The association of the gut microbiome with intermediate markers of breast cancer risk-mammographic density and blood steroid hormones-in the multiethnic cohort study.

INTRODUCTION

The gut microbiota may influence breast cancer risk through different biologic pathways. This analysis examined the association of the gut microbial composition with percent mammographic density (PMD), a strong predictor of breast cancer risk.

METHODS

Postmenopausal women in the Adiposity Phenotype Study, a cross-sectional subset of the Multiethnic Cohort, from five racial/ethnic groups, provided a stool sample. Extracted bacterial DNA was sequenced for the V1-V3 region of the 16S rRNA gene. Bioinformatic analysis determined alpha-diversity and the abundance of 10 phyla and 152 genera. PMD was assessed in routine mammograms taken before stool collection with a quantitative computer-assisted method. Blood levels of estrogen metabolites were assessed using standard assays. General linear models regressed PMD on gut microbial diversity, phyla, and genera while adjusting for relevant covariates.

RESULTS

Of 649 women (69.1 ± 2.7 years), 311 had low (<15%) and 338 had high (>=15%) PMD. Whereas alpha diversity or phyla were not associated with PMD, 10 genera were nominally related to PMD (p < 0.05) but not after adjusting for multiple comparisons: 7 positively (Bifidobacterium, Blautia, Dialister, Eubacterium_fissicatena_group, Lachnospira, Lachnospiraceae_UCG-008, Lachnospiraceae_uncultured) and 3 inversely (Alistipes, Senegalimassilia, Eubacterium_oxidoreducens_group), potentially implicating estrogen metabolism and short-chain fatty acid production. All blood steroid metabolites were significantly related to PMD, but only SHBG was associated with 2 genera after Bonferroni adjustment.

CONCLUSIONS

The nominal associations detected in this analysis suggest that certain gut microbiota may be associated with PMD, a marker of risk but not a measure of breast cancer incidence, due to their ability to affect circulating hormones or SCFA production.