Gut microbiota dysbiosis in infants and young children with severe pneumonia and sepsis: a matched case-control study identifying potential biomarkers for early risk stratification

Background: Sepsis remains a life-threatening complication of severe pneumonia in infants and young children, yet early biomarkers are lacking. The gut microbiota modulates host immunity, but the association between the gut microbiota and pediatric pneumonia-associated sepsis is unclear due to confounding factors. Methods: In this prospective, 1:1 matched case-control study, we enrolled 100 infants and young children (28 days-36 months) with severe pneumonia, stratifying them into sepsis (n=50) and non-sepsis (n=50) groups matched for age and antibiotic exposure. Fecal samples collected within 48 hours of PICU admission underwent 16S rRNA gene sequencing. Diversity, taxonomic composition, and differential taxa were analyzed. Results: The sepsis group exhibited significantly reduced alpha diversity (Shannon index: 2.30 ± 1.50 vs. 2.83 ± 1.36, P = 0.027), increased Enterobacteriaceae (18.97% vs. 9.44%, P = 0.046), and decreased Lachnospiraceae (2.01% vs. 8.11%, P = 0.010). LEfSe (Linear discriminant analysis Effect Size) further revealed distinct microbial signatures: the sepsis group exhibited enrichment of Lactobacillaceae and Clostridium butyricum, while the non-sepsis group was characterized by higher abundance of Lachnospiraceae and Segatella. Conclusion: Sepsis in infants and young children with severe pneumonia is associated with a specific gut microbiota signature, independent of major confounders. This dysbiotic profile, involving taxa associated with endotoxin production and short-chain fatty acid metabolism, may serve as an early biomarker for risk stratification and could inform microbiota-targeted interventions in critically ill infants and young children.