THE ROLE OF THE GUT-SKIN AXIS IN THE REJECTION OF ALLOGENIC TRANSPLANTS IN A MURINE EXPERIMENTAL MODEL

• Grant number: 22/13419-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2022
• End date: October 01, 2025
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Heitor Pereira Vale da Costa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM
• Associated scholarship(s): 23/13842-1 - The role of tributyrin in Treg Differentiation and Skin Graft Survival, BE.EP.IC

Abstract

The microbiota, which corresponds to the set of microorganisms that inhabit certain niches of the organism, has been widely resear due to its diverse metabolic, structural and protective functions. A new role of interest played by the microbiota is its role in modulating the immune response to transplants, which is a promising area, given its impact on novel studies in preventing rejection of transplanted organs. In addition, the role played by the microbiota may have a systemic effect since changes in the microbiota of a certain part of the organism may have repercussions on other tissues. The two most studied organs regarding the microbiota are the gut and the skin, sites of high antigenic and microbial density. The relationship amongst the gut and skin microbiota, which can even lead to clinical repercussions, is known as the 'gut-skin axis'. The intestinal microbiota is capable of generating short-chain fatty acids (SCFA), metabolites produced through fiber fermentation, capable of directly modulating the immune response. The systemic effects of these metabolites on other extraintestinal tissues suggest that they also participate in the gut-skin axis. Thus, the gut-skin axis is very relevant to the role of the microbiota in skin graft rejection, and the immune response associated is not only influenced by the local microbiota but also by the intestinal microbiota. In fact, studies in mice show that changes in the composition of the gut microbiota through use of broad-spectrum antibiotics affect the rejection response to an allogeneic skin transplant. However, there are still some questions regarding the influence of dietary changes on the immune response to the graft. This project seeks to evaluate the interaction between intestinal and skin microbiota, through short-chain fatty acids, and to verify the magnitude of transplant rejection in animals with high-fiber diets or receive SCFA by parenteral route.