Invited commentary

Abstract

The human gastrointestinal tract is colonized with around 1014 microorganisms that are collectively termed the microbiota. Disruptions in the microbiota have been shown to correlate not only with gut disease but also with obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. Short-chain fatty acid byproducts such as butyrate, propionate, and acetate act as a major energy source for intestinal epithelial cells and therefore strengthen the mucosal barrier. There is much interest in the ability to modify the gut microbiota. It has been shown that an acute change in diet, for instance, to one that is strictly animal based or plant based, can alter the microbial composition within just 24 hours of initiation. Animal studies have also shown that diets high in fat or high in sugar can cause circadian rhythm disruption. The authors of this manuscript perform a pilot study showing that baseline plasma concentrations of multiple gut microbiome-modulated indole- and phenyl-derived metabolites are associated with advanced atherosclerosis and predict risk of postoperative cardiovascular events and mortality. They specifically note that patients with advanced atherosclerosis have significantly lower baseline plasma concentrations of tryptophan and of indole and indole derivatives indole-3-aldehyde and indole-3-propionic acid and higher plasma concentrations of kynurenine/tryptophan ratio compared with age-matched controls. Tryptophan deletion has been associated with activation of inflammatory pathways. Given the fact that cardiovascular disease is a chronic inflammatory disease, it is not surprising that tryptophan metabolism has been correlated with cardiovascular disease. They further showed a significant relationship between these metabolites and ankle-brachial indexes in the entire cohort. This is the first reported association of these metabolites with peripheral arterial disease or with major postoperative adverse cardiac events. Although this is a pilot study, these are promising biomarkers to help stratify our patients and to educate are patients with more details for outcomes and progression of disease. The “cure” for atherosclerotic disease is the holy grail of cardiovascular research. Atherosclerotic disease is a complex disease, and characterization of the underlying mechanisms is therefore difficult. However, there is increasing evidence that “you may be what you eat” in that the microbiota may have a more prominent role in cardiovascular disease. How the microbiota influences atherosclerosis is still in question, but it could be through promoting plaque development by activation of the immune system, alterations in cholesterol metabolism, or production of bacterial metabolites that could be biomarkers for severity of disease. Whether cardiovascular disease can be successfully treated by targeting the microbiota is still unclear. Having patients adhere to strict diets can be troublesome; however, better education of our patients for improvement in their dietary choices may have an impact on progression of their disease. So, in fact, what your parents taught you, “you are what you eat,” may very well be true. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery Plasma microbiome-modulated indole- and phenyl-derived metabolites associate with advanced atherosclerosis and postoperative outcomesJournal of Vascular SurgeryVol. 68Issue 5PreviewMultiple studies have shown that gut microbes contribute to atherosclerosis, and there is mounting evidence that microbial metabolism of dietary nutrients influences pathophysiology. We hypothesized that indole- and phenyl-derived metabolites that originate solely or in part from bacterial sources would differ between patients with advanced atherosclerosis and age- and sex-matched controls without clinically apparent atherosclerosis. Full-Text PDF Open Archive