Probiotics and Prebiotics for the Amelioration of Type 1 Diabetes: Present and Future Perspectives

Abstract

Type 1-diabetes (T1D) is an autoimmune disease characterized by immune-mediated destruction of pancreatic beta (β)-cells. Genetic and environmental interactions play an important role in immune system malfunction by priming an aggressive adaptive immune response against β-cells. The microbes inhabiting the human intestine closely interact with the enteric mucosal immune system. Gut microbiota colonization and immune system maturation occur in parallel during early years of life; hence, perturbations in the gut microbiota can impair the functions of immune cells and vice-versa. Abnormal gut microbiota perturbations (dysbiosis) are often detected in T1D subjects, particularly those diagnosed as multiple-autoantibody-positive as a result of an aggressive and adverse immunoresponse. The pathogenesis of T1D involves activation of self-reactive T-cells, resulting in the destruction of β-cells by CD8⁺ T-lymphocytes. It is also becoming clear that gut microbes interact closely with T-cells. The amelioration of gut dysbiosis using specific probiotics and prebiotics has been found to be associated with decline in the autoimmune response (with diminished inflammation) and gut integrity (through increased expression of tight-junction proteins in the intestinal epithelium). This review discusses the potential interactions between gut microbiota and immune mechanisms that are involved in the progression of T1D and contemplates the potential effects and prospects of gut microbiota modulators, including probiotic and prebiotic interventions, in the amelioration of T1D pathology, in both human and animal models.

Keywords: autoimmune; diabetes; diet; fiber; gut; microbiota; microflora; prebiotics; probiotics.

Figure 1

Factors influencing the susceptibility of T1D. Abbreviations: HLA: Human leukocyte antigen; T1D: Type 1-Diabetes.

Figure 2

Mechanisms involved in the pathogenesis of T1D. APC: Antigen presenting cell; DCs: Dendritic cells; GALT: Gut Associated Lymphoid Tissue; MHC: Major Histocompatibility Complex; CD 8⁺ T-Cell: Cytotoxic T lymphocytes; CD4⁺ T-Cells: Helper T lymphocytes; T1D: Type-1-Diabetes.

Figure 3

Schematic representations of mechanisms of actions through which specific probiotic strains might help in the amelioration of T1D. Akt: protein kinase B; DCs: Dendritic cells; GLP-1: Glucagon-like peptide-1; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B-cells; IκBα: I kappa B kinase; IkkB: IκB kinase beta; IgA: Immunoglobulin A; Treg: T regulatory cell; Th2: T-helper cell 2.

Figure 4

Purported mechanism(s) of action through which prebiotics could manipulate gut microbiota as well as immune cells of T1D pathology. Akt: protein kinase B; DC: dendritic cell; GLP-1: glucagon-like peptide-1; GLP-2: glucagon-like peptide-2; IkkB: IκB kinase beta; IκBα: I kappa B kinase; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B-cells; SCFAs: short chain fatty acids; Th2: T-helper cell 2; Treg: T regulatory cell.