Diversity of the Gut Microbiota in Dihydrotestosterone-Induced PCOS Rats and the Pharmacologic Effects of Diane-35, Probiotics, and Berberine Original paper

What was studied?

This original research article examined gut microbiota in DHT-induced PCOS rats, exploring how hyperandrogenism reshapes intestinal microbial diversity and composition and whether three clinical interventions—Diane-35, probiotics, and berberine—could reverse these microbial disturbances. Using Illumina MiSeq sequencing of V3–V4 16S rRNA regions, the investigators quantified microbial richness, diversity, and taxonomic shifts, and connected these signatures to metabolic and reproductive phenotypes. The study design allowed evaluation of both pathogenic mechanisms and treatment-specific microbial responses, providing a controlled framework for identifying microbiome alterations associated with PCOS-like features.

Who was studied?

The study involved 36 female Wistar rats beginning at 21 days of age. Rats were assigned to six groups: control, high-fat diet (HFD), DHT-induced PCOS, and DHT rats treated with Diane-35, probiotics, or berberine. DHT exposure induced reproductive and metabolic abnormalities resembling PCOS, including obesity, acyclicity, impaired folliculogenesis, and insulin resistance. Fecal samples collected at sacrifice provided the microbial data. This controlled animal model ensured consistency of diet, environment, and hormonal manipulation, enabling clear attribution of microbial changes to DHT excess and specific therapeutic interventions.

Most important findings

DHT exposure significantly altered gut microbiota structure. Alpha-diversity indices showed reductions compared with controls, though diversity loss was most pronounced in the berberine-treated group, suggesting its strong antimicrobial effect. Firmicutes and Bacteroidetes dominated all groups, but the Firmicutes: Bacteroidetes ratio shifted, falling from 2.06 (control) to 1.60 (DHT). Specific taxa such as Prevotella_9, Bacteroides, and Desulfovibrionaceae increased in DHT rats, whereas beneficial groups, including Lachnospiraceae and Ruminococcaceae declined. Spirochaetaceae abundance dropped sharply across DHT-related groups, except in Diane-35–treated rats, where levels more closely resembled controls. Treatments diverged in microbiome effects. Diane-35 and probiotics both restored diversity and normalized taxa, bringing community composition closer to controls in principal coordinate analyses. Probiotics increased Lactobacillus abundance and improved cholesterol and progesterone profiles. By contrast, berberine dramatically suppressed microbial richness, reducing multiple commensals critical for short-chain-fatty-acid metabolism, and failed to improve metabolic or reproductive outcomes.

Key implications

This study reinforces the central role of gut microbiota in PCOS-related metabolic and reproductive dysfunction. DHT-induced microbial signatures—especially Prevotella enrichment and loss of SCFA-producing taxa—mirror those seen in human PCOS, supporting their potential diagnostic relevance. Therapeutic response patterns suggest that restoring microbial diversity, rather than broadly suppressing it, is essential for metabolic recovery. The findings encourage development of microbiome-informed interventions, including targeted probiotics and dietary strategies, and highlight microbiome signatures that may be incorporated into precision-medicine databases for PCOS management.

Citation

Zhang F, Ma T, Cui P, et al. Diversity of the gut microbiota in dihydrotestosterone-induced PCOS rats and the pharmacologic effects of Diane-35, probiotics, and berberine.Front Microbiol. 2019;10:175. doi:10.3389/fmicb.2019.00175