Mass spectrometric profiling of primary estrogens and estrogen metabolites in human stool and plasma partially elucidates the role of the gut microbiome in estrogen recycling.
Level 4 - case-series / case-control
Cross-sectional human observational study comparing metabolite levels and metagenomic profiles across demographic groups.
PubMed 40180172 · doi:10.1016/j.mce.2025.112534
What was done
Researchers developed an LC-MS/MS assay to quantify free and conjugated primary estrogens (estrone, estradiol, estriol) and hydroxyestrogen/methoxyestrogen metabolites in paired human plasma and stool samples. They analyzed samples from healthy men, premenopausal women (follicular and luteal phases), and postmenopausal women, combining metabolic profiling with stool shotgun metagenomic sequencing to measure bacterial β-glucuronidase and arylsulfatase gene copy numbers.
What was found
The abstract reports no absolute numbers, effect sizes, or p-values. Most measured estrogens were detectable in plasma and stool in all groups. Plasma and stool levels of hydroxyestrogen and methoxyestrogen metabolites correlated, whereas estrone levels did not. Stool estrogens were higher in premenopausal women and increased across the menstrual cycle. β-Glucuronidase and arylsulfatase gene copy numbers were higher in premenopausal women. Combined β-glucuronidase plus arylsulfatase gene copy numbers (but not β-glucuronidase alone) correlated with deconjugated stool estrogens across all cohorts, with combined plasma estrogens in men, and with specific plasma estrogen metabolites in men and premenopausal women.
Why it matters
This work validates a method for measuring estrogen metabolites in human stool and provides direct human correlational evidence that gut microbial deconjugation pathways modulate systemic estrogen recirculation.
Limits
Sample size (n) is not reported in the abstract, nor are numerical concentrations or statistical confidence intervals. The study design is cross-sectional and correlational, measuring metagenomic gene abundance rather than active in vivo enzyme kinetics or direct intestinal uptake.
Cited by
- supports Estrogens are recycled through the gastrointestinal tract in ways that can influence premenstrual syndrome symptoms and menstrual cycle regularity.