胞比例.
- 细菌UDCA,isoDCA和isoLCA都显示出缓解NASH的特性.
- 这些BA代表了改善动物肝脏健康的潜在新型后生物.
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