溃疡性结肠炎（UC）重要病理生理特征是肠上皮细胞损伤和肠黏膜屏障完整性破坏。我们前期使用O-糖缺陷小鼠，证明了簇细胞（Tuft cell）可调节肠上皮细胞增生和黏液分泌而修复肠道黏膜屏障功能。但尚不清楚炎症状态下如何激活和扩增簇细胞。为了探索产琥珀酸细菌是否通过琥珀酸介导激活簇细胞并调节肠黏膜屏障功能，本项目拟通过Prevotella Copri灌胃干预O-糖缺陷小鼠，分析其对结肠炎小鼠炎症病理评分、“Tuft Cell-ILC2 环路”及肠黏膜屏障的影响，并进行临床样本的验证分析。我们有望：（1）从菌株水平明确Prevotella Copri对慢性结肠炎黏膜修复的作用及机制；（2）明确琥珀酸是否可以通过激活“Tuft Cell-ILC2环路”调节肠黏膜屏障；（3）为UC开发以产琥珀酸为主的肠道益生菌及以琥珀酸为靶点的药物开发提供思路。

Ulcerative colitis (UC) is characterized by defective intestinal barrier integrity toward the microbiota and epithelial damage. Previously, by using O-glycan deficiency induced spontaneous chronic colitis mice model, our results showed that Tuft cells promote mucosal barrier repair by regulating epithelial cell reconsitution and goblet cell’s mucus secreting. However, it’s unknown how tuft cell is activated and proliferated in colitis. We aim to clarify whether succinic acid producing bacteria can activate tuft cell and regulate mucosal barrier repair in chronic colitis. By administration of Prevotella Copri in O-glycan deficiency mice, we proposed to analyze the histological score, markers related to “Tuft Cell-ILC2 Circuit” and mucosal barrier. Furthermore, we will verify our findings on UC patients samples. We are expected to clarify the role and mechanism of Prevotella Copri on mucosa repair in chronic colitis at the bacterial strain level, determine whether succinic acid can activate the intestinal "Tuft cells-ILC2 circuit", promoting intestinal mucosal barrier repair, and provide ideas for the development of succinic acid producing intestinal probiotics and succinic acid targeted drug for UC.