Effect of lactobacillus rhamnosus GG probiotic application on DNA methylation in testis tissue in streptozotocin induced diabetic rat model

Objective: Type 1 diabetes mellitus (T1DM) is an important disease due to its frequency and the various organ damages it causes, and the intestinal microbiota dysbiosis that increases in these individuals can affect epigenetic changes. Thus, here we aimed to investigate the possible effects of probiotic and parabiotic Lactobacillus Rhamnosus GG (LGG) application on the epigenetic changes through DNA methylation in the rat testis in the experimental T1DM model. Method: Control, sham, T1DM, LGG (probiotic), T1DM+LGG (probiotic therapeutic), LGG+T1DM (probiotic preventive), inactive LGG (ILGG-parabiotic), T1DM+ILGG (parabiotic therapeutic) and ILGG+T1DM (parabiotic preventive) experimental groups were created. By monitoring the body weights and blood glucose of the rats, testicular weight index, sperm motility, testosterone levels, testicular histopathology, apoptosis, global DNA methylation, immunolocalization and expression levels of DNA methyltransferases (DNMTs), and oxidative stress were evaluated. Results: While an increase was observed in blood glucose and oral glucose tolerance test (OGTT) measurements in diabetes group, there was a decrease in the diabetes treatment and preventive groups. Body and testis weights and sperm motility were lower in the diabetes group, and visceral fat was observed in addition to weight gain in the probiotic and parabiotic groups. It was determined that the expression of DNMT1, DNMT3A, DNMT3B and 5-methylcytosine decreased in the diabetes group with pathological testicular histology, but apoptosis was higher in diabetes and diabetes treatment groups. Testosterone levels were decreased and oxidative stress was increased in diabetes and diabetes treatment groups. Conclusion: The effect of LGG application on DNA methylation-related changes in the testis was described for the first time in the T1DM model. Our results provided important information regarding the effects of probiotics and parabiotics on diabetic men and may serve as a fundamental source for establishment of new hypotheses and recommendations. Key words: Diabetes mellitus, streptozotocin, Lactobacillus Rhamnosus GG, DNA methyltransferases, rat testis