Probiotic supplementation reduced carotid intima-media thickness by up to 6% and improved flow-mediated dilation by 15% in dysbiotic patients with CAD and PAD.
Does probiotic therapy reduce intima-media thickness in dysbiotic patients with coronary artery disease and peripheral artery disease?
Probiotic supplementation for 3 months significantly improves surrogate markers of vascular health (IMT and FMD) in dysbiotic patients with CAD and PAD.
Abstract Background Gut dysbiosis, an imbalance in gut microbiota, contributes to low-grade systemic inflammation, a key driver of coronary artery disease (CAD) and peripheral artery disease (PAD). In dysbiosis, pathogenic bacteria alter tryptophan (TRP) metabolism, leading to the production of toxic metabolites such as kynurenine and indoxyl sulfate, which further drive inflammation and impair barrier integrity. The kynurenine/TRP and indoxyl sulfate/TRP ratios are used as markers of this metabolic shift towards a pro-inflammatory state. Preliminary observational data suggest that modulating this pathway may improve cardiovascular health, though randomised evidence remains limited. Purpose We aimed to investigate the effects of probiotic supplementation on vascular health in dysbiotic patients with CAD and PAD. Methods The PROCARDIO study is a prospective, randomised, double-blind, placebo-controlled trial. Urine samples were collected and TRP metabolism was analysed to identify dysbiotic patients. Eligible patients were randomised to receive either probiotic therapy (Lactobacillus and Bifidobacterium species) or placebo for three months. The primary outcome was the change in intima-media thickness (IMT), while secondary outcomes included flow-mediated dilation (FMD), ankle-brachial index (ABI), inflammatory markers, and dysbiosis-related metabolites. Results Sixty patients were enrolled (31 probiotic, 29 placebo), with well-matched baseline characteristics. Probiotic supplementation significantly reduced IMT on both carotid sides, as shown by the between-group comparison of the difference between follow-up and baseline IMT values (median relative reduction: -6.0% and -4.4%, p 0.01 and p = 0.02, respectively). FMD improved by a median 15% in the probiotic group but remained unchanged in the placebo group (p 0.01). Conversely, no significant differences were observed in ABI (p = 0.83) and inflammatory marker levels. Probiotic therapy stabilised the kynurenine/TRP and indoxyl sulfate/TRP ratios, preventing tryptophan metabolism from shifting towards a more pro-inflammatory pathway. Conclusions PROCARDIO is the first interventional study demonstrating that probiotic supplementation improves vascular health (by reducing IMT) and enhances endothelial function (by improving FMD) in dysbiotic patients with CAD and PAD. These effects appear to be mediated by the modulation of TRP metabolism, gut-derived inflammation and immune responses, and they seem to be independent of renal function. Probiotics could represent a novel approach to improving vascular health and mitigating atherosclerosis progression as secondary prevention strategy in high-risk patients.Boxplot results of IMT, ABI and FMD
Ghisletti et al. (2025) studied this question. Probiotic supplementation reduced carotid intima-media thickness by up to 6% and improved flow-mediated dilation by 15% in dysbiotic patients with CAD and PAD.