Probiotic and paraprobiotic intervention modulates testicular DNA methylation in streptozotocin-induced diabetic rats: insights into the role of Lactobacillus rhamnosus GG.

Type 1 diabetes mellitus (T1DM) is a significant metabolic disorder associated with organ damage, including male reproductive dysfunction. Dysbiosis of gut microbiota in T1DM patients may influence epigenetic mechanisms such as DNA methylation. This study aimed to investigate the potential effects of probiotic and paraprobiotic Lactobacillus rhamnosus GG (LGG) administration on DNA methylation-associated epigenetic changes in the testis of rats with streptozotosin (STZ)-induced experimental T1DM. Experimental groups were designed as follows: control, sham, T1DM, LGG (probiotic), T1DM+LGG (therapeutic probiotic), LGG+T1DM (preventive probiotic), inactivated LGG (ILGG-paraprobiotic), T1DM+ILGG (therapeutic paraprobiotic), and ILGG+T1DM (preventive paraprobiotic). Body and testis weights, epididymal sperm motility, serum testosterone levels, testicular histopathology, apoptosis, oxidative stress, global DNA methylation, and expression/localization of DNA methyltransferases (DNMT1, DNMT3A, DNMT3B) and 5-methylcytosine were evaluated. In the diabetic group, blood glucose and OGTT values were elevated, while therapeutic and protective groups showed reductions. Body and testicular weights and sperm motility decreased in T1DM but were improved in probiotic and paraprobiotic groups. Diabetes impaired testicular histology and reduced DNMTs and 5-mC expression, while apoptosis increased in diabetic and therapeutic groups. Testosterone levels decreased and oxidative stress increased in T1DM. This study is the first to describe the effect of LGG on testicular DNA methylation in experimental T1DM. Our findings highlight the potential of probiotic and paraprobiotic LGG as dietary supplements to alleviate diabetes-induced testicular damage.