The Microbiome–Atherosclerosis Axis: From Association to Action

In this second issue of 2025, we present with great pleasure a number of critical and important review and original research papers underlying the mechanisms involved in atherosclerosis progress. It is well documented and appreciated that atherosclerotic cardiovascular disease (CVD) is the leading cause of death globally, despite decades of advances in lipid management, hypertension control, and smoking cessation. The persistent burden of residual cardiovascular risk has forced the field to look beyond classical risk factors toward deeper biological regulators of disease. Among the most compelling of these is the human microbiome. The studies presented in this issue provide a timely and comprehensive synthesis of how microbial communities and their metabolites shape atherosclerotic processes and point decisively toward a new frontier in cardiovascular prevention and therapy. Conventionally, atherosclerosis has been viewed as a disorder of lipid accumulation and sterile inflammation. The current body of evidence strongly reframes it as a condition profoundly shaped by host–microbe interactions. The microbiome emerges not as a passive bystander but as an active endocrine-like organ that translates dietary, genetic, and environmental inputs into biologically potent metabolites. These metabolites directly influence endothelial function, immune balance, lipid handling, and thrombosis, the four central pillars of atherogenesis, as it is well presented by Elantamilan et al., in their paper. However, despite extraordinary progress, major uncertainties remain. Foremost is the challenge of definitively proving causality in human populations. Observational studies are robust but confounded by diet, medication use, socioeconomic status, and regional variability. The roadmap ahead is both ambitious and technically demanding. High-resolution, longitudinal multiomics must replace static snapshots. Synthetic microbial ecology and Clustered Regularly Interspaced Short Palindromic Repeats-based editing promise the creation of designer microbial consortia with predefined atheroprotective functions. Artificial intelligence-driven “digital twins” may soon allow simulation of individualized microbiome – cardiovascular trajectories, enabling targeted prevention strategies. In another review paper, Konstantinos Demopoulos, a world-known and recognized biochemist, recounts the key events surrounding the elucidation of the chemical structure of platelet-activating factor (PAF), details that are largely absent from the existing scientific literature, as well as the subsequent development of PAF research, with particular emphasis on Greece. It reviews the state of PAF research at a time when the molecule’s structure was still unknown and describes the international efforts undertaken across multiple laboratories to determine it. The article also addresses historical omissions and contextual developments, drawing on correspondence exchanged among the early pioneers of PAF research during the quest to identify its structure. It highlights the profound impact that structural elucidation had on advancing the field, which continues to grow and remains an active area of scientific inquiry. Now, nearly 50 years after the discovery of PAF’s structure, this paper is a remarkable journey worth sharing, especially with younger scientists, as the experiences of earlier generations form an essential foundation for those who follow. Nowadays, vegan diets have gained widespread popularity due to growing awareness of health, environmental sustainability, and animal welfare, supported by increased availability of plant-based foods and strong social media influence. An umbrella meta-analysis of nine meta-analyses presented in this issue by Dalmyras et al., found that vegan diets are associated with lower body weight, waist circumference, blood pressure, glycemic markers, and C-reactive protein. No significant effects were observed on lipid profiles. Substantial heterogeneity and publication bias were noted, indicating cautious interpretation. Lagou et al., using data from the 20-year follow-up of the ATTICA cohort, found that total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B independently predicted cardiovascular disease risk. Non-HDL-C and LDL-C showed similar and superior ability to predict and reclassify long-term CVD incidence in an apparently healthy population. Finally, Mastoridou et al. describe a case study of a 5-year-old girl who presented with markedly elevated LDL-C and was initially misdiagnosed with familial hypercholesterolemia (FH). However, genetic testing excluded FH, prompting further investigation that led to the diagnosis of lysosomal acid lipase deficiency (LAL-D), a rare autosomal recessive metabolic disorder caused by mutations in the LIPA gene. LAL-D is often underrecognized and can mimic more common lipid disorders while also affecting liver function. The patient was treated with enzyme replacement therapy using sebelipase alfa in combination with ezetimibe, which resulted in substantial improvements in both aminotransferase levels and LDL-C concentrations. This case highlights the critical importance of considering alternative and rare causes of severe dyslipidemia, especially when patients show atypical features or inadequate response to standard lipid-lowering therapies. Increased awareness of LAL-D among clinicians is essential to avoid misdiagnosis, ensure timely intervention, and prevent long-term cardiovascular and hepatic complications. The Journal of Atherosclerosis Prevention and Treatment is envisioned not merely as a knowledge archive but as a living community of practice. Our aim is to speed the integration of robust evidence into clinical guidelines and public health action, supporting physicians, basic scientists, epidemiologists, and policymakers in their collective efforts to reduce the burden of CVD. We encourage clinicians, researchers, and innovators to join us in advancing this mission to shift cardiovascular prevention from reactive treatment to proactive health protection. Through collaboration and open scientific dialogue, our journal will continue to bridge discoveries from molecular science to global health impact.