FomA-TLR2-EC轴在IBS内脏高敏感状态中作用的研究

研究发现肠道菌群紊乱影响IBS内脏高敏感，但肠道菌群数量庞大种类繁多，具体何种细菌发挥作用目前尚无定论。我们前期研究发现IBS患者存在梭杆菌异常增殖，同时在IBS动物模型中具核梭杆菌编码的FomA蛋白灌胃加剧其内脏高敏感，上调肠上皮嗜铬细胞(EC)数量，提示FomA作用于EC影响IBS内脏高敏感。为阐明具体机制，本研究提出FomA-TLR2-EC轴的概念，拟通过临床病例、动物模型、TLR2敲除小鼠以及多种与EC细胞功能和发育相关的敲基因小鼠、细胞培养并联合应用高通量测序、基因芯片和蛋白测序多组学联合分析异常增殖的梭杆菌导致的FomA-TLR2-EC轴激活对IBS内脏高敏感的作用和机制，并探讨IBS菌群结构、肠上皮功能和内脏高敏感之间的相互作用，为IBS的诊断和个体化治疗提供新的科学依据和精准靶点。

It has been found that intestinal microbial dysbiosis affects the visceral hypersensitivity of IBS. However, the bacteria which plays a key role is still unclear. In our previous study, it has been found that the abundance of Fusobacterium in patients with IBS was elevated, and in the IBS animal model, the FomA encoded by Fusobacterium nucleatum exacerbated the degree of visceral hypersensitivity and up-regulated the number of intestinal epithelial chromaffin cells (EC), which suggesting that FomA affects the visceral hypersensitivity of IBS by acting on EC. In order to clarify its specific mechanism, the concept of FomA-TLR2-EC axis is proposed, and clinical cases, animal experiments, cell culture steps and the multi-omics analysis of 16s rRNA gene sequencing, gene chip transcriptome and protein sequencing were used to explore the effect and mechanism of FomA-TLR2-EC axis activation on visceral hypersensitivity of IBS, and explore the interaction between IBS gut mirobiota, intestinal epithelial function and visceral hypersensitivity, providing new scientific basis and precise target for the diagnosis and individualized treatment of IBS.