Oxidative phosphorylation is a key feature of neonatal monocyte immunometabolism promoting myeloid differentiation after birth.

Summary

Using multi-omic and functional analyses of healthy human monocytes across ages, the study shows neonatal monocytes rely on oxidative phosphorylation to support myeloid differentiation, with a developmental shift toward glycolysis that heightens inflammatory responsiveness. Microbial stimulation can induce adult-like metabolism in neonatal cells, while adult ketogenic diet does not recreate neonatal immunometabolism. Premature glycolytic activation may increase neonatal sepsis risk by impairing differentiation and promoting hyperinflammation.

Key Findings

• Neonatal monocytes exhibit enhanced oxidative phosphorylation supporting myeloid differentiation.
• Developmental shift toward glycolysis in early childhood increases inflammatory responsiveness.
• Microbial stimulation induces adult-like metabolism in neonatal monocytes; adult ketogenic diet does not recreate neonatal immunometabolism.
• Premature glycolytic activation may increase neonatal sepsis risk by impairing differentiation and promoting hyperinflammation.

Clinical Implications

While not yet practice-changing, the findings suggest caution against interventions that prematurely enhance glycolysis in neonates and motivate biomarker development for metabolic state to stratify sepsis risk in early life.

Limitations

• Primarily ex vivo mechanistic evidence without direct clinical outcome linkage
• Lack of interventional trials to test whether modulating metabolism alters sepsis incidence

Future Directions

Prospective neonatal cohorts linking immunometabolic states to infection outcomes, and ethically designed interventions to modulate metabolism for sepsis prevention.