近日，美国宾夕法尼亚州立大学Andrew D. Patterson团队发现，胆汁盐水解酶催化胺结合胆汁酸的形成。该研究于2024年2月7日在线发表于国际一流学术期刊《自然》。

研究人员报告了胆汁盐水解酶（BSH）在胆汁酸代谢中具有双重功能。具体来说，研究人员发现了BSH作为胺N-酰基转移酶之前所扮演的未知角色，它能将胺与胆汁酸结合，从而形成细菌胆汁酰胺化物（BBAA）。为了描述这种胺N-酰基转移酶BSH活性的特征，研究人员采用了药物抑制BSH、在大肠杆菌中异源表达bsh和突变体以及在脆弱拟杆菌中敲除bsh和进行互补的方法，证明BSH能生成BBAA。研究人员还在人类婴儿队列中进一步证明，BBAA的产生与bsh表达细菌的定植成正相关。

最后，研究人员报告说，在细胞培养模型中，BBAA激活宿主配体激活的转录因子，包括孕烷X受体和芳基烃受体。这些发现加深了人们对肠道细菌如何通过BSH的混杂作用在调节胆汁酸代谢网络中发挥重要作用的理解。

据了解，胃肠道中的细菌产生的氨基酸胆汁酸酰胺可影响宿主介导的新陈代谢过程；然而，负责产生胆汁酸酰胺的细菌基因仍然未知。

附：英文原文

Title: Bile salt hydrolase catalyses formation of amine-conjugated bile acids

Author: Rimal, Bipin, Collins, Stephanie L., Tanes, Ceylan E., Rocha, Edson R., Granda, Megan A., Solanki, Sumeet, Hoque, Nushrat J., Gentry, Emily C., Koo, Imhoi, Reilly, Erin R., Hao, Fuhua, Paudel, Devendra, Singh, Vishal, Yan, Tingting, Kim, Min Soo, Bittinger, Kyle, Zackular, Joseph P., Krausz, Kristopher W., Desai, Dhimant, Amin, Shantu, Coleman, James P., Shah, Yatrik M., Bisanz, Jordan E., Gonzalez, Frank J., Vanden Heuvel, John P., Wu, Gary D., Zemel, Babette S., Dorrestein, Pieter C., Weinert, Emily E., Patterson, Andrew D.

Issue&Volume: 2024-02-07

Abstract: Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1,2,3,4,5,6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.

DOI: 10.1038/s41586-023-06990-w

Source: https://www.nature.com/articles/s41586-023-06990-w