Exam Corner

Introduction Atherosclerosis has traditionally been viewed as a lipid-driven disease. However, emerging evidence highlights a critical role of chronic inflammation and immune activation, with the gut microbiota now recognised as a key modulator of vascular health. The concept of a gut–heart axis is reshaping our understanding of cardiovascular disease. Problem Statement Despite optimal lipid control, many patients continue to develop atherosclerosis, suggesting lipid-independent mechanisms. The challenge lies in identifying novel pathways contributing to vascular inflammation. The gut microbiota, through its interaction with host metabolism and immunity, has emerged as a potential contributor—but its exact role and therapeutic relevance remain incompletely defined. Summary This review highlights the growing evidence linking gut microbiota to atherosclerosis. Patients with cardiovascular disease exhibit gut dysbiosis, including increased translocation of oral bacteria into the intestine. Microbial-derived metabolites play a central role: harmful metabolites such as trimethylamine N-oxide (TMAO), endotoxins, and imidazole propionate promote vascular inflammation and plaque formation, whereas other metabolites, like certain tryptophan derivatives, may have protective effects. The microbiota also interacts closely with lipid metabolism, influencing lipid absorption, storage, and systemic inflammation. Additionally, it contributes to vascular ageing, further accelerating atherosclerosis. Therapeutic modulation of the microbiome—through diet, prebiotics, probiotics, or antibiotics—has shown promising results in preclinical models, though human data remain limited. Overall, the gut microbiota functions as a biological rheostat regulating vascular inflammation, offering a novel target for future cardiovascular therapies.