The interplay between the gut microbiota and the immune system in the mechanism of type 1 diabetes

2013 ◽  
Vol 20 (4) ◽  
pp. 265-270 ◽  
Author(s):  
Danny Zipris
2019 ◽  
Vol 7 (3) ◽  
pp. 67 ◽  
Author(s):  
Sidharth Mishra ◽  
Shaohua Wang ◽  
Ravinder Nagpal ◽  
Brandi Miller ◽  
Ria Singh ◽  
...  

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.


Author(s):  
James A. Pearson ◽  
Andrew Agriantonis ◽  
F. Susan Wong ◽  
Li Wen

Author(s):  
Elena Aghajanova ◽  
Arthur Melkonyan ◽  
Nina Alchujyan ◽  
Bayburdyan Gayane ◽  
Margarita Hovhannisyan ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1290-P
Author(s):  
GIUSEPPE D’ANNUNZIO ◽  
ROBERTO BIASSONI ◽  
MARGHERITA SQUILLARIO ◽  
ELISABETTA UGOLOTTI ◽  
ANNALISA BARLA ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 959 ◽  
Author(s):  
Jefferson Antônio Leite ◽  
Gabriela Pessenda ◽  
Isabel C. Guerra-Gomes ◽  
Alynne Karen Mendonça de Santana ◽  
Camila André Pereira ◽  
...  

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2−/−) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2−/− mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2−/− mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing β cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Youjia Hu ◽  
Jian Peng ◽  
Fangyong Li ◽  
F. Susan Wong ◽  
Li Wen

Author(s):  
Matthew J. Simmonds ◽  
Stephen C. L. Gough

Dysfunction within the endocrine system can lead to a variety of diseases with autoimmune attack against individual components being some of the most common. Endocrine autoimmunity encompasses a spectrum of disorders including, e.g., common disorders such as type 1 diabetes, Graves’ disease, Hashimoto’s thyroiditis, and rarer disorders including Addison’s disease and the autoimmune polyendocrine syndromes type 1 (APS 1) and type 2 (APS 2) (see Table 1.6.1). Autoimmune attack within each of these diseases although aimed at different endocrine organs is caused by a breakdown in the immune system’s ability to distinguish between self and nonself antigens, leading to an immune response targeted at self tissues. Investigating the mechanisms behind this breakdown is vital to understand what has gone wrong and to determine the pathways against which therapeutics can be targeted. Before discussing how self-tolerance fails, we first have to understand how the immune system achieves self-tolerance.


2021 ◽  
Vol 7 ◽  
Author(s):  
Cinzia Myriam Calabrese ◽  
Alessia Valentini ◽  
Giorgio Calabrese

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease resulting from a complex interplay between genetic susceptibility and environmental factors. Regarding the latter, gut microbiota has a pivotal role in the pathogenesis of T1DM, by affecting intestinal permeability, molecular mimicry, and modulating innate and adaptive immune system, as described in several previous studies. The composition of the gut microbiota is largely influenced by diet. Some observational studies have shown that a low fiber intake is associated with the development of many inflammatory and immune-mediated diseases. In this context, the Mediterranean diet (MD), which is based on high consumption of cereals (preferably as whole grains), legumes, nuts, vegetables, fruits, olive oil, and fish, could play a protective role. Many of the characteristic components of MD have functional characteristics with positive effects on health and well-being. Eating habits are the main significant determinants of the microbial multiplicity of the intestine and the food components influence both microbial populations and their metabolic activities from the early stages of life. Moreover, food metabolites influence the immune response. The intestine is considered the primary site where food metabolites mediate their effects, through epithelial integrity or mucosal immunity. The compromised epithelial integrity allows the translocation of bacteria and/or the diffusion of their products, such as food antigens and lipopolysaccharides, from the intestinal lumen to the tissues, which could enhance the stimulation of immune cells, contributing to the pathogenesis of autoimmune diseases, such as T1DM. The intake of a high amount of fiber and therefore of prebiotics with MD allows the microbiota to have a good microbial balance. Moreover, as more dietary fibers are ingested, a higher amount of short-chain fatty acids (SCFAs) is produced by anaerobic gut microbiota, promoting gut homeostasis, to which also contribute tryptophan metabolites and omega-3-fatty acids. Furthermore, the higher intake of polyunsaturated fatty acids and omega-3-fatty-acids contribute to a better metabolic control. In this review we report the relationship between gut microbiota and T1DM and we explore the effects of Mediterranean diet on microbiota as a potential therapeutic strategy, aimed at preventing or delaying progression of T1DM and its complications.


Diabetologia ◽  
2019 ◽  
Vol 62 (7) ◽  
pp. 1291-1296 ◽  
Author(s):  
Vit Neuman ◽  
Ondrej Cinek ◽  
David P. Funda ◽  
Tomas Hudcovic ◽  
Jaroslav Golias ◽  
...  

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