The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index; 2 of the 8 sources its claims cite were checked for support.
Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk
Open accessAbstract
BACKGROUND: Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). We investigated the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans. METHODS: We quantified plasma and urinary levels of TMAO and plasma choline and betaine levels by means of liquid chromatography and online tandem mass spectrometry after a phosphatidylcholine challenge (ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics. We further examined the relationship between fasting plasma levels of TMAO and incident major adverse cardiovascular events (death, myocardial infarction, or stroke) during 3 years of follow-up in 4007 patients undergoing elective coronary angiography. RESULTS: Time-dependent increases in levels of both TMAO and its d9 isotopologue, as well as other choline metabolites, were detected after the phosphatidylcholine challenge. Plasma levels of TMAO were markedly suppressed after the administration of antibiotics and then reappeared after withdrawal of antibiotics. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event (hazard ratio for highest vs. lowest TMAO quartile, 2.54; 95% confidence interval, 1.96 to 3.28; P<0.001). An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors (P<0.001), as well as in lower-risk subgroups. CONCLUSIONS: The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota. Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events. (Funded by the National Institutes of Health and others.).
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Time-dependent increases in levels of both TMAO and its d9 isotopologue, as well as other choline metabolites, were detected after the phosphatidylcholine challenge.”
- Also stated in: § PHOSPHATIDYLCHOLINE CHALLENGE · plain
“Time-dependent increases in the levels of both TMAO (Fig. 1C) and d9-TMAO (Fig. 1D) were also observed postprandially.”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > Abstract > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § PHOSPHATIDYLCHOLINE CHALLENGE · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A strong correlation was observed between plasma levels of TMAO and the absolute urine TMAO level (Spearman’s r = 0.58, P<0.001) and the urinary ratio of TMAO to creatinine (Spearman’s r = 0.91, P<0.001).”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > PHOSPHATIDYLCHOLINE CHALLENGE
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, the time courses for postprandial changes in free choline and betaine (natural isotopes and d9-isotopologues) were not altered by suppression of intestinal micro-biota (Fig. S1 in the Supplementary Appendix).”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > PHOSPHATIDYLCHOLINE CHALLENGE
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The extent to which TMAO levels in plasma at visit 3 returned to preantibiotic levels was variable, a finding that is consistent with reports describing variable recovery of intestinal microbiota after antibiotic cessation.13,14”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > PHOSPHATIDYLCHOLINE CHALLENGE
What the sources say
Strength:plain· not yet calibratedn = 6Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Examination of 24-hour urine specimens after the phosphatidylcholine challenge also showed the presence of both TMAO and d9-TMAO (Fig. S2 in the Supplementary Appendix).”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > PHOSPHATIDYLCHOLINE CHALLENGE
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The suppression of intestinal microbiota by the administration of oral broad-spectrum antibiotics for 1 week in six of the participants resulted in near-complete suppression of detectable TMAO and d9-TMAO after the phosphatidylcholine challenge during visit 2 in both plasma (Fig. 1) and urine (Fig. S2 in the Supplementary Appendix).”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > PHOSPHATIDYLCHOLINE CHALLENGE
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Participants who had major adverse cardiovascular events also had higher baseline levels of TMAO, as compared with those who did not have cardiovascular events (median, 5.0 µM [interquartile range, 3.0 to 8.8] vs. 3.5 µM [interquartile range, 2.4 to 5.9]; P<0.001) (Table 1).”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > CLINICAL OUTCOMES
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A strong correlation was observed between plasma levels of TMAO and the absolute urine TMAO level (Spearman’s r = 0.58, P<0.001) and the urinary ratio of TMAO to creatinine (Spearman’s r = 0.91, P<0.001).”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > PHOSPHATIDYLCHOLINE CHALLENGE
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events.”
- Also stated in: § DISCUSSION · boosted
“We also established a correlation between high plasma levels of TMAO and an increased risk of incident major adverse cardiovascular events that is independent of traditional risk factors, even in low-risk cohorts.”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > Abstract > CONCLUSIONS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: A single fasting plasma TMAO measurement reflects the relevant long-term exposure for cardiovascular risk.
- Also stated in: § DISCUSSION · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The inclusion of TMAO as a covariate resulted in a significant improvement in risk estimation over traditional risk factors (net reclassification improvement, 8.6% [P<0.001]; integrated discrimination improvement, 9.2% [P<0.001]; C statistic, 68.3% vs. 66.4% [P = 0.01]).”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > CLINICAL OUTCOMES
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 6
- Probably not a substantial claim. 3
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Intestinal microbiota convert the choline moiety of dietary phosphatidylcholine into trimethylamine, which is subsequently converted into TMAO by hepatic flavin-containing monooxygenases (Fig. 3).20–23”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > DISCUSSION
What the sources say
- Partly supportedcites [20] sourceExperimental — accuracy not yet measured
The Introduction says gut flora convert dietary choline to trimethylamine, and the Results report that FMO1 and FMO3 oxidize trimethylamine to TMAO; the dietary-regulation Results also describe hepatic FMO3 activity. Our copy does not establish the more specific claim that the choline came from dietary phosphatidylcholine. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [21] source
- Not checked — no full text of the sourcecites [22] source
- Partly supportedcites [23] sourceExperimental — accuracy not yet measured
The Introduction describes gut flora converting dietary choline to trimethylamine (TMA), and the Results show that FMO1 and FMO3 oxidize TMA to TMAO; another Results passage locates FMO3 expression and TMA-oxidizing activity in the liver. The paper does not specifically state that the choline comes from dietary phosphatidylcholine, so that part of the claim is not supported by our copy. (LLM, conf=0.84)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In parallel analyses, postprandial elevations in plasma trimethlyamine and d9-trimethylamine levels were observed after the phosphatidylcholine challenge, but the levels were undetectable after the administration of antibiotics (data not shown).”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > PHOSPHATIDYLCHOLINE CHALLENGE
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After the withdrawal of antibiotics and subsequent reappearance of intestinal microbiota over a period of 1 month or longer, the phosphatidylcholine challenge during visit 3 again resulted in readily detectable and time-dependent changes in TMAO and d9-TMAO in plasma (Fig. 1) and urine (Fig. S2 in the Supplementary Appendix).”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > RESULTS > PHOSPHATIDYLCHOLINE CHALLENGE
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In unpublished studies, we observed that long-term use of a single antibiotic (6 months of ciprofloxacin), which initially suppressed plasma TMAO levels in a rodent model, completely lost its suppressive effect, an observation that is consistent with the expansion of antibiotic-resistant intestinal microbiota.”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We performed Cox proportional-hazards regression analysis with adjustment for traditional cardiovascular risk factors (age, sex, systolic blood pressure, presence or absence of diabetes mellitus, low-density and high-density lipoprotein cholesterol levels, triglyceride levels, and smoking status)”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > METHODS > STATISTICAL ANALYSIS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Major adverse cardiovascular events (defined as death from any cause, nonfatal myocardial infarction, and nonfatal stroke) were ascertained and adjudicated for all participants during 3 years of follow-up.”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > METHODS > LABORATORY TESTING
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our findings suggest that pathways that are dependent on the intestinal microbiota may contribute to the pathophysiology of atherosclerotic coronary artery disease and suggest potential therapeutic targets.”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We designed and performed two prospective clinical studies, which were funded by the National Institutes of Health and approved by the institutional review board at the Cleveland Clinic. All participants provided written informed consent.”
§ Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk > METHODS > STUDY DESIGNS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
Oral broad-spectrum antibiotics suppress TMAO production by suppressing intestinal microbiota rather than through direct effects on host metabolism.
“The suppression of intestinal microbiota by the administration of oral broad-spectrum antibiotics for 1 week in six of the participants resulted in near-complete suppression of detectable TMAO and d9-TMAO after the phosphatidylcholine challenge during visit 2 in both plasma (Fig. 1) and urine (Fig. S2 in the Supplementary Appendix).”
“The ability of oral broad-spectrum antibiotics to temporarily suppress the production of TMAO is a direct demonstration that intestinal microorganisms play an obligatory role in the production of TMAO from phosphatidylcholine in humans.”
The paper relies on this without support.
The reappearance of TMAO production after antibiotic withdrawal is due to reacquisition of intestinal microbiota.
“After the withdrawal of antibiotics and subsequent reappearance of intestinal microbiota over a period of 1 month or longer, the phosphatidylcholine challenge during visit 3 again resulted in readily detectable and time-dependent changes in TMAO and d9-TMAO in plasma (Fig. 1) and urine (Fig. S2 in the Supplementary Appendix).”
The paper relies on this without support.
A single fasting plasma TMAO measurement reflects the relevant long-term exposure for cardiovascular risk.
“Fasting blood samples were obtained from all participants at the time of cardiac catheterization.”
“fasting plasma TMAO levels predict the risk of incident major adverse cardiovascular events independently of traditional cardiovascular risk factors and the presence or extent of coronary artery disease and within multiple low-risk subgroups”
The paper relies on this without support.
The six participants who received antibiotics are representative of humans for the effect of microbiota suppression on TMAO production.
“Six of these study participants were then given metronidazole (500 mg twice daily) plus ciprofloxacin (500 mg once daily) for 1 week. After receipt of the antibiotics, a repeat phosphatidylcholine challenge was performed at visit 2.”
“The ability of oral broad-spectrum antibiotics to temporarily suppress the production of TMAO is a direct demonstration that intestinal microorganisms play an obligatory role in the production of TMAO from phosphatidylcholine in humans.”
The paper relies on this without support.
The acute phosphatidylcholine challenge with eggs and labeled phosphatidylcholine reflects normal dietary phosphatidylcholine metabolism relevant to TMAO production.
“A simple dietary phosphatidylcholine–choline challenge was administered to all participants in the first study.”
“At baseline, participants were given two large hard-boiled eggs including yolk (containing approximately 250 mg of total choline each) to be eaten within a 10-minute period together with 250 mg of deuterium-labeled phosphatidylcholine (d9-phosphatidylcholine), as a tracer, contained in a gelatin capsule”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Numerous recent case–control and longitudinal studies have shown a striking association between trimethylamine N‐oxide (TMAO) levels and cardiovascular disease risks in a variety of cohorts.1, 2, 3, 4, 5, 6, 7, 8, 9, 10”
From Trimethylamine N‐Oxide Promotes Vascular Inflammation Through Signaling of Mitogen‐Activated Protein Kinase and Nuclear Factor‐κB (2016) · cites this paper as [3]
In the citing paper
“Plasma TMAO levels in subjects (N>4000) independently predicted incident (3 yr) thrombosis (heart attack, stroke) risk.”
From Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk (2016) · cites this paper as Tang et al., 2013
In the citing paper
“Finally, an association between plasma TMAO levels and both the extent of coronary atherosclerotic plaque burden and CVD risks has been observed in multiple distinct clinical studies (Wang et al., 2011; Tang et al., 2013; Tang et al., 2014; Lever et al., 2014; Tang et al., 2015).”
From Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk (2016) · cites this paper as Tang et al., 2013
In the citing paper
“Moreover, an obligatory role for gut microbes in TMAO generation in humans was affirmed by two distinct studies involving ingestion of either isotope labeled phosphatidylcholine or isotope labeled carnitine as tracer before versus following exposure to an oral cocktail of poorly absorbed antibiotics to suppress intestinal microbes (Tang et al., 2013; Koeth et al., 2013).”
From Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk (2016) · cites this paper as Tang et al., 2013
In the citing paper
“recent studies reveal participation of gut microbes in a metaorganismal pathway that contributes to the development of atherosclerosis (Wang et al., 2011; Koeth et al., 2013; Tang et al., 2013; Gregory et al., 2015).”
From Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk (2016) · cites this paper as Tang et al., 2013
In the citing paper
“circulating levels of TMAO have been shown in multiple distinct clinical studies and cohorts to be associated with CVD risks”
From Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk (2016) · cites this paper as Tang et al., 2013
In the citing paper
“Animal model and human clinical studies demonstrate an obligatory role for gut microbiota in TMAO formation from TMA-containing nutrients including choline and phosphatidylcholine9, 10, L-carnitine8, and more recently, γ-butyrobetaine15, and to a lesser degree, the choline oxidation metabolite betaine11.”
In the citing paper
“In one large study of subjects with predominantly preserved renal function, we reported the prognostic value of TMAO for predicting three year risk for major adverse cardiovascular events (MACE = myocardial infarction, stroke or death) remained significant following adjustments for renal function 9.”
In the citing paper
“Specifically, gut microbiota-mediated metabolism of phosphatidylcholine, choline or L-carnitine each have been shown to ultimately produced trimethylamine-N-oxide (TMAO), and in multiple clinical studies, TMAO levels have been shown to be associated with cardiovascular risks8–10, 13.”
In the citing paper
“in multiple clinical studies, TMAO levels have been shown to be associated with cardiovascular risks8–10, 13.”
In the citing paper
“We have also established the obligatory role of intestinal microbiota in the production of TMAO from dietary choline and other TMA nutrients in humans, 16,17 and the association between elevated fasting levels of TMAO and higher incident risks of long-term MACEs.17”
From Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide (2014) · cites this paper as [17]
In the citing paper
“Moreover, elevated levels of TMAO have been shown to predict increased prevalent cardiovascular disease (CVD) risk, and increased incident risk of major adverse cardiovascular events (MACE ¼ myocardial infarction, stroke, and death) in large-scale human clinical studies.14,16,17”
From Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide (2014) · cites this paper as [17]
In the citing paper
“Interestingly, the administration of antibiotics in humans in our prior studies had limited effects on circulating choline and betaine levels, despite abolition of TMAO levels, upon ingestion of stable-isotope-labelled d9-PC.17”
From Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide (2014) · cites this paper as [17]
In the citing paper
“Choline, betaine, and TMAO are all metabolites formed following ingestion of dietary PC. 14,17”
From Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide (2014) · cites this paper as [17]
In the citing paper
“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”
From Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis (2015) · cites this paper as Tang et al., 2013
In the citing paper
“both enhances atherosclerosis in animal models”
From Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis (2015) · cites this paper as Tang et al., 2013
In the citing paper
“Our group has recently described a mechanistic link between intestinal microbe-dependent generation of trimethylamine-N-oxide (TMAO) and increased risk for future cardiovascular events (death, myocardial infarction, and stroke) by a pathway involving dietary nutrients such as phosphatidylcholine, choline, and carnitine (10,11).”
From Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-N-Oxide in Patients With Heart Failure (2014) · cites this paper as [11]
In the citing paper
“While TMAO has been shown to possess pro-atherogenic properties (10,11,17)”
From Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-N-Oxide in Patients With Heart Failure (2014) · cites this paper as [11]
In the citing paper
“The formation of TMA, which is subsequently metabolized to TMAO, depends on the presence of an intact gut microbiota [6]”
From Microbiota‐dependent metabolite trimethylamine‐N‐oxide is associated with disease severity and survival of patients with chronic heart failure (2015) · cites this paper as [6]
In the citing paper
“In multiple human studies, elevated TMAO has been independently associated with prevalent CVD and incident risks for MI, stroke, death, and revascularization.”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [37]
In the citing paper
“Specifically, patients in the upper quartile for TMAO levels (compared with the lowest quartile) had a significant, 2.5-fold increased risk of experiencing a major adverse cardiac event (MI, stroke, or death), independent of traditional cardiovascular risk factors, renal function, and medication use, as well as overall poorer event-free survival (37).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [37]
In the citing paper
“a metabolite shown to be both mechanistically linked to atherosclerosis and whose levels are strongly linked to cardiovascular disease (CVD) risks.”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [37]
In the citing paper
“In an alternative subsequent expansion study of over 4,000 subjects undergoing elective coronary angiography, elevated TMAO levels predicted major adverse cardiac events such as death, myocardial infarction (MI), and stroke over a 3-year period.”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [37]
In the citing paper
“An obligatory role for gut microbiota in both TMA and TMAO formation from ingested PC was confirmed in animal model studies, which included germ-free mice (25), as well as human clinical investigations involving ingestion of egg yolk, isotope-labeled PC, and a cocktail of oral antibiotics (37).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [37]
In the citing paper
“These observations highlight the obligatory role of intestinal microbiota in the generation of TMAO from multiple dietary nutrients, and TMAO as the proatherogenic species likely promoting the striking associations noted between plasma levels and both prevalent and incident CVD risks.”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [37]
In the citing paper
“More recent studies examining ingestion of either hard-boiled egg or egg yolk (37,38,62) or ingestion of trimethyl-d9-PC (37) have confirmed direct generation of TMAO from PC ingestion in humans.”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [37]
In the citing paper
“In vivo studies in which trimethyl-d9-labeled betaine or PC were ingested showed a direct generation of d9-TMA and d9-TMAO within plasma and urine (37,39,55).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [37]
In the citing paper
“Choline (free and esterified forms) and L-carnitine are the most common dietary nutrients ingested that produce TMA and TMAO (30,(37)(38)(39)55).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [37]
In the citing paper
“Our laboratory has elucidated a link between intestinal microbiota, dietary trimethylamine-containing nutrients ( e.g. choline, phosphatidylcholine, and carnitine), andcardiovasculardisease(5-7).”
From Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation (2015) · cites this paper as [7]
In the citing paper
“plasma levels in subjects are associated with prevalent and incident cardiovascular disease risks (5, 7, 9, 10).”
From Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation (2015) · cites this paper as [7]
In the citing paper
“An obligatory role for gut microbes in TMAO formation in both mice (5, 6) and humans (7) was shown”
From Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation (2015) · cites this paper as [7]
In the citing paper
“Elevated plasma TMAO levels are observed in subjects at risk for incident cardiovascular disease (CVD) development and adverse CVD events including heart attack, stroke, and death.[1][2][3][4]”
From Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women (2019) · cites this paper as [2]
In the citing paper
“Trimethylamine N-oxide (TMAO) is a gut microbiota-generated metabolite with mechanistic links to the pathogenesis of atherosclerotic heart disease.[1][2][3][4][5]”
From Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women (2019) · cites this paper as [2]
In the citing paper
“Studies have also shown dose-dependent TMA/TMAO formation with egg ingestion.2,18”
From Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women (2019) · cites this paper as [2]
In the citing paper
“Trimethylamine N-oxide is generated via a metaorganismal pathway that begins with gut microbiota-dependent formation of trimethylamine (TMA) from TMA containing nutrient precursors (Figure 1A).[1][2][3]16”
From Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women (2019) · cites this paper as [2]
In the citing paper
“In humans, recent clinical studies evidence a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events.”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [52]
In the citing paper
“some studies performed with antibiotics in rats and humans reveal that the production of TMA and TMAO is almost totally suppressed with the use of broad-spectrum antibiotics, such as Ciprofloxacin, Vancomycin or Metronidazole. However, the levels of TMAO return to normal after one month of the withdrawal of the antibiotics [7,52].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [52]
In the citing paper
“Indeed, elevated plasma TMAO levels have been found in people at risk of CVD. These patients usually show greater concentrations of the TMAO precursors too.”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [52]
In the citing paper
“In this context, it is thought that TMAO could serve as a biomarker in humans to predict prevalence of CVD and increased incidence of major adverse cardiovascular events (MACE), such as myocardial infarction, stroke and even death [7,14,52,53,54,55].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [52]
In the citing paper
“However, one month after the withdrawal of antibiotics, TMAO levels are detectable again [52].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [52]
In the citing paper
“Moreover, antibiotics do not only kill harmful bacteria, but could affect the beneficial too [52].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [52]
In the citing paper
“Albeit the use of antibiotics is effective in the suppression of microbiota that produces TMA, the chronic use of antibiotics is not viable since it can lead to resistant bacterial strains and repopulation.”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [52]
In the citing paper
“The use of broad spectrum antibiotics such us ciprofloxacin and metronidazole leads to near almost complete suppression of TMAO levels.”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [52]
In the citing paper
“Elevated TMAO has been observed in patients with cardiovascular disease and atherosclerosis, highlighting a potential downside to increased protein intake.[15-17,22, 37]”
From The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level (2018) · cites this paper as [16]
In the citing paper
“Recently, it has been shown that gut microbial production of trimethylamine N-oxide (TMAO) from dietary choline and l-carnitine increases the risk of developing cardiovascular disease in both mice and humans, independently of traditional cardiometabolic risk factors (89).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [89]
In the citing paper
“Recent studies by Wang and Tang et al reported that circulating concentrations of trimethylamine N‐oxide (TMAO), a metabolite derived from the gut microbiota, were predictive of prevalent cardiovascular diseases (CVDs)1 and future cardiovascular events3 in clinical cohorts.”
In the citing paper
“All of the studies included clinical cohorts, including patients at higher cardiovascular risk, that is, enriched for baseline heart disease,3, 8, 12, 13, 14, 15, 16, 17, 21 kidney disease,10, 11, 18, 19, 20, 22, 23 peripheral artery disease,25 or diabetes mellitus.7, 26”
In the citing paper
“Of the 19 publications, a total of 16 publications, including 19 data points, were eligible for our main analysis to calculate a pooled RR of elevated TMAO levels as compared with low levels3, 7, 8, 10, 11, 13, 16, 18, 19, 20, 21, 22, 23, 24, 25, 26 (Table 1 and Figure 1).”
In the citing paper
“Wang et al. identified a novel pathway linking dietary lipid intake, the intestinal microbiota, and atherosclerosis (Figure 3)57, 58.”
From Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease (2014) · cites this paper as [58]
In the citing paper
“Catabolism of choline by the intestinal microbiota results in the formation of the gas, trimethylamine (TMA), which is metabolized by the liver into trimethylamine oxide (TMAO)—a small molecule that is strongly associated with the increased risk for coronary vascular disease in humans.”
From Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease (2014) · cites this paper as [58]
In the citing paper
“The intestinal microbiota may also contribute to development of atherosclerosis by producing metabolites of the dietary lipid phosphatidylcholine that are associated with the risk for coronary vascular disease.”
From Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease (2014) · cites this paper as [58]
In the citing paper
“However, consumption of ≥2 eggs, which contain mostly PtdCho, results in increased formation of TMAO (79,110).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [110]
In the citing paper
“During three years of follow-up in patients (n = 4,007) undergoing elective coronary angiography, increased plasma concentrations of TMAO were associated with increased risks of major adverse cardiovascular events (110).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [110]
In the citing paper
“In individuals undergoing elective coronary angiography, plasma TMAO concentrations were correlated with increased serum glucose and the patient's diabetic state (110).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [110]
In the citing paper
“multiple human and animal studies supporting both mechanistic and clinical prognostic associations between TMAO formation and cardiometabolic disease risks have been reported8–16.”
From Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential (2018) · cites this paper as [8]
In the citing paper
“A recent metabolomics approach identified that plasma trimethylamine-N-oxide (TMAO), a choline metabolite, is a novel and independent risk factor for promoting AS (2, 3).”
In the citing paper
“TMAO has been shown to induce AS by affecting cholesterol metabolism through inhibiting hepatic bile acid (BA) synthesis (2–4).”
In the citing paper
“Recently, plasma TMAO was identified as a metabolite strongly associated with AS (2–4).”
In the citing paper
“Previous studies suggest that TMAO partially contributes to the development of AS by regulating the major pathway of cholesterol metabolism and the bile acid synthetic pathway.4, 5, 6”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [5]
In the citing paper
“Trimethylamine‐N‐oxide (TMAO) has recently been identified as a novel and independent risk factor for promoting atherosclerosis through inducing vascular inflammation.”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [5]
In the citing paper
“In a large independent clinical cohort (n=4007), elevated TMAO levels were associated with significantly increased risk for major adverse cardiovascular events (2.54 for highest versus lowest TMAO quartile; P<0.001).5”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [5]
In the citing paper
“Within the cohort examined, the hazard ratio for TMAO was significantly higher than that for traditional risk factors such as LDL cholesterol.”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [5]
In the citing paper
“Furthermore, elevated TMAO levels retained a strong prognostic value for predicting the incidence of adverse cardiovascular events, even after adjustment for traditional risk factors and renal function.5”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [5]
In the citing paper
“Recently, plasma TMAO was identified as a novel and independent risk factor for promoting AS.”
From Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway (2017) · cites this paper as [5]
In the citing paper
“Hazen and coworkers showed that consumption of foods rich in choline or carnitine, such as eggs, milk, liver, meat, or fish, produced high concentrations of TMAO in both humans and animals who possessed the requisite microbiota for metabolizing choline or carnitine to trimethylamine, the immediate precursor of TMAO (108, 171, 172).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [172]
In the citing paper
“Subjects from a cohort of .2000patients with cardiovascular disease, who were in the highest quartile for plasma TMAO concentrations, had a .2-foldrisk of a heart attack or stroke compared with subjects from the lowest quartile (108, 172).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [172]
In the citing paper
“The microbiota play an important role in choline diet–induced trimethylamine N-oxide production, which has been implicated in CVD.”
From The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids (2015) · cites this paper as [8]
In the citing paper
“These observations are of interest because high TMAO levels linked to TMA oxidation by the human hepatic flavin monooxygenase FMO3 have been associated with cardiovascular diseases (CVDs) (Tang et al., 2013; Wang et al., 2011), while it is known that RYGB is associated with a lower CVD risk (Sjöström et al., 2012).”
From Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation (2015) · cites this paper as Tang et al., 2013
In the citing paper
“Likewise, gut microbes can also convert otherwise beneficial dietary compounds, such as choline, into metabolites that are detrimental to human health (7–10).”
From Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide (2015) · cites this paper as [9]
In the citing paper
“a metabolite linked to accumulation of cholesterol in macrophages and foam cell deposition127, and higher risk of a major adverse cardiac event128.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [128]
In the citing paper
“Also in humans, PC or LC administration augmented TMA plasma levels, and increased the risk for cardiovascular disease; notably, antibiotic treatment dramatically reduced TMA levels in these subjects [68, 70].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [70]
In the citing paper
“a series of recent studies [68-70] revealed a link between microbiota and atherogenesis.”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [70]
In the citing paper
“Food is a major factor that shapes the proportional representation of organisms present in the gut microbial community (microbiota), and its gene content (microbiome).”
From Persistent gut microbiota immaturity in malnourished Bangladeshi children (2014) · cites this paper as [14]
In the citing paper
“The microbiota/microbiome in turn plays an important role in extracting and metabolizing dietary ingredients9-14.”
From Persistent gut microbiota immaturity in malnourished Bangladeshi children (2014) · cites this paper as [14]
In the citing paper
“This is exemplified by trimethylamine (TMA), a microbial metabolite that is produced by various taxa of the gut microbiota from dietary quaternary amines, mainly choline and carnitine. TMA is absorbed via the intestinal epithelium and further oxidized to trimethylamine N-oxide (TMAO), which was associated with atherosclerosis and severe cardiovascular disease in several independent studies [1–4].”
From Uncovering the trimethylamine-producing bacteria of the human gut microbiota (2017) · cites this paper as [2]
In the citing paper
“The first studies revealing a potential causal link between the gut microbiome and CVD focused on trimethylamine N-oxide (TMAO), a metaorganismal metabolite formed following ingestion of dietary nutrients abundant in a Western diet (e.g. lecithin, choline, carnitine)7–9.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [8]
In the citing paper
“Through these and other studies, generation of TMAO in humans and mice has been shown to occur via a multistep, metaorganismal pathway starting with the dietary precursors choline9, phosphatidylcholine8, 9, and carnitine7.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [8]
In the citing paper
“Further evidence that the production of TMAO is dependent on metabolism by intestinal microbiota is provided by studies in healthy humans given phosphatidylcholine challenge, in which the plasma levels of TMAO were suppressed by oral administration of broad spectrum antibiotics [14].”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [14]
In the citing paper
“TMAO is then either transported to the tissues for accumulation as an osmolyte or, more commonly, cleared by the kidney [3,9,13,14].”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [14]
In the citing paper
“Indeed, in health participants, suppression of intestinal microbiota with oral broad spectrum antibiotic reduced plasma TMAO levels after a phosphatidylcholine challenge [14].”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [14]
In the citing paper
“TMAO levels increased one month after stopping antibiotics [14].”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [14]
In the citing paper
“The mechanisms through which hPDI could reduce CHD risk are likely shared with the mechanisms for type 2 diabetes risk reduction.(2, 24–32)”
From Healthful and Unhealthful Plant-Based Diets and the Risk of Coronary Heart Disease in U.S. Adults (2017) · cites this paper as [30]
In the citing paper
“all of which could aid in weight loss/maintenance, enhance glycemic control and insulin regulation, improve lipid profile, reduce blood pressure, improve vascular health, decrease inflammation, and foster more favorable diet- gut microbiome interactions (e.g. through lowered levels of trimethylamine N-oxide), thereby lowering CHD risk.”
From Healthful and Unhealthful Plant-Based Diets and the Risk of Coronary Heart Disease in U.S. Adults (2017) · cites this paper as [30]
In the citing paper
“Gut microbes transform phosphatidylcholine and l‐carnitine from ingested nutrients to trimethylamine, which is absorbed and further oxidized by hepatic flavin monooxygenase to trimethylamine‐N‐oxide (TMAO)”
From Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack (2015) · cites this paper as [4]
In the citing paper
“a metabolite that could promote atherogenesis partly by promoting the formation of foam cells from macrophages.4, 5”
From Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack (2015) · cites this paper as [4]
In the citing paper
“Although the TMAO level has been suggested to be involved in atherosclerosis,4, 5”
From Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack (2015) · cites this paper as [4]
In the citing paper
“many cohort studies have suggested that an increased number of adverse outcomes are associated with high TMAO levels,4, 5, 6, 7”
From Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack (2015) · cites this paper as [4]
In the citing paper
“However, recent data suggest that it may also play a role in the development and maintenance of CVD and metabolic disorders such as obesity, diabetes and metabolic syndrome11–14.”
From Gut Dysbiosis Is Linked to Hypertension (2015) · cites this paper as [11]
In the citing paper
“Indeed, consumption of choline and L-carnitine rich diets offer the necessary precursors for the production of TMAO.2,3”
In the citing paper
“Several recent studies have identified trimethylamine N-oxide, a metabolite of the gut microbiota, as an independent risk factor for cardiovascular disease.17,18,34”
From Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe −/− Mice (2016) · cites this paper as [34]
In the citing paper
“Trimethylamine (TMA) and TMA N-oxide, which are gut microbiota metabolites of dietary phosphatidylcholine, are known to be associated with cardiovascular disease and with the atherosclerosis process in particular.3,4”
From Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis (2018) · cites this paper as [4]
In the citing paper
“its ability to reverse fibrosis in patients with nonalcoholic steatohepatitis (NASH) was demonstrated in a proof-of-concept study followed by a randomized control trial (RCT)150,151.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [151]
In the citing paper
“Despite an explosion of associative studies involving the microbiome and vascular and cardiovascular diseases, few connections have been identified with mechanistic certainty[2,3].”
In the citing paper
“higher plasma levels of the vascular toxin trimethylamine-N-oxide (TMAO) conferred an increased risk of major cardiovascular events during a 3-year follow-up.157 They also demonstrated that plasma TMAO is the product of gut microbial metabolism of dietary choline to trimethylamine (TMA), followed by hepatic oxidation of TMA to TMAO.”
From The Gut Microbiome and the Brain (2014) · cites this paper as [157]
In the citing paper
“associations between gut ecology and cancer [16], cardiovascular disease [17], obesity [6], diabetes [18], and muscle wasting [19]”
From Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis (2018) · cites this paper as [17]
In the citing paper
“Previous studies have shown that the gut microbiota metabolizes choline, phosphatidylcholine, and l-carnitine to produce trimethylamine (TMA), which is oxidized in the liver into the proatherogenic metabolite, trimethylamine-N-oxide (TMAO)11–13.”
From The gut microbiome in atherosclerotic cardiovascular disease (2017) · cites this paper as [12]
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Metadata
- Authors
- Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L.
- Affiliations
- Cleveland Clinic (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2013-04-25
- Volume
- 368
- Issue
- 17
- Pages
- 1575-1584
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3701945
- OpenAlex
- W2162078360
- Cited by
- 3,400
- References
- 27
- Citations by year
- 2026: 286 · 2025: 261 · 2024: 250 · 2023: 263 · 2022: 343 · 2021: 328 · 2020: 328 · 2019: 266 · 2018: 266 · 2017: 243 · 2016: 193 · 2015: 173 · 2014: 137 · 2013: 56
- FWCI
- 61.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000439)
- National Heart, Lung, and Blood Institute (R01HL103931, P20HL113452, P01HL076491, P01HL098055, R01HL103866)
- National Institute of General Medical Sciences (T32GM007250)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080732)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Surgery › Abdominal vascular conditions and treatments
- Keywords
- trimethylamine N-oxide, phosphatidylcholine, gut microbiota, choline metabolism, cardiovascular risk, major adverse cardiovascular events, coronary artery disease, atherosclerosis, dietary choline, betaine
- MeSH terms
- Administration, Oral, Aged, Anti-Bacterial Agents, Betaine, Cardiovascular Diseases, Choline, Female, Humans, Intestinal Mucosa, Intestines, Male, Methylamines, Middle Aged, Phosphatidylcholines, Prospective Studies, Risk Factors, Kaplan-Meier Estimate, Metagenome
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