Major Increase in Microbiota-Dependent Proatherogenic Metabolite TMAO One Year After Bariatric Surgery

Trøseid, Marius; Hov, Johannes R.; Nestvold, Torunn Kristin; Thoresen, Hanne; Berge, Rolf K.; Svardal, Asbjørn; Lappegård, Knut Tore

doi:10.1089/met.2015.0120

Cited by 70 publications

(58 citation statements)

References 25 publications

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“…In our population, concentration of TMAO was comparable in all groups. This is consistent with recent studies reporting no difference in TMAO between HIV infected persons and healthy controls or persons with T2D and healthy controls [41, 42]. However, a larger study reported higher TMAO in persons with diabetes compared to healthy controls [20], and consensus has not been reached.…”

Section: Discussionsupporting

confidence: 87%

HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

et al. 2017

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BackgroundIncreased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD.MethodsCross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA <200 copies/mL (n = 25 with T2D (HIV + T2D+), n = 25 without T2D (HIV + T2D-)) and 50 uninfected persons (n = 22 with T2D (HIV-T2D+) and n = 28 without T2D (HIV-T2D-)). Groups were matched on age and sex.High sensitive C-reactive protein (hsCRP) was used to determine inflammation (cut-off 3 mg/L). The marker of endothelial dysfunction asymmetric dimethylarginine (ADMA) was measured using high performance liquid chromatography. Trimethylamine-N-oxide (TMAO), a microbiota-dependent, pro-atherogenic marker was measured using stable isotope dilution LC/MS/MS.ResultsThe percentage of HIV + T2D+, HIV + T2D-, HIV-T2D+, and HIV-T2D- with hsCRP above cut-off was 50%, 19%, 47%, and 11%, respectively. HIV + T2D+ had elevated ADMA (0.67 μM (0.63-0.72) compared to HIV + T2D- (0.60 μM (0.57-0.64) p = 0.017), HIV-T2D+ (0.57 μM (0.51-63) p = 0.008), and HIV-T2D- (0.55 μM (0.52-0.58) p < 0.001). No differences in TMAO between groups were found. However, a positive correlation between ADMA and TMAO was found in the total population (rs = 0.32, p = 0.001), which was mainly driven by a close correlation in HIV + T2D+ (rs = 0.63, p = 0.001).ConclusionElevated inflammation and evidence of endothelial dysfunction was found in HIV-infected persons with T2D. The effect on inflammation was mainly driven by T2D, while both HIV infection and T2D may contribute to endothelial dysfunction. Whether gut microbiota is a contributing factor to this remains to be determined.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2334-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 87%

HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

et al. 2017

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“…The authors suggest that it is possible that the adverse effect of TMAO may be more relevant when concentrations of TMAO are higher than in their sample or in later stages of the disease process . In another study comparing the concentrations of TMAO, carnitine, and choline in 34 obese individuals undergoing bariatric surgery, TMAO was not elevated in obese patients before the surgery but increased ≈2‐fold after bariatric surgery . The authors reported that these results were unexpected and suggested that one explanation could be adaptive shifts in the gut microbiota with increased ability to metabolize dietary choline and carnitine to TMAO precursors .…”

Section: Discussionmentioning

confidence: 99%

Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study

Guasch‐Ferré

Ruíz-Canela

et al. 2017

JAHA

117

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BackgroundThe relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions.Methods and ResultsWe designed a case‐cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography–tandem mass spectrometry to measure, at baseline and at 1 year of follow‐up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N‐oxide, betaine, choline, phosphocholine, and α‐glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1‐SD increase in choline and α‐glycerophosphocholine metabolites were 1.24 (1.05–1.46) and 1.24 (1.03–1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21‐fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36–3.59; P<0.001 for trend) and a 2.27‐fold higher risk of stroke (95% confidence interval, 1.24–4.16; P<0.001 for trend). Participants in the higher quartiles of the score who were randomly assigned to the control group had a higher risk of CVD compared with participants in the lower quartile and assigned to the Mediterranean diet groups (P=0.05 for interaction). No significant associations were observed for 1‐year changes in individual plasma metabolites and CVD.ConclusionsA metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk.Clinical Trial Registration URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.

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“…On the other hand, choline levels were remained positively correlated with FAI and body fat and carnitine levels showed a trend for correlation with body fat suggesting that decrease in body fat is also involved in decrease of TMAO precursors. Interestingly, weight loss by bariatric surgery resulted in an increase in TMAO levels 29,32. Human data are rather conflicting.…”

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confidence: 99%

Circulating gut microbiota metabolite trimethylamine N‐oxide and oral contraceptive use in polycystic ovary syndrome

Eyüpoğlu

Guzelce

Açıkgöz

et al. 2019

Clinical Endocrinology

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Objectives: Polycystic ovary syndrome (PCOS) is associated with an increased cardiometabolic risk that might not necessarily translate into adverse cardiovascular outcome later in life. Recently, alterations in gut microbial composition have been reported in the syndrome. Microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and its precursors are closely linked with development of atherosclerotic cardiovascular disease, independently of traditional risk factors. We aimed to assess whether TMAO and its precursors are altered in PCOS and to determine potential impact of treatment on these metabolites. Design: Prospective study.Patients: Twenty-seven overweight/obese patients with PCOS and 25 age-and BMImatched healthy control women.Measurements: At baseline, fasting serum TMAO and its precursors were measured after a 3-day standardized diet. Patients received 3-month OC therapy along with general dietary advice after which all measurements were repeated. Results: Patients had higher total testosterone (T) and free androgen index (FAI)whereas whole-body fat mass, fasting plasma glucose, insulin and lipids were similar between the groups. PCOS group showed significantly higher serum levels of TMAO and its precursors; choline, betaine and carnitine. TMAO and choline showed correlations with T. After 3 months of OC use, TMAO and its precursors significantly decreased along with reductions in BMI, T and FAI. Conclusions:This study reports for the first time that TMAO and its precursors are elevated in PCOS which might contribute to increased cardiometabolic risk of the syndrome and that short-term OC use along with lifestyle intervention is associated with reduction of these microbiome-dependent metabolites. K E Y W O R D Scardiometabolic risk, microbiome, oral contraceptives, polycystic ovary syndrome, trimethylamine N-oxide | 811 EYUPOGLU Et aL.

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Major Increase in Microbiota-Dependent Proatherogenic Metabolite TMAO One Year After Bariatric Surgery

Cited by 70 publications

References 25 publications

HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study

Circulating gut microbiota metabolite trimethylamine N‐oxide and oral contraceptive use in polycystic ovary syndrome

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