Body mass index-associated gut microbial taxa and functional pathways in women with benign and malignant breast disease.

PURPOSE: Obesity is an established risk factor for breast cancer and is associated with alterations in gut microbial composition. We evaluated associations among body mass index (BMI), breast density, gut microbial diversity and composition and microbial functional pathways in women undergoing surgery for benign, high-risk/non-invasive, and invasive breast disease. METHODS: Preoperative stool samples were collected from 131 women (median age 59) with benign (n = 23), high-risk/non-invasive (n = 47), or malignant (n = 61) disease. Shallow shotgun metagenomic sequencing was performed. Taxonomic profiling used Sourmash 4.2.4 (GTDBv207 reference database); functional profiling employed HUMAnN 3.6 with gene families mapped to MetaCyc pathways. RESULTS: α-diversity differed across diagnosis groups and inversely correlated with increasing BMI (Inverse Simpson p = 0.025). β-diversity differed by diagnosis group and BMI. No significant differences in diversity were observed based on age, menopausal status or mammographic breast density. BMI was also associated with enrichment of Dorea, Blautia, and Streptococcus species. Functional pathway profiling showed greater relative abundance of genes involved in NAD biosynthesis, folate metabolism, and aromatic amino acid metabolism pathways with higher BMI. Cross-referencing the most significant taxonomic and functional pathway findings suggested enrichment of Blautia species, via tryptophan metabolism, might link to NAD biosynthesis. CONCLUSION: In this study of women with benign, high-risk/non-invasive, and invasive breast disease, BMI was associated with distinct differences in gut microbial taxonomy and functional pathway profiles. These hypothesis-generating findings provide a rationale for future study to determine how the obesity-associated microbiome contributes to breast cancer development. CLINICAL TRIAL NUMBER: Not applicable.