Hyperandrogenic women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including obesity, insulin resistance, hypertension, and dyslipidemia that result in an increased risk of hypertensive disorders of pregnancy, type 2 diabetes and CVD events. Surveys also show significant dissatisfaction amongst women with PCOS regarding long-term counselling and management of their cardiometabolic risk. Although lifestyle interventions and oral contraceptive pills (OCPs) are recommended as first-line treatment for PCOS, there are no dietary or pharmacological recommendations for prevention of CVD risk in PCOS, indicating a considerable knowledge gap. Resistant starch, a type of dietary fiber, may offer a promising solution with significant improvements in CVD risk factors and CVD events in the general population. In addition, resistant starch use has been associated with increased abundance of short chain fatty acids (SCFA)- producing gut bacteria, such as Bifidobacteria, and SCFAs in the general population. Recent studies also showed that Bifidobacteria and SCFAs are decreased in women with PCOS, and that exposure to a healthy gut microbiome via cohousing or fecal microbiome transplantation improved cardiometabolic parameters in PCOS rodent models. These studies indicate that modulation of the gut microbiome may be a potential novel treatment target for cardiometabolic dysregulation in PCOS. While increased dietary fiber improves cardiometabolic and gut health in the general population, the impact of resistant starch supplementation on cardiometabolic parameters or the gut microbiome in women with PCOS treated with OCPs has not been investigated. Use of OCPs especially in women with overweight /obesity is associated with dyslipidemia, hypertension and glucose dysregulation. We will test the hypothesis that treatment with resistant starch in combination with OCPs results in improvement in cardiometabolic parameters, as well as specific gut microbes and metabolites, such as Bifidobacteria and SCFAs compared to OCPs alone. In Aim 1, we will enroll 100 women with hyperandrogenic PCOS and overweight/obesity in a double-blind placebo-controlled 2-arm RCT for 12 weeks: Arm A) OCP + resistant starch and Arm B) OCP + maltodextrin (resistant starch placebo). We will investigate how resistant starch treatment in combination with OCPs improves individual cardiometabolic parameters, markers of insulin resistance, glucoregulatory status and inflammation compared to OCPs alone. In Aim 2, we will use metagenomics and metabolomics to determine how OCPs + resistant starch impact abundances of Bifidobacteria and other gut microbes, microbial genes and SCFAs compared to OCPs alone and if changes in the gut microbiome correlate with changes in specific cardiometabolic parameters. Results from this proposal will provide support for the implementation of a low-cost, nutritional therapy to counter negative cardiometabolic eff...