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Evaluation of oral and intestinal dysbiosis in type 1 diabetes patients and correlation with autoantibodies against pancreatic beta-cells

Grant number: 18/07838-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2018
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Gislane Lelis Vilela de Oliveira
Grantee:Larissa Ramos Ribeiro
Home Institution: Faculdade de Ciências da Saúde de Barretos Dr Paulo Prata (FACISB). Barretos , SP, Brazil

Abstract

In humans, more than 100 trillion microorganisms, mainly bacteria, colonize the oral-gastrointestinal tract, and the vast majority of these reside in the distal portion of the intestine and comprise the commensal microbiota. The most important contributions of the microbiota to the host include carbohydrate digestion and fermentation, vitamin production, development of mucosal associated lymphoid tissues, polarization of specific immune responses, and prevention of pathogen colonization. However, when this relationship between host and commensal is disrupted, the microbiota may cause or contribute to the development of chronic inflammatory and autoimmune diseases, such as type 1 diabetes (T1D). The aim of this work is to evaluate the oral and intestinal dysbiosis in T1D patients and correlate these findings with clinical data and serum concentrations of GAD65 autoantibodies against pancreatic beta cells. The study will include 40 participants, 20 healthy control subjects and 20 T1D patients, attended at the Department of Health from Barretos and in the Medical Specialist Ambulatories. The project was submitted to the research ethics committee from Barretos Cancer Hospital and all participants will sign the informed consent form and respond a questionnaire concerning lifestyle and dietary habits. Clinical data from patients, such as disease duration, fasting blood glycemia, glycated hemoglobin, GAD65 autoantibodies, and C-peptide will be recorded. Samples of the oral mucosa and feces will be collected for the characterization of the oral and intestinal microbiota by real-time PCR, and peripheral blood samples for anti-GAD65 quantification by ELISA. The results of the oral and intestinal microbiota from patients and controls will be analyzed by using Mann-Whitney test and the correlations of the microbiota results with autoantibodies and the clinical data will be evaluated by Spearmans' test. It is expected to find differences in the composition of the oral and intestinal microbiota in T1D patients, when compared with control subjects, and possible correlations with clinical data and autoantibodies. The relationship dysbiosis with autoimmune diseases is not fully understood and possibly, immunomodulatory probiotics and microbiota transplantation may help in the treatment of autoimmune diseases such as T1D.