Abstract
Disclosure: N.M. Iyengar: None. A. Chiba: None. M. Howard-McNatt: None. A. Thomas: None. D.R. Soto-Pantoja: None. K.L. Cook: None. Obesity is one of the few modifiable risk factors for postmenopausal breast cancer. While obesity influences on the gut microbiome are established, the effect of diet and adiposity on tissue resident microbiome populations are underexplored. Studies have shown that breast tissue has a distinct microbiome, which is shifted in the presence of tumors or diet. However, whether obesity and menopause modify the breast microbiome is unknown. Using a cohort of non-cancerous breast tissue samples (n=80) taken at surgery from women that underwent mastectomy for breast cancer, we now demonstrate that obesity and aging interact to shift the breast microbiome. DNA isolated from breast tissue collected at surgery was used to perform V3-V4 amplicon 16S bacterial sequencing. Breast tissue from postmenopausal women with obesity (mean BMI 34.7 ±3.7) displayed a significantly higher α-diversity than breast tissue from postmenopausal lean women (mean BMI 21.9 ±1.7). Postmenopausal women with obesity also displayed a significantly different β-diversity than all other groups (Bray-Curtis; PERMANOVA p<0.02). At the species level, breast tissue from postmenopausal women with obesity had a significantly elevated Akkermansia mucinphila proportional abundance (5.6%) when compared with all other groups (0.05-0.3% proportional abundance), demonstrating obesity and menopause interact to modify the breast tissue microbiome. Akkermansia muciniphila is a mucin-degrading bacteria. Breast tumors display aberrant mucin glycosylation and abundance, which previously were shown to promote carcinogenesis. Staining ER+ breast tumors for mucin-1 from patients with or without obesity indicates patient BMI positively correlates with tumor mucin-1 abundance, suggesting obesity regulation of mucin and/or mucin-degrading bacteria may promote breast tumorigenesis. To determine physiological relevance of breast Akkermansia muciniphila abundance, Western diet-fed MMTV-PyMT mice were intra-nipple injected with saline or Akkermanisa muciniphila bacteria into the mammary gland (MG) at 5, 7, and 9 weeks of age and palpated weekly for tumor formation. Elevated MG Akkermansia presence was associated with increased mammary tumorigenesis and multiplicity. Tumor mucin-1 was decreased with A. muciniphila administration. Flow cytometry analysis of single cell suspensions of breast tumors indicate A. muciniphila modified infiltrating immune populations. Overall, these results suggest obesity and aging may interact to enrich breast mucin-degrading bacteria abundance as a risk factor for postmenopausal breast cancer. Presentation: Saturday, June 17, 2023