EN
TÜRKÇE
Poster - 269
Bile Acid Dysregulation and Gut Microbiome Alterations in Pediatric Sepsis: Therapeutic Potential of Ursodeoxycholic Acid
Linhua Tan, Yan Ni, Yanfei Wang, Huiying Wang, Zhigang Gao, Qiang Shu
Children's Hospital, Zhejiang University School of Medicine
Background The bile acid (BA) metabolism is critically involved in the pathogenesis and progression of sepsis. This study explores the role of BA dysregulations and gut dysbiosis in pediatric sepsis and evaluates the therapeutic effect of ursodeoxycholic acid (UDCA).
Methods Targeted BA profiling and metagenomic sequencing were used to analyze serum and fecal samples of pediatric patients with sepsis (n=86) and controls (n=80). Key BAs, microbiota, and their correlations were identified. The potential anti-inflammatory mechanism of UDCA was further validated using intestinal cell models and sepsis mice models.
Results Children with sepsis exhibited significant BA dysregulations, with elevated primary BAs and reduced secondary BAs, notably the significant reductions of UDCA species. A combination of 3β-UDCA and UDCA also effectively predicted the survival outcome in children with sepsis with ROC value 0.828. Metagenomics analysis indicated the increase of pathogens and reduction of beneficial bacterial genera. In addition, the decreased microbial expressions of BA-metabolizing enzymes supported the BA metabolic imbalance. We further confirmed that UDCA could ameliorate the inflammatory response and barrier dysfunction of the intestinal cell monolayer model induced by lipopolysaccharide (LPS). Finally, UDCA could improve sepsis by inhibiting intestinal inflammatory responses and enhancing intestinal barrier function in LPS/cecal ligation and puncture (CLP) induced mice models. UDCA also had a protective effect on inflammatory damage of distal organs including the liver, lung and spleen.
Conclusions BA metabolism and microbial community were disrupted in pediatric sepsis. UDCA shows promise in improving gut barrier integrity and reducing systemic inflammation, offering a translational foundation for sepsis treatment strategies in children.