房颤是最常见的心律失常疾病。肠道菌群紊乱参与高血压等众多房颤危险因素发病。前期研究中我们的宏基因组和代谢组结果显示房颤患者肠道菌群紊乱失调，伴有菌群功能异常和代谢改变，如肠道菌Flavonifractor (Flav.)、Hungatella (Hung.)减低，代谢物亚油酸（LA）、α-亚麻酸（ALA）缺乏，但肠道菌群紊乱与房颤发病的因果关系及其作用机制尚不明确。本研究拟：1、通过无菌（GF）小鼠菌群移植模型证明肠道菌群紊乱是房颤发病的直接诱因；2、通过GF菌株移植模型阐明肠道菌Flav.、Hung.通过代谢产物LA/ALA抑制心房纤维化及房颤发病；3、采用TGF-β1转基因及基因敲除小鼠模型，明确Flav.、Hung.通过LA/ALA-TGF-β1/p38 MAPKs/CTGF信号通路抑制房颤发病，揭示肠道菌群紊乱参与房颤发病的分子机制，为临床防治房颤提供新思路，具有重要科学意义。

Atrial Fibrillation (AF) is the most common arrhythmia with heavy global burdens, intensifying disability and morbidity. Recently, various studies reported that gut microbiota (GM) dysbiosis contributed to the development of hypertension, diabetes millitus and obesity, which were the risk factors of AF either. Yet, little evidence has been reported characterizing the GM shift in AF. Based on our previous findings of metagenomics and metabonomics changes in AF patients, such as decreased abundance of Flavonifractor (Flav.), Hungatella (Hung.) and LA/ALA, the current study was designated to identify the underlying mechanism among dysbiotic GM and the development of AF. We plan to demonstrate the direct influence of gut microbiota on susceptibility of AF by fecal transplantation from AF human donors to germ-free mice. Next, the influence of Flav., Hung. and LA/ALA on atrial fibrosis and AF susceptibility will be investigated to testify the specific role of Flav., Hung. and LA/ALA participating the progression of AF. Furthermore, we determine to illuminate Flav., Hung. and LA/ALA inhibit atrial fibrosis and reduce AF onset through TGF-β1/p38 MAPKs/CTGF signaling pathway based on TGF-β1 transgenic and gene knock model. By performing this project, we aimed to find out a novel preventative and therapeutic target in AF.