Introduction: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder associated with insulin resistance, hyperandrogenism, and infertility. Gut microbiota dysbiosis is suspected to play a significant role in the pathogenesis of PCOS through the gut-brain-gonad axis, an axis that remains incompletely understood. Methods: This study aims to evaluate the role of gut microbiota dysbiosis in the mechanism of PCOS with insulin resistance by analyzing the abundance of Lactobacillus sp., levels of Zonulin, Short Chain Fatty Acids (SCFAs), Insulin-Like Growth Factor-1 (IGF-1), and ovarian follicle count in a rat model of PCOS with insuline resistance, which in this study devided into 2 groups, control and treatment group, consist of 20 rats each. This experimental study employed an SEM-- PLS approach to assess the relationships among microbiota, inflammation, metabolism, and ovarian function variables in an insulin-resistant PCOS rat model with insulin resistance. Results: The results showed decreases in Lactobacillus sp., SCFAs, and ovarian follicle counts, along with an increase in IGF-1 levels in PCOS model rats. Discussion: The study, utilizing an insulin-resistant Polycystic Ovary Syndrome (PCOS) rat model, established a strong, statistically significant link between gut microbiota dysbiosis and endocrine/ metabolic dysfunction. These were observed through increased levels of key markers: Zonulin (Control: 3.775, Treatment: 5.545), HOMA-IR (Control: 78.3400, Treatment: 140.9760), and IGF-1 (Control: 141.9665, Treatment: 189.5700). The Structural Equation Modeling (SEM) analysis confirmed two primary pathogenic pathways: (1) Gut Microbe/Metabolite Pathway: A reduction in beneficial Lactobacillus sp. was linked to lower SCFA levels, which influenced IGF-1 and negatively affected ovarian follicle development; (2) Inflammation/Insulin Resistance Pathway: The model established a statistically significant cascade where PCOS induction was strongly associated with Zonulin (β = -0.717), which then positively predicted HOMA-IR (β = 0.630), and HOMA-IR, in turn, strongly predicted IGF-1 (β = 0.662), defining the mechanism as PCOS → Zonulin → HOMA-IR → IGF-1. Conclusion: The dysbiosis mechanism involving gut microbiota in this study’s model includes PCOS, Zonulin, HOMA-IR, and IGF-1, as these variables demonstrated statistically significant relationships
Usman et al. (Mon,) studied this question.