Guardians in the gut: mechanistic insights into a hidden ally against triple-negative breast cancer

The gut microbiome possesses a diverse range of biological properties that play a role in maintaining host health and preventing disease. Gut microbial metabolites, including short-chain fatty acids, natural purine nucleosides, ellagic acid derivatives, and tryptophan metabolites, have been observed to have complex and multifaceted roles in the gut and in wider body systems in the management of disease, including cancer. Triple-negative breast cancer is the most aggressive subtype of breast cancer, with restricted treatment options and poor prognoses. Recently, preclinical research has investigated the antiproliferative potential of gut microbial metabolites against this type of breast cancer with promising results. However, little is understood about the mechanisms of action and molecular pathways driving this antiproliferative potential. Understanding the complex mechanisms of action of gut microbial metabolites on triple-negative breast cancer will be instrumental in the investigation of the combined administration with standard chemotherapeutic drugs. To date, there is a paucity of research studies investigating the potential synergistic interactions between gut microbial metabolites and standard chemotherapeutic drugs. The identification of synergistic potential between these compounds may provide alternate and more effective therapeutic options in the treatment and management of triple-negative breast cancer. Further investigation into the mechanistic action of gut microbial metabolites against this breast cancer subtype may support the administration of more cost-effective treatment options for breast cancer, with an aim to reduce side effects associated with standard treatments. Additionally, future research will aim to identify more potent metabolite–drug combinations in the mitigation of triple-negative breast cancer progression and metastasis.