The underappreciated diversity of bile acid modifications

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 Moraïs, Dhimant Desai, Shantu Amin, Imhoi Koo, Christoph W. Turck, Itzhak Mizrahi, Penny M. Kris-Etherton, Kristina S. PetersenJennifer A. Fleming, Tao Huan, Andrew D. Patterson, Dionicio Siegel, Lee R. Hagey, Mingxun Wang, Allegra T. Aron, Pieter C. Dorrestein

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish
Pages (from-to)1801-1818.e20
JournalCell
Volume187
Issue number7
DOIs
StatePublished - 28 Mar 2024

Keywords

  • GABA
  • MassQL
  • agmatine
  • bile acids
  • diet
  • fastMASST
  • microbial
  • polyamines
  • putrescine
  • spectral resource

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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