Journey through the gut-inflammation axis in polycystic ovary syndrome: the microbiota’s role in shaping inflammatory pathways

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease in women in their reproductive phase of life. It could be characterized by irregularity in menstrual cycles, abnormal levels of androgen, and multiple cyst formations in the ovaries. It involves a complex and multifaceted pathophysiology including endocrine and metabolic irregularity, genetic and epigenetic abnormality, inflammation, and gut microbiota dysbiosis. PCOS interferes with the fertility of the patient directly due to irregular ovulation caused by hormonal imbalances. Further, this condition is also associated with increased risk for other health conditions such as type2 diabetes and cardiovascular disease, as well as psychological conditions such as anxiety and depression. Among various other factors, metabolic profiles and gut health also play a crucial role in PCOS pathogenesis. Various recent studies have reported an association of gut microbiota dysbiosis with PCOS. gut microbiota: The microbial population residing in the host organism influences our health status, and their diversity and balance are crucial to maintaining the healthy status of the body. There is growing evidence of the involvement of gut microbe dysbiosis in different diseases, including PCOS. Further inflammation is another key hallmark of PCOS. The inflammatory status of the host body depends on various factors; gut microbe dysbiosis is one such factor that can modulate the inflammatory status and thus contribute to various health conditions such as PCOS. In the present article, we have thoroughly reviewed the current status of research on the involvement of gut microbiota dysbiosis in PCOS pathogenesis and the inflammatory mechanism by which it leads to PCOS, including MCP-1/IL-2 mediated cytokine signaling, LPS-induced leaky gut inflammation, JNK/NF-KB and IKK pathways, tight junction disruption, and oxidative stress. Further, we have also discussed the factors affecting gut microbe dysbiosis and the current status of therapeutic interventions targeting gut dysbiosis in PCOS. These insights emphasize the clinical potential of targeting gut dysbiosis and associated inflammatory pathways to improve the metabolic, reproductive, and psychological outcomes in women with PCOS.