Gut Microbiota–Dependent Trimethylamine N-Oxide Predicts Risk of Cardiovascular Events in Patients With Stroke and Is Related to Proinflammatory Monocytes
Arash Haghikia,Xinmin S. Li,Thomas G. Liman,Nils Bledau,David Schmidt,Friederike Zimmermann,Nicolle Kränkel,Christian Widera,Kristina Sonnenschein,Aiden Haghikia,Karin Weissenborn,Daniela Fraccarollo,Markus M. Heimesaat,Johann Bauersachs,Zeneng Wang,Weifei Zhu,Udo Bavendiek,Stanley L. Hazen,Stanley L. Hazen,Matthias Endres,Ulf Landmesser +20 more
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TLDR
The data support the notion that TMAO-related increase of proinflammatory monocytes may add to elevated cardiovascular risk of patients with increased TMAOs, as well as in mice with depleted gut microbiota.Abstract:
Objective- Gut microbiota-dependent metabolites, in particular trimethylamine N-oxide (TMAO), have recently been reported to promote atherosclerosis and thrombosis. Here, we examined for the first time the relation of TMAO and the risk of incident cardiovascular events in patients with recent first-ever ischemic stroke in 2 independent prospective cohorts. Moreover, the link between TMAO and proinflammatory monocytes as a potential contributing factor for cardiovascular risk in stroke patients was studied. Approach and Results- In a first study (n=78), higher TMAO plasma levels were linked with an increased risk of incident cardiovascular events including myocardial infarction, recurrent stroke, and cardiovascular death (fourth quartile versus first quartile; hazard ratio, 2.31; 95% CI, 1.25-4.23; P<0.01). In the second independent validation cohort (n=593), high TMAO levels again heralded marked increased risk of adverse cardiovascular events (fourth quartile versus first quartile; hazard ratio, 5.0; 95% CI, 1.7-14.8; P<0.01), and also after adjustments for cardiovascular risk factors including hypertension, diabetes mellitus, LDL (low-density lipoprotein) cholesterol, and estimated glomerular filtration rate (hazard ratio, 3.3; 95% CI, 1.2-10.9; P=0.04). A significant correlation was also found between TMAO levels and percentage of proinflammatory intermediate CD14++CD16+ monocytes ( r=0.70; P<0.01). Moreover, in mice fed a diet enriched with choline to increase TMAO synthesis, levels of proinflammatory murine Ly6Chigh monocytes were higher than in the chow-fed control group (choline: 9.2±0.5×103 per mL versus control: 6.5±0.5×103 per mL; P<0.01). This increase was abolished in mice with depleted gut microbiota (choline+antibiotics: 5.4±0.7×103 per mL; P<0.001 versus choline). Conclusions- The present study demonstrates for the first time a graded relation between TMAO levels and the risk of subsequent cardiovascular events in patients with recent prior ischemic stroke. Our data support the notion that TMAO-related increase of proinflammatory monocytes may add to elevated cardiovascular risk of patients with increased TMAO levels.read more
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Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target.
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References
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Journal ArticleDOI
Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment
Harold P. Adams,Birgitte H. Bendixen,L J Kappelle,José Biller,Betsy B. Love,David Lee Gordon,E. Eugene Marsh +6 more
TL;DR: The TOAST stroke subtype classification system is easy to use and has good interobserver agreement and should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke.
Journal ArticleDOI
A core gut microbiome in obese and lean twins
Peter J. Turnbaugh,Micah Hamady,Tanya Yatsunenko,Brandi L. Cantarel,Alexis E. Duncan,Ruth E. Ley,Mitchell L. Sogin,William J. Jones,Bruce A. Roe,Jason P. Affourtit,Michael Egholm,Bernard Henrissat,Andrew C. Heath,Rob Knight,Jeffrey I. Gordon +14 more
TL;DR: The faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers are characterized to address how host genotype, environmental exposure and host adiposity influence the gut microbiome.
Journal ArticleDOI
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Zeneng Wang,Elizabeth Klipfell,Brian J. Bennett,Robert A. Koeth,Bruce S. Levison,Brandon DuGar,Ariel E. Feldstein,Earl B. Britt,Xiaoming Fu,Yoon-Mi Chung,Yuping Wu,Phil Schauer,Jonathan D. Smith,Hooman Allayee,W.H. Wilson Tang,Joseph A. DiDonato,Aldons J. Lusis,Stanley L. Hazen +17 more
TL;DR: Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
Journal ArticleDOI
Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis
Robert A. Koeth,Zeneng Wang,Bruce S. Levison,Jennifer A. Buffa,Elin Org,Brendan Sheehy,Earl B. Britt,Xiaoming Fu,Yuping Wu,Lin Li,Jonathan D. Smith,Joseph A. DiDonato,Jun Chen,Hongzhe Li,Gary D. Wu,James D. Lewis,Manya Warrier,J. Mark Brown,Ronald M. Krauss,W.H. Wilson Tang,Frederic D. Bushman,Aldons J. Lusis,Stanley L. Hazen +22 more
TL;DR: It is demonstrated that metabolism by intestinal microbiota of dietary l-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice, and intestinal microbiota may contribute to the well-established link between high levels of red meat consumption and CVD risk.
Journal ArticleDOI
Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk
W.H. Wilson Tang,Zeneng Wang,Bruce S. Levison,Robert A. Koeth,Earl B. Britt,Xiaoming Fu,Yuping Wu,Stanley L. Hazen +7 more
TL;DR: The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota and increased levels are associated with an increased risk of incident major adverse cardiovascular events.
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