Effect of an episode of acute gastrointestinal infection on the pathogenesis and progression of type 1 diabetes mellitus

Author(s)

Leticia Gama e Silva Calixtro

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2023-06-29

Examining board members

Denise Morais da Fonseca; Cristina Ribeiro de Barros Cardoso; Ana Paula Lepique; Tatiani Uceli Maioli

• Advisor: Denise Morais da Fonseca

Abstract

The gastrointestinal tract harbors a wide variety of commensal microorganisms that actively participate in several physiological and immunological processes of the host, including the modulation of the metabolism. In addition to the microbiota, the intestinal mucosa is constantly exposed to several environmental antigens deriving from the diet, commensal microorganisms and pathogens, so a highly specialized immune system is needed, which allows the host to tolerate innocuous antigens, but also to elaborate responses against potential pathogens. This balance between the immune system and the environment, which also supports the composition of the microbiota, is essential for maintaining homeostasis in the intestinal tissue, and disturbances in this balance are commonly observed in patients with autoimmune diseases, such as type 1 diabetes mellitus (T1D). Thus, the objective of this project was to investigate the impact of an episode of acute infection by Yersinia pseudotuberculosis on the development of DM1, with the hypothesis that it would negatively impact the pathogenesis and progression of the disease. For this, an animal model of T1D induced by multiple low-doses of streptozotocin (MLD-STZ) and non-obese-diabetic (NOD) mice, which spontaneously develop diabetes, were used. In the MLD-STZ model, the infection did not have any significant impact on the pathogenesis and progression of DM1. However, in the NOD model, previously infected mice had a lower incidence of DM1, reduced pancreatic insulitis score, and improvements in metabolic control. Furthermore, only the transplantation of fecal microbiota from previously infected C57BL/6 mice to NOD mice was able to reproduce these observed protective effects, indicating that alterations in the microbiota caused by the infection are involved in protection against DM1. (AU)

• FAPESP's process: 20/16648-3 - Effect of an episode of acute gastrointestinal infection on pathogenesis and progression of type 1 diabetes mellitus
• Grantee: Letícia Gama e Silva Calixtro
• Support Opportunities: Scholarships in Brazil - Master