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Peer-reviewedCC BY-NC-NDNature Communications

Glucuronidation metabolomic fingerprinting to map host-microbe metabolism

  • Nina R. Boyle1
  • Josh J. Sekela2
  • Mingxun Wang3
  • Helena Mannochio-Russo4
  • Jeong Joo Pyo5
  • Minkyu Kim6
  • Shuchang Tian6
  • Imhoi Koo7
  • Elliot S. Friedman8,9
  • Ceylan Tanes10,9
  • Mallappa Anitha11
  • Yuan Tian11,1
12 more authors
  • Ethan W. Morgan7,11
  • Iain A. Murray7,11
  • Joseph P. Zackular12,9
  • Kyle L. Bittinger10,9
  • James D. Lewis13
  • Gary H. Perdew7,11
  • Gary D. Wu8
  • Babette S. Zemel10
  • Pieter C. Dorrestein4
  • Jordan E. Bisanz6,1,14
  • Matthew R. Redinbo5,2
  • Andrew D. Patterson15,16,17,18,19
19 affiliations
  1. 1Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA
  2. 2Departments of Chemistry, Biochemistry, Microbiology and Genomics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  3. 3Department of Computer Science, University of California Riverside, Riverside, CA, USA
  4. 4Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
  5. 5Curriculum in Toxicology & Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  6. 6Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA
  7. 7Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA, USA
  8. 8Division of Gastroenterology and Hepatology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, USA
  9. 9The Center for Microbial Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
  10. 10Division of Gastroenterology and Hepatology and Nutrition, Department of Pediatrics, Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA
  11. 11Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA
  12. 12Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  13. 13Center for Clinical Epidemiology and Biostatistics, Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  14. 14One Health Microbiome Center, Huck Life Sciences Institute, University Park, PA, USA
  15. 15Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA, USA. [email protected]
  16. 16Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA. [email protected]
  17. 17Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA. [email protected]
  18. 18Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA. [email protected]
  19. 19One Health Microbiome Center, Huck Life Sciences Institute, University Park, PA, USA. [email protected]
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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.

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Cite

BibTeXRIS
BibTeX
@article{boyle2026glucuronidation,
  title = {{Glucuronidation metabolomic fingerprinting to map host-microbe metabolism}},
  author = {Nina R. Boyle and Josh J. Sekela and Mingxun Wang and Helena Mannochio-Russo and Jeong Joo Pyo and Minkyu Kim and Shuchang Tian and Imhoi Koo and Elliot S. Friedman and Ceylan Tanes and Mallappa Anitha and Yuan Tian and Ethan W. Morgan and Iain A. Murray and Joseph P. Zackular and Kyle L. Bittinger and James D. Lewis and Gary H. Perdew and Gary D. Wu and Babette S. Zemel and Pieter C. Dorrestein and Jordan E. Bisanz and Matthew R. Redinbo and Andrew D. Patterson},
  journal = {Nature Communications},
  year = {2026},
  month = may,
  doi = {10.1038/s41467-026-73398-1},
  url = {https://doi.org/10.1038/s41467-026-73398-1},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Glucuronidation metabolomic fingerprinting to map host-microbe metabolism
AU  - Nina R. Boyle
AU  - Josh J. Sekela
AU  - Mingxun Wang
AU  - Helena Mannochio-Russo
AU  - Jeong Joo Pyo
AU  - Minkyu Kim
AU  - Shuchang Tian
AU  - Imhoi Koo
AU  - Elliot S. Friedman
AU  - Ceylan Tanes
AU  - Mallappa Anitha
AU  - Yuan Tian
AU  - Ethan W. Morgan
AU  - Iain A. Murray
AU  - Joseph P. Zackular
AU  - Kyle L. Bittinger
AU  - James D. Lewis
AU  - Gary H. Perdew
AU  - Gary D. Wu
AU  - Babette S. Zemel
AU  - Pieter C. Dorrestein
AU  - Jordan E. Bisanz
AU  - Matthew R. Redinbo
AU  - Andrew D. Patterson
PY  - 2026
DA  - 2026/05/20
JO  - Nature Communications
DO  - 10.1038/s41467-026-73398-1
UR  - https://doi.org/10.1038/s41467-026-73398-1
AB  - 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.
SN  - 2041-1723
ER  -