Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease

Autor: Amrisha Bhosle, Sena Bae, Yancong Zhang, Eunyoung Chun, Julian Avila-Pacheco, Ludwig Geistlinger, Gleb Pishchany, Jonathan N Glickman, Monia Michaud, Levi Waldron, Clary B Clish, Ramnik J Xavier, Hera Vlamakis, Eric A Franzosa, Wendy S Garrett, Curtis Huttenhower
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecular Systems Biology, Vol 20, Iss 4, Pp 338-361 (2024)
Druh dokumentu: article
ISSN: 1744-4292
DOI: 10.1038/s44320-024-00027-8
Popis: 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.
Databáze: Directory of Open Access Journals
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