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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/10/2065 |
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| author | Karen J. Ho Joel L. Ramirez Rohan Kulkarni Katharine G. Harris Irene Helenowski Liqun Xiong C. Keith Ozaki S. Marlene Grenon |
| author_facet | Karen J. Ho Joel L. Ramirez Rohan Kulkarni Katharine G. Harris Irene Helenowski Liqun Xiong C. Keith Ozaki S. Marlene Grenon |
| author_sort | Karen J. Ho |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T19:44:56Z |
| format | Article |
| id | doaj.art-fcc71e19a01842ed85759467b15f4570 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T19:44:56Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-fcc71e19a01842ed85759467b15f45702023-11-24T01:27:51ZengMDPI AGMicroorganisms2076-26072022-10-011010206510.3390/microorganisms10102065Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac EventsKaren J. Ho0Joel L. Ramirez1Rohan Kulkarni2Katharine G. Harris3Irene Helenowski4Liqun Xiong5C. Keith Ozaki6S. Marlene Grenon7Division of Vascular Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADivision of Vascular & Endovascular Surgery, University of California San Francisco, San Francisco, CA 94143, USADivision of Vascular Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Biology, Franklin College, Franklin, IN 46131, USADepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADivision of Vascular Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADivision of Vascular and Endovascular Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USADivision of Vascular & Endovascular Surgery, University of California San Francisco, San Francisco, CA 94143, USACardiovascular 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.https://www.mdpi.com/2076-2607/10/10/2065peripheral artery diseaseankle-brachial indexmicrobiome |
| spellingShingle | Karen J. Ho Joel L. Ramirez Rohan Kulkarni Katharine G. Harris Irene Helenowski Liqun Xiong C. Keith Ozaki S. Marlene Grenon Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events Microorganisms peripheral artery disease ankle-brachial index microbiome |
| title | Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events |
| title_full | Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events |
| title_fullStr | Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events |
| title_full_unstemmed | Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events |
| title_short | Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events |
| title_sort | plasma gut microbe derived metabolites associated with peripheral artery disease and major adverse cardiac events |
| topic | peripheral artery disease ankle-brachial index microbiome |
| url | https://www.mdpi.com/2076-2607/10/10/2065 |
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