Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis
Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis
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DOI：
10.1038/s41586-019-1865-0
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发表时间：
2019-12-25
期刊：
影响因子：
64.8
通讯作者：
Kasper, Dennis L.
中科院分区：
文献类型：
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作者：
Song, Xinyang;Sun, Ximei;Kasper, Dennis L.
由人体肠道微生物群编码的代谢途径通过许多生物活性分子与宿主基因产物不断相互作用(1)。初级胆汁酸(BA)是在肝细胞内合成的，并释放到十二指肠以促进脂类或脂溶维生素的吸收(2)。一些BAs(约5%)逃逸到结肠，在那里肠道共生细菌将它们转化为各种肠道BAs2，BAs2是通过几个核受体和/或G蛋白偶联受体(3，4)调节宿主胆固醇代谢和能量平衡的重要激素。这些受体在塑造宿主先天免疫反应中起着关键作用(1，5)。然而，这种宿主-微生物胆道网络对适应性免疫系统的影响仍然缺乏特征。在这里，我们报告了饮食和微生物因素都影响肠道BA池的组成，并调节结肠FOXP3(+)调节性T(T-reg)细胞表达转录因子RORγ的重要群体。单个肠道共生体中BA代谢途径的遗传取消显著减少了T-reg细胞数量。肠道BA池的修复可增加结肠ROR-γT-+(REG)细胞计数，并通过BA核受体改善宿主对炎症性结肠炎的易感性。因此，宿主和细菌共生体之间的泛基因组胆道网络相互作用可以通过所产生的代谢产物来控制宿主的免疫动态平衡。饮食和微生物因素都会影响肠道胆汁酸池的组成，进而调节表达RORγ的结肠FOXP3(+)调节性T细胞的频率和功能，有助于预防炎症性结肠炎。
The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules(1). Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins(2). 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 receptors(3,4). These receptors have pivotal roles in shaping host innate immune responses(1,5). 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 (T-reg) cells expressing the transcription factor ROR gamma. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this T-reg cell population. Restoration of the intestinal BA pool increases colonic ROR gamma T-+ (reg) 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.Both dietary and microbial factors influence the composition of the gut bile acid pool, which in turn modulates the frequencies and functionalities of ROR gamma-expressing colonic FOXP3(+) regulatory T cells, contributing to protection from inflammatory colitis.