Effects of Glucagon-Like Peptide-1 Receptor Agonists on Gut Microbiota in Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome Mice: Compared Evaluation of Liraglutide and Semaglutide Intervention Original paper

What was studied?

This original research article investigated how irisin supplementation alters reproductive endocrinology, ovarian morphology, gut microbiota, and fecal metabolomics in a polycystic ovary syndrome (PCOS) mouse model. The investigators used a DHEA + high-fat diet model to induce PCOS and then tested whether recombinant irisin could reverse endocrine abnormalities and gut microbial dysbiosis. The experimental design included vaginal cytology, hormone profiling, ovarian histology, 16S rRNA sequencing, and untargeted LC–MS metabolomics. Together, these methods allowed the team to examine whether irisin’s benefits extended beyond reproductive tissues into gut microbial networks and metabolite pathways known to contribute to PCOS pathophysiology.

Who was studied?

The study used female C57BL/6 mice, 21 days old, divided into three groups: control, DHEA + HFD–induced PCOS, and PCOS treated with irisin (400 μg/kg every other day for 21 days). Fecal samples taken immediately before sacrifice were used for microbial and metabolic profiling. This murine model reliably recapitulates human PCOS-like traits—hyperandrogenemia, estrous cycle arrest, cystic ovarian morphology, and metabolic disturbances—allowing direct comparison of endocrine and microbial signatures.

Most important findings

Irisin partially restored estrous cyclicity, lowered testosterone, and reduced cyst-like follicles while increasing markers of healthy folliculogenesis (GDF-9, CX37/GJA4, aromatase). Although metabolic parameters such as insulin sensitivity did not improve, the gut microbiota shifted substantially. Irisin reversed PCOS-associated microbial patterns, notably increasing Odoribacter (a short-chain-fatty-acid producer) and reducing Eisenbergiella and Dubosiella, genera that expanded under hyperandrogenic conditions. These changes were visible in the heatmaps and bar plots on pages 6–8, where relative abundance patterns move toward control levels following irisin therapy. Untargeted metabolomics revealed fecal metabolites perturbed by PCOS, highlighted in the volcano plots, and showed that methallenestril and oxidized phosphatidylserine PS(22:5/LTE4) were elevated in PCOS but normalized with irisin. Both metabolites were positively correlated with Eisenbergiella and Dubosiella abundance, suggesting an androgen-microbe–metabolite axis.

Key implications

This study strengthens the concept that exercise-linked myokines can influence PCOS phenotypes through the gut microbiota. Irisin did not correct insulin resistance but significantly affected androgen levels, ovarian morphology, microbial community structure, and fecal metabolite signatures. These findings imply that targeted manipulation of irisin or irisin-responsive microbial pathways could form the basis of novel microbiome-informed therapies for PCOS. The consistent microbial shifts, particularly involving Odoribacter, Eisenbergiella, and Dubosiella, highlight potential additions to microbiome signature databases focused on endocrine–metabolic disorders.

Citation

Yang M, Deng H, Zhou S, Lu D, Shen X, Huang L, Chen Y, Xu L. Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics.Frontiers in Microbiology. 2024;15:1373077. doi:10.3389/fmicb.2024.1373077