The Interplay between Immune System and Microbiota in Diabetes

Abstract

Diabetes is not a single and homogeneous disease, but a cluster of metabolic diseases characterized by the common feature of hyperglycemia. The pathogenesis of type 1 diabetes (T1D) and type 2 diabetes (T2D) (and all other intermediate forms of diabetes) involves the immune system, in terms of inflammation and autoimmunity. The past decades have seen an increase in all types of diabetes, accompanied by changes in eating habits and consequently a structural evolution of gut microbiota. It is likely that all these events could be related and that gut microbiota alterations might be involved in the immunomodulation of diabetes. Thus, gut microbiota seems to have a direct, even causative role in mediating connections between the environment, food intake, and chronic disease. As many conditions that increase the risk of diabetes modulate gut microbiota composition, it is likely that immune-mediated reactions, induced by alterations in the composition of the microbiota, can act as facilitators for the onset of diabetes in predisposed subjects. In this review, we summarize recent evidence in the field of gut microbiota and the role of the latter in modulating the immune reactions involved in the pathogenesis of diabetes.

Role of Gut Microbiota on Onset and Progression of Microvascular Complications of Type 2 Diabetes (T2DM)

“…Among the mechanism involved in GM dysbiosis and T2DM is an imbalance in the immune system. GM and its metabolites maintain the balance and function of intestinal T helper 17/regulatory T cell (Th17/Treg) and gut-associated lymphoid tissues (GALT) such as Peyer's patches, mesenteric lymph nodes and isolated lymphoid follicles [73]. GM is essential in helping the immune system to differentiate self from non-self (invaders), and it promotes innate hematolymphoid cells (ILC1, -2 and -3), natural killer (NK) cells, cytotoxic and noncytotoxic cells and helper lymphoid cells synthesis.…”

“…Intestinal Th17 cells are able to modulate glucose homeostasis, adipogenesis, control immune tolerance and participate in IR development via a reduction of intestinal RORγt+ and IL-17-producing CD4+ [73,75]. Additionally, various studies demonstrated how GM and its products can regulate the harmony of intestinal Th1/Th2 cells functions.…”

The role of autoimmunity in the pathophysiology of type 2 diabetes: Looking at the other side of the moon

“…In particular, structural and functional changes of the intestinal microbiota are present in diabetes, obesity, and metabolic syndrome, and these alterations are believed to activate innate and adaptive immune responses that finally result in the development of overt diabetes. 55 Obesity-associated dysbiosis relates to increased gut permeability, resulting in leakage of microbial products and oral antigens across the gut epithelium. The latter, together with excessive lipid accumulation and dead adipocytes, represent potential sources of antigens that trigger the activation of B-and T-cells, a process occurring either in the lymph nodes or in the adipose tissue.…”

Endocrine Disrupting Chemicals and Type 1 Diabetes

“…Gut microbiota has an important role in the regulation of metabolism. Although causality between dysbiosis and T1D has not been proved yet in humans because long-term placebo-controlled trials are missing, literature data suggested a role of the gut microbiota in the disease development [27,28,104,105] and a recent published review concluded that the altered abundance of specific members or reduced diversity of gut microbiota was associated with the progression of T1D [106].…”