PP315 - POSTPRANDIAL MULTI-OMICS REVEALS DIET- AND MICROBIOTA-DRIVEN METABOLIC MEDIATORS OF VASCULAR DYSFUNCTION IN OBESITY

PP315

POSTPRANDIAL MULTI-OMICS REVEALS DIET- AND MICROBIOTA-DRIVEN METABOLIC MEDIATORS OF VASCULAR DYSFUNCTION IN OBESITY

H. Liu^1,*, H. Dai¹, S. Zheng¹, Q. Xu¹, Q. Fu¹

¹Department of Endocrinology & Metabolism, The first Affiliated Hospital with Nanjing Medical University, Nanjing, China

Rationale: Fasting metabolic measurements fail to capture dynamic postprandial metabolic fluctuations from daily dietary intake. However, dynamic multi-omic links between diet, gut microbiota, and vascular function remain unclear.

Methods: A mixed meal tolerance test (MMTT) was conducted in 147 non-diabetic participants. Serial blood samples were collected at fasting, 60 min, and 120 min postprandially for metabolomics, lipidomics, proteomics and hormone quantification. Gut microbiota was profiled via 16S rRNA sequencing. Statistical analyses included Spearman correlation, pathway enrichment, network analysis, random forest regression, and mediation analysis. Key microbial findings were validated in ApoE⁻/⁻ mice administered Clostridium botulinum.

Results: Postprandial profiles (125 metabolites, 18 lipids, 4 proteins) associated with PWV/SBP/DBP only at 120 min, with more differential molecules than fasting. Random forest predicted SBP (60min R²=0.48; 120min R²=0.42; AUC R²=0.54) and DBP (60min R²=0.30; 120min R²=0.47; AUC R²>0.42).  Mediation analysis revealed that hexaminolevulinate mediated vitamin B6–PWV at fasting, 60 min, and 120 min (14%, 16.3%, 17.5%; all p<0.01). Hexaminolevulinate also mediated C. botulinum–PWV across the same time points (13.3%, 19.7%, 16.84%; all p<0.01). Validation in ApoE⁻/⁻ mice demonstrated that C. botulinum increased aortic plaque by 50.7% (p<0.01), raised TG/TC (p<0.05), and worsened vascular injury.

Conclusion: Postprandial multi-omic profiles (especially 120 min) are more informative than fasting for evaluating vascular function. Hexaminolevulinate mediates vitamin B6/C. botulinum-PWV associations. Animal data confirm C. botulinum aggravates atherosclerosis and vascular injury. These findings support postprandial multi-omics for identifying mediators and microbial targets in vascular risk management.

Disclosure of Interest: None declared