Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications

Abstract

Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition. In this review, we discuss the evidence suggesting a potential bidirectional association between AF and gut microbiota, identifying gut microbiota-derived metabolites as possible regulators of the AF substrate. We summarize the effect of gut microbiota on the development and progression of AF risk-factors, including heart failure, hypertension, obesity and coronary artery disease. We also discuss the potential antiarrhythmic effects of pharmacological and diet-induced modifications of gut microbiota composition, which may modulate and prevent the progression to AF. Finally, we highlight important gaps in knowledge and areas requiring future investigation. Although data supporting a direct relationship between gut microbiota and AF are very limited at the present time, emerging preclinical and clinical research dealing with mechanistic interactions between gut microbiota and AF is important as it may lead to new insights into AF pathophysiology and the discovery of novel therapeutic targets for AF.

Aggravated Gut Microbiota and Metabolomic Imbalances Are Associated with Hypertension Patients Comorbid with Atrial Fibrillation

“…Accumulating evidence demonstrates that trillions of gut microbiota (GM) colonizing the human gastrointestinal tract generate bioactive metabolites, impacting host homeostasis, and function as the largest endocrine organ in the body [ 5 ]. In particular, disturbed gut microbial structure and function, and its derived metabolites, play pivotal roles in the progression of cardiovascular disease, including HTN and AF [ 6 , 7 ]. Aberrant GM composition and related metabolites, including trimethylamine N-oxide (TMAO) and lipopolysaccharides (LPS), contribute to HTN and its complication (e.g., chronic kidney disease, stroke, heart failure, and myocardial infarction) [ 7 , 8 ].…”

Coffee and cardiac arrhythmias: Up-date review of the literature and clinical studies

“…Clinical trials have shown that coffee consumption was associated with a reduced risk of heart failure (HF) [49]. It has also been suggested that the antiarrhythmic properties of coffee may result from its influence on the composition of the gut microbiota [50][51][52]. Chlorogenic acid may reduce the production of trimethylamine (TMA; precursor of arrhythmogenic trimethylamine N-oxide [TMAO]) [53], while coffee consumption may increase the level of Bifidobacterium spp.…”

Targeting Gut Microbiota as a Novel Strategy for Prevention and Treatment of Hypertension, Atrial Fibrillation and Heart Failure: Current Knowledge and Future Perspectives

“…In vitro, TMAO has driven increased collagen production by the fibroblasts, thereby contributing to cardiac fibrosis development [ 55 ]. In addition, TMAO could also indirectly increase AF susceptibility through pro-atherosclerotic effects, cardiac remodeling and aortic stiffening [ 56 ]. Numerous small observational clinical studies have demonstrated that elevated serum TMAO levels were predictive of thromboembolic complications of AF [ 57 , 58 ].…”