Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics Original paper

What was studied?

This study investigated how irisin, a myokine induced by physical activity, influences reproductive endocrine abnormalities and gut microbiome–metabolome patterns in a polycystic ovary syndrome (PCOS) mouse model. Because PCOS involves metabolic dysfunction, hyperandrogenism, disrupted folliculogenesis, and gut microbiota dysbiosis, the authors examined whether irisin could modify these outcomes. They used dehydroepiandrosterone plus a high-fat diet to induce PCOS-like phenotypes, then tested whether irisin administration altered ovarian morphology, hormone levels, bacterial communities, and fecal metabolites. The central aim was to determine whether irisin—acting as a surrogate for exercise—could attenuate PCOS progression through microbiome-related mechanisms.

Who was studied?

The research used 21-day-old female C57BL/6 mice divided into control, PCOS, and PCOS+irisin groups. PCOS mice received daily DHEA injections plus high-fat diet, while the intervention group additionally received intraperitoneal recombinant irisin (400 µg/kg every other day for 21 days). Fecal samples from these mice were processed using full-length 16S rRNA gene sequencing and untargeted metabolomics, generating detailed microbial and metabolite profiles. Ovarian tissues were also evaluated histologically and via immunohistochemistry to assess follicle development, atresia, and steroidogenic signaling.

Most important findings

Irisin did not meaningfully improve insulin resistance or glucose tolerance but substantially reversed reproductive endocrine disturbances. Treated PCOS mice exhibited reduced serum testosterone, partial normalization of estrous cycling, reduced cystic follicle formation, and restored expression of folliculogenic markers, including GDF-9, CX37/GJA4, and CYP19A1. Microbiome analysis revealed distinct beta-diversity clustering across all groups, with irisin shifting several PCOS-altered taxa. Notably, irisin restored Odoribacter—a short-chain fatty acid–producing genus commonly reduced in metabolic dysfunction—while decreasing Eisenbergiella and Dubosiella, both of which were elevated in PCOS mice. These genera showed strong correlations with altered metabolites, especially methallenestril and PS(22:5/LTE4), which irisin significantly lowered. The table below summarizes major microbiome-metabolite associations relevant to signature building.

Key implications

These findings position irisin as a biologically plausible mediator of exercise benefits in PCOS, particularly through modulation of gut microbial ecology and metabolite production rather than direct improvement in insulin sensitivity. By restoring SCFA-producing bacteria and reducing taxa associated with androgen excess and inflammatory metabolites, irisin may reshape the intestinal environment in ways that improve ovarian signaling and reduce hyperandrogenism. Because both methallenestril and oxidized phosphatidylserine derivatives normalized with irisin, these molecules may represent candidate biomarkers for therapeutic monitoring. While translation to humans requires caution, the study suggests that irisin-based therapies could complement lifestyle interventions by manipulating microbe-derived metabolic signatures underlying PCOS.

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.Front Microbiol. 2024;15:1373077. doi:10.3389/fmicb.2024.1373077 fmicb-15-1373077