Detailed Description:

Endothelial dysfunction (ED) is a pathological state of vessel function characterized by increased expression of pro-vasoconstrictive mediators and increased thrombotic risk. ED is associated with the development of atherosclerosis, including coronary artery disease (CAD), and with increased risk of cardiovascular events Therefore, there is an ongoing research effort to restore endothelial function in order to reduce the risk of cardiovascular morbidity associated with endothelial dysfunction. The gut microbiome has been well correlated with the presence of CAD and alterations to the gut microbiome have been mechanistically linked to the severity of myocardial infarction. Animal experiments showed that alteration of gut bacteria with supplementation of Lactobacillus plantarum 299v (Lp299v) and vancomycin is associated with reduced leptin levels, size of myocardial infarction and improved post -ischemic cardiac function. In humans, dietary supplementation with Lp299v was associated with significant reductions in LDL-cholesterol, fibrinogen, and leptin concentrations in smokers.The investigatorsrecently showed in men with stable CAD that six weeks' supplementation with Lp299v improved endothelial function as assessed by brachial artery flow-mediated dilation (BA-FMD), a widely accepted noninvasive modality of assessing vascular endothelial function. This intervention concurrently reduced serum inflammatory markers IL-8, IL-12 and leptin, and post-probiotic plasma drove an anti-inflammatory transcriptomic response in cultured peripheral blood mononuclear cells. Interestingly, these beneficial changes were not accompanied by changes in gut microbiome constituents. Instead, the increase seen in BA-FMD was positively correlated with an increase in serum propionic acid, one of the short-chain fatty acids, a set of molecules produced by gut microbes and freely absorbed into human circulation. Propionic acid is known to improve endothelial function, reduce systemic inflammation, and improve glucose homeostasis in several models. These experiments suggested that Lp299v's beneficial effects were mediated by changes to the existing gut microbiome's metabolism as opposed to changes to microbial constituents. The investigators identified propionic acid as a potential mediator of these beneficial outcomes. In this study, the investigator's objective is to assess if there is any impact of sodium propionate dietary supplementation on vascular endothelial function and on the levels of circulating inflammatory markers related to endothelial dysfunction. In addition, the investigators also will study if the impact on endothelial function is associated with either: anti-inflammatory changes in relevant vascular cell types (e.g. endothelial cells, peripheral blood mononuclear cells), or on the constituents of the gut microbiome itself. Endothelial function is easily measurable by non-invasive means. Endothelial dysfunction measured non-invasively independently predicts future cardiovascular risk in patients both with and without clinically apparent cardiovascular disease. Conduit vessel endothelial function in humans is commonly quantified by measurement of BA-FMD, which represents the endothelium-dependent relaxation of a conduit artery-typically the brachial artery - due to an increased blood flow. BA-FMD correlates with impaired endothelium-dependent relaxation in the coronary arteries and is a commonly recognized "barometer" of cardiovascular risk. BA-FMD is an ideal surrogate marker of cardiovascular risk to monitor the acute impact of Lp299v supplementation on vascular endothelial function.}}