肠道菌群组成变化及其相关代谢产物与心房颤动相关性

    Relationship between alternation of intestinal flora composition and its metabolites and the progression of atrial fibrillation

      摘要
    • 摘要:
      目的 探索肠道菌群组成变化及其相关代谢产物与心房颤动（atrial fibrillation, AF）进展的关系。
      方法 连续入选48例AF患者，分为PaAF组（paroxysmal AF，阵发性房颤，n=23）和PeAF组（persistent AF，包括持续性房颤和长期持续性房颤，n=25），并入选11例窦性心律（SR）患者作为对照，采用16S rRNA测序和液相色谱法检测其肠道菌群和血清氧化三甲胺（TMAO）、肉碱（carnitine）和胆碱（choline）的水平。
      结果 在门水平的菌种中，拟杆菌门在SR组患者肠道菌群中占比76.6%、在PaAF组占比69.1%，两组比例显著高于在PeAF组的45.0%（均P<0.01）；两组之间无统计学差异；厚壁菌门（Firmicutes ）在SR组患者肠道菌群中占比18.7%、在PaAF组占比29.7%，两组比例显著低于在PeAF组的52.0%（均P<0.01），两组间无统计学差异。其他菌种类型如放线菌门（Actinobacteria）、变形菌门（Proteobacteria）和疣微菌门（Verrucomicrobia）等占比较低，且三组间差异无统计学意义。在科水平的菌种组成SR组、PaAF组和PeAF三组间多数菌种的组成无统计学差异。PCA分析提示SR组和PaAF组肠道菌群组成相似，但PeAF组与之显著不同。血清TMAO、肉碱和胆碱水平在三组间表达水平呈递增趋势，血清TMAO水平在SR组、PaAF组和PeAF组患者中的表达水平分别为1.21 μmol/L、2.49 μmol/L和3.28 μmol/L，血清肉碱水平分别为34.85 μmol/L、38.20 μmol/L和46.47 μmol/L，血清胆碱水平分别为10.41 μmol/L、15.18 μmol/L和18.49 μmol/L，差异有统计学意义（趋势检验均P<0.01）。
      结论 肠道菌群组成变化及其相关代谢产物，TMAO、肉碱和胆碱水平与AF的进展相关，提示它们可能是促进AF发生发展的危险因素。

       

      Abstract:
      AIM To evaluate the relationship between alternation of intestinal flora composition and its metabolites and the progression of atrial fibrillation.
      METHODS Fifty-nine patients were consecutively enrolled and were divided into sinus rhythm (SR) group (n=11), paroxysmal AF (PaAF) group (n=23) and persistent AF (PeAF) group (n=25). 16S rRNA sequencing and liquid chromatography were employed for the analysis of gut microbiota composition and serum TMAO, carnitine and choline levels, respectively.
      RESULTS At the phylum level, Bacteroidetes accounted for 76.6% of the gut microbiota in the SR group and 69.1% in the PaAF group, significantly higher than 45.0% in the PeAF group (both P<0.01); There was no statistically significant difference between the two groups; Firmicutes accounted for 18.7% of the gut microbiota in the SR group and 29.7% in the PaAF group, significantly lower than the 52.0% in the PeAF group (both P<0.01), and there was no statistically significant difference between the two groups. The proportion of other bacterial types such as Actinobacteria, Proteobacteria, and Verrucomicrobia is relatively low, and there is no statistically significant difference among the three groups. There was no statistically significant difference in the composition of most bacterial species among the SR group, PaAF group, and PeAF groups at the family level. PCA analysis suggests that the composition of gut microbiota is similar between the SR group and the PaAF group, but significantly different from the PeAF group. The expression levels of serum trimethylamine (TMAO), carnitine, and choline showed an increasing trend among the three groups, with values of 1.21, respectively μmol/L, 2.49 μmol/L and 3.28 μmol/L; 34.85 μmol/L, 38.20 μmol/L and 46.47 μmol/L; 10.41 μmol/L, 15.18 μmol/L and 18.49 μmol/L, the difference is statistically significant (trend P-values are all<0.01).
      CONCLUSION The alternation of intestinal flora composition and its metabolites, including TMAO, Carnitineand Choline, are associated with the progression of AF, indicating that gut flora might be an underlying risk factor for AF development.

       

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