Metabolomics-Microbiome Crosstalk in the Breast Cancer Microenvironment

Abstract

Breast cancer, the most frequent cancer diagnosed among females, is associated with a high mortality rate worldwide. Alterations in the microbiota have been linked with breast cancer development, suggesting the possibility of discovering disease biomarkers. Metabolomics has emerged as an advanced promising analytical approach for profiling metabolic features associated with breast cancer subtypes, disease progression, and response to treatment. The microenvironment compromises non-cancerous cells such as fibroblasts and influences cancer progression with apparent phenotypes. This review discusses the role of metabolomics in studying metabolic dysregulation in breast cancer caused by the effect of the tumor microenvironment on multiple cells such as immune cells, fibroblasts, adipocytes, etc. Breast tumor cells have a unique metabolic profile through the elevation of glycolysis and the tricarboxylic acid cycle metabolism. This metabolic profile is highly sensitive to microbiota activity in the breast tissue microenvironment. Metabolomics shows great potential as a tool for monitoring metabolic dysregulation in tissue and associating the findings with microbiome expression.

Keywords: breast cancer; metabolomics; microbiome; microenvironment.

Figure 1

Workflow of common methods for studying the breast tissue microbiome. After extracting microbial DNA from breast tissue or cell lines. (a) a PCR amplification based on the 16S rRNA gene of variable regions (V1-V9) is conducted using specific primers to bacterial sequence species, where 16S rRNA is a shared region between bacteria and archaea. (b) Metagenomics is based on whole DNA sequencing generated from the sample, and the reads are matched with the library specific to the particular species. 16S rRNA gene provides phylogeny and community composition. Metagenomics also provides the community composition and function of genes. (c) Microbiome Microarray is designed using the high-density Axiom platform for microbiome analysis, containing ~1.38 million DNA probes specific to microbiota species.