Study of the effects of Lactococcus lactis expressing IL-6 on the intestinal Th17 response and prevention of obesity-induced experimental T2D

• Grant number: 22/09797-8
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): September 01, 2022
• Effective date (End): August 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Daniela Carlos Sartori
• Grantee: Thaílla Cristina Faria Pacheco
• Host 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

The etiology of DM2 is multifactorial interconnected to genetic, environmental, dietary, and metabolic factors. Recent studies demonstrate the relevance of Th17 lymphocytes in maintaining homeostasis between the mucosal immune system and the gut microbiota. Unlike the human genome, the genome of microorganisms present in the gut microbiota is subject to dynamic changes in the configuration of its components in order to adapt an individual component or a community in response to the type of food, some abnormality or use of antibiotics. Our group has already demonstrated that the expression of Th17 profile cytokines, such as IL-6, IL-17, and IL-22, is elevated early on, but a marked decrease occurs with DM2 progression that correlated with the process of intestinal dysbiosis, suggesting that these cytokines are important to minimize changes in microbiota composition and prevent DM2 worsening. Indeed, we found that the IL-17/IL-17R axis promotes intestinal neutrophil migration, controls intestinal dysbiosis, and attenuates inflammatory and metabolic changes associated with experimental DM2. Therefore, we believe that oral administration of recombinant L. lactis expressing IL-6 is able to restore the Th17 response profile in the gut and prevent the development of DM2. (AU)