Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice Original paper

What was studied?

This original research study investigated how the focus keyphrase: omega-3 PUFAs gut microbiota PCOS influences ovarian and metabolic outcomes in a dehydroepiandrosterone-induced mouse model of polycystic ovary syndrome (PCOS). The central goal was to determine whether omega-3 polyunsaturated fatty acids (PUFAs) alleviate PCOS-associated endocrine dysfunction, ovarian pathology, insulin resistance, and inflammation, and to identify how these effects are mediated by changes in gut microbiota composition. Using a combination of 16S rDNA sequencing, fecal microbiota transplantation, and antibiotic depletion, the researchers explored causal relationships between dietary omega-3 intake, specific microbial shifts, and downstream metabolic and reproductive phenotypes. The paper emphasizes microbiome-level alterations—particularly abundance changes in Akkermansia, Alistipes, and Alloprevotella—and tracks how these taxa correspond to improvements in inflammation and adipose thermogenic pathways.

Who was studied?

The experimental subjects were female C57BL/6 mice induced to develop PCOS by 21 days of subcutaneous DHEA injections. Following PCOS induction, mice received 8 weeks of omega-3 PUFA oral supplementation or placebo (corn oil). Additional groups underwent antibiotic depletion or received fecal microbiota transplants from omega-3-treated donors. Across these cohorts, the authors collected ovarian histology, serum hormone measurements, glucose tolerance data, and gut microbiota profiles to evaluate endocrine, metabolic, inflammatory, and microbial outcomes. This controlled animal framework allowed the authors to dissect microbiota-dependent and microbiota-independent effects of omega-3s on PCOS phenotypes.

Most important findings

Omega-3 supplementation reversed hallmark PCOS phenotypes—normalizing LH, estradiol, testosterone, fasting glucose, and improving insulin tolerance—without altering body weight. Ovarian histology showed fewer cystic follicles and restored corpus lutea, and estrous cyclicity was normalized. Microbiome sequencing revealed that omega-3 PUFAs significantly modified α-diversity and shifted microbial composition, reducing Alloprevotella and increasing Akkermansia and Alistipes, taxa repeatedly implicated in metabolic and inflammatory regulation. A heatmap on page 9 highlights 20 operational taxonomic units (OTUs) corrected by omega-3 treatment, many belonging to Firmicutes and Bacteroidetes genera known for short-chain fatty acid production. FMT transferred partial metabolic benefits—improving fasting glucose and LH/FSH ratio—but did not fully replicate ovarian improvements, indicating that ovarian anti-inflammatory effects of omega-3s occur largely independent of microbial transfer. Pages 11–13 show that omega-3 supplementation downregulated ovarian IL-1β, TNF-α, and IL-18, confirming a direct anti-inflammatory effect. In adipose tissue, omega-3s enhanced thermogenic markers (Ucp1, Pgc1a, Cited1, Cox8b), but these effects were microbiota-dependent, disappearing with antibiotic depletion.

Key implications

The study demonstrates that omega-3 PUFAs modulate PCOS phenotypes through dual mechanisms: direct ovarian anti-inflammatory actions and indirect microbiota-mediated improvements in adipose thermogenesis and insulin sensitivity. Microbiome-relevant findings—especially increased Akkermansia and Alistipes and decreased Alloprevotella—represent potential microbial biomarkers or therapeutic targets for PCOS. For clinicians and researchers building microbiome signature databases, this paper provides clear evidence linking specific microbial shifts to endocrine, inflammatory, and metabolic improvements, supporting the development of microbiota-informed interventions for PCOS.

Citation

Zhang H, Zheng L, Li C, Jing J, Li Z, Sun S, et al. Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.Journal of Ovarian Research. 2023;16:138. doi:10.1186/s13048-023-01227-w