Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease

Author:

Bhosle AmrishaORCID,Bae Sena,Zhang YancongORCID,Chun EunyoungORCID,Avila-Pacheco JulianORCID,Geistlinger Ludwig,Pishchany Gleb,Glickman Jonathan NORCID,Michaud Monia,Waldron LeviORCID,Clish Clary BORCID,Xavier Ramnik J,Vlamakis Hera,Franzosa Eric AORCID,Garrett Wendy SORCID,Huttenhower CurtisORCID

Abstract

AbstractMicrobial 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.

Funder

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Springer Science and Business Media LLC

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