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 Petersen; Jennifer A Fleming; Tao Huan; Andrew D Patterson; Dionicio Siegel; Lee R Hagey; Mingxun Wang; Allegra T Aron; Pieter C Dorrestein

doi:10.1016/j.cell.2024.02.019

The underappreciated diversity of bile acid modifications

Cell. 2024 Mar 28;187(7):1801-1818.e20. doi: 10.1016/j.cell.2024.02.019. Epub 2024 Mar 11.

Authors

Ipsita Mohanty¹, Helena Mannochio-Russo¹, Joshua V Schweer², Yasin El Abiead¹, Wout Bittremieux³, Shipei Xing⁴, Robin Schmid⁵, Simone Zuffa¹, Felipe Vasquez¹, Valentina B Muti⁶, Jasmine Zemlin⁷, Omar E Tovar-Herrera⁸, Sarah Moraïs⁸, Dhimant Desai⁹, Shantu Amin⁹, Imhoi Koo¹⁰, Christoph W Turck¹¹, Itzhak Mizrahi⁸, Penny M Kris-Etherton¹², Kristina S Petersen¹², Jennifer A Fleming¹², Tao Huan¹³, Andrew D Patterson¹⁰, Dionicio Siegel¹, Lee R Hagey¹⁴, Mingxun Wang¹⁵, Allegra T Aron¹⁶, Pieter C Dorrestein¹⁷

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.

MeSH terms

Animals
Bile Acids and Salts* / chemistry
Databases, Chemical
Gastrointestinal Microbiome*
Humans
Metabolomics* / methods
Polyamines
Tandem Mass Spectrometry* / methods

Substances

Bile Acids and Salts
Polyamines