Pathophysiology of Type 1 Diabetes and Gut Microbiota Role

Abstract

Type 1 diabetes (T1D) is a multifactorial autoimmune disease driven by T-cells against the insulin-producing islet β-cells, resulting in a marked loss of β-cell mass and function. Although a genetic predisposal increases susceptibility, the role of epigenetic and environmental factors seems to be much more significant. A dysbiotic gut microbial profile has been associated with T1D patients. Moreover, new evidence propose that perturbation in gut microbiota may influence the T1D onset and progression. One of the prominent features in clinically silent phase before the onset of T1D is the presence of a microbiota characterized by low numbers of commensals butyrate producers, thus negatively influencing the gut permeability. The loss of gut permeability leads to the translocation of microbes and microbial metabolites and could lead to the activation of immune cells. Moreover, microbiota-based therapies to slow down disease progression or reverse T1D have shown promising results. Starting from this evidence, the correction of dysbiosis in early life of genetically susceptible individuals could help in promoting immune tolerance and thus in reducing the autoantibodies production. This review summarizes the associations between gut microbiota and T1D for future therapeutic perspectives and other exciting areas of research.

Keywords: butyrate production; dysbiosis; gut microbiome; insulin resistance; intestine permeability; type 1 diabetes (T1D).

Figure 1

Increasing gut paracellular permeability in T1D patients. The alteration of tight junction (TJ) proteins leads to the increase of intestinal permeability, providing access to the lamina propria environment for foreign agents (e.g., bacteria and bacterial and diet products). The accumulation of these bacteria and molecules can trigger inflammation pathways, causing intestinal inflammation. The activated and expanded T-cells in the gut-associated lymphoid tissue (GALT) could travel via mesenteric and pancreatic lymph nodes to the pancreas and induce T1D. Created with BioRender.com.