Carbohydrate metabolism, i.e. whether oxidative phosphorylation or glycolysis predominates, impacts on the inflammatory phenotype of macrophages. Enhanced glycolysis characterizes inflammatory macrophages, and regulatory macrophages pre-dominantly use fatty acid oxidation. Oxygen tension impacts on metabolism. Normoxia promotes oxidative phosphorylation (Krebs cycle), and hypoxia promotes glycolysis for ATP production. Furthermore, bacterial metabolites such as butyrate drive the Krebs cycle, whereas lipopolysaccharide (LPS) promotes glycolysis. At the beginning of life, several cues potentially affect imunmetabolism,
a) the transition from fetal hypoxia to a postnatal normoxia,
b) bacterial colonization of the in utero largely sterile intestinal mucosa, and
c) the nutritional provision of fatty acids.
This project studies the impact of neonatal immunometabolic changes on the antimicrobial resistance against pathobionts, which colonize the mucocutaneous surfaces at the beginning of life.