The underappreciated diversity of bile acid modifications

  • Cell. 2024 Mar 28;187(7):1801-1818.e20. doi: 10.1016/j.cell.2024.02.019.
Ipsita Mohanty  1 ,  Helena Mannochio-Russo  1 ,  Joshua V Schweer  2 ,  Yasin El Abiead  1 ,  Wout Bittremieux  3 ,  Shipei Xing  4 ,  Robin Schmid  5 ,  Simone Zuffa  1 ,  Felipe Vasquez  1 ,  Valentina B Muti  6 ,  Jasmine Zemlin  7 ,  Omar E Tovar-Herrera  8 ,  Sarah Moraïs  8 ,  Dhimant Desai  9 ,  Shantu Amin  9 ,  Imhoi Koo  10 ,  Christoph W Turck  11 ,  Itzhak Mizrahi  8 ,  Penny M Kris-Etherton  12 ,  Kristina S Petersen  12 ,  Jennifer A Fleming  12 ,  Tao Huan  13 ,  Andrew D Patterson  10 ,  Dionicio Siegel  1 ,  Lee R Hagey  14 ,  Mingxun Wang  15 ,  Allegra T Aron  16 ,  Pieter C Dorrestein  17
Affiliations
  • 1. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
  • 2. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA; Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA, USA.
  • 3. Department of Computer Science, University of Antwerp, 2020 Antwerpen, Belgium.
  • 4. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA; Department of Chemistry, Faculty of Science, University of British Columbia, Vancouver Campus, Vancouver, BC, Canada.
  • 5. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
  • 6. Department of Computer Science and Engineering, University of California, Riverside, Riverside, CA, USA; Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80210, USA.
  • 7. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA.
  • 8. Department of Life Sciences, Ben-Gurion University of the Negev, Be'er Sheva, Israel; Goldman Sonnenfeldt School of Sustainability and Climate Change, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
  • 9. Department of Pharmacology, Penn State University College of Medicine, Hershey, PA, USA.
  • 10. Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA.
  • 11. Max Planck Institute of Psychiatry, Proteomics and Biomarkers, Kraepelinstrasse 2-10, Munich 80804, Germany; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
  • 12. Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA.
  • 13. Department of Chemistry, Faculty of Science, University of British Columbia, Vancouver Campus, Vancouver, BC, Canada.
  • 14. Department of Medicine, University of California, San Diego, San Diego, CA, USA.
  • 15. Department of Computer Science and Engineering, University of California, Riverside, Riverside, CA, USA.
  • 16. Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80210, USA.
  • 17. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
PMID: 38471500 DOI: 10.1016/j.cell.2024.02.019
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.

Keywords
GABA; MassQL; agmatine; bile acids; diet; fastMASST; microbial; polyamines; putrescine; spectral resource.
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