Cargando…

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

BACKGROUND: Although 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,...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318127/
https://www.ncbi.nlm.nih.gov/pubmed/37400975
http://dx.doi.org/10.1002/ctm2.1321
_version_ 1785067969596882944
author 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
author_facet 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
author_sort Ma, Haitao
collection PubMed
description BACKGROUND: Although 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. METHODS: Single‐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. RESULTS: We 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. CONCLUSIONS: This 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.
format Online
Article
Text
id pubmed-10318127
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-103181272023-07-05 Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing 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 Clin Transl Med Research Articles BACKGROUND: Although 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. METHODS: Single‐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. RESULTS: We 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. CONCLUSIONS: This 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. John Wiley and Sons Inc. 2023-07-03 /pmc/articles/PMC10318127/ /pubmed/37400975 http://dx.doi.org/10.1002/ctm2.1321 Text en © 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
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
Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing
title Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing
title_full Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing
title_fullStr Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing
title_full_unstemmed Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing
title_short Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing
title_sort dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318127/
https://www.ncbi.nlm.nih.gov/pubmed/37400975
http://dx.doi.org/10.1002/ctm2.1321
work_keys_str_mv AT mahaitao dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT lixiaolong dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT panyiyang dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT wangliucan dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT hanben dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT xiehuichao dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT zhenghong dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT jiangenlai dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT chenjianghong dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT liyunbo dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT jiguangyan dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT qiuyuan dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing
AT xiaoweidong dissectingtheeffectofilealfaecaldiversionontheintestineusingsinglecellsequencing