Reciprocal Interactions Between the Gut Microbiome and Mammary Tissue Mast Cells Promote Metastatic Dissemination of HR plus Breast Tumors

Establishing commensal dysbiosis, defined as an inflamma-tory gut microbiome with low biodiversity, before breast tumor initiation, enhances early dissemination of hormone receptor- positive (HR+) mammary tumor cells. Here, we sought to determine whether cellular changes occurring in normal mam-mary tissues, before tumor initiation and in response to dys-biosis, enhanced dissemination of HR+ tumors. Commensal dysbiosis increased both the frequency and profibrogenicity of mast cells in normal, non-tumor-bearing mammary tissues, a phenotypic change that persisted after tumor implantation. Pharmacological and adoptive transfer approaches demonstrat-ed that profibrogenic mammary tissue mast cells from dysbiotic animals were sufficient to enhance dissemination of HR+ tumor cells. Using archival HR+ patient samples, we determined that enhanced collagen levels in tumor-adjacent mammary tissue positively correlated with mast cell abundance and HR+ breast cancer recurrence. Together, these data demonstrate that mast cells programmed by commensal dysbiosis activate mammary tissue fibroblasts and orchestrate early dissemination of HR+ breast tumors.

Automated summary

Establishing commensal dysbiosis before breast tumor initiation enhances early dissemination of hormone receptor-positive (HR+) mammary tumor cells. Dysbiosis increases both the frequency and profibrogenicity of mast cells in normal mammary tissues, which can persist after tumor implantation. Enhanced collagen levels in tumor-adjacent mammary tissue positively correlate with mast cell abundance and HR+ breast cancer recurrence.