THE ROLE OF NUTRITIONAL STATUS AS AN EPIGENETIC MODULATOR IN TYPE 1 DIABETES IN PEDIATRIC POPULATION OF QATAR

Abstract

Type 1 Diabetes Mellites (T1DM), is an autoimmune disorder caused by the destruction of pancreatic b?-cells and is considered to be among the most prevalent chronic conditions in Qatar. This study aimed to identify the differential methylation status in pediatric T1DM subjects from the population of Qatar. Also, to explore the correlation between nutritional factors and gut microbial composition and its metabolites with DNA methylation. In this study, we recruited a total of 72 subjects that were divided into four groups (T1DM = 35, T1DM-OB = 9, obese = 16, and healthy = 12). Different measurements were collected from the study subjects, which are 24- hour dietary recall, physical and biochemical data along with blood samples. Nutritionist Pro software (Axxya Inc) was used for the determination of the micro-and macro-nutrients intake for each study subject. CpG DNA methylation level was measured by Illumina Infinium EPIC Array and analysis of the generated data was conducted through the use of GenomeStudio. Differential methylated genes were identified using ParteK Genomic Suite software and then analyzed using Ingenuity Pathway Analysis (IPA) for functional pathway analysis. Network analysis was performed to identify the potential correlation of DNA methylation with dietary factors, gut microbiome, and SCFAs was explored in pediatric T1DM subjects. Based on the dietary analysis, the T1DM group was found to have a lower intake of SFA and vitamin K compared to healthy and obese groups. DNA methylation analysis showed the up-regulation of the SAPCD1 gene in T1DM patients and the down-regulation of the DNAJC7 gene in T1DM-OB subjects, in comparison to healthy and obese subjects. The significant canonical pathways identified to be downregulated in T1DM-OB are aldosterone signaling in epithelial cells, xenobiotic metabolism CAR/PXR pathways and NRF2 mediated oxidative stress response. Furthermore, T1DM patients were found to have low gut microbial abundance compared to healthy controls . Our network analysis, showed a positive correlation of DNA methylation level with folate and thiamin intake in healthy controls. We have also identified a positive correlation between the microbial genus Lachnospira with DNA methylation in obese subjects. In this study, we were able to shed the light on the possible interaction between dietary components, DNA methylation and gut microbiome in T1DM development in children. However, more studies are needed for further exploration of such association.