Background: The occurrence of atrial fibrillation is often accompanied by myocardial fibrosis. An increasing number of studies have shown that intestinal flora is involved in the occurrence and development of a variety of cardiovascular diseases. This study explores the relationship between changes in the structure and function of intestinal flora and the progression of myocardial fibrosis in patients with persistent atrial fibrillation.Methods: Serum and stool samples were collected from 10 healthy people and 10 patients with persistent atrial fibrillation (PeAF), and statistical analyses were performed on the subjects' clinical baseline conditions. ELISA was used to measure the levels of carboxy-terminal telopeptide of type I collagen (CTX-I), propeptide of type I procollagen (PICP), procollagen III N-terminal propeptide (PIIINP), fibroblast growth factor-23 (FGF-23), and transforming growth factor-beta 1 (TGF-β1) in serum. Through 16S rRNA sequencing technology, the structural composition of the intestinal flora was detected and analyzed. In addition, metabolomics data were analyzed to determine the differences in the metabolites produced by the intestinal flora of the subjects.Results: By comparing the baseline data of the subjects, it was found that compared with those of the control group, the levels of creatinine (CRE) and serum uric acid (SUA) in the serum of PeAF patients were significantly increased. In addition, we found that the levels of CTX-I, PICP, PIIINP, and TGF-β1 in the serum of PeAF patients were significantly higher than those of the control group subjects. Although the control and PeAF groups exhibited no significant differences in the α diversity index, there were significant differences in the β diversity indexes (Bray-Curtis, weighted UniFrac and Anosim). At the phylum, family and species levels, the community structure and composition of the intestinal flora of the control group and those of the PeAF group showed significant differences. In addition, the compositions of the intestinal metabolites in the two different groups of people were significantly different. They were correlated considerably with PIIINP and specific communities in the intestinal flora.Conclusion: Pathologically, PeAF patients may have a higher risk of myocardial fibrosis. Systematically, abnormal changes in the structure and composition of the intestinal flora in PeAF patients may lead to differences in intestinal metabolites, which are involved in the process of myocardial fibrosis through metabolite pathways.

No abstract

In this interesting paper, the authors revealed that nine out of 268 investigated biomarkers were significantly and independently associated with the risk of bleeding and reflect pathophysiologic processes of inflammation, apoptosis, oxidative stress, vascular calcification, coagulation, and fibrinolysis. 1 Recent studies have shown that accurate assessment to balance the risk of stroke and systemic embolic events, against the risk of major bleeding is, therefore, an important therapeutic goal in the clinical management of atrial fibrillation (AF) patients. 2 Although the results showed a strong correlation between the TRAIL-R2 protein marker and the risk of bleeding, the potential mechanistic remain to be elucidated. It is known that TRAIL-R2 is a marker of apoptosis and belongs to the tumor necrosis factor receptor superfamily. 3,4 However, a recent study by Tymon Pol et al. 4 published on Cardiovascular Research proposed TRAIL-R2 is not specific for AF but rather a marker that rises in several disease states just indicating poor prognosis. Meanwhile, Isabel Gonçalves et al. 5 showed that sTRAIL-R2 and sTRAIL are associated with human plaque cell apoptosis, plaque inflammatory activity, and symptomatic carotid plaques, especially for high plasma levels of sTRAIL-R2 in plasma predict, independently, future cardiovascular events in individuals. Thus, it is unclear whether the strong correlation between the increased level of TRAIL-R2 and the risk of bleeding uncovered in Agneta Siegbahn's study is confounded by other unknown factors. We speculate that the potential mechanism is that TRAIL-R2 induces the inflammatory activity of cells, leading to inflammatory injury of endothelial cells and apoptosis of the vascular wall. 1,5 Taken together, we can reasonably speculate that TRAIL-R2 may be a biomarker and contribute to predicting future cardiovascular events in AF patients by affecting the risk of bleeding. Clearly, a great number of research opportunities could be further explored following Agneta Siegbahn's interesting study.Despite some limitations, the work by authors not only provides novel candidate biomarkers associated with major bleeding for AF but also opens a new avenue to future basic and clinical studies in AF.