Associations of Circulating Estrogens and Estrogen Metabolites with Fecal and Oral Microbiome in Postmenopausal Women in the Ghana Breast Health Study

Abstract

The human fecal and oral microbiome may play a role in the etiology of breast cancer through modulation of endogenous estrogen metabolism. This study aimed to investigate associations of circulating estrogens and estrogen metabolites with the fecal and oral microbiome in postmenopausal African women. A total of 117 women with fecal (N = 110) and oral (N = 114) microbiome data measured by 16S rRNA gene sequencing, and estrogens and estrogen metabolites data measured by liquid chromatography tandem mass spectrometry were included. The outcomes were measures of the microbiome and the independent variables were the estrogens and estrogen metabolites. Estrogens and estrogen metabolites were associated with the fecal microbial Shannon index (global P , 0.01). In particular, higher levels of estrone (b = 0.36, P = 0.03), 2-hydroxyestradiol (b = 0.30, P = 0.02), 4-methoxyestrone (b = 0.51, P = 0.01), and estriol (b = 0.36, P = 0.04) were associated with higher levels of the Shannon index, while 16alpha-hydroxyestrone (b = 20.57, P , 0.01) was inversely associated with the Shannon index as indicated by linear regression. Conjugated 2-methoxyestrone was associated with oral microbial unweighted UniFrac as indicated by MiRKAT (P , 0.01) and PERMANOVA, where conju gated 2-methoxyestrone explained 2.67% of the oral microbial variability, but no other estrogens or estrogen metabolites were associated with any other beta diversity meas ures. The presence and abundance of multiple fecal and oral genera, such as fecal gen era from families Lachnospiraceae and Ruminococcaceae, were associated with several estrogens and estrogen metabolites as indicated by zero-inflated negative binomial regression. Overall, we found several associations of specific estrogens and estrogen metabolites and the fecal and oral microbiome.