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Cancer Causes & Control
Published in: Cancer Causes & Control 10/2023

07-06-2023 | Breast Cancer | Original Paper

Associations of gut microbiome with endogenous estrogen levels in healthy postmenopausal women

Authors: Lusine Yaghjyan, Volker Mai, Lancia N. F. Darville, Jayden Cline, Xuefeng Wang, Maria Ukhanova, Massimiliano S. Tagliamonte, Yessica C. Martinez, Shannan N. Rich, John M. Koomen, Kathleen M. Egan

Published in: Cancer Causes & Control | Issue 10/2023

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Abstract

Purpose

The gut microbiome is a potentially important contributor to endogenous estrogen levels after menopause. In healthy postmenopausal women, we examined associations of fecal microbiome composition with levels of urinary estrogens, their metabolites, and relevant metabolic pathway ratios implicated in breast cancer risk.

Methods

Eligible postmenopausal women (n = 164) had a body mass index (BMI) ≤ 35 kg/m2 and no history of hormone use (previous 6 months) or cancer/metabolic disorders. Estrogens were quantified in spot urine samples with liquid chromatography-high resolution mass spectrometry (corrected for creatinine). Bacterial DNA was isolated from fecal samples and the V1–V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of gut microbiome’s indices of within-sample (alpha) diversity (i.e., Shannon, Chao1, and Inverse Simpson), phylogenetic diversity, and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with individual estrogens and metabolic ratios, adjusted for age and BMI.

Results

In this sample of 164 healthy postmenopausal women, the mean age was 62.9 years (range 47.0–86.0). We found significant inverse associations of observed species with 4-pathway:total estrogens (p = 0.04) and 4-pathway:2-pathway (p = 0.01). Shannon index was positively associated with 2-catechols: methylated 2-catechols (p = 0.04). Chao1 was inversely associated with E1:total estrogens (p = 0.04), and 4-pathway:2-pathway (p = 0.02) and positively associated with 2-pathway:parent estrogens (p = 0.01). Phylogenetic diversity was inversely associated with 4-pathway:total estrogens (p = 0.02), 4-pathway:parent estrogens (p = 0.03), 4-pathway:2-pathway (p = 0.01), and 4-pathway:16-pathway (p = 0.03) and positively associated with 2-pathway:parent estrogens (p = 0.01). F/B ratio was not associated with any of the estrogen measures.

Conclusion

Microbial diversity was associated with several estrogen metabolism ratios implicated in breast cancer risk. Further studies are warranted to confirm these findings in a larger and more representative sample of postmenopausal women, particularly with enrichment of minority participants.
Appendix
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Metadata
Title
Associations of gut microbiome with endogenous estrogen levels in healthy postmenopausal women
Authors
Lusine Yaghjyan
Volker Mai
Lancia N. F. Darville
Jayden Cline
Xuefeng Wang
Maria Ukhanova
Massimiliano S. Tagliamonte
Yessica C. Martinez
Shannan N. Rich
John M. Koomen
Kathleen M. Egan
Publication date
07-06-2023
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 10/2023
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-023-01728-5

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