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

Author:

Hu Xiaomin,Zhou Ruilin,Li Hanyu,Zhao Xinyue,Sun Yueshen,Fan Yue,Zhang Shuyang

Abstract

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.

Funder

Natural Science Foundation of Beijing Municipality

National Natural Science Foundation of China

National Key Research and Development Program of China

Publisher

Frontiers Media SA

Subject

Cardiology and Cardiovascular Medicine

Cited by 13 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3