TMAO and Gut Microbial-Derived Metabolites TML and γBB Are Not Associated with Thrombotic Risk in Patients with Venous Thromboembolism.

Marina Canyelles,Maribel Diaz-Ricart,Sergi Mojal,Josep Julve,Noemí Rotllan,Joan Carles Souto,José Manuel Soria,Dolors Llobet,Francisco Blanco-Vaca,Melania Plaza,Mireia Tondo,Joan Carles Escolà-Gil

doi:10.3390/jcm11051425

Abstract

Background: The present work evaluates the association between circulating concentrations of Trimethylamine-N-oxide (TMAO), gamma butyrobetaine (γBB), and trimetyllisine (TML) in controls and patients with venous thromboembolism (VTE) with coagulation parameters. Methods: The study involved 54 VTE patients and 57 controls. Platelet function, platelet hyperreactivity, platelet adhesiveness, thrombosis-associated parameters, and thrombin generation parameters were studied. Plasma TMAO, γBB, and TML determination was performed using an ultra-high-performance liquid chromatography system coupled with mass spectrometry. Results: No differences were found for TMAO, γBB, or TML concentrations between controls and VTE patients. In thrombin generation tests, TMAO, γBB, and TML showed a positive correlation with lag time and time to peak. TMAO, γBB, and TML negatively correlated with peak height. No significant differences were observed regarding TMAO, γBB, and TML concentrations between the two blood withdrawals, nor when the control and VTE patients were analyzed separately. No correlation was observed between these gut metabolites and platelet function parameters. Conclusions: No differences were found regarding TMAO, γBB, and TML concentrations between the control and VTE groups. Some correlations were found; however, they were mild or went in the opposite direction of what would be expected if TMAO and its derivatives were related to VTE risk.

Highlights

Trimethylamine-N-oxide (TMAO) is a small organic compound formed in the liv-er and produced by the action of hepatic flavin monooxygenase 3 (FMO3) on trime-thylamine (TMA)
A significant decrease in Platelet Function Analysis (PFA) and estimated glomerular filtration rate was observed in venous thromboembolism (VTE) patients compared to the control group (Table 2)
Some correlations were observed for parameters evaluating thrombin generation: lag time (LAG) and time to peak (TTP) positively correlated with TMAO, TML, and γBB; peak height (PEAK) negatively correlated with TMAO, TML, and γBB; and endogen thrombin potential (ETP) negatively correlated with TMAO. These negative correlations are in the opposite direction of what would be expected if TMAO and its derivatives were related to VTE risk

Summary

Introduction

Trimethylamine-N-oxide (TMAO) is a small organic compound formed in the liv-er and produced by the action of hepatic flavin monooxygenase 3 (FMO3) on trime-thylamine (TMA). TMA is generated by the action of gut microbiota using precursors from the diet as choline or other choline-containing compounds, betaine, or L-carnitine, as a part of microbial-mammalian metabolism [1]. The present work evaluates the association between circulating concentrations of Trimethylamine-N-oxide (TMAO), gamma butyrobetaine (γBB), and trimetyllisine (TML) in controls and patients with venous thromboembolism (VTE) with coagulation parameters. Results: No differences were found for TMAO, γBB, or TML concentrations between controls and VTE patients. No significant differences were observed regarding TMAO, γBB, and TML concentrations between the two blood withdrawals, nor when the control and VTE patients were analyzed separately. Conclusions: No differences were found regarding TMAO, γBB, and TML concentrations between the control and VTE groups. Some correlations were found; they were mild or went in the opposite direction of what would be expected if TMAO and its derivatives were related to VTE risk

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