Characterization of the Gut Microbiota and Serum Metabolomics in Patients with Type 2 Diabetes Mellitus and Newly Diagnosed Acute Coronary Syndrome

Biomarkers for the early identification of acute coronary syndrome (ACS) risk remain inadequately investigated, particularly in patients with type 2 diabetes mellitus (T2DM), for whom timely clinical intervention may substantially enhance prognostic outcomes. The gut microbiota and serum metabolites may serve as pivotal mediators in the occurrence and progression of ACS among patients with T2DM, and whether these factors can be used for the precise discrimination of patients with T2DM complicated by ACS remains to be explored. Overall, 76 participants were enrolled (38 patients diagnosed with T2DM complicated by ACS and another 38 with T2DM without ACS). 16S rRNA sequencing combined with untargeted LC-MS metabolomics revealed a dysregulated gut-serum axis in patients with T2DM complicated by ACS: enrichment of proinflammatory microorganisms (Enterococcus spp.), reduction of butyrate producers (Butyricimonas spp.) and concomitant dysregulation of circulating lipid metabolites-upregulation of PC(16:0/9:0 (CHO)) and arachidonic acid alongside downregulation of cholesterol sulfate. By integrating multiomics data and applying various feature selection methods, we subsequently identified six key biomarkers. The final constructed combined model robustly distinguished patients with T2DM complicated by ACS from those with T2DM alone (AUC = 0.983), outperforming the other single omics models. Our study revealed that the gut microbiota and related serum metabolites serve as key mediators in the onset and progression of ACS among patients with T2DM, and demonstrated their potential value as noninvasive biomarkers for the early diagnosis of T2DM complicated by ACS. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSWe combined 16S rRNA sequencing with untargeted LC-MS metabolomics to dissect the gut-serum axis in patients with T2DM complicated by newly diagnosed ACS. We identified distinct gut microbial and serum metabolic signatures that distinguish ACS progression within the T2DM population. A multiomics classifier integrating clinical, microbial, and metabolic variables achieved robust diagnostic performance (AUC = 0.983) and outperformed single omics models. What Are the Clinical Implications?Integrated multiomics biomarkers facilitate the early identification of ACS progression in patients with T2DM, offering novel avenues for precision prevention, dynamic clinical surveillance, and individualized therapeutic strategies. Dysregulations of the gut microbiota and serum metabolome may play an important role in the development and progression of ACS in patients with T2DM.