肠系膜脂肪炎性增生是影响克罗恩病（CD）进程的特征性表现，但原因不明。本课题组临床数据表明，CT测得的肠系膜内炎性体积与CD炎症程度及疗效明显相关，且CD肠系膜中存在以产酸克雷伯氏(K.O)菌为主的细菌异位，提示K.O菌可能与CD肠系膜炎症有关。本项目拟进一步对CD系膜标本中的K.O菌进行体外培养筛选，结合组织培养、流式分选、电镜和细菌感染等方法明确脂肪前体细胞对K.O菌的吞噬作用，通并过对生长、分化、迁移、促炎等表型的检测，明确吞噬K.O菌可诱发脂肪前体细胞的炎性增生；针对K.O菌特有的Tilivalline毒素基因，构建野生、敲除和回补型菌株，利用人肠系膜来源的脂肪前体细胞和无菌DSS肠炎小鼠模型，阐明K.O菌通过Tilivalline毒素诱发肠系膜炎性增生的作用和机制。本项目将明确细菌异位诱发肠系膜炎性增生的机制，为针对CD肠系膜炎症的治疗方式奠定理论基础。

Inflammatory hypertrophy of the mesentery of Crohn’s disease is one of the major characteristics that could affect the progression of this disease, while detailed mechanism remains unknown. We previously found that, the enhanced volume of mesentery under CT scan was correlated with endoscopic activity and treatment effect, and bacteria was found in the mesentery by 16s sequencing featuring Klebsiella oxytoca (K.O). This made us to wonder whether K.O could affect CD progression. We aim to culture K.O in vitro from the mesenteric tissue from operation. Combining flowcytometry sorting, electronic scanning and co-culturing, we could verify whether the preadipocyte could engulf KO and showed inflammatory proliferative status. As to the special genotoxin Tilivalline, wildtype, mutant and rescue K.O strain were constructed, and infect preadipocyte in vitro and sterile DSS colitis mice, to confirm the effect of K.O in the pathogenesis of Crohn’s disease. This project would help clarify the hypertrophy of mesentery in Crohn’s disease, and set the ground for treatment strategies against the inflammation in mesentery.