The Interplay Between Diet and the Epigenome in the Pathogenesis of Type-1 Diabetes

Abstract

The autoimmune disease, Type 1 Diabetes Mellitus (T1DM), results in the destruction of pancreatic β-cells, and the International Diabetes Federation reports that its incidence is increasing worldwide. T1DM is a complex disease due to the interaction between genetic and environmental factors. Certain dietary patterns and nutrients are known to cause epigenetic modifications in physiological conditions and diseases. However, the interplay between diet and epigenetics is not yet well-understood in the context of T1DM. Several studies have described epigenetic mechanisms involved in the autoimmune reactions that destroy the β-cells, but few explored diet components as potential triggers for epigenetic modifications. Clarifying the link between diet and epigenome can provide new insights into the pathogenesis of T1DM, potentially leading to new diagnostic and therapeutic approaches. In this mini review, we shed light on the influence of the diet-epigenome axis on the pathophysiology of T1DM.

Keywords: DNA methylation; diet; epigenetics; histone modifications; micro-RNA; type 1 diabetes.

Figure 1

The figure summarizes the potential diet—epigenetic axis in T1DM development. The intake of unhealthy diet may lead to T1DM development through epigenetic modifications (DNA methylation, miRNA, and histone modifications). Diet nutrients can contribute to the hypermethylation and subsequent downregulation of IRS-2 leading to insulin deficiency. In addition, diet can contribute to the up- and down-regulation of certain miRNAs activates NF-kB pathway and the activation of the inflammatory response. The role of histone modification in T1DM is explicated mainly through elevating the expression of H3K9Ac and H4 in the promoter region of Foxp3. Finally, unhealthy diet affects the gut microbiota and its metabolites, such as SCFA. The failure of SCFA binding to the free fatty acid receptors 2/3 (FFAR2 and FFAR3) due to its absence or reduction, leads to the activation of histone deacetylase (HDAC1, HDAC3) and the inflammatory cascade that contribute to β-cell depletion and T1DM development (Created using Biorender.com).