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微生物胆汁酸代谢物调节肠道RORγ+调节性T细胞稳态
2019-12-26 14:22

美国哈佛医学院Dennis L. Kasper团队在研究中取得进展。他们的研究显示,微生物胆汁酸代谢物调节肠道RORγ+调节性T细胞稳态。2019年12月25日,《自然》杂志在线发表了这项成果。

研究人员表示,人类肠道微生物组编码的代谢途径通过许多生物活性分子不断与宿主基因产物相互作用。初级胆汁酸(BA)在肝细胞内合成并释放到十二指肠中,以促进脂质或脂溶性维生素的吸收。一些BA(约5%)逃逸到结肠,肠道共生细菌将其转化为各种肠道BA,从而成为重要的激素,通过几个核受体和/或G蛋白偶联受体调节宿主胆固醇的代谢和能量平衡。这些受体在塑造宿主先天免疫反应中起关键作用。但是,这种宿主与微生物胆管网络对适应性免疫系统的作用仍然很差。

研究人员发现饮食和微生物因素都影响肠道BA池的组成,并调节重要的表达转录因子RORγ的结肠FOXP3+调节性T(Treg)细胞。个体肠共生体中BA代谢途径的遗传敲除显著降低了该Treg细胞群。肠道BA池的恢复增加了结肠RORγ+Treg细胞的数量,并通过BA核受体改善了宿主对炎性结肠炎的敏感性。因此,宿主与其细菌共生体之间的全基因组胆道网络相互作用可以通过产生的代谢物控制宿主的免疫稳态。

附:英文原文

Title: Microbial bile acid metabolites modulate gut RORγ +  regulatory T cell homeostasis

Author: Xinyang Song, Ximei Sun, Sungwhan F. Oh, Meng Wu, Yanbo Zhang, Wen Zheng, Naama Geva-Zatorsky, Ray Jupp, Diane Mathis, Christophe Benoist, Dennis L. Kasper

Issue&Volume: 2019-12-25

Abstract: The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules1. Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins2. Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors3,4. These receptors have pivotal roles in shaping host innate immune responses1,5. However, the effect of this host–microorganism biliary network on the adaptive immune system remains poorly characterized. Here we report that both dietary and microbial factors influence the composition of the gut BA pool and modulate an important population of colonic FOXP3+ regulatory T (Treg) cells expressing the transcription factor RORγ. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this Treg cell population. Restoration of the intestinal BA pool increases colonic RORγ+ Treg cell counts and ameliorates host susceptibility to inflammatory colitis via BA nuclear receptors. Thus, a pan-genomic biliary network interaction between hosts and their bacterial symbionts can control host immunological homeostasis via the resulting metabolites.

DOI: 10.1038/s41586-019-1865-0

Source: https://www.nature.com/articles/s41586-019-1865-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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