A biosynthetic pathway for a prominent class of microbiota-derived bile acids.
A biosynthetic pathway for a prominent class of microbiota-derived bile acids.
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一类重要的微生物胆汁酸的生物合成途径。
DOI：
10.1038/nchembio.1864
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发表时间：
2015-09
影响因子：
14.8
通讯作者：
Fischbach MA
中科院分区：
文献类型：
--
作者：
Devlin AS;Fischbach MA
肠道胆汁酸池的浓度为毫摩尔，个体之间的组成差异很大，并且与代谢疾病和癌症有关。尽管这些分子几乎完全来自微生物群，但对于哪些细菌种类和基因负责其生物合成却知之甚少。在这里，我们报告了肠道中第二丰富的异（3β-羟基）胆汁酸的生物合成途径，其水平在一些人中超过 300 µM，而在其他人中则不存在。我们首次证明，异胆汁酸是由疣状瘤胃球菌产生的，这是一种比以前已知的生产者丰富得多的共生菌；异胆汁酸途径可以解毒脱氧胆酸，有利于关键拟杆菌属的生长。通过揭示大量胆汁酸的生物合成基因，我们的工作为预测和合理改变胆汁酸库的组成奠定了基础。
The gut bile acid pool is millimolar in concentration, varies widely in composition among individuals, and is linked to metabolic disease and cancer. Although these molecules derive almost exclusively from the microbiota, remarkably little is known about which bacterial species and genes are responsible for their biosynthesis. Here, we report a biosynthetic pathway for the second most abundant class in the gut, iso (3β-hydroxy) bile acids, whose levels exceed 300 µM in some humans and are absent in others. We show, for the first time, that iso bile acids are produced by Ruminococcus gnavus, a far more abundant commensal than previously known producers; and that the iso bile acid pathway detoxifies deoxycholic acid, favoring the growth of the keystone genus Bacteroides. By revealing the biosynthetic genes for an abundant class of bile acids, our work sets the stage for predicting and rationally altering the composition of the bile acid pool.