Evaluation of the microbiome and intestinal permeability of mice with Sickle Cell Anemia and the relationship with inflammatory processes and the effects of treatment with hydroxyurea and probiotics

• Grant number: 23/01379-5
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: CNPq
• Principal Investigator: Nicola Amanda Conran Zorzetto
• Grantee: Nicola Amanda Conran Zorzetto
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/18886-1 - Pathophysiological mechanisms and treatment of red blood cell abnormalities, AP.TEM
• Associated scholarship(s): 23/10650-4 - Evaluation of the microbiome and intestinal permeability of mice with sickle cell anemia and the relationship with inflammatory processes and the effects of treatment with hydroxyurea and probiotics, BP.JD

Abstract

Sickle cell anemia (SCD) is an inherited disease characterized by alteration in red blood cells. Hemolytic processes due to the altered chemical-physical properties of the red blood cells induce vascular inflammation and eventually vaso-occlusive processes. Vaso-occlusive events result in the main clinical complications of SCD, as they obstruct the small blood vessels, causing tissue ischemic injury, pulmonary hypertension, episodes of intense pain and many other complications. Several evidences provide support for the fundamental role of activated neutrophils in vaso-occlusion, however, it is unknown which is the main source of neutrophil activation and inflammation in sickle cell anemia. The intestinal microbiota is responsible for regulating the number of senescent neutrophils, a subset of neutrophils that are overactivated, and that the reduction of these neutrophils in vivo has protected the sickled mice from vaso-occlusive crises. It is known that there is damage to the integrity of the intestinal barriers in sickle cell anemia and a chronic imbalance of the intestinal microbiota. However, very little is known about this relationship between the microbiota and the disease. We believe there are abnormalities in the integrity of intestinal barriers in sickle cell disease or a chronic imbalance of the intestinal microbiota, or both. Failure of the protective intestinal barrier results in recurrent translocation of intestinal bacteria that can stimulate inflammation without causing obvious infection. Therefore, the objective of this project is to investigate intestinal microbiota and possible alteration in intestinal permeability and to relate inflammatory processes in sickle cell disease and evaluate the effects of hydroxyurea and probiotics. (AU)