Engineering probiotic consortia to improve chemotherapy tolerance and reduce toxicity in breast cancer patients: a new frontier in supportive precision oncology.

Chemotherapy is a cornerstone of breast cancer treatment but is often limited by systemic toxicities, gastrointestinal mucositis, immunosuppression, and treatment interruptions, which compromise patient outcomes. Emerging evidence highlights the gut microbiome as a central mediator of chemotherapy tolerance and toxicity. Cytotoxic regimens induce dysbiosis, characterized by depletion of beneficial commensals, expansion of pathobionts, and impaired microbial metabolic function, exacerbating mucosal injury, inflammation, and systemic side effects. Engineered probiotic consortia-rationally designed multi-strain microbial communities-offer a novel strategy to restore microbial balance, reinforce epithelial barrier function, modulate immune responses, and enhance chemotherapy tolerance. Preclinical and emerging clinical studies demonstrate that multi-strain consortia can increase short-chain fatty acid production, reduce pro-inflammatory signaling, preserve mucosal integrity, and improve patient resilience during treatment. Advances in synthetic biology and microbiome engineering enable precise design of microbial consortia with complementary functions and ecological stability. This review provides a comprehensive overview of the mechanistic rationale, preclinical and clinical evidence, technological strategies, and translational implications of engineered probiotic consortia, highlighting their potential to transform supportive care in breast cancer therapy.