Lactobacillus rhamnosus supplementation ameliorates high fat diet-induced epigenetic alterations and prevents its intergenerational inheritance

Abstract

AimMultiple studies have reported the epigenetic inheritance of parental metabolic traits could increase the risk of developing metabolic disorders in offsprings. L. rhamnosus (LR) as a probiotic has been found to be beneficial in metabolic diseases. Current study was aimed to explore the effects of LR on high-fat diet induced epigenetic alterations and their transgenerational inheritance. MethodsPrediabetes was induced in SD rats by feeding HFD for 16 weeks, followed by LR supplementation for 12 weeks, and were put on mating. Biochemical parameters and histopathological changes were assessed in both F0 and F1 generations. Epigenetic alterations were assessed in liver and paternal sperms using Western blotting and qRT-PCR. ResultsHFD fed animals displayed alterations in metabolic indices and histopathological features in liver and pancreas which were more prominent in males. These alterations were also inherited to male offsprings. LR supplementation reversed these metabolic and histological alterations in F0 animals and also prevented their intergenerational inheritance. At molecular level, LR supplementation reversed the alterations in miRNA (miR-155-5p, miR-26a-5p, miR-21-5p, miR-200c-3p, and miR-let7a-5p) expression, DNMT1 expression and the histone modification landscape within liver involving H3K36me2, H3K79me2 and H3K27me3 histone marks. Furthermore, expression of the mentioned miRNAs was found to be altered in the sperms of F0 males which was partly restored by LR supplementation. SignificancePresent study indicates that parental HFD-induced prediabetes can transfer the altered epigenetic memory to offspring. Parental LR supplementation can erase this memory and protect the offspring from intergenerational transfer of pathological traits.