The Role of Microbiota in Ovarian Cancer: Implications for Treatment Response and Therapeutic Strategies
Cancer remains a global health challenge (18.1 million new cases in 2020), with incidence projected to reach 28 million within two decades. Ovarian cancer (OC) is the deadliest gynecologic malignancy, usually diagnosed at advanced stages and with poorly understood etiology. Emerging evidence implicates reproductive tract and gut microbiota in OC biology. Microbiota shape carcinogenesis via turnover, immunity, and metabolism; dysbiosis promotes DNA damage, inflammation, and carcinogenic metabolites, engaging multiple hallmarks of cancer. In OC, microbes may reach tumors by local ascent, translocation, or hematogenous spread, originating from vagina, upper reproductive tract, peritoneal fluid, or gut. Lactobacillus-dominant vaginal communities support mucosal integrity, whereas anaerobes disrupt barriers, increase inflammation, and correlate with OC risk; mouse models show vaginal dysbiosis accelerates tumor progression. Distinct microbial profiles in upper reproductive sites and peritoneal fluid associated with immune remodeling. Gut dysbiosis drives barrier loss, immune imbalance, and estrogen reactivation. Microbial metabolites (lipopolysaccharides, short-chain fatty acids) modulate oncogenic pathways, altering epithelial–mesenchymal transition, immune evasion, and drug resistance. Across cohorts, OC tissues and fluids show Pseudomonadota/Bacteroidota enrichment and Akkermansia depletion; fecal microbiota from OC patients accelerates tumor growth in mice, whereas Akkermansia supplementation restores antitumor immunity. Antibiotic exposure and platinum resistance associate with reduced diversity and expansion of lactate-producing taxa. Microbiome-informed interventions–diet, probiotics/postbiotics, fecal microbiota transfer, and selective antibiotics–may augment chemotherapy and immunotherapy. Overall, the microbiome is a modifiable determinant of OC risk, progression, and treatment response, warranting rigorous, standardized, multi-omics studies.
