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Effect of administration of Bifidobacterium longum, with or without inulin prebiotic, on the production of AGCC and on the immunoregulation of DM1 in an experimental model

Grant number: 19/13858-0
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2019
Effective date (End): January 31, 2021
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Daniela Carlos Sartori
Grantee:Jhefferson Barbosa Guimarães
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:18/14815-0 - Evaluation of the intestinal microbioma profile and of the therapeutic potential of intervention strategies in the immunopathogeny of type 1 and 2 Diabetes, AP.JP2

Abstract

Type 1 diabetes mellitus (DM1) is an autoimmune disease characterized by the progressive loss of ²-pancreatic antigen self-tolerance, which leads to the selective destruction of these cells by activated autoreactive lymphocytes as a result of inflammation in pancreatic islets (insulitis). DM1 is one of the most common chronic diseases in childhood and has also been increasingly diagnosed in adults. Although the exact etiology of the disease remains unknown, it is already clear that its development occurs in individuals susceptible genetically, affected by certain environmental factors, which act as triggers. Several studies have demonstrated the relationship between intestinal homeostasis breakdown and various diseases such as obesity, asthma, allergy, inflammatory bowel diseases, rheumatoid arthritis and DM 1 and 2. This demonstrates the local and systemic influence of the intestinal microenvironment in human physiology. In DM1, there are reports in the literature that show the occurrence of intestinal dysbiosis with decrease of certain bacterial species, such as Bifidobacterium adolescents and Bifidobacterium pseudocatenulatum. In addition, other studies have shown that Bifidobacterium spp. can exert their anti-diabetic and immunomodulatory effects through several mechanisms, such as modulation of antimicrobial peptides, lipid metabolism and short chain fatty acid production (SCFAs). The effect of SCFAs is related to the maintenance of intestinal homeostasis and immunoregulation, functioning as an energy source for epithelial cells, increasing intestinal barrier integrity, inhibiting NF-kB expression and TNF-± production in macrophages and cells dendritic cells and increasing the generation and function of regulatory T lymphocytes (Tregs). Thus, we will evaluate whether prebiotic inulin supplementation, which has a bifidogenic effect, or the probiotic Bifidobacterium longum, contributes to the protection of DM 1, using two experimental models (induced by streptozotocin (STZ) and genetically determined in NOD mice). In addition, we intend to identify if the beneficial effect is mediated by the intestinal microbiota through the production of SCFAs, as well as to determine the immunological mechanisms of regulation triggered in the intestinal mucosa and in the pancreatic tissue, in order to propose a potential therapeutic target of prevention or treatment. The differential of this approach is the fact that it is a reestablishment of the local and systemic homeostasis of the health of the body instead of counteracting the symptoms of the disease. (AU)