No abstract available.
Methylamines ; Migraine Disorders ; Stroke

Air Pollutants, Occupational ; analysis ; Chromatography, Gas ; methods ; Dimethylamines ; analysis ; Methylamines ; analysis ; Workplace

Cardiovascular Diseases ; Gastrointestinal Microbiome ; Humans ; Methylamines

Humans ; Gastrointestinal Microbiome ; Atherosclerosis ; Methylamines/metabolism*

OBJECTIVEThis review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target.

DATA SOURCESThis study was based on data obtained from PubMed and EMBASE up to June 30, 2015. Articles were selected using the following search terms: "Intestinal microbiota", "trimethylamine N-oxide (TMAO)", "trimethylamine (TMA)", "cardiovascular", and "atherosclerosis".

STUDY SELECTIONStudies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included.

RESULTSA new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear.

CONCLUSIONSIntestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management.

Trimethylamine-N-oxide (TMAO) is a biologically active molecule which is metabolized by intestinal microflora and excreted by the kidney. The incidence and mortality of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) are significantly increased, which seriously affects the prognosis of patients with CKD. Recent studies have shown that TMAO can cause myocardial fibrosis and cardiovascular damage. Plasma TMAO levels are elevated in CKD patients, and TMAO was an independent predictor for all-cause mortality in patients with CKD, including CVD events. As a "uremic toxin", TMAO can promote the progression and the occurrence of CVD in CKD patients through its toxic effects, such as inflammatory response and oxidative stress. Taken together, it may suggest that reducing TMAO production and plasma TMAO levels may decrease the occurrence of CVD events in CKD and that TMAO may be a therapeutic target for ameliorating the prognosis of CKD.
Biomarkers ; Cardiovascular Diseases ; Humans ; Methylamines ; Oxides ; Renal Insufficiency, Chronic

Coronary artery disease (CAD) is a chronic disease but causes the highest mortality and morbidity among the cardiovascular diseases worldwide. Correlations between CAD and gut microbiota have been observed. This suggests that the gut microbiota could become a vital diagnostic marker of CAD, and restoring the gut habitat may become a promising strategy for CAD therapy. The elevated level of trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, was found to be associated with the increased risk of cardiovascular disease and the all-cause mortality. Preclinical studies have shown that it has pro-arteriosclerosis properties. It is likely that regulating the production of TMAO by gut microbiota may become a promising strategy for anti-atherosclerosis therapy. This review summarizes the clinical and preclinical researches on the intervention of CAD by regulating the gut microbiota and the microbiota-derived metabolite TMAO, with the aim to provide new target for the therapy of CAD.
Coronary Artery Disease ; Gastrointestinal Microbiome ; Humans ; Methylamines ; Oxides

The main cause of death in patients with end-stage renal disease (ESRD) is cardiovascular disease, and trimethylamine-N-oxide (TMAO) has been found to be one of the specific risk factors in the pathogenic process in recent years. TMAO is derived from intestinal bacterial metabolism of dietary choline, carnitine and other substances and subsequently catalyzed by flavin monooxygenase enzymes in the liver. The changes of intestinal bacteria in ESRD patients have contributed to the accumulation of gut-derived uremic toxins such as TMAO, indoxyl sulfate and indole-3-acetic acid. While elevated TMAO concentration accelerates atherosclerosis through mechanisms such as inflammation, increased scavenger receptor expression, and inhibition of reverse cholesterol transport. In this review, this research introduces the biological function, metabolic processes of TMAO and mechanisms by which TMAO promotes the progression of cardiovascular disease in ESRD patients and summarizes current interventions that may be used to reverse gut microbiota disturbances, such as activated carbon, fecal microbial transplantation, dietary improvement, probiotic and probiotic introduction. It also focuses on exploring intervention targets to reduce the gut-derived uremic toxin TMAO in order to explore the possibility of more cardiovascular disease treatments for ESRD patients.
Cardiovascular Diseases ; Humans ; Kidney Failure, Chronic ; Methylamines ; Oxides ; Uremic Toxins

Adult ; Carbodiimides ; poisoning ; Humans ; Male ; Methylamines ; poisoning ; Occupational Exposure ; Young Adult

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Carnitine ; Choline/metabolism* ; Chronic Disease ; Heart Failure/genetics* ; Humans ; Methylamines ; Oxygenases ; Prospective Studies