RS2 and AX reduced body weight and improved insulin sensitivity in mice over 35 days.
Insulin sensitivity improved as indicated by lower HOMA-IR levels (p < 0.05).
Regular estrous cycles were restored in RS2 and AX treated PCOS mice.
The treatment reduced the presence of ovarian cystic follicles in the PCOS model.
Increased levels of Ligilactobacillus were observed in the gut microbiota of treated groups (p < 0.05).
Higher serum levels of , specifically acetic acid and butyrate, were associated with the interventions.
Increased expression of AMPK signaling proteins was noted in the liver of treated PCOS mice (p < 0.05).
Simplified
BACKGROUND: (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.
Key numbers
p < 0.05
Decrease in HOMA-IR
Significant reduction in insulin resistance markers in RS2 and AX groups.
36 mice
Weight Loss
Total number of healthy female C57BL/6 mice used in the interventions.
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Declarations. Ethics approval: The study was approved by the Animal Welfare and Ethics Committee of Shantou University Medical College (Protocol number STUM2023-477). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
