申请人既往研究表明，大肠癌发生过程中肠道菌群的紊乱发挥重要的作用。我国传统中成药物小檗碱（Berberine，BBR），是一种常见的异喹啉生物碱。在本课题组主持的一项大规模多中心随机双盲对照的临床试验发现，小檗碱对于临床上大肠癌发生具有一定保护作用。动物学实验进一步表明: 小檗碱预防大肠癌的作用与其调整肠道菌群生态结构有关。根据前期预实验的结果，申请人证实了小檗碱抑制肠道微生态失衡，其机制很可能是通过LINC01410 与miR-124-3p 直接结合或通过RNA 诱导沉默复合体中关键蛋白募集miR-124-3p，导致WNT/Elf3/ β-catenin 通路的抑制作用减弱，进而促进大肠癌的发生发展。这一机制研究可能为小檗碱预防大肠癌提供进一步理论基础。

According to the previous research of the applicant, dysbiosis of gut microbiota plays a significant role in tumorgenesis of colorectal cancer (CRC). Berberine (BBR), a traditional Chinese medicine, is a common kind of isoquinoline alkaloids. In a large-scale multi-center double-blind random clinical trial conducted by our research group, BBR has a preventive effect on the occurrence of CRC in clinical practice. Animal experiments further indicate that this preventive effect is associated to the regulation of the structure of gut microbiota. On the basis of the earlier preliminary experiment, we presume that BBR probably inhibits the disorder of gut microbiota through the direct combination of LINC01410 with miR-124-3p or through the recruitment of miR-124-3p by key proteins in RNA-induced silencing complex, impairing the inhibition of Wnt/Elf3/ β-catenin signaling pathway, thus blocking the carcinogenesis of CRC. Reveal of this mechanism will further lay the theriotical foundation of the preventive effect on CRC of BBR.