The role of obesity-related changes in the intestinal microbiota in skin graft rejection

• Grant number: 18/06152-0
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: August 27, 2018
• End date: February 26, 2019
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Fernanda Fernandes Terra
• Supervisor: Markus Geuking
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Calgary, Canada
• Associated to the scholarship: 17/03248-4 - The role of obesity-related intestinal microbiota in experimental allogeneic skin transplantation, BP.MS

Abstract

Given the epidemic rates of obesity worldwide, it is of great importance to study the consequent physiological and pathological effects to this change. Studies show that excess accumulation of body fat is associated with multiple increased comorbidities in recent decades. Furthermore, it is now known that in addition to modulating different systems related to energy metabolism, adipose tissue is also an immunological regulatory tissue. Moreover, the persistence of high rates of chronic rejection reveals the need for more studies to understand the underlying factors that restrict graft and patient survivals. In this context, a recent paper highlighted the intestinal microbiota as a key player in organ transplant rejection. Previous data obtained in our lab suggest that obesity has a damaging role in skin allografts. Furthermore, increasing evidence indicates that obesity is also directly linked to intestinal dysbiosis. Hence, we postulate that the microbiota is an important mechanism in the aggravation of skin allograft rejection. Therefore, our aim is to distinguish the role of intestinal dysbiosis promoted by obesity in graft rejection. This will be done by associating specific obesity-related enterotypes to transplant outcome using gnotobiotic, metagenomics, and immunophenotyping assays. This study should elucidate the role of obesity-related gut microbiota in graft rejection and potentially indicate specific enterotypes associated with disease complication. In consequence, this could clarify new biomarkers of disease progression and possibly indicate therapeutic measures to reduce allograft rejection.