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Microbe diversity may influence estrogen metabolism, reduce breast cancer risk in postmenopause
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Women with greater diversity of gut microbiota appear to have an elevated urinary ratio of hydroxylated estrogen metabolites to parent estrogen, according to research published in The Journal of Clinical Endocrinoloty & Metabolism.
Whether the ratios observed with a diverse microbiome could discourage the development of breast cancer in women during their postmenopausal years warrants further investigation, the researchers wrote.
“We observed that the composition and diversity of the intestinal microbiota were associated with patterns of estrogen metabolism that are predictive of the risk of breast cancer in postmenopausal women,” the researchers wrote.
In a cross-sectional study, Barbara J. Fuhrman, PhD, of the University of Arkansas for Medical Sciences, Little Rock, and colleagues looked at 60 healthy postmenopausal women aged 55 to 69 years to determine the relationships between the urinary estrogens and metabolites and diverse gut composition.
Participants were not currently, or recently, treated with antibiotics or hormone therapy and none had a history of cancer or gastrointestinal disease.
The creatinine-standardized urinary estrogens estrone and estradiol, along with 13 hydroxylated estrogen metabolites, were measured in spot urines using liquid chromatography-tandem mass spectrometry. Through pyrosequencing of 16S rRNA amplicons, the researchers assessed the fecal microbiome.
General linear models were used to assess associations of diversity and composition of the fecal microbiome with parent estrogen (estrone plus estradiol), total estrogens, and estrogen metabolites and the ratio of estrogen metabolites to parent estrogen; previous studies have demonstrated this ratio to be predictive of postmenopausal breast cancer risk, the researchers noted.
A direct association was observed between the ratio of metabolites to parents and whole-tree phylogenetic diversity (R=0.35; P=.01). Relative abundances of the order clostridiales (R=0.32; P=.02) and the genus bacteroides (R=-0.30; P=.03) also correlated with the ratio of metabolites to parents. These associations were independent of age, BMI and study design factors.
The measures of microbial diversity showed similar correlations with analogous ratios for each metabolic pathway — 2-, 4-, and 16-hydroxylation.
“Because higher ratios of 2- and 4-hydroxylated metabolites to parent estrogens have been associated with a reduced risk of postmenopausal breast cancer, our data suggest that postmenopausal breast cancer risk may be reduced for women who have high intestinal microbial diversity,” the researchers wrote.
Disclosures: The work was supported by federal funds from the National Cancer Institute Intramural Research Program.
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