The impact of the gut microbiome on the development of atherosclerosis and peripheral arterial disease: A narrative review.

Abstract

Atherosclerosis is a chronic, progressive process affecting medium and large arteries, while peripheral artery disease (PAD) represents one of its clinical manifestations in the limb arteries. Although classical risk factors such as poor diet, hypertension, diabetes, and smoking are well established, increasing evidence indicates that the gut microbiome is an important and modifiable contributor to vascular pathophysiology. This paper reviews current knowledge on the role of the gut microbiome in the initiation and progression of atherosclerosis and PAD, with emphasis on bacterial metabolites, proinflammatory mechanisms, and potential therapeutic interventions. Gut dysbiosis-an imbalance in the intestinal microbial community-has been associated with increased cardiovascular risk. Patients with vascular diseases show higher levels of pro-atherogenic taxa, including Enterobacteriaceae, Streptococcus spp., Lachnoclostridium, and Family XI, alongside a reduction of beneficial short-chain fatty acid (SCFA)-producing bacteria such as Roseburia, Faecalibacterium, Coprococcus2, and Ruminococcaceae. Two key microbial metabolites influence vascular health. Trimethylamine N-oxide (TMAO), formed from choline and L-carnitine via microbial and hepatic metabolism, promotes endothelial dysfunction, inflammation, and platelet reactivity, thereby accelerating atherosclerosis. Conversely, SCFAs-acetate, propionate, and butyrate-exert anti-inflammatory effects, improve insulin sensitivity, and enhance nitric oxide synthesis, resulting in vascular protection. Therapeutic strategies targeting the gut microbiota show promising potential. These include the use of probiotics and prebiotics (notably Lactobacillus rhamnosus GG), adherence to a Mediterranean diet, and fecal microbiota transplantation (FMT), all aimed at restoring eubiosis and a favorable intestinal metabolic profile. In summary, the gut microbiome appears to be a key modulator of the pathogenesis of atherosclerosis and PAD. Targeted modulation of gut microbial composition and activity may emerge as an innovative and effective strategy for the prevention and treatment of cardiovascular diseases.