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SpiR is a gut microbial enzyme that drives cholesterol conversion
Gabriela Arp1, Sophia Levy1, Angela K Jiang1,2
1Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA.
Nature Communications
|April 14, 2026
Summary
Researchers identified spiR, a key enzyme from gut bacteria, that converts cholesterol into a non-absorbable form. This discovery enhances understanding of microbial cholesterol metabolism and offers a new biomarker for its reduction.
Area of Science:
- Microbiology
- Biochemistry
- Human Gut Microbiome Research
Background:
- The gut microbiota plays a role in cholesterol homeostasis by transforming cholesterol into coprostanol.
- The specific enzymes responsible for this crucial conversion have not been fully identified.
Purpose of the Study:
- To identify and characterize the enzymes involved in the initial steps of microbial cholesterol conversion to coprostanol.
- To establish the role of identified enzymes as biomarkers for microbiome-mediated cholesterol metabolism.
Main Methods:
- Enzyme identification and characterization (steroid Δ5-4 isomerase/3-keto reductase activity).
- Phylogenetic analysis of identified genes.
- Multi-omic data analysis from human cohorts to correlate gene presence with cholesterol conversion.
Main Results:
- Identified spiR from Eubacterium coprostanoligenes as a steroid Δ5-4 isomerase/3-keto reductase catalyzing cholesterol oxidation to cholestenone.
- Demonstrated SpiR's substrate specificity, cofactor dependency (NAD(H)), and homodimeric structure.
- Phylogenetic analysis revealed spiR's restriction to a specific bacterial clade and its frequent co-occurrence with ismA.
- spiR homologs were significantly enriched in individuals with cholesterol conversion and showed higher predictive power than ismA homologs.
Conclusions:
- spiR is a critical enzyme in the gut microbiome's conversion of cholesterol to coprostanol.
- spiR serves as a superior biomarker for microbial cholesterol metabolism compared to previously implicated genes like ismA.
- These findings refine the enzymatic model of gut cholesterol metabolism and highlight spiR's role in microbiome-mediated cholesterol reduction.
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