Exploring Emerging Concepts in the Pathophysiology of PCOS: Microbiome Dysbiosis and Immunological Dysregulation

Abstract: Polycystic ovarian syndrome (PCOS) is a complex yet common endocrine disorder, affecting 5-20% of reproductive-age women, characterised by a combination of hyperandrogenism, anovulation, and metabolic dysfunction. This combination of factors has traditionally been assumed to be the causative factors for the subfertility associated with PCOS, but significant microbial dysbiosis and alterations in immune function are identified in women with PCOS, suggesting a more complicated multifactorial impact on reproduction. Microbiome alterations vary between different PCOS subtypes, suggesting that hyperandrogenism and insulin resistance can impact microbial communities. The immunological implications of these microbiome changes are still poorly understood, along with their impact on reproductive outcomes such as implantation, miscarriage, and assisted reproduction success rates. Although therapeutic interventions are chosen based on their endocrine and metabolic effects, many of these also target the microbiome and have immunomodulatory effects. Understanding these microbiome-host interactions and immunological factors provides new insights into the complex spectrum of PCOS pathophysiology and provides the potential for novel therapeutic approaches. Lay Summary: Polycystic Ovary Syndrome (PCOS) is a common hormonal condition affecting up to one in five women of reproductive age. It can cause irregular periods, excess hair growth, acne, and difficulties with fertility. Recent research suggests that PCOS is not only a hormonal disorder but also involves changes in the body's bacteria, known as the microbiome, and disturbances in the immune system. These changes may contribute to inflammation, insulin resistance, and hormone imbalance. Understanding how the microbiome and immune system interact in PCOS could lead to new ways to diagnose and treat the condition. Future therapies may focus on restoring a healthy microbiome to improve metabolic and reproductive health.