SpiR is a gut microbial enzyme that drives cholesterol conversion
isomerases and is restricted to an uncultured clade within Acutalibacteraceae, where it frequently co-occurs with species encoding ismA, a gene previously implicated in cholesterol conversion. We analyze a multi-omic dataset from three human cohorts and find that spiR homologs were strongly enriched in individuals exhibiting cholesterol conversion. We also show that spiR homologs have a greater predictive power for cholesterol conversion than ismA homologs, establishing them as superior markers of microbial cholesterol metabolism. Our findings refine the enzymatic model of cholesterol metabolism in the gut and establish spiR as a critical biomarker and mechanistic driver for microbiome-mediated cholesterol reduction.
Authors
- Gabriela Arp (ORCID: https://orcid.org/0009-0004-3819-5648)
- Keith Dufault‐Thompson (ORCID: https://orcid.org/0000-0002-0991-2255)
- Y Li
- Aoshu Zhong (ORCID: https://orcid.org/0000-0002-5793-3990)
- Brantley Hall (ORCID: https://orcid.org/0000-0001-7553-8209)
- Sophia Levy (ORCID: https://orcid.org/0009-0003-8055-3202)
- Angela K Jiang (ORCID: https://orcid.org/0009-0005-5525-6251)
- Maggie Grant
- Xiaofang Jiang
Institutions
- National Institutes of Health (US)
- United States National Library of Medicine (US)
- Wake Forest University (US)
- University of Maryland, College Park (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-14
- DOI
- https://doi.org/10.1038/s41467-026-70820-6
- Primary Topic
- Steroid Chemistry and Biochemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Health and Human Services
- National Institutes of Health
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- U.S. National Library of Medicine
- NHLBI Division of Intramural Research