The Relationship Between Trimethylamine-N-Oxide and Prevalent Cardiovascular Disease in a Multiethnic Population Living in Canada

Mente, Andrew; Chalcraft, Kenneth R.; Ak, Handan; Davis, A. Darlene; Lonn, Eva; Miller, Ruby; Potter, Murray; Yusuf, Salim; Anand, Sonia S.; McQueen, Matthew

doi:10.1016/j.cjca.2015.06.016

Cited by 114 publications

(97 citation statements)

References 19 publications

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“…These observations were further corroborated and extended by subsequent studies from the same group and others (X. S. Li et al, 2017; Mente et al, 2015; Tang et al, 2014; 2013; 2015; Trøseid et al, 2015; Z. Wang et al, 2014).…”

Section: The Role Of the Microbiome In Metabolic Diseasessupporting

confidence: 79%

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

2017

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SUMMARY The human gastrointestinal tract is populated by a diverse, highly mutualistic microbial flora, which is known as the microbiome. Disruptions to the microbiome have been shown to be associated with severe pathologies of the host including metabolic disease, cancer and inflammatory bowel disease. Mood and behavior are also susceptible to alterations in the gut microbiota. A particularly striking example of the symbiotic effects of the microbiome is the immune system, whose cells depend critically on a diverse array of microbial metabolites for normal development and behavior. This includes metabolites that are produced by bacteria from dietary components; metabolites that are produced by the host and biochemically modified by gut bacteria; and metabolites that are synthesized de novo by gut microbes. In this review, we highlight the role of the intestinal microbiome in human metabolic and inflammatory diseases and focus in particular on the molecular mechanisms that govern the gut-immune axis.

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Section: The Role Of the Microbiome In Metabolic Diseasessupporting

confidence: 79%

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

2017

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“…Specifically, choline, phosphatidylcholine and carnitine, trimethylamine (TMA)-containing nutrients abundant in foods like meat, egg yolk and high fat dairy products, serve as dietary precursors for trimethylamine N-oxide (TMAO) generation in mice and humans, a metabolite that accelerates atherosclerosis in animal models (Koeth et al, 2013; Tang et al, 2013; Wang et al, 2011). Blood TMAO levels are associated with risks for both prevalent atherosclerotic heart disease and incident major adverse cardiac events in multiple independent cohorts (Koeth et al, 2013; Lever et al, 2014; Mente et al, 2015; Tang et al, 2014; Tang et al, 2013; Troseid et al, 2015; Wang et al, 2011; Wang et al, 2014b). TMAO lowering interventions are thus of considerable interest for their potential therapeutic benefit (Brown and Hazen, 2015).…”

Section: Introductionmentioning

confidence: 99%

Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis

Wang

Roberts

Buffa

et al. 2015

Cell

1,039

846

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SUMMARY Trimethylamine N-oxide (TMAO), a gut microbiota dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial trimethylamine (TMA) production, on diet-induced atherosclerosis. A structural analogue of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (eg intestinal contents, human feces) and reduce TMAO levels in mice fed a high choline or carnitine diet. DMB inhibited choline diet-enhanced endogenous macrophage foam cell formation and atherosclerotic lesion development in apolipoprotein e−/− mice without alterations in circulating cholesterol levels. The present studies suggest gut microbial production of TMA specifically, and non-lethal microbial inhibitors in general, may serve as a potential therapeutic approach for the treatment of cardiometabolic diseases.

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“…Although animal models indicate that TMAO influences CVD risk through atherosclerosis, there have been no prospective studies of early atherosclerosis progression in population‐based samples. Previous human studies of TMAO and atherosclerosis have been small or cross‐sectional and have yielded mixed results . Studies of TMAO and CVD events have been conducted in older clinic‐based samples with a high prevalence of comorbidities, and the relationship between TMAO and atherosclerotic disease in younger and healthier individuals is not known.…”

Section: Introductionmentioning

confidence: 99%

Microbiota‐Dependent Metabolite Trimethylamine N‐Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA)

Meyer

Benton

Bennett

et al. 2016

JAHA

147

115

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BackgroundClinical studies implicate trimethylamine N‐oxide (TMAO; a gut microbiota‐dependent nutrient metabolite) in cardiovascular disease risk. There is a lack of population‐based data on the role of TMAO in advancing early atherosclerotic disease. We tested the prospective associations between TMAO and coronary artery calcium (CAC) and carotid intima‐media thickness (cIMT).Methods and ResultsData were from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of US adults recruited in 1985–1986 (n=5115). We randomly sampled 817 participants (aged 33–55 years) who attended examinations in 2000–2001, 2005–2006, and 2010–2011, at which CAC was measured by computed tomography and cIMT (2005–2006) by ultrasound. TMAO was quantified using liquid chromotography mass spectrometry on plasma collected in 2000–2001. Outcomes were incident CAC, defined as Agatston units=0 in 2000–2001 and >0 over 10‐year follow‐up, CAC progression (any increase over 10‐year follow‐up), and continuous cIMT. Over the study period, 25% (n=184) of those free of CAC in 2000–2001 (n=746) developed detectable CAC. In 2000–2001, median (interquartile range) TMAO was 2.6 (1.8–4.2) μmol/L. In multivariable‐adjusted models, TMAO was not associated with 10‐year CAC incidence (rate ratio=1.03; 95% CI: 0.71–1.52) or CAC progression (0.97; 0.68–1.38) in Poisson regression, or cIMT (beta coefficient: −0.009; −0.03 to 0.01) in linear regression, comparing the fourth to the first quartiles of TMAO.ConclusionsIn this population‐based study, TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT. These data indicate that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early‐middle‐aged adults.

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The Relationship Between Trimethylamine-N-Oxide and Prevalent Cardiovascular Disease in a Multiethnic Population Living in Canada

Cited by 114 publications

References 19 publications

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis

Microbiota‐Dependent Metabolite Trimethylamine N‐Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA)

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