GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE319nnn/GSE319552/primaryOK200TranscriptomicsSus scrofaExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319552GEOGSEfalseKetone and glycolytic metabolism are key modulators of inflammation during neonatal sepsisNeonatal sepsis is a life-threatening condition in preterm infants, primarily due to a dysregulated immunometabolic response to infection. Sepsis and infection mortality are associated with excessive glycolysis-induced inflammation, impaired mitochondrial oxidative phosphorylation (OXPHOS) and loss of disease tolerance. Reduced glucose intake can reverse these dysregulations, but it is unclear how the mechanistic control of glycolysis-OXPHOS balance drives defense strategies and infection outcomes. Here, in a preterm piglet model of neonatal sepsis, glycolysis inhibition with 2-deoxyglucose (2-DG) completely prevents acute infection mortality, reduces systemic inflammation and markers of liver injury, accompanied by enhanced mitochondrial metabolism and disease tolerance. Strikingly, this protection by 2-DG is conferred despite elevated blood glucose levels and higher bacterial burdens than the infected controls. Alternatively, partial replacement of glucose intake with the ketone beta-hydroxybutyrate (BHB) abolishes sepsis-related mortality via improving disease tolerance and clinical parameters.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 scrofa