Dietary Secoisolariciresinol Diglucoside Alleviates Polycystic Ovary Syndrome in Rats Through Inhibiting Inflammation and Modulating Gut/Vaginal Microbiota

Background: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by hyperandrogenism, anovulation, and polycystic ovaries, and it is frequently associated with low-grade inflammation and microbiota dysbiosis. Secoisolariciresinol diglucoside (SDG), a flax-derived polyphenol, exhibits estrogenic and anti-inflammatory properties. This study explored the therapeutic potential of dietary SDG in a rat model of PCOS. Methods: Female Sprague-Dawley rats were divided into four groups: control, model, SDG-treated control, and SDG-treated model. After 3 weeks of PCOS modeling, dietary SDG was administered for 8 weeks. Samples were collected after the intervention for subsequent analyses. Results: SDG improved estrous cyclicity, ovulation, ovarian morphology, and sex hormone balance. It reduced obesity, dyslipidemia, insulin resistance, and oxidative stress. Inflammation was alleviated through reductions in interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α, along with an elevation in IL-10. SDG increased splenic regulatory T cells and intestinal γδT cells while reducing ovarian and peritoneal macrophages. Gut microbiota composition was reshaped, with increased abundances of Bifidobacterium, Butyrivibrio, and Ruminiclostridium, and decreased abundances of Bacteroides and Parasutterella. Vaginal microbiota composition improved, as indicated by increased Lactobacillus and decreased Enterobacteriaceae. Plasma lipopolysaccharide levels decreased, whereas short-chain fatty acids increased. Metabolomic analysis highlighted alterations in histidine metabolism. Conclusion: SDG ameliorates PCOS by suppressing inflammation and modulating gut and vaginal microbiota.