线粒体功能障碍相关的微生物群在性结肠炎期间对抗TNF疗法建立了可传播的耐火反应
Ainize Peña-Cearra1,2, Janire Castelo1, Jose Luis Lavín1,3
1CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain.
Gut microbes
|October 16, 2023
概括
缺少线粒体复合体I的抑制剂MCJ,改变了肠道微生物群,导致炎症性肠病模型中对抗TNF疗法的不响应.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 抗瘤坏死因子 (TNF) 治疗对炎症性肠病 (IBD) 有效,但30%的患者表现出初级无反应.
- 在IBD中抗TNF不响应背后的机制在很大程度上是未知的.
研究的目的:
- 为了研究MCJ (形状不佳的卷状卷 1) 的作用,一个线粒体复合物I抑制剂,在抗TNF治疗反应中.
- 在小鼠模型中探索MCJ缺乏,肠道微生物群和炎症之间的联系.
主要方法:
- 在人类结肠组织中评估了MCJ表达.
- 从患有DSS诱导的大肠炎的小鼠身上进行了结肠巨细胞的转录组分析.
- 在MCJ缺乏的小鼠中分析了肠道微生物组成.
主要成果:
- MCJ表达局限于人类结肠中的巨细胞.
- 缺乏MCJ的巨细胞表现出FcγR信号通路基因表达和抗TNF耐火特征.
- 缺少MCJ会改变肠道微生物群,增加诸如Ruminococcus gnavus和Oscillospira*之类的结肠杆菌.
- 与微生物群相关的治疗耐药性是可传播的.
结论:
- 巨细胞的线粒体功能,特别是MCJ的存在,对于IBD的抗TNF治疗反应至关重要.
- 由MCJ缺陷驱动的肠道微生物群失调有助于抗TNF不响应.
- 向巨细胞的线粒体功能和肠道微生物群可能会改善IBD治疗结果.
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