Alterations of gut viral signals in atrial fibrillation: complex linkage with gut bacteriome

The gut microbiota has a known complex association with atrial fibrillation (AF) progression, but the association of gut viruses with AF is undefined. Metagenomic data in a cohort of 50 AF patients and 50 matched controls were examined to profile the gut viral signals and determine their associations with intestinal bacteria and the AF phenotype. The gut viral alterations were examined, and the marked elevation of viral diversity, including increased Simpson, Shannon, and Pielou index, was revealed in AF patients. The specific alteration of the intestinal viral population, such as overgrowth of Streptococcus virus DT1 and Pseudomonas phage, as well as imbalanced gut viral function, dominated by integral component of the membrane, and metal ion binding were detected in AF patients. Moreover, regarding co-occurrence networks connecting viruses and bacterial organisms, increasingly disordered virus-bacteria linkages were seen in AF cases with severe AF progression. Notably, the associations of Synechococcus phage S-SM1 and Cronobacter phage CR5 with bacterial species were very tight in control individuals but markedly dampened in AF cases. Furthermore, the viral score built by the selected discriminative taxa between AF cases with or without recurrence after ablation was still significantly associated with recurrence (HR = 2.959, P = 0.0085), with a survival AUC of 0.878. We demonstrated for the first time that gut viral signatures are associated with AF, and suppressed viral-bacterial associations in AF suggest the gut virus might participate in AF progression, which has a potential value in predicting ablation outcomes.