Year: 2026
Type: article
Abstract: Glucuronidation is an important detoxification pathway that operates in balance with gastrointestinal microbial β-glucuronidase (GUS) activity, which can regenerate bioactive metabolites from their glucuronidated forms. How this host-microbe interaction shapes the distribution and pool of glucuronidated metabolites (i.e., the glucuronidome) remains poorly understood. In this study, we employed pattern-filtering data science approaches in conjunction with untargeted LC-MS/MS metabolomics to map the glucuronidome in urine, serum, and colon/fecal samples from gnotobiotic and conventional mice, and in humans. We find that microbial colonization and GUS activity compress the colonic glucuronidome and expand urinary glucuronidome diversity, revealing a compartmental redistribution of glucuronidated metabolites. Reverse metabolomics of known glucuronidated chemicals and glucuronidation pattern filtering searches in public metabolomics datasets exposed the diversity of glucuronidated metabolites in human and mouse ecosystems. In summary, we present a glucuronidation fingerprint resource that provides broader access to and analysis of the glucuronidome. Together, this work establishes a scalable analytical framework and provides mechanistic insight into how microbial activity reshapes systemic glucuronidation, with implications for drug metabolism, diet-microbe interactions, and biomarker discovery.
Source: Nature Communications
Authors: Nina R. Boyle, Josh J. Sekela, Mingxun Wang, Helena Mannochio-Russo, Jeong Joo Pyo, Min Soo Kim, Shuchang Tian, Imhoi Koo, Elliot S. Friedman, Ceylan Tanes, Mallappa Anitha, Yuan Tian, Ethan W. Morgan, Iain A. Murray, Joseph P. Zackular, Kyle Bittinger, James D. Lewis, Gary H. Perdew, Gary D. Wu, Babette S. Zemel, Pieter C. Dorrestein, Jordan E. Bisanz, Matthew R. Redinbo, Andrew D. Patterson
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Agriculture, Children's Hospital of Philadelphia, Leona M. and Harry B. Helmsley Charitable Trust, American Beverage Foundation for a Healthy America, National Institutes of Health, National Institute of Food and Agriculture, Huck Institutes of the Life Sciences, NIH Office of the Director, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Research Resources
Awards: G126153243, G131241240, Acquisition of an Orbitrap Fusion Lumos Tribid Mass Spectrometer to Accelerate Metabolite Identification and Pathway Analysis, G2746178889, G2761940466, Molecular interactions in the gut microbiota during early life colonization and perturbation, Gut Microbial Enzymes and Human Disease, G4353297237, Mapping the Glucuronidome, G5026544017, G5532691166, Activation of the Ah receptor and epithelial integrity, Integrative Analysis of Metabolic Phenotypes (IAMP) Predoctoral Training Program, G9000097019, G9000278650, Collaborative Microbial Metabolite Center, Gut microbial beta-glucuronidases as a biomarker for mycophenolic acid enterohepatic recirculation and associated toxicities, Decoding Microbial Diversity in the Human Gut Microbiome, Institutional Clinical and Translational Science Award, Environmental Chemical Impact on the Host-Microbiome Interaction, Center for Molecular Studies in Digestive and Liver Diseases, Decoding the polymicrobial interactions in bile acid metabolism by the gut microbiome., Infant Growth and Microbiome Study 2
OpenAlex ID: W7161810683