Dissecting the effect of ileal faecal diversion on the intestine using single-cell sequencing

作者全名："Ma, Haitao; Li, Xiaolong; Pan, Yiyang; Wang, Liucan; Han, Ben; Xie, Huichao; Zheng, Hong; Jiang, Enlai; Chen, Jianghong; Li, Yunbo; Ji, Guangyan; Qiu, Yuan; Xiao, Weidong"

作者地址："[Ma, Haitao; Li, Xiaolong; Pan, Yiyang; Wang, Liucan; Xie, Huichao; Jiang, Enlai; Chen, Jianghong; Li, Yunbo; Qiu, Yuan; Xiao, Weidong] Army Med Univ, Xinqiao Hosp, Dept Gen Surg, Chongqing, Peoples R China; [Han, Ben] Army Med Univ, Xinqiao Hosp, Nutr Dept, Chongqing, Peoples R China; [Zheng, Hong] Army Med Univ, Xinqiao Hosp, Dept Thorac Surg, Chongqing, Peoples R China; [Ji, Guangyan] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China; [Qiu, Yuan; Xiao, Weidong] Army Med Univ, Xinqiao Hosp, Dept Gen Surg, Chongqing 400037, Peoples R China"

通信作者："Qiu, Y; Xiao, WD (通讯作者)，Army Med Univ, Xinqiao Hosp, Dept Gen Surg, Chongqing 400037, Peoples R China."

来源：CLINICAL AND TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001038254100011

JCR分区：Q1

影响因子：7.9

年份：2023

卷号：13

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：Crohn's disease; fibrosis; ileal faecal diversion; intestinal goblet cells; single-cell RNA sequencing; TRPA1

摘要："BackgroundAlthough ileal faecal diversion is commonly used in clinical settings, complications accompany it. Elucidating the intestinal changes caused by ileal faecal diversion will help resolve postoperative complications and elucidate the pathogenic mechanisms of associated intestinal disorders, such as Crohn's disease (CD). Therefore, our study aimed to provide new insights into the effects of ileal faecal diversion on the intestine and the potential mechanisms. MethodsSingle-cell RNA sequencing was performed on proximal functional and paired distal defunctioned intestinal mucosae from three patients with ileal faecal diversion. We also performed in vitro cellular and animal experiments, tissue staining and analysed public datasets to validate our findings. ResultsWe found that the epithelium in the defunctioned intestine tended to be immature, with defective mechanical and mucous barriers. However, the innate immune barrier in the defunctioned intestine was enhanced. Focusing on the changes in goblet cells, we demonstrated that mechanical stimulation promotes the differentiation and maturation of goblet cells through the TRPA1-ERK pathway, indicating that the absence of mechanical stimulation may be the main cause of defects in the goblet cells of the defunctioned intestine. Furthermore, we found obvious fibrosis with a pro-fibrotic microenvironment in the defunctioned intestine and identified that monocytes may be important targets for faecal diversion to alleviate CD. ConclusionsThis study revealed the different transcription landscapes of various cell subsets and the potential underlying mechanisms within the defunctioned intestine, when compared to the functional intestine, based on the background of ileal faecal diversion. These findings provide novel insights for understanding the physiological and pathological roles of the faecal stream in the intestine."

基金机构："Natural Science Foundation of Chongqing, China [2022NSCQ-MSX4686]; National Natural Science Foundation of China [82270585]; Army Medical University Project [CX2019JS212, 2021XJS25]"

基金资助正文："ACKNOWLEDGEMENTS This study was supported by the Natural Science Foundation of Chongqing, China (No. 2022NSCQ-MSX4686 to YQ), the National Natural Science Foundation of China (No. 82270585 to WX) and Army Medical University Project (No. CX2019JS212 to WX and No. 2021XJS25 to WX)."