The interplay between glucogenic amino acids and carbohydrate metabolisms in regulating the clinical fate of preterm infected newborns

Early-life sepsis remains one of the leading causes of global morbidity and mortality in the neonatal population, especially preterm infants. Using a preterm piglet model of neonatal sepsis to test nutritional interventions as a therapeutic approach, we demonstrated that high parenteral glucose induced hyperglycemia with severe sepsis, whereas glucose restriction offered protection against infection but led to severe hypoglycemia. Building on this, our current study aims to maintain normoglycemia through galactose metabolism or gluconeogenesis and reduce sepsis risks by substituting glucose with galactose, or supplementing glucogenic amino acids (GAAs). Overall design: Three experiments were designed with similar setups, 74 cesarean-delivered preterm pigs (90% gestation) were challenged with Staphylococcus epidermidis (SE) or saline control (CON) and nourished with different compositions of PN for 15~20 h. Clinical symptoms, physiological, metabolic, and immunological responses to infection were evaluated across the study. In study 1, animals were randomly allocated to sGAL group: standard galactose (10%, 14.4g/kg/d) or sGLU group: standard glucose (10%, 14.4g/kg/d). In study 2, animals were randomly allocated to rGLU-GAAs group: restricted glucose (1.4%, 2g/kg/d) plus four GAAs (glutamine/valine/aspartate/asparagine, 1g/kg/d each) or sGLU group: standard glucose (10%, 14.4g/kg/d). In study 3, animals were randomly allocated to rGLU-GAAs group: restricted glucose (1.4%, 2g/kg/d) plus four GAAs (glutamine/valine/aspartate/asparagine, 1g/kg/d each) or rGLU group: restricted glucose alone (1.4%, 2g/kg/d). Liver samples at euthanasia were collected and liver RNA was extracted for RNAseq.