Abstract

Introduction: There is a significant unmet clinical need to identify novel therapies to prevent and treat the progression of cardiovascular disease. This requires identification of additional contributory processes to the pathogenesis of heart disease so that mechanism-based interventions may be developed. Hypothesis: Our objective was to translate the recently discovered mechanistic link in rats between changes in the intestinal microbiota and the pathogenesis of cardiovascular disease to humans. Methods: Twenty male adult patients with stable coronary heart disease on stable doses of vasoactive medications and HMG-CoA reductase inhibitors consumed a probiotic drink containing Lactobacillus plantarum 299v (3 oz. serving containing 20 billion colony forming units) once a day for 42 days. Vascular endothelial function was measured at the beginning and end of the study period by brachial flow-mediated dilation. Results: The probiotic improved brachial artery flow mediated dilation, a surrogate marker of cardiovascular risk, by 33% from 3.55 + 1.96% to 4.73 + 2.33% with a trend towards decreased LDL-cholesterol by 8% from 96 + 11 mg/dl to 88 + 10 mg/dl. Probiotic therapy decreased circulating levels of the inflammatory cytokines IL-8 by 24% (17±2 to 13±1 pg/ml) and IL-12 by 20% (56±7 to 45±6 pg/ml). Whole microbiome analysis based on abundance of 2,206 taxa using hierarchical clustering revealed no separation of the overall intestinal microbial population between pre- and post-probiotic treatment samples. Bacterial genus richness ranged from 334 to 530 and archaeal ranged from 8 to 25, with no significant differences between pre- and post-probiotic samples. Lactobacillus and Bacillus species were enriched in post-probiotic samples. Lactobacillus plantarum 299v levels were elevated in post-probiotic samples, confirming patient compliance. Conclusions: Our discovery of a relationship between Lactobacillus plantarum 299v, improved vascular endothelial function and decreased inflammation indicates intestinal microbiota may be developed as therapies to prevent and treat the progression of cardiovascular disease.

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