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.

Untargeted metabolomics analysis reveals spatial metabolic heterogeneity in different intestinal segments of type 1 diabetic mice

“…The gut microbiota has been reported to be closely associated with the onset and progression of T1D. 63,64 Moreover, host metabolism can be regulated by the intestinal flora, for example, the gut microbiota of T1D patients exhibited a specific metabolic characteristic including lower butyrate production and bile acid metabolism and higher lipopolysaccharide biosynthesis and thereby promoted the development of T1D. 65 Herein, amino acid metabolism and fatty acid metabolism were detected as the mainly disrupted metabolic pathways in the gut of T1D mice, and these two metabolic pathways have been revealed to be mediated by the gut microbiota.…”

Unveiling the Link: A Comprehensive Narrative Review of the Relationship Between Type 1 Diabetes Mellitus and Celiac Disease

“…In addition, the death of the islets is held down by processes, such as changes to the surface antigens [14,15]. A decline in cell volume and the malfunctioning of the cells contribute to the start of hyperglycemia [16].…”

“…Recent research describes the role of cell-associated immunogenicity in addition to the autoimmune component. This role could be linked to genetic or environmental variables [16].…”

Exploring the severity and early onset of familial type 1 diabetes in Romania: genetic and microbiota insights

“…A negative correlation was observed among butyrate-producers, intestinal permeability, and the risk of T1DM development. Even during the late phase of prediabetes, a reduced number of butyrate producers were identified, indicating the microbiota's influence on beta-cell autoimmunity and disease progression [ 9 - 11 ].…”