AUTHOR=Li Wan , Li Changxia , Ren Cheng , Zhou Shiju , Cheng Huan , Chen Yuanrong , Han Xiaowei , Zhong Yiming , Zhou Licheng , Xie Dongming , Liu Haiyue , Xie Jiahe 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1038472

DOI=10.3389/fcimb.2023.1038472

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>The 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.</p></sec><sec><title>Methods</title><p>In 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.</p></sec><sec><title>Results</title><p>The gut microbiota differed between the AF-OAC and AF groups. The abundance of <italic>Bifidobacterium</italic> and <italic>Lactobacillus</italic> decreased in the two disease groups at the genus level, but OACs treatment mitigated the decreasing tendency and increased beneficial bacterial genera, such as <italic>Megamonas</italic>. In addition, OACs reduced the abundance of pro-inflammatory taxa on the genus <italic>Ruminococcus</italic> but increased certain potential pathogenic taxa, such as genera <italic>Streptococcus</italic>, <italic>Escherichia-Shigella</italic>, and <italic>Klebsiella</italic>. The Subgroup Linear discriminant analysis effect size (LEfSe) analyses revealed that <italic>Bacteroidetes</italic>, <italic>Brucella</italic>, and <italic>Ochrobactrum</italic> were more abundant in the anticoagulated bleeding AF patients, <italic>Akkermansia</italic> and <italic>Faecalibacterium</italic> 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 (<italic>P</italic> &lt; 0.05). <italic>Ruminococcus</italic> was positively correlated with the NLR and negatively correlated with the CHA2DS2-VASc score (<italic>P</italic> &lt; 0.05), and the OACs-enriched species (<italic>Megamonas</italic> and <italic>Actinobacteria</italic>) was positively correlated with the prothrombin time (PT) (<italic>P</italic> &lt; 0.05). <italic>Ruminococcus</italic> and <italic>Roseburia</italic> were negatively associated with bleeding events (<italic>P</italic> &lt; 0.05).</p></sec><sec><title>Conclusions</title><p>Our 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 <italic>Faecalibacterium</italic> and <italic>Akkermansia</italic> might be a prophylactic strategy for AF-OAC patients to lower the risk of bleeding after anticoagulation.</p></sec>