Abstract
BackgroundThe gut bacteria-derived metabolite trimethylamine-N-oxide (TMAO) has been discussed in various cardiometabolic diseases. However, evidence characterizing the microbial population responsible for TMAO accumulation in patients with atrial fibrillation (AF), an increasingly prevalent arrhythmia, is yet lacking. In order to understand the key gut microorganisms that produce TMAO in AF, trimethylamine (TMA)-synthesis enzymes and metabolic pathways, as well as the potential TMA-producers in gut microbiome were assessed based on metagenomic data-mining in a northern Chinese cohort consisting of 50 non-AF controls and 50 patients with different types of AF.ResultsCompared to the control subjects, AF patients showed a marked increase in the microbial genes underlying TMA formation in the gut, which included 12 potential TMA-synthesis functional orthologs and 1 module. The specific bacterial genes, including choline-TMA lyase, carnitine monooxygenase, glycine betaine reductase, and TMAO reductase, were elevated in the gut of AF patients. Furthermore, 16 genera were assigned and significantly correlated with TMA-enzymatic genes, where 9 genera were remarkably enriched in the gut communities of AF patients. Neither of these TMA-synthesis pathways nor the microbial players showed a significant discrepancy between different types of AF in the current cohort. These gut microbes might participate in the formation of TMA by activating the key TMA-synthesis enzymes and contributing to the functional pathways in AF patients.ConclusionsThe present study provides an in-depth insight into the potential bacteria and metabolic pathways involved in TMA production in the gut of AF patients. These findings emphasize a key role of the gut bacteria in driving TMAO formation during AF pathogenesis, thereby indicating its therapeutic potential as an intervention strategy of AF by targeting TMA-synthesis pathways and dysbiotic gut microbiota.
Highlights
The gut bacteria-derived metabolite trimethylamine-N-oxide (TMAO) has been discussed in various cardiometabolic diseases
On the basis of atrial fibrillation (AF) duration and character of electrocardiogram, the 50 patients with AF were divided into 30 paroxysmal AF (PAF) and 20 persistent AF
The 20 persistent AF (psAF) patients were further classified into twelve psAF < 12 months (Pers< 12 m) subjects with psAF duration for shorter than 12 months and eight psAF > 12 months (Pers> 12 m) individuals with psAF duration for more than 12 months
Summary
The gut bacteria-derived metabolite trimethylamine-N-oxide (TMAO) has been discussed in various cardiometabolic diseases. The dysbiosis of gut microbiota (GM) is associated with the pathogenesis of various cardiovascular disorders, such as coronary atherosclerotic heart disease [1,2,3,4], chronic heart failure [5, 6], hypertension [7,8,9,10], and atrial fibrillation (AF) [11]. High systemic levels of TMAO heighten the platelet hyperreactivity that increases the risk of thrombosis and elevates the macrophage-specific cholesterol. These features promote atherosclerosis, which in turn, contributes to adverse cardiovascular events, such as acute myocardial infarction, cerebral infarction, and heart failure [12,13,14,15,16,17]. Relevant bacterial species and metabolic pathways underlying TMAO production in the gut of AF patients and whether TMAO serves as a pathological link between disordered GM and AF are yet to be elucidated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
