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微生物群-IPA轴通过Hopx相关程序促进肠道干细胞在结肠炎中介的再生

Yanan Zhang¹, Jinxin Meng¹, Shuyu Tu^1,2

¹Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China.

Nature communications

|February 25, 2026

概括

在炎症性肠病 (IBD) 中降低的蓝斑,通过促进β-基酸盐 (BHB) 生产来促进肠道愈合. 这增强了肠干细胞 (ISC) 再生和上皮细胞修复.

科学领域:

胃肠病学胃肠病学
微生物学微生物学
干细胞生物学干细胞生物学

背景情况:

肠道微生物群对于肠道干细胞 (ISC) 稳态和上皮屏障功能至关重要.
在炎症性肠病 (IBD) 患者和DSS诱导的大肠炎模型中,发现蓝斑虫 (B. coccoides) 显著减少.

研究的目的:

调查B. coccoides在肠道上皮质修复中的作用,并确定潜在的分子机制.
探索微生物群衍生代谢物的潜力,作为IBD的治疗剂.

主要方法:

在粘膜损伤模型中对RNA测序,新陈代谢分析和ISC谱系追踪的综合分析.
利用工程Escherichia coli来评估细菌酶在代谢产生的功能.

主要成果:

B. coccoides的殖民增加了肠上皮细胞 (IEC) 中的β-基酸盐 (BHB),激活了储备ISC,并促进了LGR5+ISC池的再生.
B. coccoides 衍生品的印-3-乳酸 (ILA) 被其他类动物转化为印-3-propionic 酸 (IPA),刺激 BHB 合成和粘膜愈合.
饮食中的托和细菌fldH活性对于ILA/IPA生成和上皮细胞修复至关重要.

结论:

确定了一种新的微生物群-代谢物-ISC调节轴,对于上皮再生至关重要.
B. coccoides及其代谢物代表IBD和肠道屏障功能障碍的潜在治疗点.

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