Remodeling gut microbiota and enhancing SCFA production in mice: mechanisms of RS2 and arabinoxylan in ameliorating PCOS phenotypes.

BACKGROUND

Polycystic ovary syndrome (PCOS) is linked to hyperandrogenism and gut microbiota dysbiosis. Dietary fibers (DFs), such as resistant starch type 2 (RS2) and arabinoxylan (AX), modulate the gut microbiota and produce short-chain fatty acid (SCFA), potentially ameliorating PCOS symptoms. This study investigated the therapeutic potential of RS2 and AX in a mouse model of letrozole-induced PCOS and explored the underlying mechanisms involving the gut microbiota-SCFA-liver signaling pathways.

METHODS

Letrozole-induced PCOS mice were divided into six groups: control (C), RS2 (R), AX (A), PCOS model (M), RS2-treated PCOS (RM), and AX-treated PCOS (AM) groups. The interventions lasted 35 days. Body weight, glucose tolerance, insulin resistance, ovarian morphology, estrous cycles, the gut microbiota (16 S rRNA sequencing), serum SCFA levels, fecal bile acids, and hepatic proteomics (DIA-MS) were analyzed.

RESULTS

RS2 and AX reduced body weight, improved insulin sensitivity (lower HOMA-IR, p < 0.05), restored regular estrous cycles, and mitigated ovarian cystic follicles in PCOS mice. Gut microbiota analysis revealed an increased prevalence of Ligilactobacillus in the RM and AM groups (p < 0.05), which was correlated with elevated SCFA (acetic acid, butyrate) levels. Hepatic proteomics revealed increased expression of AMPK signaling proteins (Prkag2 and Pck1) in treated PCOS mice (p < 0.05), which was linked to the SCFA-mediated activation of GPRs (GPR41/43). AX also modulated pathways associated with nonalcoholic fatty liver disease. Bile acid metabolism showed no significant intervention-related changes.

CONCLUSION

RS2 and AX alleviated PCOS phenotypes by enriching Ligilactobacillus, increasing SCFA production, and activating hepatic AMPK signaling. These findings highlight gut microbiota modulation and SCFA-driven metabolic pathways as therapeutic targets for PCOS. This study provides mechanistic insights into dietary fiber interventions for endocrine disorders.