MON-244 Alterations in Gut Microbiota Virulence Factor Genes and Their Association with Hepatic Metabolic Inflammation in Overweight/Obese Children

Abstract Disclosure: P. Li: None. J. Jiang: None. Z. Fan: None. L. Feng: None. F. Yang: None. Objective This study aimed to investigate the correlation between gut microbiota composition, virulence factor (VF) gene alterations, and hepatic metabolic inflammation in overweight/obese children, providing novel insights for the prevention and management of obesity-related metabolic disorders in pediatric populations.Methods: A nested case-control study was conducted. Thirty-one overweight/obese children [aged 6.1 (3.9–8.6) years; 17 males] were recruited from the "Southwest China Childhood Obesity Prevention Study" at West China Second University Hospital of Sichuan University (August 2021–April 2022). Twenty-two healthy children [aged 5.3 (5.1–5.4) years; 10 males] served as controls. Body mass index (BMI), fasting blood glucose (FBG), liver enzymes, uric acid, and other metabolic-inflammatory biomarkers were measured. Fecal samples were analyzed via metagenomic sequencing to characterize gut microbiota composition, VF gene abundance, and KEGG signaling pathways. Group comparisons were performed using t-tests or Mann-Whitney U tests; Spearman’s rank correlation was applied for association analysis.Results: The overweight/obese group exhibited significantly higher BMI [20.44 (17.45–22.80) kg/m² vs. 13.45 (12.25–14.28) kg/m²; P = 0.000] and elevated metabolic-inflammatory markers, including alanine aminotransferase (ALT) [17.00 (10.00–21.00) U/L vs. 15.00 (13.00–17.00) U/L; P = 0.011] and γ-glutamyl transferase (γ-GT) [15.00 (10.00–18.00) U/L vs. 11.00 (9.00–12.00) U/L; P < 0.001]. Metagenomic analysis revealed higher abundances of Coprococcus_A [0.76 (0.00–3.11) vs. 0.00 (0.00–0.00); FDR < 0.05] and Parasutterella [0.89 (0.08–1.79) vs. 0.00 (0.00–0.08); FDR < 0.05] in the overweight/obese group. Overweight/obese children demonstrated greater VF gene diversity, with higher Simpson [0.9919 (0.9915–0.9928) vs. 0.9905 (0.9898–0.9912); P < 0.05] and Shannon indices [5.51 (5.42–5.56) vs. 5.37 (5.30–5.43); P < 0.05], and a higher number of annotated VF types [941.00 (886.00–977.00) vs. 890.00 (806.75–919.50); P = 0.028]. FBG, γ-GT, and ALT levels positively correlated with VF abundance (r > 0.3, FDR < 0.05), with γ-GT showing the strongest association with lipopolysaccharide biosynthesis-related VFs (LpxH, LpxB, LpxK).Conclusion: Overweight/obese children display elevated hepatic metabolic-inflammatory markers, which may be linked to gut microbiota dysbiosis and enrichment of VF genes. These findings highlight the potential role of gut microbial virulence factors in modulating liver immune-metabolic pathways, offering a novel perspective for targeting gut-liver axis interactions in childhood obesity management. Presentation: Monday, July 14, 2025