Biology subjects

Aasmul-Olsen, K.

Publications and source records attributed to Aasmul-Olsen, K..

3 recordsLinked to original sources

bioRxiv2026

Reduced parenteral glucose supply in preterm neonatal infection ameliorates the pulmonary damage

Preterm infants are acutely susceptible to neonatal sepsis, a syndrome characterized by systemic pro-inflammatory activity and life-threatening multi-organ dysfunction. However, the specific pulmonary pathological response to sepsis and the potential for metabolic interventions to mitigate lung injury remain poorly characterized. Herein, we evaluated the impact of varying parenteral glucose regimens on pulmonary outcomes during severe infection using a preterm piglet model. Genome-wide gene expression analysis was used to characterize lung transcriptome profiles. The relationships between gene expression and circulating biochemical and immune profiles were also investigated. Our findings demonstrate that significant pulmonary tissue damage is a hallmark of neonatal sepsis. A reduced-glucose regimen markedly attenuated pulmonary tissue damage while simultaneously alleviating systemic metabolic acidosis and hyperlactatemia. Mechanistically, lung transcriptome profiling revealed a profound activation of pathways associated with inflammatory signaling, programmed cell death, and the dysregulation of glucose, amino acid, and lipid metabolism. The low-glucose intervention effectively mitigated these widespread molecular and metabolic disturbances, suggesting a restorative effect on the pulmonary transcriptome landscape. To facilitate further mechanistic exploration and the identification of novel therapeutic targets, we developed the NeoSepPulmoExplorer (https://pharmaco-omicslab.shinyapps.io/NeoSepPulmoExplorer/), an interactive web-based toolkit for better mechanistic understanding and the identification of potential treatment targets. These results collectively underscore the importance of metabolic modulation in preserving organ function, though further translational studies are requisite to improve clinical outcomes in septic neonates.

immunology↗

bioRxiv2025

Harnessing systemic glycolysis-TCA cycle axis to boost the host defense against newborn infection

Energy metabolism and immune response are tightly connected, but it is poorly understood how this interplay is regulated in early life to dictate host defense strategy, infection risks and severity. This interplay is particularly relevant for preterm, low birthweight or otherwise immunocompromised infants, who have poor metabolic control and increased risks of sepsis. Here, we utilized data from the COPSAC2010 cohort with 700 mother-child pairs and showed that plasma levels of TCA cycle metabolites in early life were associated with reduced childhood risk of bacterial infection and an attenuated systemic inflammatory response. Next, we explored how two distinct nutritional strategies, which were aimed at boosting TCA cycle activity instead of glycolysis, impacted neonatal host defense against a serious bloodstream infection in preterm piglets. Substituting galactose for glucose in parenteral nutrition enhanced disease tolerance in early phase of infection and overall glucose homeostasis, improving survival. Further, combining glucose restriction with supplementation of glucogenic amino acids conferred glycemic control and completely prevented sepsis and abnormal changes of organ injury markers. Mechanistically, this intervention enhanced both disease resistance and tolerance, accompanied by metabolic rewiring from glycolysis towards gluconeogenesis, TCA cycle activity and oxidative phosphorylation. Thus, optimized nutritional strategies controlling the interplay of energy metabolism and host defense may be lifesaving for infected infants. In briefNewborns rely on two distinct defense strategies to combat infections in early life. Disease resistance, fueled by aerobic glycolysis, seeks to actively eliminate microorganisms while disease tolerance, fueled by mitochondrial oxidative phosphorylation, seeks to reduce collateral tissue damage during infections. We found that in healthy human newborns, increased plasma levels of metabolites from the tricarboxylic acid (TCA) cycle were associated with lower burden of childhood infections and reduced pro-inflammatory status. In a newborn animal model of bloodstream infection, nutritional strategies boosting systemic TCA cycle activity, while reducing aerobic glycolysis, enhanced both host disease tolerance and resistance, thereby improving survival. These findings could pave a path for improved infection management in human newborns. HighlightsO_LIIn healthy children, higher plasma levels of TCA cycle metabolites are associated with lower infection risks and systemic inflammation. C_LIO_LIIn a neonatal infection model, the supply of galactose, instead of glucose, improves host glucose homeostasis and TCA cycle activity, improving disease tolerance and survival. C_LIO_LIA combination of glucose restriction and glucogenic amino acid supply also improves TCA cycle activity, enhancing both disease resistance and tolerance and completely preventing lethal sepsis. C_LI

immunology↗

bioRxiv2021

Parenteral glucose supply and pharmacological glycolysis inhibition determine the clinical fate of infected preterm newborns

Preterm infants are susceptible to bloodstream infection that can lead to sepsis. High parenteral glucose supplement is commonly used to support their growth and energy expenditure, but may exceed endogenous regulation during infection, causing dysregulated immune response and clinical deterioration. Using a preterm piglet model of neonatal sepsis induced by Staphylococcus epidermidis infection, we demonstrate the delicate interplay between immunity and energy metabolism to regulate the host infection response. Circulating glucose levels, glycolysis and inflammatory response to infection are closely connected across the states of tolerance, resistance and immunoparalysis. Further, high parenteral glucose provision during infection induces hyperglycemia, elevated glycolysis and inflammation, leading to lactate acidosis and sepsis, whereas glucose restricted individuals are clinically unaffected with increased gluconeogenesis to maintain moderate hypoglycemia. Finally, pharmacological glycolysis inhibition during normoglycemia enhances bacterial clearance and dampens inflammation but fails to prevent sepsis. Our results uncover how blood glucose controls immune cell metabolism and function, in turn determining the clinical fate of infected preterm neonates. This also questions the current practice of parenteral glucose supply for infected preterm infants.

pathology↗