小柯机器人

美国哈佛医学院A. Sloan Devlin和Jun R. Huh研究组宣布他们发现了人类肠道细菌会产生影响辅助T细胞（T_H17细胞）的胆汁酸代谢物。2022年3月16日出版的《自然》杂志发表了这项成果。

研究人员发现了将次级胆汁酸石胆酸转化为3-oxolithocholic acid (3-oxoLCA)以及肠道丰富代谢物异石胆酸(isoLCA)的人类肠道细菌和相应的酶。与3-oxoLCA类似，isoLCA通过抑制视黄酸受体相关的孤核受体-γt（一种关键的T_H17细胞促进转录因子）来抑制T_H17细胞分化。炎症性肠病患者体内3-oxoLCA和isoLCA以及其生物合成所需的3α-羟基类固醇脱氢酶基因水平显著下降。

此外，这些胆汁酸水平与T_H17细胞相关基因的表达呈负相关。总体而言，该研究数据表明细菌产生的胆汁酸抑制了T_H17细胞的功能，这种活性可能与炎症性疾病（如炎症性肠病）的病理有关。

研究人员表示，微生物群调节肠道免疫稳态。细菌影响宿主免疫细胞的发育和功能，包括表达IL-17A的辅助T细胞（T_H17细胞）。之前的研究发现胆汁酸代谢物3-oxoLCA抑制T_H17细胞分化。虽然有证据表明肠道细菌会产生3-oxoLCA，但此类细菌的身份尚不清楚，并且也不清楚3-oxoLCA和其他免疫调节胆汁酸是否与人类的炎症有关。

附：英文原文

Title: Human gut bacteria produce ΤΗ17-modulating bile acid metabolites

Author: Paik, Donggi, Yao, Lina, Zhang, Yancong, Bae, Sena, DAgostino, Gabriel D., Zhang, Minghao, Kim, Eunha, Franzosa, Eric A., Avila-Pacheco, Julian, Bisanz, Jordan E., Rakowski, Christopher K., Vlamakis, Hera, Xavier, Ramnik J., Turnbaugh, Peter J., Longman, Randy S., Krout, Michael R., Clish, Clary B., Rastinejad, Fraydoon, Huttenhower, Curtis, Huh, Jun R., Devlin, A. Sloan

Issue&Volume: 2022-03-16

Abstract: The microbiota modulates gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17A (TH17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits TH17 cell differentiation1. Although it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown, and it was unclear whether 3-oxoLCA and other immunomodulatory bile acids are associated with inflammatory pathologies in humans. Here we identify human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite isolithocholic acid (isoLCA). Similar to 3-oxoLCA, isoLCA suppressed TH17 cell differentiation by inhibiting retinoic acid receptor-related orphan nuclear receptor-γt, a key TH17-cell-promoting transcription factor. The levels of both 3-oxoLCA and isoLCA and the 3α-hydroxysteroid dehydrogenase genes that are required for their biosynthesis were significantly reduced in patients with inflammatory bowel disease. Moreover, the levels of these bile acids were inversely correlated with the expression of TH17-cell-associated genes. Overall, our data suggest that bacterially produced bile acids inhibit TH17 cell function, an activity that may be relevant to the pathophysiology of inflammatory disorders such as inflammatory bowel disease.

DOI: 10.1038/s41586-022-04480-z

Source: https://www.nature.com/articles/s41586-022-04480-z

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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