Distinct microbial and metabolic shifts characterize acute coronary syndrome and recovery

Early identification of patients at risk of acute coronary syndrome (ACS) remains a major unmet need, particularly among those with stable coronary artery disease (sCAD), where timely intervention could markedly improve outcomes. The gut microbiota has been implicated in coronary artery disease (CAD), but its ability to distinguish ACS from sCAD is not well defined. Here, we performed cross-sectional multi-omics profiling of fecal microbiota and plasma metabolites in 548 individuals, including participants with normal coronary arteries (<i>N</i> = 175), primary sCAD (<i>N</i> = 161), and ACS (<i>N</i> = 212). To assess whether disease-associated changes resolve with treatment, we further analyzed an independent cohort of ACS patients (<i>N</i> = 52) who transitioned to sCAD following standard therapy. We identified profound ACS-associated alterations in gut microbial composition and systemic metabolism, marked by enrichment of pro-inflammatory taxa such as <i>Streptococcus</i> spp. and elevated circulating levels of 3-hydroxybutyrate (3-HB). Strikingly, many of these ACS-specific microbial and metabolic signatures, including 3-HB and related microbial functional pathways, were restored toward sCAD-like levels after clinical recovery. Integrative models combining microbial taxa, metabolites, and clinical biomarkers robustly discriminated ACS from healthy controls (AUC = 0.91) and from sCAD (AUC = 0.83), significantly outperforming clinical markers alone (AUC = 0.69 for NCA vs. ACS; 0.59 for sCAD vs. ACS). These findings establish the gut microbiome and its metabolic outputs as key discriminators of ACS, reveal their dynamic resolution during disease recovery, and highlight their potential as biomarkers and therapeutic targets for cardiovascular risk stratification and management.

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Journal
iMeta
Published
2025-09-19
DOI
https://doi.org/10.1002/imt2.70079
Citations
2
Primary Topic
Diet and metabolism studies
Type
article
Field-Weighted Citation Impact
2.33
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article

Distinct microbial and metabolic shifts characterize acute coronary syndrome and recovery

Guofeng Gao, Jingyuan Fu, Xiaoliang Luo, Yanmin Yang et al.
2 citations
iMeta
Diet and metabolism studies
2.33
article

Distinct microbial and metabolic shifts characterize acute coronary syndrome and recovery

Guofeng Gao, Jingyuan Fu, Xiaoliang Luo, Yanmin Yang, Xueyan Zhao, Fang Luo, Tao Tian, Shubin Qiao, Tianjie Wang, Fenghuan Hu, Yong‐Gang Sui, Yuejin Yang, Wu Yuan, Cheng Cui, Daoming Wang, Jingang Yang, Chongming Wu, Die Dai, Jiqiu Wu, Wentao Ma, Jun Zhang, Chao Guo, Wei‐Hua Chen, Yanan Yang, Jiuming He, Haoran Peng, Jia Li, Xiaolu Sun, Ping Jiang, Shan Gao, Tingting Guo, Chaoran Dong, Jiansong Yuan, Jing Xu, Xiaojin Gao, Jinqing Yuan, Weixian Yang
article en
2 citations

Abstract

Early identification of patients at risk of acute coronary syndrome (ACS) remains a major unmet need, particularly among those with stable coronary artery disease (sCAD), where timely intervention could markedly improve outcomes. The gut microbiota has been implicated in coronary artery disease (CAD), but its ability to distinguish ACS from sCAD is not well defined. Here, we performed cross-sectional multi-omics profiling of fecal microbiota and plasma metabolites in 548 individuals, including participants with normal coronary arteries (<i>N</i> = 175), primary sCAD (<i>N</i> = 161), and ACS (<i>N</i> = 212). To assess whether disease-associated changes resolve with treatment, we further analyzed an independent cohort of ACS patients (<i>N</i> = 52) who transitioned to sCAD following standard therapy. We identified profound ACS-associated alterations in gut microbial composition and systemic metabolism, marked by enrichment of pro-inflammatory taxa such as <i>Streptococcus</i> spp. and elevated circulating levels of 3-hydroxybutyrate (3-HB). Strikingly, many of these ACS-specific microbial and metabolic signatures, including 3-HB and related microbial functional pathways, were restored toward sCAD-like levels after clinical recovery. Integrative models combining microbial taxa, metabolites, and clinical biomarkers robustly discriminated ACS from healthy controls (AUC = 0.91) and from sCAD (AUC = 0.83), significantly outperforming clinical markers alone (AUC = 0.69 for NCA vs. ACS; 0.59 for sCAD vs. ACS). These findings establish the gut microbiome and its metabolic outputs as key discriminators of ACS, reveal their dynamic resolution during disease recovery, and highlight their potential as biomarkers and therapeutic targets for cardiovascular risk stratification and management.

iMetaVol. 4(5)
Tianjin University of Traditional Chinese Medicine (CN), University Medical Center Groningen (NL), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Fu Wai Hospital (CN), Huazhong University of Science and Technology (CN), Jining Medical University (CN)
Openalex Percentile: Top 10%
Diet and metabolism studies
2.33
DOIOpen Access PDFOpenAlex
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