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Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9

BACKGROUND: Despite advances in anastomotic techniques and perioperative care, the incidence of anastomotic leak (AL) has not substantially decreased over time. Although it is known that AL etiology is multifactorial and the mechanisms involved remain unclear, there is accumulating evidence pointing...

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Autores principales: Shi, Shang, Liu, Yang, Wang, Zhiyue, Jin, Xiangren, Yan, Wei, Guo, Xiao, Lin, Baiqiang, Wang, Haoran, Li, Bowen, Zheng, Jianjun, Wei, Yunwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794562/
https://www.ncbi.nlm.nih.gov/pubmed/36590433
http://dx.doi.org/10.3389/fmicb.2022.1031882
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author Shi, Shang
Liu, Yang
Wang, Zhiyue
Jin, Xiangren
Yan, Wei
Guo, Xiao
Lin, Baiqiang
Wang, Haoran
Li, Bowen
Zheng, Jianjun
Wei, Yunwei
author_facet Shi, Shang
Liu, Yang
Wang, Zhiyue
Jin, Xiangren
Yan, Wei
Guo, Xiao
Lin, Baiqiang
Wang, Haoran
Li, Bowen
Zheng, Jianjun
Wei, Yunwei
author_sort Shi, Shang
collection PubMed
description BACKGROUND: Despite advances in anastomotic techniques and perioperative care, the incidence of anastomotic leak (AL) has not substantially decreased over time. Although it is known that AL etiology is multifactorial and the mechanisms involved remain unclear, there is accumulating evidence pointing at AL related to gut microbiota. METHOD: We firstly performed a clinical study to analyze the gut microbiota between colorectal cancer patients who developed AL and those who did not (nAL) using 16S-rRNA sequencing and quantitative real-time PCR to identify AL risk bacterial taxa. Then we built a rat anastomosis model and performed a bacteria transplantation to ensure the cause-effect relationship. The anastomotic healing score was used to evaluate the healing of anastomosis. In addition, we assessed the adhesion ability of bacteria by staining with fluorescein isothiocyanate and attachment assay. The expression of matrix metalloproteinase 9 (MMP9) was detected by western blot, and the activity was detected by gelatin zymography. RESULTS: We found that the abundance and positive rate of Fusobacterium nucleatum (Fn) were higher in the AL patients. Exposure of the rat’s colon anastomosis to Fn contributes to the loss of submucosa collagen I and III, leading to AL’s pathogenesis. Fn can attach to the gut epithelial cells and stimulate intestinal MMP9 expression in vitro and in vivo. We further confirmed that these effects of Fn depended on the E-cadherin/β-catenin signaling pathway. CONCLUSION: This work demonstrates that Fn attaches and then stimulates the expression of epithelial cells MMP9 by the E-cadherin/β-catenin signaling pathway. These effects contribute to collagen break down in the intestinal tissue, finally leading to AL.
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spelling pubmed-97945622022-12-29 Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9 Shi, Shang Liu, Yang Wang, Zhiyue Jin, Xiangren Yan, Wei Guo, Xiao Lin, Baiqiang Wang, Haoran Li, Bowen Zheng, Jianjun Wei, Yunwei Front Microbiol Microbiology BACKGROUND: Despite advances in anastomotic techniques and perioperative care, the incidence of anastomotic leak (AL) has not substantially decreased over time. Although it is known that AL etiology is multifactorial and the mechanisms involved remain unclear, there is accumulating evidence pointing at AL related to gut microbiota. METHOD: We firstly performed a clinical study to analyze the gut microbiota between colorectal cancer patients who developed AL and those who did not (nAL) using 16S-rRNA sequencing and quantitative real-time PCR to identify AL risk bacterial taxa. Then we built a rat anastomosis model and performed a bacteria transplantation to ensure the cause-effect relationship. The anastomotic healing score was used to evaluate the healing of anastomosis. In addition, we assessed the adhesion ability of bacteria by staining with fluorescein isothiocyanate and attachment assay. The expression of matrix metalloproteinase 9 (MMP9) was detected by western blot, and the activity was detected by gelatin zymography. RESULTS: We found that the abundance and positive rate of Fusobacterium nucleatum (Fn) were higher in the AL patients. Exposure of the rat’s colon anastomosis to Fn contributes to the loss of submucosa collagen I and III, leading to AL’s pathogenesis. Fn can attach to the gut epithelial cells and stimulate intestinal MMP9 expression in vitro and in vivo. We further confirmed that these effects of Fn depended on the E-cadherin/β-catenin signaling pathway. CONCLUSION: This work demonstrates that Fn attaches and then stimulates the expression of epithelial cells MMP9 by the E-cadherin/β-catenin signaling pathway. These effects contribute to collagen break down in the intestinal tissue, finally leading to AL. Frontiers Media S.A. 2022-12-14 /pmc/articles/PMC9794562/ /pubmed/36590433 http://dx.doi.org/10.3389/fmicb.2022.1031882 Text en Copyright © 2022 Shi, Liu, Wang, Jin, Yan, Guo, Lin, Wang, Li, Zheng and Wei. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Shi, Shang
Liu, Yang
Wang, Zhiyue
Jin, Xiangren
Yan, Wei
Guo, Xiao
Lin, Baiqiang
Wang, Haoran
Li, Bowen
Zheng, Jianjun
Wei, Yunwei
Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9
title Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9
title_full Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9
title_fullStr Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9
title_full_unstemmed Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9
title_short Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9
title_sort fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express mmp9
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794562/
https://www.ncbi.nlm.nih.gov/pubmed/36590433
http://dx.doi.org/10.3389/fmicb.2022.1031882
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