Reduction of secondary bile acids following microbiome pre-conditioning was associated with reduced breast cancer progression

Abstract

Abstract Breast cancer is the most common cause of cancer-related death in women worldwide. We previously reported that a primary bile acid mimetic reduced tumor progression in vivo. Here, we hypothesized that elevating primary bile acids through preconditioning of the gut microbiome may be an unexplored opportunity to improve breast cancer. We utilized the antibiotic vancomycin previously reported to deplete Gram-positive, anaerobic microbes that convert primary bile acids to secondary bile acids. Preconditioning with vancomycin significantly delayed tumor onset, decreased burden, promoted regression, and reduced the number of mice with lung colonization. Vancomycin reduced overall microbiome diversity and specific microbes in Clostridium Cluster XIVa , which associated with increased primary bile acid levels. We report that vancomycin significantly associated with elevated circulating bile acid tauro-alpha/beta-muricholic acid and reduced secondary bile acids that correlated with worsened tumor outcomes. Flow analysis of tumor content and systemic immune responses was associated with immune changes consistent with anti-tumor responses, including conventional dendritic cells and activated CD8 + T cells. In sum, we demonstrated that manipulation of the bile acid pools associated with improved breast cancer outcomes. The altered bile acids corresponded to an elevation of key immune cells, which may contribute to protection from primary breast cancer progression and lung colonization.