The Gut Microbiota-Ovarian Cancer Axis: Mechanisms of Influence and Therapeutic Implications.

Abstract

Ovarian cancer (OC), one of the most lethal gynecological malignancies, urgently requires breakthrough diagnostic and therapeutic strategies due to its low survival rate and high recurrence rate. The gut microbiota (GM), which colonizes the human gastrointestinal tract, significantly influences human health. Recent technological advancements have enabled deeper investigation into tumor-bacteria interactions. The GM profoundly participates in OC initiation, progression, and treatment resistance by dynamically regulating the host's immune response, metabolism, and inflammatory microenvironment. This review focuses on three primary mechanisms by which the GM influences OC development and its impact on cancer therapies (chemotherapy, immunotherapy, and targeted therapy). At the mechanistic level, GM dysbiosis promotes OC through multiple pathways: (1) Modulating the tumor microenvironment (TME), including inducing immunosuppressive cell infiltration and impairing anti-tumor immunity; (2) Interfering with estrogen metabolism, thereby elevating bioactive estrogen levels; (3) Producing metabolites that mediate systemic inflammatory signaling and energy metabolism reprogramming. These alterations collectively drive tumor proliferation and metastasis. Although microbiota-based interventions offer novel opportunities for precision therapy in OC, clinical translation faces challenges such as mechanistic complexity and individual heterogeneity. Future research should integrate multi-omics technologies and large-scale clinical trials to advance microbiota modulation strategies from bench to bedside, thereby improving OC prognosis.