Microbiome-Microbial Metabolome-Cancer Cell Interactions in Breast Cancer-Familiar, but Unexplored

Abstract

Breast cancer is a leading cause of death among women worldwide. Dysbiosis, an aberrant composition of the microbiome, characterizes breast cancer. In this review we discuss the changes to the metabolism of breast cancer cells, as well as the composition of the breast and gut microbiome in breast cancer. The role of the breast microbiome in breast cancer is unresolved, nevertheless it seems that the gut microbiome does have a role in the pathology of the disease. The gut microbiome secretes bioactive metabolites (reactivated estrogens, short chain fatty acids, amino acid metabolites, or secondary bile acids) that modulate breast cancer. We highlight the bacterial species or taxonomical units that generate these metabolites, we show their mode of action, and discuss how the metabolites affect mitochondrial metabolism and other molecular events in breast cancer. These metabolites resemble human hormones, as they are produced in a "gland" (in this case, the microbiome) and they are subsequently transferred to distant sites of action through the circulation. These metabolites appear to be important constituents of the tumor microenvironment. Finally, we discuss how bacterial dysbiosis interferes with breast cancer treatment through interfering with chemotherapeutic drug metabolism and availability.

Keywords: FFAR; OXPHOS; TAAR; TGR5; breast cancer; cadaverine; estrogen deconjugation; lithocholic acid; microbiome; mitochondrial metabolism; secondary bile acids.

Figure 1

Schematic representation of the pathways elicited by bacterial metabolites that modulate mitochondrial metabolism in breast cancer.