In this study, we discovered that AF patients compared to SR patients had lower species richness and α-diversity, but there were no significant differences. Whereas, the phylogenetic diversity of AF patients was significant decreased. Furthermore, the β-diversity indexes revealed statistical difference in GM community structure in AF group and SR group. More importantly, t-test and LEfSe analysis revealed that several taxa showed significant difference in abundance between AF patients and SR patients. Especially in AF group, a significant decreased in Bifidobacterium and a greater abundance of Lactobacillus, Fusobacterium, Haemophilus, and the variation of these bacteria may be the key of AF development and establishment. Therefore, we hypothesized that the increase or decrease of specific group of GM may negatively affect human health, interfere with the progression of AF, and may even play an important role in the establishment of AF. As a consequence, a discriminant model based on bacterial characteristic spectrum could be established, which can be used as a biomarker for AF in the future, and intervention strategies targeting GM can be used to improve the progression of AF.
For all we know, GM abundance and diversity have been assessed in variety of diseases, especially in cardiovascular disease such as hypertension [4, 8], atherosclerosis [25], coronary heart disease [9] and heart failure [10]. In these states, the diversity, composition and related metabolic functions of GM changed, leading to disruption of important physiological processes, including inflammation, lipid metabolism, bacterial translocation, and glucose homeostasis, which may contribute to the development and progression of cardiovascular disease [26]. One study discovered symptomatic atherosclerotic patients had a greater abundance of Collinsella compared with healthy controls [27]. A recent metagenome association study from atherosclerosis patients observed that increased relative abundance of Escherichia coli, Enterobacter aerogenes, Klebsiella and Streptococcus were associated with an increased incidence of atherosclerotic cardiovascular disease. These changes of GM will affect the metabolism and transport of molecules functionally, such as trimethylamine-N-oxide, and have more pro-inflammatory effects [28]. In addition, another study also showed that the GM abundance of heart failure patients decreased, and the composition of GM changed significantly with the progress of the disease, that is, the increase of pathogenic bacteria, including Campylobacter, Shigella, Salmonella, Yersinia enterocolitica and Candida species [29]. Therefore, the assessing the abundance and diversity of GM can reflect the imbalance of intestinal environment, which is characterized by more harmful bacteria and fewer symbiotic or beneficial bacteria. This is consistent with our study.
Our study found that AF as a common cardiovascular disease, the richness and diversity of GM also changed. However, it was different from the previous report [30]. It was worth noting that the increased Lactobacillus, Fusobacterium and Haemophilus in AF patients were also reflected in other cardiovascular diseases, such as heart failure [31], hypertension [32], and coronary heart disease [33]. One study had found that the heat-shock protein GroEL of Fusobacterium could induced the expression of chemokines such as monocyte chemoattractant protein-1 and interleukin-8 as well as cell adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, leading to increased inflammatory response and endothelial dysfunction [34]. Another study also found that Haemophilus could reduce nitric oxide levels, promote endothelial dysfunction and increase cardiovascular risk [35]. Additionally, patients with coronary heart disease [36] and hypertension [37] often have decreased levels of Bifidobacterium, which was short-chain fatty acids producing specie identified as important restoring the normal composition of microbiota [38]. Bifidobacterium, on the other hand, have been considered common beneficial bacteria in the gut because it improves intestinal barrier function and play a protective role in inflammatory diseases by regulating inflammation and pro-inflammatory cytokines [39]. It can be seen from the above that these changes in GM composition are present in multiple cardiovascular diseases. Therefore, we have reason to believe that this alteration plays an important role in the development of cardiovascular diseases. Although the underlying mechanisms remain unclear, some cardiovascular diseases share some common pathophysiological pathways including endothelial dysfunction [40] and inflammatory reaction [41]. More recently, more and more people also have recognized that AF is also associated with systemic inflammation and endothelial dysfunction, rather than just an atrial disease [42, 43]. Repairing defective GM and re-establishing a fully functioning ecological population are critical to a healthy GM and may mitigate or attenuate the progression of cardiovascular disease, including AF. Intervention the intestinal microecosystem toward beneficial changes may provide a new treatment for cardiovascular diseases, such as AF, caused by intestinal microbiome disorders or other potential disorders related to ecological disorders [44].
To date, a number of observational studies have described the changes of GM in AF patients, but these studies have been inconsistent about GM changes [30, 45, 46, 47]. Zuo et al. founded that the GM of AF patients was different from SR patients including a significant elevation in microbial diversity and a specific change of gut microbiota composition. Increased abundance of Ruminococcus, Streptococcus, and Enteroccus, while decreased abundance of Faecalibacterium, Alistipes, Oscillibacter, and Bilophila were detected in AF patients [30, 46, 47]. Another study showed that GM richness was lower in AF patients, reduction of Enterobacter and overgrowth of Parabacteroides, Lachnoclostridium, Streptococcus, and Alistipes were detected in AF patients [45]. Notably, the bacterial variation in our study exhibited some unique features that unlike those in previous reports. Complex and diverse factors involved in pathophysiological processes may be partly responsible for this inconsistent phenomenon. Whereas, all of the above studies suggested that GM composition was different in AF patients and SR patients. In addition, regulating the composition of the microbiome through probiotics, diet patterns, sleep habits and physical activity, may affect the progression of cardiovascular disease and risk factors associated with cardiovascular disease [48, 49, 50], which is also expected to be a new treatment method for AF and will be explored in our future study.
Study limitations. There were several limitations in this study. The most importantly, this study was an observational study and could not determine the causal relationship between GM and AF, therefore, a prospective cohort study is needed to determine whether changes in GM are associated with the etiology of AF. Furthermore, the sample size of this study was small, thus, larger studies are needed to validate our results. In addition, we cannot exclude the influence of confounding factors, such as sleep, diet and drugs, on the GM of AF patients.