美国康奈尔大学郭春君团队的研究显示，微生物来源的胆汁酸拮抗宿主雄激素受体并驱动抗肿瘤免疫。2025年4月15日出版的《细胞》杂志发表了这项成果。
在此，研究组推测，表征以前未定义的微生物群衍生的ba将揭示以前未知的BA感知受体及其生物学功能。研究小组将BA代谢组学和微生物遗传学结合起来，对200个假定的微生物群BA代谢基因进行了功能分析。该研究团队确定了56种特征较差的BAs，其中许多在人类/哺乳动物中检测到。值得注意的是，这些BAs的一个子集是人类雄激素受体（hAR）的强效拮抗剂。它们抑制AR相关基因表达，与人类相关。作为原理证明，小组证明了这些BAs中的一种以AR依赖的方式抑制肿瘤进展并增强抗PD-1治疗的功效。他们的研究结果表明，结合生物信息学、BA代谢组学和微生物遗传学的方法可以扩大他们对微生物群代谢潜力的了解，并揭示意想不到的微生物群BA-AR相互作用及其在调节宿主生物学中的作用。
据了解，微生物来源的胆汁酸（BAs）与宿主生物学/疾病有关，但其化学效应在很大程度上仍不明确。
附：英文原文
Title: Microbiota-derived bile acids antagonize the host androgen receptor and drive anti-tumor immunity
Author: Wen-Bing Jin, Leyi Xiao, Mingeum Jeong, Seong-Ji Han, Wen Zhang, Hiroshi Yano, Huiqing Shi, Mohammad Arifuzzaman, Mengze Lyu, Daoming Wang, Yuelin Angelina Tang, Shanshan Qiao, Xiaoyu Yang, He S. Yang, Jingyuan Fu, Gregory F. Sonnenberg, Nicholas Collins, David Artis, Chun-Jun Guo
Issue&Volume: 2025-04-15
Abstract: Microbiota-derived bile acids (BAs) are associated with host biology/disease, yet their causal effects remain largely undefined. Herein, we speculate that characterizing previously undefined microbiota-derived BAs would uncover previously unknown BA-sensing receptors and their biological functions. We integrated BA metabolomics and microbial genetics to functionally profile >200 putative microbiota BA metabolic genes. We identified 56 less-characterized BAs, many of which are detected in humans/mammals. Notably, a subset of these BAs are potent antagonists of the human androgen receptor (hAR). They inhibit AR-related gene expression and are human-relevant. As a proof-of-principle, we demonstrate that one of these BAs suppresses tumor progression and potentiates the efficacy of anti-PD-1 treatment in an AR-dependent manner. Our findings show that an approach combining bioinformatics, BA metabolomics, and microbial genetics can expand our knowledge of the microbiota metabolic potential and reveal an unexpected microbiota BA-AR interaction and its role in regulating host biology.
DOI: 10.1016/j.cell.2025.02.029
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00256-9