Androgen-induced gut dysbiosis disrupts glucolipid metabolism and endocrinal functions in polycystic ovary syndrome Original paper

What was studied?

The study investigated how androgen-induced gut dysbiosis in PCOS contributes to metabolic and endocrine disruption, using a dehydroepiandrosterone (DHEA) rat model to determine whether microbiome alterations merely accompany or actively participate in the pathophysiology of polycystic ovary syndrome. The researchers examined metabolic outcomes, ovarian morphology, hormonal changes, microbial composition, microbial metabolite shifts, and hepatic gene-expression signatures. By manipulating the microbiome through antibiotics and fecal microbiota transplantation (FMT), the study probed causality—testing whether androgen-shaped microbial communities themselves can induce PCOS-like disturbances in pseudo–germ-free rats.

Who was studied?

Female Sprague Dawley rats (three weeks old) were assigned to DHEA-treated, antibiotic-treated, or control conditions, followed by FMT recipient groups that received either DHEA-derived microbiota or control microbiota. s40168-021-01046-5 This controlled design allowed the authors to isolate microbial contributions from androgenic effects while eliminating common environmental confounders found in human PCOS. Although extrapolation to human physiology requires caution, the model replicates hallmark PCOS phenotypes—hyperandrogenism, anovulation, cystic ovaries, and impaired glucose tolerance—providing functional insight relevant to clinical metabolic–reproductive interactions.

Most important findings

The study confirmed that DHEA reliably induced PCOS-like phenotypes and significant gut microbial shifts, including marked reductions in Turicibacter, Clostridium sensu stricto, Anaerofustis, and Erysipelotrichaceae taxa. Antibiotic depletion did not prevent DHEA-driven ovarian cyst formation or glucose intolerance, suggesting hyperandrogenism independently drives these features. However, antibiotics reduced testosterone and gonadotropins, highlighting microbially mediated androgen reabsorption and possible gut–pituitary signaling. Critically, FMT from DHEA-treated donors transferred metabolic and endocrine abnormalities to pseudo–germ-free rats. Recipients developed glucose intolerance, disrupted estrous cycles, cyst-like follicles, elevated testosterone, reduced FSH, increased NEFAs, and hepatic steatosis. Microbiome analyses showed donor-recipient replication of dysbiotic signatures, including depletion of Turicibacter and Clostridium sensu stricto, taxa negatively associated with testosterone, fasting glucose, GTT AUC, and other metabolic markers. Metabolomic profiling identified shifts in amino-acid metabolism—especially arginine, alanine, aspartate, and glutamate pathways—linking microbiome perturbation with altered glucolipid handling. Hepatic transcriptomics revealed 725 differentially expressed genes, with dysregulated cholesterol biosynthesis, LXR/RXR signaling, inflammatory pathways, and fatty-acid accumulation networks centered on TNF and PTGS2.

Key implications

These results clarify that while hyperandrogenism initiates PCOS-like pathology, androgen-induced gut dysbiosis amplifies metabolic and hormonal dysfunction. FMT experiments demonstrate that dysbiotic communities can independently trigger hyperandrogenism, impaired glucose homeostasis, ovarian abnormalities, and hepatic metabolic disturbances via gut–liver and gut–brain–ovary axes. Clinically, this indicates that microbiome signatures—particularly depletion of Turicibacter and Clostridium sensu stricto alongside arginine-pathway disruptions—may serve as biomarkers or therapeutic targets. The work strengthens the rationale for microbiome-modulating interventions as adjuncts to traditional PCOS care.

Citation

Han Q, Wang J, Li W, Chen ZJ, Du Y. Androgen-induced gut dysbiosis disrupts glucolipid metabolism and endocrinal functions in polycystic ovary syndrome. Microbiome. 2021;9:101. doi:10.1186/s40168-021-01046-5