The microbiota in breast cancer: dysbiosis, microbial metabolites, and therapeutic implications

Abstract

The human microbiome plays a pivotal role in host health and disease, with emerging evidence underscoring its significant influence on the development and progression of breast cancer. Studies have revealed that dysbiosis in both the gut and breast tissue microbiota is strongly associated with an elevated risk of breast cancer. Distinct microbial profiles have been identified among healthy individuals, patients with benign breast conditions, and those with malignant tumors, with further variations observed across different ethnic groups and breast cancer subtypes. The complex interplay between breast cancer risk factors and microbial populations, coupled with the direct impact of microbial communities and their metabolites on inflammatory pathways and immune responses, underscores the importance of this field. Additionally, the interaction between gut microbiota and therapeutic modalities such as chemotherapy and radiotherapy is of particular interest, as these interactions can significantly influence treatment outcomes, either enhancing or diminishing efficacy. This review explores the effects of the Mediterranean diet, probiotics, prebiotics, and natural medicinal products on gut microbiota, emphasizing their potential as innovative therapeutic strategies. Notably, the use of engineered probiotics within the tumor microenvironment represents a promising frontier in breast cancer treatment. In conclusion, research on the human microbiome not only deepens our understanding of breast cancer pathogenesis but also lays the groundwork for the development of novel and targeted therapeutic interventions.

Keywords: Gut microbiome; breast cancer; chemotherapy; metabolism; probiotics; radiotherapy.

Figure 1

The impact of breast cancer-related risk factors on the gut microbiota (By Figdraw). Menopause, smoking, alcohol consumption, obesity, and vitamin D receptor (VDR) deficiency contribute to an increase in the abundance of harmful bacteria and a reduction in α-diversity, shifting the microbial profile from a normal to an oncogenic state and influencing the initiation and progression of breast cancer.

Figure 2

The regulatory network of gut microbiota and metabolism on tumor microenvironment and cancer cell behavior (By Figdraw). Cadaverine (CAD) inhibits tumor cell invasion and stem cell-like properties; indolepropionic acid (IPA) reduces cancer stem cells and enhances anti-tumor immunity; succinic acid promotes a mesenchymal phenotype and metabolic reprogramming; and trimethylamine N-oxide (TMAO) enhances the efficacy of immunotherapy; pathogenic microbe-associated molecular patterns (PAMPs) stimulate immune cells to produce pro-inflammatory cytokines, including IL-6, IL-12, and TNF-α.

Figure 3

Pathogenesis and treatment options with gut microbiota as the intervention point (By Figdraw). The Mediterranean diet, probiotics and prebiotics, fecal transplantation, and natural medicines and traditional Chinese medicines modulate the composition and function of the gut microbiota, affects the production of metabolites and the inflammatory and immune responses, thereby exerting positive effects in the treatment and prevention of breast cancer.