The gut-vascular axis in diabetes: exploring impaired blood flow, cardiovascular disease, and peripheral arterial complications

The gut-vascular axis-a dynamic, bidirectional interface between the gut microbiota and vascular system-has emerged as a pivotal regulator of metabolic homeostasis and cardiovascular health, especially in the context of type 2 diabetes mellitus (T2DM). This comprehensive review delineates how microbial dysbiosis, compromised intestinal barrier function, and microbial metabolite imbalances contribute to chronic inflammation, endothelial dysfunction, and vascular complications such as atherosclerosis, coronary artery disease (CAD), and peripheral arterial disease (PAD). Key microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and secondary bile acids influence insulin resistance and vascular remodeling. The manuscript also highlights the indirect modulatory roles of SGLT2 inhibitors and GLP-1 receptor agonists on gut microbial dynamics and vascular integrity. Current evidence underscores significant inter-individual variability in microbiota profiles, necessitating personalized therapeutic strategies. Despite compelling preclinical data, translational research in human cohorts remains limited. The review further explores cutting-edge microbiome-based therapeutic strategies, including probiotics, fecal microbiota transplantation (FMT), and engineered microbial therapeutics, while identifying critical research gaps in the development of microbiota-targeted interventions for diabetic vascular disease. Overall, the gut-vascular axis is positioned as a promising frontier in precision medicine for metabolic and cardiovascular complications in diabetes.