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Alterations of Gut Microbiome and Serum Metabolome in Coronary Artery Disease Patients Complicated With Non-alcoholic Fatty Liver Disease Are Associated With Adverse Cardiovascular Outcomes
Rationale: Patients suffering from coronary artery disease (CAD) complicated with nonalcoholic fatty liver disease (NAFLD) present worse cardiovascular outcomes than CAD patients without NAFLD. The progression of CAD is recently reported to be associated with gut microbiota and microbe-derived metab...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761954/ https://www.ncbi.nlm.nih.gov/pubmed/35047580 http://dx.doi.org/10.3389/fcvm.2021.805812 |
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author | Hu, Xiaomin Zhou, Ruilin Li, Hanyu Zhao, Xinyue Sun, Yueshen Fan, Yue Zhang, Shuyang |
author_facet | Hu, Xiaomin Zhou, Ruilin Li, Hanyu Zhao, Xinyue Sun, Yueshen Fan, Yue Zhang, Shuyang |
author_sort | Hu, Xiaomin |
collection | PubMed |
description | Rationale: Patients suffering from coronary artery disease (CAD) complicated with nonalcoholic fatty liver disease (NAFLD) present worse cardiovascular outcomes than CAD patients without NAFLD. The progression of CAD is recently reported to be associated with gut microbiota and microbe-derived metabolites. However, it remains unclear how the complication of NAFLD will affect gut microbiota and microbe-derived metabolites in CAD patients, and whether or not this interplay is related to the worse cardiovascular outcomes in CAD-NAFLD patients. Methods: We performed 16S rRNA sequencing and serum metabolomic analysis in 27 CAD patients with NAFLD, 81 CAD patients without NAFLD, and 24 matched healthy volunteers. Predicted functional profiling was achieved using PICRUSt2. The occurrence of cardiovascular events was assessed by a follow-up study. The association of alterations in the gut microbiome and metabolome with adverse cardiovascular events and clinical indicators was revealed by Spearman correlation analysis. Results: We discovered that the complication of NAFLD was associated with worse clinical outcomes in CAD patients and critical serum metabolome shifts. We identified 25 metabolite modules that were correlated with poor clinical outcome in CAD-NAFLD patients compared with non-NAFLD patients, represented by increased cardiac-toxic metabolites including prochloraz, brofaromine, aristolochic acid, triethanolamine, and reduced potentially beneficial metabolites including estradiol, chitotriose, palmitelaidic acid, and moxisylyte. In addition, the gut microbiome of individuals with CAD-NAFLD was changed and characterized by increased abundances of Oscillibacter ruminantium and Dialister invisus, and decreased abundances of Fusicatenibacter saccharivorans, Bacteroides ovatus and Prevotella copri. PICRUSt2 further confirmed an increase of potential pathogenic bacteria in CAD-NAFLD. Moreover, we found that variations of gut microbiota were critically correlated with changed circulating metabolites and clinical outcomes, which revealed that aberrant gut microbiota in CAD-NAFLD patients may sculpt a detrimental metabolome which results in adverse cardiovascular outcomes. Conclusions: Our findings suggest that CAD patients complicated with NAFLD result in worse clinical outcomes possibly by modulating the features of the gut microbiota and circulating metabolites. We introduce “liver-gut microbiota-heart axis” as a possible mechanism underlying this interrelationship. Our study provides new insights on the contribution of gut microbiota heterogeneity to CAD-NAFLD progression and suggests novel strategies for disease therapy. |
format | Online Article Text |
id | pubmed-8761954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87619542022-01-18 Alterations of Gut Microbiome and Serum Metabolome in Coronary Artery Disease Patients Complicated With Non-alcoholic Fatty Liver Disease Are Associated With Adverse Cardiovascular Outcomes Hu, Xiaomin Zhou, Ruilin Li, Hanyu Zhao, Xinyue Sun, Yueshen Fan, Yue Zhang, Shuyang Front Cardiovasc Med Cardiovascular Medicine Rationale: Patients suffering from coronary artery disease (CAD) complicated with nonalcoholic fatty liver disease (NAFLD) present worse cardiovascular outcomes than CAD patients without NAFLD. The progression of CAD is recently reported to be associated with gut microbiota and microbe-derived metabolites. However, it remains unclear how the complication of NAFLD will affect gut microbiota and microbe-derived metabolites in CAD patients, and whether or not this interplay is related to the worse cardiovascular outcomes in CAD-NAFLD patients. Methods: We performed 16S rRNA sequencing and serum metabolomic analysis in 27 CAD patients with NAFLD, 81 CAD patients without NAFLD, and 24 matched healthy volunteers. Predicted functional profiling was achieved using PICRUSt2. The occurrence of cardiovascular events was assessed by a follow-up study. The association of alterations in the gut microbiome and metabolome with adverse cardiovascular events and clinical indicators was revealed by Spearman correlation analysis. Results: We discovered that the complication of NAFLD was associated with worse clinical outcomes in CAD patients and critical serum metabolome shifts. We identified 25 metabolite modules that were correlated with poor clinical outcome in CAD-NAFLD patients compared with non-NAFLD patients, represented by increased cardiac-toxic metabolites including prochloraz, brofaromine, aristolochic acid, triethanolamine, and reduced potentially beneficial metabolites including estradiol, chitotriose, palmitelaidic acid, and moxisylyte. In addition, the gut microbiome of individuals with CAD-NAFLD was changed and characterized by increased abundances of Oscillibacter ruminantium and Dialister invisus, and decreased abundances of Fusicatenibacter saccharivorans, Bacteroides ovatus and Prevotella copri. PICRUSt2 further confirmed an increase of potential pathogenic bacteria in CAD-NAFLD. Moreover, we found that variations of gut microbiota were critically correlated with changed circulating metabolites and clinical outcomes, which revealed that aberrant gut microbiota in CAD-NAFLD patients may sculpt a detrimental metabolome which results in adverse cardiovascular outcomes. Conclusions: Our findings suggest that CAD patients complicated with NAFLD result in worse clinical outcomes possibly by modulating the features of the gut microbiota and circulating metabolites. We introduce “liver-gut microbiota-heart axis” as a possible mechanism underlying this interrelationship. Our study provides new insights on the contribution of gut microbiota heterogeneity to CAD-NAFLD progression and suggests novel strategies for disease therapy. Frontiers Media S.A. 2022-01-03 /pmc/articles/PMC8761954/ /pubmed/35047580 http://dx.doi.org/10.3389/fcvm.2021.805812 Text en Copyright © 2022 Hu, Zhou, Li, Zhao, Sun, Fan and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Hu, Xiaomin Zhou, Ruilin Li, Hanyu Zhao, Xinyue Sun, Yueshen Fan, Yue Zhang, Shuyang Alterations of Gut Microbiome and Serum Metabolome in Coronary Artery Disease Patients Complicated With Non-alcoholic Fatty Liver Disease Are Associated With Adverse Cardiovascular Outcomes |
title | Alterations of Gut Microbiome and Serum Metabolome in Coronary Artery Disease Patients Complicated With Non-alcoholic Fatty Liver Disease Are Associated With Adverse Cardiovascular Outcomes |
title_full | Alterations of Gut Microbiome and Serum Metabolome in Coronary Artery Disease Patients Complicated With Non-alcoholic Fatty Liver Disease Are Associated With Adverse Cardiovascular Outcomes |
title_fullStr | Alterations of Gut Microbiome and Serum Metabolome in Coronary Artery Disease Patients Complicated With Non-alcoholic Fatty Liver Disease Are Associated With Adverse Cardiovascular Outcomes |
title_full_unstemmed | Alterations of Gut Microbiome and Serum Metabolome in Coronary Artery Disease Patients Complicated With Non-alcoholic Fatty Liver Disease Are Associated With Adverse Cardiovascular Outcomes |
title_short | Alterations of Gut Microbiome and Serum Metabolome in Coronary Artery Disease Patients Complicated With Non-alcoholic Fatty Liver Disease Are Associated With Adverse Cardiovascular Outcomes |
title_sort | alterations of gut microbiome and serum metabolome in coronary artery disease patients complicated with non-alcoholic fatty liver disease are associated with adverse cardiovascular outcomes |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761954/ https://www.ncbi.nlm.nih.gov/pubmed/35047580 http://dx.doi.org/10.3389/fcvm.2021.805812 |
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