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来自Faecalibacterium prausnitzii的细胞外囊泡通过巨细胞代谢重编程来缓解慢性结肠炎相关的肠纤维化
Ying Wang1, Linjie Li2, Shuze Chen2
1Integrative Clinical Microecology Center, Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Technology Research Center of Gut Microbiota Transplantation, Shenzhen Hospital, Southern Medical University, Shenzhen, China; Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
Pharmacological research
|June 30, 2024
概括
菌的细胞外囊泡 (FEVs) 通过重编程巨细胞来减少肠道纤维化. FEVs促进抗纤维化M2b巨细胞,为克罗恩病提供潜在的治疗策略.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 菌 (F. prausnitzii) 提供健康益处,其减少与克罗恩氏病 (CD) 纤维化有关.
- 在CD中肠道纤维化是一个重要的临床挑战.
研究的目的:
- 研究F. prausnitzii及其细胞外囊泡 (FEV) 在缓解肠道纤维化的治疗潜力.
- 阐明FEVs调节巨细胞极化和功能的机制.
主要方法:
- 在DSS诱导的小鼠纤维化模型中,口服活生F. prausnitzii或FEVs.
- 对外围血液单核细胞 (PBMC) 的体外研究,以评估巨细胞的两极分化.
- 蛋白质组学和RNA测序来分析巨细胞中的分子变化.
主要成果:
- 在小鼠中,FEV显著降低了纤维化严重程度.
- FEVs诱导了M2b巨细胞两极化,与抗纤维细胞活性相关,抵抗亲纤维细胞表型.
- FEVs通过损害线粒体,抑制氧化酸化和糖解来重新编程巨细胞代谢.
- FEV治疗降低了PPARγ的表达,并改变了巨细胞中的脂质处理.
结论:
- FEVs是巨细胞重编程的关键媒介.
- 口服FEVs可以缓解肠道中的纤维化疾病.
- 用FEV准M2b巨细胞两极化为CD相关纤维化提供了一个有前途的治疗途径.
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