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

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 ex...

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Detalles Bibliográficos
Autores principales: Ho, Karen J., Ramirez, Joel L., Kulkarni, Rohan, Harris, Katharine G., Helenowski, Irene, Xiong, Liqun, Ozaki, C. Keith, Grenon, S. Marlene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609963/
https://www.ncbi.nlm.nih.gov/pubmed/36296342
http://dx.doi.org/10.3390/microorganisms10102065
Descripción
Sumario: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.