Associations of the Fecal Microbiome With Urinary Estrogens and Estrogen Metabolites in Postmenopausal Women: The Journal of Clinical Endocrinology & Metabolism: Vol 0, No 0

The gut microbiota may influence the risk of breast cancer through effects on endogenous estrogens.

The objective of the study was to investigate whether urinary estrogens and
estrogen metabolites are associated with the diversity and composition
of the fecal microbiome.

This was a cross-sectional study among women enrolled in Kaiser Permanente of Colorado.

A total of 60 women drawn from a random sample of healthy postmenopausal  women (aged 55–69 y), without current or recent use of antibiotics or  hormone therapy and no history of cancer or gastrointestinal disease  participated in the study.

Creatinine-standardized urinary estrogens (estrone and estradiol) and 13 hydroxylated estrogen
metabolites were measured in spot urines by liquid chromatography-tandem mass spectrometry. The fecal microbiome was assessed using  pyrosequencing of 16S rRNA amplicons. General linear models were used to test for associations of diversity and composition of the fecal  microbiome with parent estrogen (estrone + estradiol), total estrogens,  and estrogen metabolites and the ratio of estrogen metabolites to parent estrogen, which has been predictive of postmenopausal breast cancer  risk in previous studies.

The ratio of metabolites to parents was directly associated with whole-tree phylogenetic diversity (R = 0.35, P= .01). Relative abundances of the order Clostridiale (R = 0.32, P= .02) and the genus Bacteroides (R = -0.30, P= .03) were also correlated with the ratio of metabolites to parents.
Associations were independent of age, body mass index, and study design  factors.

Our data suggest that women with a more diverse gut microbiome exhibit an  elevated urinary ratio of hydroxylated estrogen metabolites to parent  estrogen. Further research is warranted to confirm and relate these  findings to clinical disease.

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