Gut microbiota derived metabolites in cardiovascular health and disease DOI Creative Commons
Zeneng Wang,

Yongzhong Zhao

Protein & Cell, Journal Year: 2018, Volume and Issue: 9(5), P. 416 - 431

Published: May 1, 2018

Trillions of microbes inhabit the human gut, not only providing nutrients and energy to host from ingested food, but also producing metabolic bioactive signaling molecules maintain health elicit disease, such as cardiovascular disease (CVD). CVD is leading cause mortality worldwide. In this review, we presented gut microbiota derived metabolites involved in including trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile lipopolysaccharide. These play critical roles maintaining a healthy function, if dysregulated, potentially causally linked CVD. A better understanding function dynamics holds great promise toward mechanistic predicative biomarker discoveries precise interventions.

Language: Английский

Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk DOI Creative Commons
Weifei Zhu,

Jill C. Gregory,

Elin Org

et al.

Cell, Journal Year: 2016, Volume and Issue: 165(1), P. 111 - 124

Published: March 1, 2016

Language: Английский

Citations

1597

Gut Microbiota in Cardiovascular Health and Disease DOI Open Access
W.H. Wilson Tang, Takeshi Kitai, Stanley L. Hazen

et al.

Circulation Research, Journal Year: 2017, Volume and Issue: 120(7), P. 1183 - 1196

Published: March 30, 2017

Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence revealed that intestinal microbiota play an important role human health and disease, including cardiovascular diseases. Changes the composition of associated with referred to as dysbiosis, have been linked pathologies such atherosclerosis, hypertension, heart failure, chronic kidney obesity, type 2 diabetes mellitus. In addition alterations composition, metabolic potential identified a contributing factor development Recent studies can elicit variety effects host. Indeed, microbiome functions like endocrine organ, generating bioactive metabolites, impact host physiology. Microbiota interact through many pathways, trimethylamine/trimethylamine

Language: Английский

Citations

1398

The gut microbiome in atherosclerotic cardiovascular disease DOI Creative Commons
Zhuye Jie,

Huihua Xia,

Shilong Zhong

et al.

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Oct. 4, 2017

The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of microbiome in relation diseases have not systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic disease (ACVD) 187 healthy controls. ACVD deviates status by increased abundance Enterobacteriaceae Streptococcus spp. and, functionally, potential for metabolism or transport several molecules important health. Although drug treatment represents confounding factor, status, current use, is major distinguishing feature this cohort. We identify common themes comparison data associated other cardiometabolic (obesity type 2 diabetes), liver cirrhosis, rheumatoid arthritis. Our represent comprehensive resource further investigations role promoting preventing as well related diseases.The may play authors controls, identifying microbial strains functions disease.

Language: Английский

Citations

1327

Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis DOI Creative Commons
Zeneng Wang, Adam Roberts,

Jennifer A. Buffa

et al.

Cell, Journal Year: 2015, Volume and Issue: 163(7), P. 1585 - 1595

Published: Dec. 1, 2015

Language: Английский

Citations

1125

Gut Microbiota-Dependent Trimethylamine N -Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease DOI Open Access
W.H. Wilson Tang, Zeneng Wang, David J. Kennedy

et al.

Circulation Research, Journal Year: 2014, Volume and Issue: 116(3), P. 448 - 455

Published: Nov. 7, 2014

Trimethylamine-N-oxide (TMAO), a gut microbial-dependent metabolite of dietary choline, phosphatidylcholine (lecithin), and l-carnitine, is elevated in chronic kidney diseases (CKD) associated with coronary artery disease pathogenesis.To both investigate the clinical prognostic value TMAO subjects versus without CKD, test hypothesis that plays direct contributory role development progression renal dysfunction.We first examined relationship between fasting plasma all-cause mortality over 5-year follow-up 521 stable CKD (estimated glomerular filtration rate, <60 mL/min per 1.73 m(2)). Median level among was 7.9 μmol/L (interquartile range, 5.2-12.4 μmol/L), which markedly higher (P<0.001) than non-CKD (n=3166). Within subjects, (fourth quartile) 2.8-fold increased risk. After adjustments for traditional risk factors, high-sensitivity C-reactive protein, estimated levels remained predictive (hazard ratio, 1.93; 95% confidence interval, 1.13-3.29; P<0.05). provided significant incremental (net reclassification index, 17.26%; P<0.001 differences area under receiver operator characteristic curve, 63.26% 65.95%; P=0.036). Among portend poorer prognosis within cohorts high low cystatin C. In animal models, choline or directly led to progressive tubulointerstitial fibrosis dysfunction.Plasma are patients long-term survival. Chronic exposures increase contributes dysfunction models.

Language: Английский

Citations

1040

Trimethylamine N‐Oxide Promotes Vascular Inflammation Through Signaling of Mitogen‐Activated Protein Kinase and Nuclear Factor‐κB DOI Creative Commons
Marcus M. Seldin, Yonghong Meng,

Hongxiu Qi

et al.

Journal of the American Heart Association, Journal Year: 2016, Volume and Issue: 5(2)

Published: Feb. 23, 2016

Background The choline‐derived metabolite trimethylamine N‐oxide ( TMAO ) has been demonstrated to contribute atherosclerosis and is associated with coronary artery disease risk. Methods Results We explored the impact of on endothelial smooth muscle cell function in vivo, focusing disease‐relevant outcomes for atherogenesis. Initially, we observed that aortas LDLR −/− mice fed a choline diet showed elevated inflammatory gene expression compared controls. Acute injection at physiological levels was sufficient induce same markers activate well‐known mitogen‐activated protein kinase, extracellular signal–related nuclear factor‐κB signaling cascade. These observations were recapitulated primary human aortic cells vascular cells. also found promotes recruitment activated leukocytes Through pharmacological inhibition, further activation necessary both these relevant types as well adhesion leukocytes. Conclusions Our results suggest likely contributory mechanism ‐dependent enhancement cardiovascular risks.

Language: Английский

Citations

733

Gut Microbiota and Cardiovascular Disease DOI Open Access
Marco Witkowski,

Taylor L. Weeks,

Stanley L. Hazen

et al.

Circulation Research, Journal Year: 2020, Volume and Issue: 127(4), P. 553 - 570

Published: July 30, 2020

Fecal microbial community changes are associated with numerous disease states, including cardiovascular (CVD). However, such data merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, transplantation studies, specific microbiota-dependent pathways, and downstream metabolites have all shown to influence host metabolism CVD, sometimes through identified receptors. Multiple metaorganismal pathways (involving both microbe host) impact animal models show striking clinical associations human studies. For example, trimethylamine N-oxide and, recently, phenylacetylglutamine whose blood levels incident risks large-scale Importantly, link these other metabolites/pathways mechanistic model Phenylacetylglutamine, was recently promote adverse phenotypes the via interaction multiple ARs (adrenergic receptors)-a class key receptors that regulate homeostasis. In this review, we summarize recent advances microbiome research related cardiometabolic helped move field forward from associative causative results. We focus on compounds/pathways, attention paid short-chain fatty acids, secondary bile N-oxide, phenylacetylglutamine. also discuss novel therapeutic strategies directly targeting improve outcomes.

Language: Английский

Citations

730

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System DOI Creative Commons
Thomas S. Postler, Sankar Ghosh

Cell Metabolism, Journal Year: 2017, Volume and Issue: 26(1), P. 110 - 130

Published: June 15, 2017

Language: Английский

Citations

725

Dietary metabolism, the gut microbiome, and heart failure DOI
W.H. Wilson Tang,

Daniel Y. Li,

Stanley L. Hazen

et al.

Nature Reviews Cardiology, Journal Year: 2018, Volume and Issue: 16(3), P. 137 - 154

Published: Nov. 8, 2018

Language: Английский

Citations

605

Role of gut microbiota in atherosclerosis DOI

Annika Lindskog Jonsson,

Fredrik Bäckhed

Nature Reviews Cardiology, Journal Year: 2016, Volume and Issue: 14(2), P. 79 - 87

Published: Dec. 1, 2016

Language: Английский

Citations

548