Bidirectional effects of oral anticoagulants on gut microbiota in patients with atrial fibrillation

Abstract

BackgroundThe imbalance of gut microbiota (GM) is associated with a higher risk of thrombosis in patients with atrial fibrillation (AF). Oral anticoagulants (OACs) have been found to significantly reduce the risk of thromboembolism and increase the risk of bleeding. However, the OAC-induced alterations in gut microbiota in patients with AF remain elusive.MethodsIn this study, the microbial composition in 42 AF patients who received long-term OAC treatment (AF-OAC group), 47 AF patients who did not (AF group), and 40 volunteers with the risk of AF (control group) were analyzed by 16S rRNA gene sequencing of fecal bacterial DNA. The metagenomic functional prediction of major bacterial taxa was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software package.ResultsThe gut microbiota differed between the AF-OAC and AF groups. The abundance of Bifidobacterium and Lactobacillus decreased in the two disease groups at the genus level, but OACs treatment mitigated the decreasing tendency and increased beneficial bacterial genera, such as Megamonas. In addition, OACs reduced the abundance of pro-inflammatory taxa on the genus Ruminococcus but increased certain potential pathogenic taxa, such as genera Streptococcus, Escherichia-Shigella, and Klebsiella. The Subgroup Linear discriminant analysis effect size (LEfSe) analyses revealed that Bacteroidetes, Brucella, and Ochrobactrum were more abundant in the anticoagulated bleeding AF patients, Akkermansia and Faecalibacterium were more abundant in the non-anticoagulated-bleeding-AF patients. The neutrophil-to-lymphocyte ratio (NLR) was lower in the AF-OAC group compared with the AF group (P < 0.05). Ruminococcus was positively correlated with the NLR and negatively correlated with the CHA2DS2-VASc score (P < 0.05), and the OACs-enriched species (Megamonas and Actinobacteria) was positively correlated with the prothrombin time (PT) (P < 0.05). Ruminococcus and Roseburia were negatively associated with bleeding events (P < 0.05).ConclusionsOur study suggested that OACs might benefit AF patients by reducing the inflammatory response and modulating the composition and abundance of gut microbiota. In particular, OACs increased the abundance of some gut microbiota involved in bleeding and gastrointestinal dysfunction indicating that the exogenous supplementation with Faecalibacterium and Akkermansia might be a prophylactic strategy for AF-OAC patients to lower the risk of bleeding after anticoagulation.

A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for acute pancreatitis

“…In a separate study, Li et al observed that oral anticoagulants (OACs) altered the composition of gut microbiota, speci cally increasing the abundance of Megamonas and decreasing pro-in ammatory colonies in patients with atrial brillation (AF). This shift in microbiota was associated with reduced thrombosis and highlighted the potential modulatory role of Megamonas in abnormal lipid metabolism [ 57]. In conclusion, our ndings reinforce the aforementioned conclusions and identify novel therapeutic targets for the management of acute pancreatitis.…”

The correlation between gut microbiome and atrial fibrillation: pathophysiology and therapeutic perspectives

“…Intestinal flora might have an indirect effect on OACs through the metabolites generated, or a direct effect on vitamin K-producing bacteria and structural modifications of drug molecules. Correspondingly, Li et al [ 134 ] demonstrated that the implementation of OACs in AF patients might mitigate inflammation, atherosclerosis, and thrombosis by altering the abundance of gut microbiota. Nonetheless, OACs might raise the risk of bleeding in the gastrointestinal tract and other parts of the body through certain potential pathogens.…”