Gut microbiota and pattern recognition receptors in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is increasingly recognized as a disorder of impaired immune-endocrine homeostasis. Emerging evidence indicates that intestinal dysbiosis and microbial metabolite imbalance can activate pattern recognition receptors (PRRs), forming a PRR microbiota reproductive axis that contributes to PCOS pathophysiology. This review synthesizes current insights into how gut-derived signals, including LPS, peptidoglycans, SCFAs, bile acids, and tryptophan metabolites, modulate TLR-, NLR-, and RLR-mediated pathways to disrupt ovarian, endometrial, and systemic immune regulation. We further propose a unifying framework, the Reproductive Immune Tolerance Disruption Theory, which posits that chronic PRR activation shifts reproductive tract immunity from a tolerogenic to a low-grade inflammatory state, thereby promoting hyperandrogenism, anovulation, insulin resistance, and metabolic dysfunction. We also summarize recent multi-omics and immunometabolic studies that clarify the crosstalk between gut microbial signatures and innate immune signaling. Finally, we highlight precision strategies, including PRR-selective immunomodulation, microbiota-based therapies, and epigenetic metabolic interventions that hold translational potential for redefining PCOS management. Understanding PRR-driven microbial immunomodulation provides a mechanistic framework for reconciling endocrine, metabolic, and reproductive abnormalities in PCOS, guiding the development of targeted therapeutic approaches.