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Published on: July 20, 2022
Gut-microbe derived TMAO and its association with more progressed forms of AF: Results from the AF-RISK study
B O Nguyen1, L M G Meems1, M van Faassen2
1Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Introduction:
The importance of gut microbiome in cardiovascular disease has been increasingly recognized. Trimethylamine N-oxide (TMAO) is a gut microbe-derived metabolite that is associated with cardiovascular disease, including atrial fibrillation (AF). The role of TMAO in clinical AF progression however remains unknown.
Methods And Results:
In this study we measured TMAO and its precursor (betaine, choline, and L- carnitine) levels in 78 patients using plasma samples from patients that participated in the AF-RISK study. 56 patients suffered from paroxysmal AF and 22 had a short history of persistent AF. TMAO levels were significantly higher in patients with persistent AF, as compared to those with paroxysmal AF (median [IQR] 5.65 [4.7-9.6] m/z versus 4.31 [3.2-6.2] m/z, p < 0.05), while precursor levels did not differ. In univariate analysis, we observed that for every unit increase in TMAO, the odds for having persistent AF increased with 0.44 [0.14-0.73], p < 0.01. Conclusion: These results suggest that higher levels of TMAO are associated with more progressed forms of AF. We therefore hypothesize that increased TMAO levels may reflect disease progression in humans. Larger studies are required to validate these preliminary findings.Trial Registration number: Clinicaltrials.gov NCT01510210.
Insights
Higher levels of trimethylamine N-oxide (TMAO) are linked to advanced atrial fibrillation (AF). This gut microbe metabolite may indicate disease progression in patients with AF. Further research is needed to confirm these findings.
Area of Science:
- Cardiovascular Research
- Gut Microbiome Studies
- Metabolomics
Background:
- Gut microbiome's role in cardiovascular disease is increasingly recognized.
- Trimethylamine N-oxide (TMAO), a gut microbe metabolite, is linked to cardiovascular disease, including atrial fibrillation (AF).
- The specific role of TMAO in the clinical progression of AF is not well understood.
Purpose of the Study:
- To investigate the association between TMAO levels and the progression of atrial fibrillation.
- To compare TMAO and its precursor levels in patients with paroxysmal AF versus persistent AF.
Main Methods:
- Plasma samples from 78 patients (56 with paroxysmal AF, 22 with persistent AF) from the AF-RISK study were analyzed.
- Levels of TMAO and its precursors (betaine, choline, L-carnitine) were measured.
- Statistical analysis, including univariate analysis, was performed to assess the relationship between TMAO and AF type.
Main Results:
- TMAO levels were significantly higher in patients with persistent AF compared to paroxysmal AF.
- No significant difference was found in the levels of TMAO precursors between the two groups.
- Each unit increase in TMAO was associated with a 0.44-fold increase in the odds of having persistent AF (p < 0.01).
Conclusions:
- Elevated TMAO levels are associated with more advanced forms of atrial fibrillation.
- The study hypothesizes that increased TMAO may reflect disease progression in humans.
- Larger studies are recommended to validate these preliminary findings.

