美国加州大学圣迭戈分校Pieter C. Dorrestein课题组揭示被低估的胆汁酸修饰多样性。2024年3月11日，《细胞》杂志在线发表了这项成果。

研究人员表示，宿主和微生物新陈代谢对胆汁酸和相关类固醇脂质的一系列修饰仍未完全定性。

为了填补这一知识空白，研究人员创建了一个可重复使用的串联质谱（MS/MS）光谱资源，通过过滤12亿个公开的MS/MS光谱来寻找胆汁酸选择性离子模式。在动物和人体以及微生物培养物中分布着数千种修饰。研究人员利用这个MS/MS文库来鉴定多胺胆汁酰胺化物。它们也存在于人类体内，而且随着饮食习惯从地中海饮食转变为典型的美国饮食，它们的含量也会发生变化。

这项工作凸显了胆汁酸修饰的存在比以前认识到的要多得多，以及利用公开的大规模非靶向代谢组学数据发现代谢物的价值。以修饰为中心的胆汁酸MS/MS库的可用性，将为未来研究胆汁酸在健康和疾病中的作用提供信息。

附：英文原文

Title: The underappreciated diversity of bile acid modifications

Author: Ipsita Mohanty, Helena Mannochio-Russo, Joshua V. Schweer, Yasin El Abiead, Wout Bittremieux, Shipei Xing, Robin Schmid, Simone Zuffa, Felipe Vasquez, Valentina B. Muti, Jasmine Zemlin, Omar E. Tovar-Herrera, Sarah Moras, Dhimant Desai, Shantu Amin, Imhoi Koo, Christoph W. Turck, Itzhak Mizrahi, Penny M. Kris-Etherton, Kristina S. Petersen, Jennifer A. Fleming, Tao Huan, Andrew D. Patterson, Dionicio Siegel, Lee R. Hagey, Mingxun Wang, Allegra T. Aron, Pieter C. Dorrestein

Issue&Volume: 2024-03-11

Abstract: The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns. Thousands of modifications are distributed throughout animal and human bodies as well as microbial cultures. We employed this MS/MS library to identify polyamine bile amidates, prevalent in carnivores. They are present in humans, and their levels alter with a diet change from a Mediterranean to a typical American diet. This work highlights the existence of many more bile acid modifications than previously recognized and the value of leveraging public large-scale untargeted metabolomics data to discover metabolites. The availability of a modification-centric bile acid MS/MS library will inform future studies investigating bile acid roles in health and disease.

DOI: 10.1016/j.cell.2024.02.019

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00185-5