A searchable metadata network graph for microbiome metabolomics
Establishing the biological context of microbial metabolites remains a major challenge. We present microbiomeMASST, a metadata-driven network graph that maps metabolites across 467 available datasets with 144,424 mass spectrometry files from humans, animals, and microbial culture systems. MicrobiomeMASST integrates monocultures, synthetic communities, and host-associated samples across multiple body sites and plants. MS/MS spectra can be queried to trace occurrence across hosts, experimental conditions, and interventions, enabling cross-study integration. We demonstrate this framework by contextualizing microbial-conjugated bile acids and interrogating microbiome-mediated drug metabolism. Screening gut bacteria revealed deprolylation of the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril. Using microbiomeMASST, we traced this metabolite across human cohorts, microbial isolates, environmental samples, and in <i>Gorilla gorilla</i> . Structural modeling and enzymatic assays showed that microbial deprolylation abolishes ACE inhibition, thereby inactivating its therapeutic effect. Together, microbiomeMASST links MS/MS spectra to biological context, converting isolated observations into an interpretable microbiome map for cross-study analysis.
Authors
- Gail Ackermann
- Adrián Jinich (ORCID: https://orcid.org/0000-0001-8616-9250)
- M. C. Wang
- Anthony J. A. Molina (ORCID: https://orcid.org/0000-0002-5786-4622)
- Selene F. H. Shore (ORCID: https://orcid.org/0000-0003-3029-4604)
- Lucas Patel (ORCID: https://orcid.org/0000-0001-8607-2782)
- Santosh Lamichhane (ORCID: https://orcid.org/0000-0002-9292-3595)
- April L. Lukowski (ORCID: https://orcid.org/0000-0003-4865-0910)
- Manuela Raffatellu (ORCID: https://orcid.org/0000-0001-6487-4215)
- Harsha Gouda (ORCID: https://orcid.org/0000-0003-4511-5875)
- Julius Agongo
- Sarkis K. Mazmanian (ORCID: https://orcid.org/0000-0003-2713-1513)
- Grant J. Norton (ORCID: https://orcid.org/0000-0003-0264-1154)
- Ricardo Almada-Monter
- Anthony Martin (ORCID: https://orcid.org/0000-0002-7857-6478)
- Shipei Xing (ORCID: https://orcid.org/0000-0001-6227-6959)
- Rocío Paz-González (ORCID: https://orcid.org/0000-0002-2219-2440)
- Kine Eide Kvitne (ORCID: https://orcid.org/0000-0001-8118-7660)
- Loryn Chin
- Erin R. Reilly (ORCID: https://orcid.org/0000-0002-7290-0003)
- Jaclyn Bergstrom (ORCID: https://orcid.org/0000-0002-0212-0802)
- Simone Renwick (ORCID: https://orcid.org/0000-0002-2786-893X)
- Liang Liang (ORCID: https://orcid.org/0000-0001-5718-0717)
- Yuhan Weng (ORCID: https://orcid.org/0009-0005-3453-1402)
- Maria L. Marco (ORCID: https://orcid.org/0000-0002-3643-9766)
- Prajit Rajkumar (ORCID: https://orcid.org/0009-0002-5538-5270)
- V. Kalai Gandhi
- Corinn Walker
- N. Pérez
- A. Norman
- Victoria Deleray (ORCID: https://orcid.org/0009-0002-3201-2578)
- Vincent Charron-Lamoureux
- Nadia Suryawinata
- Anna E. Skrip
- Monica Guma
- Andres Mauricio Caraballo Rodriguez
- Karsten Zengler
- Allegra Aron
- Marta Sala-Climent
- Thomas D. Horvath
- Subhomitra Ghoshal
- Haoqi Nina Zhao
- Eric Kemen
- Heejung Yang
- Samira Dahesh
- Sadie Giddings
- Andrew D. Patterson
- Antonio Gonzalez
- Evi Stegmann
- Jasmine Zemlin
- Ipsita Mohanty
- Paolo Stincone
- Daniel McDonald
- Abubaker Patan
- Suzanne Devkota
- Melinda A. Engevik
- Monae Pinner
- Victor Nizet
- Pieter C. Dorrestein
- Dionicio Siegel
- Rob Knight
- Zhewen Hu
Institutions
- University of California, Riverside (US)
- California Institute of Technology (US)
- Cedars-Sinai Medical Center (US)
- Pennsylvania State University (US)
- La Jolla Institute for Immunology (US)
- University of Denver (US)
- Scripps Institution of Oceanography (US)
- Medical University of South Carolina (US)
- University of San Diego (US)
- Kangwon National University (KR)
- Baylor College of Medicine (US)
- Medical College of Wisconsin (US)
- Turku University Hospital (FI)
- University of California San Diego (US)
- Therapeutics Clinical Research (US)
- German Center for Infection Research (DE)
- La Jolla Bioengineering Institute (US)
- Institute on Aging (US)
- Texas Children's Hospital (US)
- Instituto de Investigación Biomédica de A Coruña (ES)
- Mothers’ Milk Bank (US)
- University of Houston (US)
- University of Guelph (CA)
- University of Tübingen (DE)
- University of California, Davis (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-02-05
- DOI
- https://doi.org/10.64898/2026.02.04.703849
- Citations
- 2
- Primary Topic
- Metabolomics and Mass Spectrometry Studies
- Type
- article
- Field-Weighted Citation Impact
- 44.47
Funders
- National Science Foundation
- Gordon and Betty Moore Foundation
- Hong Kong University of Science and Technology
- National Institutes of Health
- University of California, San Diego
- Natural Sciences and Engineering Research Council of Canada
- Fonds de Recherche du Québec - Santé
- Biotechnology and Biological Sciences Research Council
- National Institute of General Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases