Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?

Papandreou, Christopher; Moré, Margret I.; Bellamine, Aouatef

doi:10.3390/nu12051330

Cited by 89 publications

(74 citation statements)

References 210 publications

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“…Similarly, Sumarriva et al ( 6 ) demonstrated that higher plasma carnitine, a metabolite highly present in food that contains meat, was associated to the presence of PDR compared with NPDR. Carnitine is further metabolized by the gut microbiota into trimethylamine- N -oxide, which has been associated to cardiovascular and metabolic diseases ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating Metabolites and Lipids Are Associated to Diabetic Retinopathy in Individuals With Type 1 Diabetes

et al. 2020

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Omics-based methods may provide new markers associated to diabetic retinopathy (DR). We investigated a wide omics panel of metabolites and lipids related to DR in type 1 diabetes. Metabolomic analyses were performed using two-dimensional gas chromatography with time-of-flight mass spectrometry and lipidomic analyses using an ultra-high-performance liquid chromatography quadruple time-of-flight mass spectrometry method in 648 individuals with type 1 diabetes. Subjects were subdivided into no DR, mild nonproliferative DR (NPDR), moderate NPDR, proliferative DR, and proliferative DR with fibrosis. End points were any progression of DR, onset of DR, and progression from mild to severe DR tracked from standard ambulatory care and investigated using Cox models. The cohort consisted of 648 participants aged a mean of 54.4 ± 12.8 years, 55.5% were men, and follow-up was 5.1–5.5 years. Cross-sectionally, 2,4-dihydroxybutyric acid (DHBA), 3,4-DHBA, ribonic acid, ribitol, and the triglycerides 50:1 and 50:2 significantly correlated ( P < 0.042) to DR stage. Longitudinally, higher 3,4-DHBA was a risk marker for progression of DR ( n = 133) after adjustment ( P = 0.033). We demonstrated multiple metabolites being positively correlated to a higher grade of DR in type 1 diabetes and several triglycerides being negatively correlated. Furthermore, higher 3,4-DHBA was an independent risk marker for progression of DR; however, confirmation is required.

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Section: Discussionmentioning

confidence: 99%

Circulating Metabolites and Lipids Are Associated to Diabetic Retinopathy in Individuals With Type 1 Diabetes

et al. 2020

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“…After absorption, TMA is oxidized into trimethylamine-N-oxide (TMAO) by the hepatic enzyme flavin mono-oxygenase (FMO)-3 [ 114 ]. Plasma levels of TMAO have both a high within-individual and inter-individual variability, which hampers comparison of studies [ 115 ]. In addition, TMAO levels are higher in women, presumably due to different expression of the converting enzyme FMO3 and higher excretion rates in men [ 114 ].…”

Section: Gut Microbiota In Atherosclerosismentioning

confidence: 99%

Gut Microbiota in Hypertension and Atherosclerosis: A Review

et al. 2020

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Gut microbiota and its metabolites such as short chain fatty acids (SCFA), lipopolysaccharides (LPS), and trimethylamine-N-oxide (TMAO) impact cardiovascular health. In this review, we discuss how gut microbiota and gut metabolites can affect hypertension and atherosclerosis. Hypertensive patients were shown to have lower alpha diversity, lower abundance of SCFA-producing microbiota, and higher abundance of gram-negative bacteria, which are a source of LPS. Animal studies point towards a direct role for SCFAs in blood pressure regulation and show that LPS has pro-inflammatory effects. Translocation of LPS into the systemic circulation is a consequence of increased gut permeability. Atherosclerosis, a multifactorial disease, is influenced by the gut microbiota through multiple pathways. Many studies have focused on the pro-atherogenic role of TMAO, however, it is not clear if this is a causal factor. In addition, gut microbiota play a key role in bile acid metabolism and some interventions targeting bile acid receptors tend to decrease atherosclerosis. Concluding, gut microbiota affect hypertension and atherosclerosis through many pathways, providing a wide range of potential therapeutic targets. Challenges ahead include translation of findings and mechanisms to humans and development of therapeutic interventions that target cardiovascular risk by modulation of gut microbes and metabolites.

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“…Some inconsistencies revolve around L-carnitine and betaine showing protective effects against CVD and therefore casts doubt on TMAO’s involvement. However, we cannot rule out the possibility that betaine or L-carnitine have some regulatory effect on TMAO that reduces the proatherogenic effect of TMAO just as much, as these studies suggest that TMAO is beneficial [ 123 , 124 ]. As a result, these present an inherent problem when trying to draw conclusions about the effects of choline intake on disease.…”

Section: Choline Intake and Its Relationship To Diseasementioning

confidence: 99%

The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases

et al. 2020

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Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.

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Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?

Cited by 89 publications

References 210 publications

Circulating Metabolites and Lipids Are Associated to Diabetic Retinopathy in Individuals With Type 1 Diabetes

Circulating Metabolites and Lipids Are Associated to Diabetic Retinopathy in Individuals With Type 1 Diabetes

Gut Microbiota in Hypertension and Atherosclerosis: A Review

The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases

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