Relationship between metabolites of intestinal microbiota and major adverse cardiovascular events in patients with coronary heart disease

Xu Zhenkun; Zang Jingjing; Guo Xiaoning; Hao Yafeng; Ren Liwei; Wang Xuezhi; Wang Xianzhong

doi:10.3969/j.issn.1674-4055.2025.07.18

Abstract：Objective To investigate the relationship between metabolites of intestinal microbiota and occurrence of major adverse cardiovascular events(MACE)in patients with coronary heart disease(CHD).Methods Selected from Sept.2021 to Apr.2022,CHD patients(n=376)who underwent percutaneous coronary intervention(PCI)at Handan First Hospital were enrolled as the study subjects.After 1∶1 propensity score matching,patients with intestinal dysbacteriosis were finally included as study group(n=56),and patients with normal intestinal flora were included as control group(n=56).Fasting venous blood samples(5 ml)were collected from both groups in the morning,and the plasma levels of trimethylamine oxide(TMAO)in each specimen were detected by using stable isotope dilution high-performance liquid chromatography-tandem mass spectrometry.Additionally,appropriate stool samples were collected from both groups before the procedure to quantify the viable counts of Bifidobacteria,Lactobacilli and Escherichia coli.Postoperative follow-up was conducted for 1 y through outpatient reviews,telephone calls,and WeChat to record the occurrence of MACE in both groups.Results The counts of Lactobacilli and Bifidobacteria were significantly lower,but Escherichia coli count and expression of TMAO(metabolites of intestinal microbiota)was significantly higher in study group than those in control group(P＜0.05).The incidence of MACE was significantly higher in study group than those in control group(P＜0.05).The results of Spearman correlation analysis showed that Lactobacilli and Bifidobacteria were negatively correlated to MACE incidence,and Escherichia coli and TMAO expression were positively correlated to MACE incidence.The results of ROC curve analysis showed that,in predicting MACE incidence,cutoff value of Lactobacilli,Bifidobacteria,Escherichia coli or TMAO was,respectively,43.64,33.24,33.32 and 5.86,and AUC was,respectively,0.619,0.627,0.796 and 0.817,and AUC of intestinal microbiota combined with TMAO was 0.928.Conclusion CHD patients with intestinal dysbacteriosis have fewer intestinal probiotics but higher levels of pathogenic bacteria such as Escherichia coli and microbial metabolites,and study group showed a higher MACE incidence.Analysis revealed that Lactobacillus and Bifidobacterium were negatively correlated to MACE occurrence,whereas Escherichia coli and TMAO expression were positively correlated to MACE incidence.Combining intestinal microbiota with their metabolites for predicting MACE occurrence demonstrated higher accuracy and sensitivity.