Polycystic ovarian syndrome (PCOS) is a condition that affects 7-10% of women in their reproductive years, accounting for roughly 5 million women in the United States. Approximately, 80% of PCOS women suffer from hyperandrogenemia increasing the risk for developing comorbidities, such as obesity, chronic inflammation, increased blood pressure, type II diabetes, insulin resistance, dyslipidemias, and hyperleptinemia. In addition, approximately 42% of PCOS women suffer from gastrointestinal (GI) symptoms, such as abdominal pain, constipation, diarrhea, and/or bloating. Many of these symptoms are associated with sub-acute GI inflammation. Metformin, a common treatment for metabolic dysfunction in PCOS women, causes GI side effects, often resulting in patient non-compliance with treatment. However, the mechanisms that contribute to these GI symptoms are unknown. My exciting preliminary data in the hyperandrogenemic female (HAF) rat model of PCOS show mitochondrial dysfunction, increased mitochondrial reactive oxygen species (mtROS), and inflammation in the colon. Furthermore, my preliminary data show that colonic mtROS and inflammation are further increased in HAF rats given metformin. We hypothesize then: 1) the development of sub-acute GI inflammation in PCOS women is due to androgen- and AR-mediated impairment of colonic mitochondrial oxidative phosphorylation, leading to increased mtROS, gut dysbiosis, and inflammation that is further exacerbated by metformin; 2) the use of a mitochondrial targeted antioxidant therapy, such as MitoTEMPO, will improve mitochondrial function, decrease mtROS and inflammation, thus preventing development of sub-acute GI inflammation in PCOS women. These hypotheses will be tested our well characterized and clinically relevant model of PCOS, the HAF rat, in the following specific aims: Aim 1: To test the hypothesis that colon mitochondrial dysfunction and increased mtROS in HAF rats is linked to increased gut dysbiosis and sub-acute GI inflammation, and that mitochondrial-targeted antioxidant therapies, such as MitoTEMPO, will attenuate these changes; Aim 2: To test the hypothesis that metformin in the HAF rat exacerbates colonic mitochondrial dysfunction increasing gut dysbiosis and inflammation, and that addition of an antioxidant, such as MitoTEMPO, will improve the mitochondrial function with metformin.