The human microbiome and atherosclerotic coronary heart disease

This editorial refers to ‘The gut microbiome across the cardiovascular risk spectrum’, by F.M. Prins et al. https://doi.org/10.1093/eurjpc/zwad377. The correlation between the human gut microbiota (GM) and coronary artery disease (CAD) is evident in both the risk and prognosis of the disease.1,2 As the ‘second genome’ of humans, the GM exerts influence on atherogenesis through metabolites such as trimethylamine N-oxide and short-chain fatty acids, modulation of host lipid metabolism, and promotion of systemic inflammation.3,4 In the context of ST-elevation myocardial infarction (STEMI), characterized by acute thrombotic coronary artery occlusion at the site of a ruptured pre-existing atherosclerotic plaque, the translocation to atherosclerotic plaques and reduced diversity of GM could elucidate the pathogenesis of acute myocardial infarction (AMI), encompassing both STEMI and non-STEMI. Significant differences in faecal microflora were observed between AMI and healthy groups, as well as between STEMI and non-STEMI groups.5 This dysbiosis of GM may impact on different platelet reactivity after treatment with antiplatelets6 and clinical outcomes7 of patients with STEMI. The study conducted by Prins et al.8 demonstrated an intriguing methodology and outcomes. The study population consisted of Dutch individuals with STEMI and various coronary risk factors, a departure from previous studies that predominantly focused on comparing STEMI with healthy individuals, often in Asian populations.5–7,9 The research highlighted the relationship and progression of the CAD continuum with GM, identifying specific species persistently found in individuals across all coronary risk groups and STEMI. The findings contributed additional evidence supporting the notion that GM may play a role in CAD pathogenesis and could serve as a predictor of future cardiovascular (CV) events. Moreover, the analysis of biosynthesis pathways in patients with STEMI revealed a reduction in pathways of vitamin B1 derivatives, B6, and B7, suggesting potential avenues for preventive concepts that warrant further exploration. Several aspects merit further discussion in the context of this study. First, the application of the Framingham risk score for classifying coronary risk groups, while common, might benefit from considering newer risk prediction algorithms such as SCORE210 and SCORE2-OP,11 which are tailored for predicting 10-year risk of first-onset CV diseases (CVDs), particularly in European populations, and may be more applicable to the Dutch population. Secondly, each GM profile depends on age, gender, local food or lifestyle, and medications. A further comparative analysis between the Dutch population with STEMI and healthy individuals could provide valuable insights into the diversity of GM concerning racial, food, and lifestyle factors. Thirdly, discrepancies in the abundance of GM in STEMI patients between studies were noted, which the phylum Bacteroidetes was commonly found to decrease, as similar as this study. This phylum’s reduction is commonly associated with coronary risk factors, CAD, and STEMI,6,7,9 resulting in decreased gut microbial lipopolysaccharide production and the inhibition of atherosclerosis and immune responses.12 Notably, an increase in the butyrate producer group (Genus Oscillospiraceae) in STEMI patients, contributing to a heightened Firmicutes to Bacteroidetes ratio indicative of gut dysbiosis, aligns with prior research.13 However, this contrasts with findings in CAD patients where the same group of bacteria was observed to decrease. This incongruity may arise from the role of these bacteria in modulating the intestinal immune system for post-STEMI cardiac protection and repair,13 necessitating further exploration into the causal effects and associated factors of specific GM taxa on patients with acute coronary syndrome and STEMI. Microbial dysbiosis not only plays a pivotal role in the pathogenesis of CVD but also in chronic kidney disease (CKD) and its progression. It also demonstrated a paradoxical situation of renoprotection.14 The apparent similarity and potential causal relationship between GM dysbiosis and CVD raise the hypothesis that GM dysbiosis is associated with established CVD risk factors, thereby increasing the risk of developing CVD. A comprehensive investigation into the direct and indirect effects of GM, mediated through traditional CVD risk factors such as diabetes, hypertension, dyslipidaemia, and CKD, could elucidate the intricate relationship between GM, CVD, and the cardiovascular-kidney-metabolic (CKM) syndrome. Furthermore, modulation of the GM through interventions such as faecal microbiota transplantation, prebiotics, and probiotics consumption may serve as protective and therapeutic tools for CVD and CKM syndrome. Faecal microbiota transplantation, involving the transplantation of a faecal solution from a healthy donor to the recipient's intestinal tract, has shown potential in retarding atherosclerosis, while prebiotics provide an energy source for GM bacteria to produce anti-inflammatory metabolites, such as short-chain fatty acids. In conclusion, while progress has been made in understanding the scientific underpinnings of GM and atherosclerotic coronary heart disease, further investigation into their causal relationship is imperative. Gut microbiota dysbiosis appears to be intertwined with the pathophysiological interactions among CVD, CKD, and metabolic risk factors in CKM health and mortality. Prospective human research efforts are also essential for elucidating the role of personalized medicine targeting beneficial bacterial species in preventing and mitigating CV morbidity and mortality.