Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms

Abstract

Type 1 diabetes (T1D) is a multifactorial autoimmune disease mediated by genetic, epigenetic, and environmental factors. In recent years, the emergence of high-throughput sequencing has allowed us to investigate the role of gut microbiota in the development of T1D. Significant changes in the composition of gut microbiome, also termed dysbiosis, have been found in subjects with clinical or preclinical T1D. However, whether the dysbiosis is a cause or an effect of the disease remains unclear. Currently, increasing evidence has supported a causal link between intestine microflora and T1D development. The current review will focus on recent research regarding the associations between intestine microbiome and T1D progression with an intention to evaluate the causality. We will also discuss the possible mechanisms by which imbalanced gut microbiota leads to the development of T1D.

Keywords: causality; dysbiosis; gut microbiota; mechanisms; type 1 diabetes.

Figure 1

The possible mechanisms whereby gut microbiota influences the type 1 diabetes (T1D) development. The gut microbiota plays a decisive role in the maturation of immune system in early life. Gut dysbiosis will lead to the dysregulation of immune response including both innate and adaptive immune system, eventually resulting in beta cell destruction and the onset of T1D in genetically susceptible individuals. On the other hand, the gut dysbiosis can lead to the disassembly of tight junctions, thereby disrupting the integrity of intestinal barrier. The enhanced intestinal permeability will allow unregulated passage of microbial antigens such as microbiota and their products. These antigens escaping from intestinal tract could be untaken by antigen-presenting cells (APCs), which can process and present antigens to autoreactive T cells and subsequently promote the destruction of pancreatic beta cells in genetically predisposed individuals.