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Cardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in patients with chronic stable angina (CSA) and acute coronary syndrome (ACS) compared with healthy controls. Bacterial alpha diversity in stool from patients with ACS or CSA was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units (OTUs) assigned to commensal taxa differentiating patients with ACS from healthy controls at both baseline and follow-up. Patients with CSA and ACS had significantly higher levels of trimethylamine N -oxide compared with healthy controls (CSA: 0.032 ± 0.023 mmol/L, P < 0.01 vs. healthy, and ACS: 0.032 ± 0.023 mmol/L, P = 0.02 vs. healthy, respectively). Patients with ACS had reduced levels of propionate and butyrate (119 ± 4 vs. 139 ± 5.1 µM, P = 0.001, and 14 ± 4.3 vs. 23.5 ± 8.1 µM, P < 0.001, respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs. 1834 ± 45.8 ng/mL, P < 0.0001) and sCD163 levels (457.3 ± 31.8 vs. 326.8 ± 20.7 ng/mL, P = 0.001), compared with healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in patients with CSA and ACS compared with healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD. Future time course studies in patients to observe temporal changes and subsequent associations with gut microbiome composition are required to provide insight into how these are affected by transient changes following an acute coronary event. NEW & NOTEWORTHY The study found discriminative microorganisms differentiating patients with acute coronary syndrome (ACS) from healthy controls. In addition, reduced levels of certain bacterial metabolites and elevated sCD14 and sCD163 were observed in patients with ACS compared with healthy controls. Furthermore, modified small molecule metabolomic and lipidomic signatures were found in both patient groups. Although it is not known whether these differences in profiles are associated with disease development and/or progression, the findings provide exciting options for potential new disease-related mechanism(s) and associated therapeutic target(s).

Heart failure (HF) is the end stage of most cardiovascular diseases and remains a significant health problem globally. We aimed to assess whether patients with left ventricular ejection fraction ≤45% had alterations in both the gut microbiome profile and production of associated metabolites when compared with a healthy cohort. We also examined the associated inflammatory, metabolomic, and lipidomic profiles of patients with HF. This single center, observational study, recruited 73 patients with HF and 59 healthy volunteers. Blood and stool samples were collected at baseline and 6-mo follow-up, along with anthropometric and clinical data. When compared with healthy controls, patients with HF had reduced gut bacterial alpha diversity at follow-up ( P = 0.004) but not at baseline. The stool microbiota of patients with HF was characterized by a depletion of operational taxonomic units representing commensal Clostridia at both baseline and follow-up. Patients with HF also had significantly elevated baseline plasma acetate ( P = 0.007), plasma trimethylamine- N -oxide (TMAO) ( P = 0.003), serum soluble CD14 (sCD14; P = 0.005), and soluble CD163 (sCD163; P = 0.004) levels compared with healthy controls. Furthermore, patients with HF had a distinct metabolomic and lipidomic profile at baseline when compared with healthy controls. Differences in the composition of the gut microbiome and the levels of associated metabolites were observed in patients with HF when compared with a healthy cohort. This was also associated with an altered metabolomic and lipidomic profile. Our study identifies microorganisms and metabolites that could represent new therapeutic targets and diagnostic tools in the pathogenesis of HF. NEW & NOTEWORTHY We found a reduction in gut bacterial alpha diversity in patients with heart failure (HF) and that the stool microbiota of patients with HF was characterized by depletion of operational taxonomic units representing commensal Clostridia at both baseline and follow-up. Patients with HF also had altered bacterial metabolites and increased inflammatory profiles compared with healthy controls. A distinct metabolomic and lipidomic profile was present in patients with HF at baseline when compared with healthy controls.