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From Dysbiosis to Vascular Disease: the Gut Microbiota in Type 2 Diabetes and Atherosclerosis

Year: 2026
Type: article
Abstract: Purpose of Review Type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) are closely linked chronic disorders and leading causes of morbidity and mortality worldwide. Increasing evidence identifies the gut microbiota (GM), including its microbial genes and metabolites, as potential modifiers of these processes. This narrative review summarizes mechanistic, translational, and clinical evidence linking GM dysbiosis with T2D and atherosclerosis and evaluates microbiota-directed therapeutic strategies. Recent Findings Converging mechanistic, translational, and clinical evidence supports GM dysbiosis as a plausible shared contributor to T2D and atherosclerosis through interconnected pathways involving impaired intestinal barrier integrity and metabolic endotoxemia, TLR4/NF-κB- and inflammasome-mediated inflammation, and microbial metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAGln), and tryptophan-derived indoles. These pathways can influence glucose and lipid metabolism, insulin signaling, immune activation, endothelial function, and vascular inflammation, providing a biological framework linking dysglycemia with increased cardiovascular risk and supporting the GM as a potential therapeutic target. However, the field remains limited by predominantly observational and confounded human data, incomplete causal evidence, and heterogeneous responses to microbiota-directed interventions. Dietary modification, prebiotics, probiotics, synbiotics, next-generation probiotics and postbiotics, fecal microbiota transplantation, and microbiota-modulating antidiabetic therapies have shown signals of benefit on metabolic or vascular surrogate endpoints, but evidence for durable clinical benefit remains limited and inconsistent across strains, populations, and study designs. Summary Future progress in GM manipulation to improve cardiometabolic outcomes will require function-focused, causally grounded research and adequately powered, outcome-driven clinical trials incorporating GM-guided patient stratification. Until such evidence is available, the GM should be viewed as a biologically compelling and promising, but not yet clinically actionable, link between metabolic and atherosclerotic disease.
Language: English
Open Access status: hybrid
Estimated APC paid: $5,190
OpenAlex ID: W7225662670
FWCI:
Cites: 123
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