Payen, DidierVelho, Tiago R.Moita, Luis2025-06-042025-06-042025Intensive Care Med. 2025 Jun 30342-4642http://hdl.handle.net/10400.5/101288© 2025 Springer-Verlag GmbH Germany, part of Springer NatureSepsis is a life-threatening organ dysfunction syndrome that results from a dysregulated host response to infection. Our evolving understanding of sepsis pathophysiology now incorporates insights from molecular advances, particularly in the felds of immunity and, more recently, metabolism. The concept that sepsis induces metabolic perturbations is not new. In fact, hyperlactatemia, metabolic acidosis, hypocholesterolaemia, or hyperglycaemia are essential indicators of sepsis severity [2]. Conversely, chronic metabolic conditions may contribute to the severity and type of host response to infection. However, the mechanistic contribution of specifc metabolic pathways to the quality and magnitude of immune responses in sepsis and other conditions that impose signifcant stress on the organism has only recently begun to be explored. In this perspective, we briefy highlight critical aspects of metabolic reprogramming (changes in metabolic pathways to meet diferent energy demands, support growth, adapt to environmental conditions, or survive stress) associated with sepsis. We then explore how knowledge of different metabolic signatures (distinct, measurable profles of metabolites or metabolic activities that characterize a particular biological state, disease, cell type, or response to treatment) may lead to innovative diagnostic and therapeutic approaches.engjournal article10.1007/s00134-025-07948-41432-1238