The Underappreciated Diversity of Bile Acid Modifications

Abstract

The repertoire of modifications on bile acids and related steroidal lipids furnished by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of candidate tandem mass spectrometry (MS/MS) spectra by filtering approximately 1.2 billion publicly available MS/MS spectra bile acid-specific MS/MS ion patterns. The thousands of different modifications are distributed throughout animal bodies, including humans, and microbial cultures. We employed this MS/MS library to identify bile acids amidated with polyamines, which were prevalent in carnivores and individuals with inflammatory bowel disease or sleep/circadian disruption. This work not only highlights the existence of many more bile acid modifications than previously recognized but also the value of leveraging public large-scale untargeted metabolomics data as an alternative approach to discovering new metabolites. The availability of a modification-centric bile acid MS/MS library will facilitate future studies investigating the roles of bile acids in health and disease.