Early Gut Microbiome-Short-Chain Fatty Acid Axis Disruption May Be Associated with Delayed Recovery in Critically Ill...

Background: The gut microbiome contributes to immune-metabolic homeostasis through microbial-derived metabolites such as short-chain fatty acids (SCFAs). However, whether early disruption of the gut microbiome-SCFA axis identifies impaired clinical recovery in pediatric intensive care unit (PICU) patients remains unclear. Biological markers reflecting the recovery trajectory beyond conventional severity scores remain poorly characterized in pediatric critical illness. We therefore investigated whether early microbiome disruption and fecal SCFA profiles are associated with recovery trajectory in critically ill children. Methods: In this prospective observational study (N = 26), fecal samples were collected within 5 days of PICU admission. Microbial diversity was assessed using 16S rRNA gene sequencing (Shannon index), and fecal SCFAs were quantified using targeted metabolomics. Disease severity was assessed using the Pediatric Index of Mortality 3 (PIM3). The primary outcome was PICU length of stay (LOS) as a pragmatic indicator of metabolic and functional recovery trajectory in critically ill children. Results: Younger age and higher disease severity showed a trend toward reduced microbial diversity (β = 0.066, p = 0.089, and β = -0.054, p = 0.089). Early loss of gut microbial diversity was associated with reduced fecal butyric acid concentrations (r = 0.440, p = 0.024). Importantly, lower microbial diversity in the early sampling window showed a significant inverse correlation with PICU LOS (ρ = -0.428, p = 0.029), whereas fecal butyric acid alone was not directly associated with LOS (p = 0.321). In multivariable regression models adjusting for age, disease severity, and clinical exposures, microbial diversity showed a consistent inverse association with PICU LOS, although statistical significance was not reached. Conclusions: Early disruption of the gut microbiome-SCFA axis, characterized by reduced microbial diversity and lower fecal butyrate, showed trend-level associations with delayed clinical recovery in this pilot cohort. Gut microbial ecosystem integrity may serve as a biologically relevant marker of recovery trajectory beyond conventional severity scoring.