Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women Original paper

What was studied?

This original research article investigated the relationship between the diversity and composition of the fecal microbiome and urinary estrogen profiles in postmenopausal women. The study specifically aimed to determine whether urinary concentrations of estrogens and their metabolites, which are known to influence breast cancer risk, were associated with measures of gut microbial diversity and the relative abundance of specific microbial taxa. The researchers used 16S rRNA gene pyrosequencing to profile the fecal microbiome and liquid chromatography-tandem mass spectrometry to quantify urinary estrone, estradiol, and 13 hydroxylated estrogen metabolites. Statistical analyses assessed associations between microbiome diversity metrics, microbial taxa, and various estrogen metabolite ratios that have been linked to breast cancer risk in prior studies, adjusting for confounders such as age, body mass index (BMI), and study design factors.

Who was studied?

The study population comprised 60 healthy postmenopausal women aged 55–69 years, randomly selected from members of Kaiser Permanente Colorado. Key exclusion criteria included current or recent use of antibiotics or hormone therapy, and any history of cancer or gastrointestinal disease. The participants were predominantly white (91%) and non-Hispanic (95%), with a median age of 64 years and a median BMI of 27, reflecting an overweight to obese cohort. All had received a recent normal screening mammogram and had not taken medications or had conditions likely to impact gut microbiota or systemic hormone levels. Fecal and urine samples were collected, shipped, and analyzed under standardized conditions.

Most important findings

The study found a statistically significant positive association between whole-tree phylogenetic diversity of the fecal microbiome and the urinary ratio of estrogen metabolites to parent estrogens. This ratio, as well as pathway-specific ratios, has been previously associated with a reduced risk of postmenopausal breast cancer. The relative abundance of the order Clostridiales (especially the family Ruminococcaceae) was directly correlated with the metabolites-to-parent estrogen ratio, while the genus Bacteroides was inversely correlated. These associations persisted after adjusting for age, BMI, sample collection variables, and study design. Notably, overall measures of microbial diversity, rather than the abundance of dominant phyla (Firmicutes or Bacteroidetes), were most strongly linked to favorable estrogen metabolite profiles.

Key implications

This study provides evidence that greater gut microbial diversity is associated with estrogen metabolite profiles considered protective against breast cancer in postmenopausal women. The findings suggest that the gut microbiota, particularly the diversity and specific taxa such as Clostridiales and Ruminococcaceae, may modulate systemic estrogen metabolism, possibly through deconjugation and enterohepatic recycling of estrogens. These data support the hypothesis that manipulation of the gut microbiome could influence estrogen homeostasis and, by extension, breast cancer risk. However, due to the cross-sectional design and small sample size, causality cannot be established, and findings regarding specific microbial associations should be considered exploratory. Further research with larger cohorts and longitudinal designs is warranted to confirm these associations and elucidate underlying mechanisms.