2. Academic Validation
  3. The underappreciated diversity of bile acid modifications

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

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: pdorrestein@health.ucsd.edu.
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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