Journal Article

Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events

Grenon, S. Marlene, Harris, Katharine G., Ho, Karen J., Xiong, Liqun, Ozaki, C. Keith, Ramirez, Joel L., Kulkarni, Rohan, Helenowski, Irene

2022

Overview

Cardiovascular diseases are associated with gut dysbiosis, but the role of microbe-derived metabolites as biomarkers or modulators of cardiovascular disease are not well understood. This is a targeted metabolomics study to investigate the association of nine microbe-derived metabolites with lower extremity peripheral artery disease (PAD), a form of atherosclerosis, and major adverse cardiac events (MACE). The study cohort consists of individuals with intermittent claudication and ankle-brachial index (ABI) < 0.9 (N = 119) and controls without clinically-apparent atherosclerosis (N = 37). The primary endpoint was MACE, a composite endpoint of myocardial infarction, coronary revascularization, stroke, transient ischemic attack, or cardiac-related death. Plasma metabolite concentrations differed significantly between the PAD and control groups. After adjustment for traditional atherosclerosis risk factors, kynurenine, hippuric acid, indole-3-propionic acid (IPA), and indole-3-aldehyde (I3A) concentrations were negatively associated with PAD, whereas indoxyl sulfate and 3-hydroxyanthranilic acid were positively associated. Hippuric acid, IPA, and I3A correlated with ABI, a surrogate for atherosclerotic disease burden. Those in the highest I3A concentration quartile had significantly improved freedom from MACE during follow-up compared to those in the lowest quartile. This study identifies specific indole- and phenyl-derived species impacted by gut microbial metabolic pathways that could represent novel microbiome-related biomarkers of PAD.

• Publisher: MDPI AG,MDPI
• Subject: Aldehydes / Ankle / ankle-brachial index / Arteriosclerosis / Atherosclerosis / Biological markers / Biomarkers / Blood / Cardiovascular disease / Cardiovascular diseases / Cardiovascular research / Cerebral infarction / Chemical properties / Coronary artery disease / Coronary vessels / Dysbacteriosis / Health aspects / Heart diseases / Hippuric acid / Hyperlipidemia / Hypertension / Indoles / Intermittent claudication / Ischemia / Measurement / Metabolic pathways / Metabolites / Metabolomics / microbiome / Microbiomes / Microbiota (Symbiotic organisms) / Microorganisms / Modulators / Myocardial infarction / peripheral artery disease / Peripheral vascular diseases / Plasma / Propionic acid / R&D / Research & development / Risk analysis / Risk factors / Smoking / Stroke / Transient ischemic attack / Vascular diseases / Vein & artery diseases