1703-P: Integrated Transcriptome, Proteome, Metabolome, and Microbiome Analyses Identify Multiomics Signature of Glycolipid Metabolism Disorder-A Cross-Sectional Study

Introduction: The prevalence of glycolipid metabolism disorder continues to increase globally and has become a serious threat to human health. Multi-omics provide unprecedented insights into the underlying pathophysiological mechanisms of glycolipid metabolism disorder and identifying potential biomarkers and therapeutic targets. Methods: We collected blood/stool samples from 30 patients with type 2 diabetes and dyslipidemia (GL), 30 patients with hyperlipidemia (HL), and 30 healthy controls, conducted transcriptome/proteome/metabolome/microbiome analysis, and correlated it with clinical phenotypes. We further integrated multi-omics features and tested the discriminant efficacy of multi-omics datasets using receiver operating characteristic curves. Results: Among patients with GL, insulin like growth factor binding protein 3 (IGFBP3) in the p53 signaling pathway was highly expressed at both the transcription and protein levels. Joint analysis of proteomics and metabolomics confirmed the link between fructose-bisphosphate aldolase B and altered N-acetylornithine metabolism in the amino acid biosynthetic pathway. The gut microbiota dysbiosis in patients with GL was characterized by a significantly reduced abundance of short-chain fatty acids-producing bacteria, and this reduction was related to a decrease in dodecanoic acid. The extracellular matrix-receptor interaction pathway was associated with HL, and collagen type I alpha 1 chain in this pathway was lowly expressed at both the transcription and protein levels. The abundance of Parabacteroides gordonii was significantly reduced in patients with HL. Matrix metallopeptidase 2 and IGFBP3, key differential molecules between GL and HL, were highly expressed at both the transcription and protein levels. Conclusion: This study revealed the multi-omics signature and key drivers of glycolipid metabolism disorder.