Quinoa ameliorates polycystic ovary syndrome via regulating gut microbiota through PI3K/AKT/mTOR pathway and autophagy Original paper

What was studied?

This study investigated quinoa ameliorates polycystic ovary syndrome by examining how quinoa supplementation influences the PI3K/AKT/mTOR pathway, autophagy regulation, and gut microbiota in a letrozole-induced PCOS rat model. Researchers explored endocrine, metabolic, ovarian, intestinal, and microbial mechanisms to determine whether quinoa could reverse PCOS-related hormonal disruption, insulin resistance, ovarian pathology, increased intestinal permeability, and dysbiosis. The work integrated in vivo rat experiments with 16S rDNA microbiome sequencing, histological evaluation, immunohistochemistry, Western blotting, and network pharmacology to identify molecular pathways and microbial signatures involved in quinoa’s therapeutic activity. These findings aim to clarify mechanistic relationships between diet, microbiome composition, and metabolic-reproductive signaling disruptions characteristic of PCOS.

Who was studied?

The study used 10-week-old female Sprague-Dawley rats, first induced into a PCOS-like phenotype through 24 days of letrozole administration. Rats exhibiting estrous cycle arrest and metabolic disturbances were enrolled and randomized into control, PCOS, and quinoa-treated groups. Quinoa was provided for eight weeks at 20 g/kg/day alongside standard chow. Biological samples (ovary, pancreas, duodenum, colon, serum, and feces) were collected to assess hormonal profiles, tissue morphology, tight junction integrity, autophagy markers, and microbial community structure. Spearman correlations linked specific microbial taxa with hormone concentrations to evaluate PCOS-relevant associations.

Most important findings

Quinoa significantly improved estrous cyclicity, reduced body and ovary weight, and normalized testosterone, LH, LH/FSH ratio, and estradiol levels. Hyperinsulinemia and HOMA-IR were also lowered. Histology showed restoration of ovarian follicles, granulosa cell layers, and pancreatic islet structure. Ovarian PI3K, AKT, mTOR, Bcl-2, and p62 were downregulated in PCOS but increased with quinoa, while Beclin-1, ULK1, and LC3B were elevated in PCOS and reduced by quinoa—indicating suppressed excessive autophagy and restored PI3K/AKT/mTOR signaling. Colon analyses revealed improved villus architecture and increased tight junction proteins Claudin-5 and Occludin, indicating restored barrier integrity. In parallel, quinoa reversed colonic autophagy abnormalities. Microbiome sequencing demonstrated key shifts: quinoa decreased the Firmicutes/Bacteroidetes ratio and reduced proinflammatory genera such as Prevotella and Blautia, while increasing beneficial taxa such as Lactobacillus, Bacteroides, Coprococcus, and Oscillospira. LEfSe and heatmap analyses show quinoa-treated rats cluster distinctly with enriched SCFA-producing and anti-inflammatory microbes. Correlation heatmaps showed Prevotella positively associated with LH and testosterone, while Lactobacillus, Bacteroides, and Bifidobacterium correlated with healthier hormonal profiles.

Key implications

This study demonstrates that quinoa supplementation beneficially modulates hormonal imbalance, insulin resistance, ovarian autophagy disruption, intestinal barrier damage, and gut microbial dysbiosis characteristic of PCOS. The coordinated restoration of PI3K/AKT/mTOR signaling and microbial taxa associated with inflammation and androgen excess suggests quinoa may serve as a functional food capable of modifying metabolic–reproductive pathways via gut-mediated mechanisms. These findings support incorporating microbiome-impactful dietary strategies into PCOS management and provide valuable microbial signature data for clinical microbiome databases.

Citation

Dou J, Wu Y, Hu R, et al. Quinoa ameliorates polycystic ovary syndrome via regulating gut microbiota through PI3K/AKT/mTOR pathway and autophagy. Nutrition & Metabolism. 2024;21:80. doi:10.1186/s12986-024-00855-3