Novel Microbiome-Driven Approaches to Counteract Chemotherapy-Induced Mucositis in Breast Cancer Patients

Abstract

Chemotherapy-induced mucositis (CIM) is a clinically important toxicity in breast cancer care that adversely affects oral and gastrointestinal mucosa, quality of life, nutritional status, and treatment tolerability. While CIM is less frequently dose-limiting in contemporary standard regimens (eg, AC–T, TC) compared with hematologic and neurotoxicities, it remains a significant supportive care challenge, particularly in dose-dense schedules, older cytotoxic protocols, and with selected targeted agents and antibody–drug conjugates. Emerging evidence indicates that chemotherapy-associated dysbiosis can amplify mucosal inflammation and barrier dysfunction, acting as a modifier of injury rather than the primary driver, which is direct epithelial cytotoxicity. A narrative review was conducted using structured searches of PubMed/Medline, Scopus, and Web of Science up to 2025 to identify preclinical and clinical studies addressing the pathobiology of CIM, chemotherapy-associated microbiome perturbations in breast cancer, and microbiome-targeted preventive or therapeutic strategies. Evidence was synthesized qualitatively, with explicit distinction between mechanistic preclinical data and emerging clinical findings. Chemotherapy induces reproducible alterations in oral and gut microbial communities, characterized by reduced microbial diversity, depletion of commensal taxa involved in epithelial homeostasis, and relative expansion of pathobionts. Preclinical models demonstrate that dysbiosis can exacerbate inflammatory signaling, impair epithelial repair, and increase susceptibility to ulceration and infection. Early-phase clinical studies and small randomized trials in heterogeneous oncology populations suggest that selected probiotics, prebiotics, and dietary interventions may modestly attenuate the incidence or severity of mucositis, although robust breast cancer–specific evidence remains limited. More advanced approaches, including postbiotics, fecal microbiota–based strategies, and engineered live biotherapeutics, are largely investigational. CIM in breast cancer is a multifactorial toxicity primarily driven by direct chemotherapy-induced epithelial injury, with the microbiome functioning as an important biological modifier of inflammation, barrier integrity, and mucosal repair. Microbiome-targeted interventions represent a promising adjunct to conventional supportive care rather than a stand-alone solution. Well-designed, breast cancer–specific clinical trials incorporating longitudinal microbiome and metabolomic profiling are required to define clinical efficacy, safety, and patient subgroups most likely to benefit from precision microbiome modulation.