Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease
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44320_2024_Article_27.pdf
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15.12 MB
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Checksum (MD5)
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Author(s)
Bhosle, Amrisha
Bae, Sena
Zhang, Yancong
Chun, Eunyoung
Avila-Pacheco, Julian
Geistlinger, Ludwig
Pishchany, Gleb
Glickman, Jonathan N
Michaud, Monia
Waldron, Levi
Date Issued
March 11, 2024
Journal
Molecular Systems Biology
Publisher
Springer Science and Business Media LLC
Citation
Bhosle, Amrisha, Bae, Sena, Zhang, Yancong, Chun, Eunyoung, Avila-Pacheco, Julian et al. 2024. "Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease." Molecular Systems Biology.
Version
Final published version
Abstract
Microbial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates.
Subjects
Applied Mathematics
Computational Theory and Mathematics
General Agricultural and Biological Sciences
General Immunology and Microbiology
General Biochemistry, Genetics and Molecular Biology
Information Systems
MIT Department
Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics
Terms of Use
Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1038/s44320-024-00027-8
