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Journal of Radiation Research and Applied Sciences
By Qing Li, Wanying Zhang and Wenyan Wang.
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder. Women with PCOS are frequently overweight or obese. This study aimed to examine gut microbiota-related and metabolic changes associated with ketogenic diet intervention in PCOS with obesity.
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A PCOS model with obesity was established in female C57BL/6 mice by subcutaneous implantation of a sustained-release dihydrotestosterone (DHT) pellet. The intervention group received a 3-week ketogenic diet after a 3-week DHT establishment period while DHT exposure continued. Ovarian morphology and healthy antral follicle counts were assessed histologically, while gut microbiota and serum metabolites were profiled using 16 S rRNA sequencing and LC-MS. The microbiota-dependent contribution was further examined using fecal microbiota transplantation in pseudo-sterile mice.
DHT stimulation increased body weight and testosterone, decreased follicle-stimulating hormone, and induced polycystic-like ovarian changes. The ketogenic diet significantly alleviated these obesity and PCOS-like symptoms. Gut microbiota composition was significantly altered by DHT and/or ketogenic diet, with significant separation among groups in β-diversity. Mesomycoplasma , Eggerthella , Enterorhabdus , and Berryella were identified as DHT-associated discriminant genera; Faecalibaculum and Bifidobacterium were associated with the diet-response group. Positive-ion MS1 profiling revealed 364 increased and 992 decreased metabolic features in the DHT group versus control, with 557 increased and 785 decreased features in the DHT + diet group versus DHT. Among 325 MS/MS-identified metabolites, 20 were differential in the three-group comparison. Differential metabolites were enriched in arginine/proline metabolism and lysine degradation pathways. Fecal microbiota transplantation transferred part of the endocrine and ovarian phenotype to pseudo-sterile recipients, supporting a microbiota-dependent component of the ketogenic diet response.
The ketogenic diet was associated with improvements in obesity- and PCOS-like phenotypes while modulating gut microbiota composition and host metabolic profiles, supporting a contributory rather than exclusive role of the microbiota.
Published in Journal of Radiation Research and Applied Sciences. The abstract is shown as published and remains the work of its authors; read the full article at the source.
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