Markers of Sepsis Evolution: Regulators of Mitochondrial Function and Oral Microbiota

• Grant number: 25/02588-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Heraldo Possolo de Souza
• Grantee: Fernanda Ishihara Casagrande
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

IntroductionSepsis is characterized by a dysregulated immune response to infection, which can lead to multiple organ failure and death. The main factor associated with the morbidity and mortality of the condition is the uncontrolled inflammatory response. However, the metabolic changes that occur in circulating leukocytes are not yet fully understood, nor is it clear how the oral microbiota influences its evolution.Objectives Our objective is to determine the pattern of expression of the coactivators PGC-1alpha and PGC-1beta during the evolution of patients with sepsis and to define whether their dosage can be useful to identify the pattern of the immune response (whether there is a greater tendency towards hyperinflammation or immunosuppression) and/or as prognostic markers in septic patients. In parallel, we will describe the oral microbiota and determine whether its changes may be related to the development of sepsis.Methodology Patients diagnosed with sepsis will have blood samples collected upon admission and over the next three days. The expression of PGC-1s and circulating cytokines will be measured. The association of PGC-1 expression with the outcomes and the immune response pattern of septic patients will be made. Oral microbiota samples will be characterized on the same days.Relevance The great difficulty in clinical trials for the treatment of sepsis is to define at what stage the patient is. By concomitantly analyzing the expression of PGC-1 coactivators and their relationship with the mediators of the inflammatory response, we will be able to define whether the patient with sepsis is in a phase in which the pro-inflammatory response or immunosuppression predominates. At the same time, the characterization of the microbiota and its possible relationship with the prognosis may bring new therapeutic possibilities. These data may be extremely useful in future clinical trials and for a better understanding of the pathophysiology of sepsis.