Effect of Ketogenic Diet Versus Vegan Diet on Obesity-Induced Testicular Dysfunction and Mediating Role of Gut Microbiota

Abstract

Obesity is associated with metabolic dysregulation and impaired male reproductive capacity, where the gut microbiota affects male reproductive function through diverse mechanisms that warrant further elucidation. This study aims to evaluate the effects of ketogenic and vegan dietary interventions in attenuating obesity-associated testicular injury and to examine the extent to which specific gut microbiota profiles mediate their impact. Forty-nine male adult albino rats were assigned to seven groups: control group, obese group (HFD), obese group + modified microbiota, obese group + ketogenic diet, obese group + ketogenic diet + modified microbiota, obese group + vegan diet, and obese group + vegan diet + modified microbiota. Metabolic markers (glucose, insulin, leptin, and HOMA-IR), reproductive hormones (testosterone, FSH, and LH), and testicular gene expression (IL-6, eNOS, and androgen receptor) were analyzed over five months. Gut microbiota composition (qPCR) and testicular histology/immunohistochemistry were assessed. HFD-fed rats exhibited hyperglycemia, insulin resistance, hypogonadism, and testicular degeneration. Both diets improved metabolic and hormonal profiles, restored testicular architecture, and downregulated inflammatory genes. Microbiota modification additively enhanced these effects, increasing the abundance of Lactobacillus and Akkermansia while reducing inflammation. The vegan diet showed superior efficacy in improving metabolic parameters, modulating pituitary–gonadal hormones, and attenuating testicular structural and functional alterations. Our findings demonstrate that ketogenic and vegan diets alleviate obesity-induced testicular dysfunction and that microbiota modulation amplifies these benefits by regulating the gut–testicular axis. Integrating dietary and microbial interventions may provide a basis for a promising approach to managing obesity-related male infertility.