Effect of antibiotic-induced gut dysbiosis on modulation of neutrophils

• Grant number: 23/00221-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: July 01, 2023
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Bruna Toledo Nunes Pereira
• Supervisor: Irina Udalova
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Oxford, England
• Associated to the scholarship: 20/00465-7 - Relevance of SCFAs-induced histone acylation in neutrophils production of inflammatory mediators, BP.DD

Abstract

Neutrophils constitute the most abundant population of circulating leukocyte cells and are the first cells to migrate and accumulate in tissues during inflammation and microbial infections. In addition to their ability to phagocyte and eliminate infectious agents through their antimicrobial mechanisms, they also constitute a relevant source of cytokines and eicosanoids that regulate the activation and recruitment of other cells. Microbiota signals, including the short-chain fatty acids (SCFAs), regulate the recruitment, phagocytic capacity and production of cytokines by these cells. However, there is scarce information on how modifications of gut microbiota composition and functions impact on neutrophils. In this study, we will evaluate the effect of antibiotics on SCFAs production and their impact and relevance on epigenetic modulation and effector responses of neutrophils. Mice will undergo 3 days of treatment with the antibiotics neomycin, vancomycin and metronidazole. Blood and stool samples will be collected before and after antibiotic treatment. Antibiotic-induced gut dysbiosis model will be validated by 16S rRNA sequencing. Circulating neutrophils will be isolated and analysed for their chromatin accessibility, gene expression profile, and effector function. We believe that this study will bring new perspectives on the mechanisms and contribution of the gut microbiota on neutrophil modulation and effector response. (AU)