Unveiling the link between gut microbiome and atrial fibrillation: insights from a large population study

A recent study poses the basis for the use of microbiome profile in AF risk prediction.
Table of Contents

What is already known
Atrial fibrillation (AF) is a significant heart rhythm disorder prevalent in older population and approximately half of the risk of AF can be attributed to classical cardiovascular risk factors. Emerging evidence link the gut microbiota composition to risk factors for cardiovascular disease, however the extent to which the gut microbiota influences the risk of AF remains uncertain.

What this research adds
Researchers examined how the prevalence and long-term incidence of AF is associated with the composition and function of the gut microbiome in a random population sample of 6763 individuals. Both prevalent and prospective AF were found associated with different microbial genera and the bacterial composition was shifted towards a spectrum similar to the microbiome reported in hypertension and heart failure, highlighting a shared underlying pathophysiology.

The microbiome composition in prevalent and incident AF was different from that of non-affected individuals with a number of genera and species which differed in abundance. Therefore, the present study poses the basis for the use of microbiome profile in AF risk prediction.

Atrial fibrillation (AF) is a complex disease mainly occurring after the age of 60 years, characterized by several cardiovascular risk factors which have been associated with an altered composition and function of the gut microbiome. Previous studies suggest that different gut microbiome signatures in AF exist and changes in microbial diversity and predominant microbiome pattern have been observed in AF.

In a recent study published in the Lancet journal, Schnabel and colleagues from the University of California, performed microbiome analysis using whole-genome sequencing and found associations of prevalent and incident AF with gut microbiome in a large, well-established population-based cohort.

In particular, Enorma (one of the families related to heart failure), Bifidobacterium, and Eisenbergiella genera were among the top associations of prevalent and incident AF.

Prevalent AF had 9 significant associations with common microbial genera. The associations were positive for Eisenbergiella, Enorma, Enterobacter, and Kluyvera; and negative for Bacteroides, Bifidobacterium, Holdemanella, Parabacteroides, and Turicibacter. These findings suggest that specific genus level gut microbial abundances have potential to identify individuals with AF. Following further analysis, the researchers found that the potential link between gut microbiota and AF is mainly driven by specific gut species rather than general gut microbial composition. 

Eight associations were observed between incident AF and baseline common microbial genera. These associations were positive for Bifidobacterium, Enorma, Lactococcus, Mitsuokella, and Sellimonas, and negative for Tyzzerella, Hungatella, and Sanguibacteroides. 

The negative association of prevalent AF with Bifidobacterium, and a positive relation for incident AF, may reflect different disease stages with higher impact of concurrent conditions, such as heart failure, in individuals with AF at baseline. In fact, in heart failure patients, the genus Bifidobacterium is depleted. 

Moreover, Eisenbergiella borderline differentially abundant in incident AF and significantly related to prevalent AF is in line with reports showing how Eisenbergiella is more abundant in normotensive individuals. In addition, the abundance of this genus is different in coronary artery disease patients, which is a strong predictor and established risk factor of AF.

Researchers performed follow-up analysis of people and observed that half of the bacterial genera associated with incident AF remained significant and had relatively unchanged effect sizes when follow-up was limited to 7.5 years. The eight genera associated with incident AF remained significant with similar effect sizes when additional covariates for exercise and healthy food choices were included in the model.

Overall, some plausible species and genera, which are known in the context of established AF risk factors, such as blood pressure control and heart failure, were identified in relation to AF. Although further research is needed to understand whether the microbiome composition represents a modifiable risk factor or risk marker of lifestyle components and comorbidities in AF patients, and to elucidate the mechanisms between changes in gut microbiome composition and AF, the aspect of its modifiability is attractive.

In the future, modulating the intestinal microbiome and metabolism could represent new approaches to prevention of AF, and tracking the gut microbiome composition may help to guide lifestyle interventions and management in AF patients.