Author
W.H. Wilson Tang
Other affiliations: Cleveland Clinic
Bio: W.H. Wilson Tang is an academic researcher from Cleveland Clinic Lerner Research Institute. The author has contributed to research in topics: Trimethylamine N-oxide & Heart failure. The author has an hindex of 25, co-authored 38 publications receiving 13521 citations. Previous affiliations of W.H. Wilson Tang include Cleveland Clinic.
Papers
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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.
Abstract: Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. 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.
4,107 citations
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.
Abstract: Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.
3,222 citations
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.
Abstract: 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,...
2,188 citations
TL;DR: Fecal samples from 46 patients with depression are analyzed to enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera.
Abstract: Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.
1,444 citations
TL;DR: Gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential, revealing a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thromBosis risk.
1,219 citations
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TL;DR: Since 1980, the American College of Cardiology and American Heart Association have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health.
Abstract: Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. In 2013, the National Heart, Lung, and Blood Institute (NHLBI) Advisory
4,604 citations
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.
Abstract: Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. 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.
4,107 citations
TL;DR: The next generation of scientists and decision-makers will have a greater understanding of what constitutes a credible threat to public health and how to protect them from that threat.
3,748 citations
TL;DR: A deeper understanding of the axes that physiologically connect the gut, liver, muscle, and brain are a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
Abstract: The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
3,509 citations
TL;DR: Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, the world will be in a better position to develop treatments for metabolic disease.
Abstract: The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.
3,436 citations