The Glutamate-Glutamine Axis in Pediatric Septic Shock: Immunometabolic Mechanisms, Biomarker Potential, and Clinical Implications.

Pediatric septic shock remains a major cause of morbidity and mortality in critically ill children and is increasingly recognized as a syndrome of profound immunometabolic dysregulation. This narrative review synthesizes current clinical, translational, and mechanistic evidence on the glutamate-glutamine axis in pediatric septic shock. The review focuses on how glutamine and glutamate metabolism may interact with immune-cell function, mitochondrial substrate handling, redox defense, and intestinal barrier integrity, while distinguishing biological plausibility from validated clinical utility. Current evidence supports the glutamate-glutamine axis as a mechanistically relevant pathway and a source of candidate biomarkers, but pediatric-specific data remain limited and do not yet justify routine biomarker use or glutamine-based intervention in unselected children with septic shock. Future studies should use standardized sampling, reproducible analytical methods, pediatric validation cohorts, and phenotype-guided trial designs before this axis can be translated into clinical decision making.