Functional mucous layer and healing of proximal colonic anastomoses in an experimental model

J. W.A.M. Bosmans, A. C.H.M. Jongen, G. M.H. Birchenough, E. E.L. Nyström, M. J.J. Gijbels, J. P.M. Derikx, N. D. Bouvy, G. C. Hansson

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model. Methods: Mice of different Muc2 genotypes were used in a proximal colonic AL model. Tissues were scored histologically for inflammation, bacterial translocation was determined by quantitative PCR of bacterial 16S ribosomal DNA, and epithelial cell damage was determined by assessing serum levels of intestinal fatty acid-binding protein. Results: Of 22 Muc2-deficient (Muc2−/−) mice, 20 developed AL, compared with seven of 22 control animals (P < 0·001). Control mice showed normal healing, whereas Muc2−/− mice had more inflammation with less collagen deposition and neoangiogenesis. A tendency towards higher bacterial translocation was seen in mesenteric lymph nodes and spleen in Muc2−/− mice. Intestinal fatty acid-binding protein levels were significantly higher in Muc2−/− mice compared with controls (P = 0·011). Conclusion: A functional mucous layer facilitates the healing of colonic anastomoses. Clinical relevance Colorectal anastomotic leakage remains the most dreaded complication after colorectal surgery. It is known that the aetiology of anastomotic leakage is multifactorial, and a role is suggested for the interaction between intraluminal content and mucosa. In this murine model of proximal colonic anastomotic leakage, the authors investigated the mucous layer at the intestinal mucosa, as the first line of defence, and found that a normal, functioning mucous layer is essential in the healing process of colonic anastomoses. Further research on anastomotic healing should focus on positively influencing the mucous layer to promote better postoperative recovery.

Original languageEnglish
Pages (from-to)619-630
Number of pages12
JournalBritish Journal of Surgery
Volume104
Issue number5
DOIs
Publication statusPublished - 1 Apr 2017

Cite this

Bosmans, J. W. A. M., Jongen, A. C. H. M., Birchenough, G. M. H., Nyström, E. E. L., Gijbels, M. J. J., Derikx, J. P. M., ... Hansson, G. C. (2017). Functional mucous layer and healing of proximal colonic anastomoses in an experimental model. British Journal of Surgery, 104(5), 619-630. https://doi.org/10.1002/bjs.10456
Bosmans, J. W.A.M. ; Jongen, A. C.H.M. ; Birchenough, G. M.H. ; Nyström, E. E.L. ; Gijbels, M. J.J. ; Derikx, J. P.M. ; Bouvy, N. D. ; Hansson, G. C. / Functional mucous layer and healing of proximal colonic anastomoses in an experimental model. In: British Journal of Surgery. 2017 ; Vol. 104, No. 5. pp. 619-630.
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title = "Functional mucous layer and healing of proximal colonic anastomoses in an experimental model",
abstract = "Background: Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model. Methods: Mice of different Muc2 genotypes were used in a proximal colonic AL model. Tissues were scored histologically for inflammation, bacterial translocation was determined by quantitative PCR of bacterial 16S ribosomal DNA, and epithelial cell damage was determined by assessing serum levels of intestinal fatty acid-binding protein. Results: Of 22 Muc2-deficient (Muc2−/−) mice, 20 developed AL, compared with seven of 22 control animals (P < 0·001). Control mice showed normal healing, whereas Muc2−/− mice had more inflammation with less collagen deposition and neoangiogenesis. A tendency towards higher bacterial translocation was seen in mesenteric lymph nodes and spleen in Muc2−/− mice. Intestinal fatty acid-binding protein levels were significantly higher in Muc2−/− mice compared with controls (P = 0·011). Conclusion: A functional mucous layer facilitates the healing of colonic anastomoses. Clinical relevance Colorectal anastomotic leakage remains the most dreaded complication after colorectal surgery. It is known that the aetiology of anastomotic leakage is multifactorial, and a role is suggested for the interaction between intraluminal content and mucosa. In this murine model of proximal colonic anastomotic leakage, the authors investigated the mucous layer at the intestinal mucosa, as the first line of defence, and found that a normal, functioning mucous layer is essential in the healing process of colonic anastomoses. Further research on anastomotic healing should focus on positively influencing the mucous layer to promote better postoperative recovery.",
author = "Bosmans, {J. W.A.M.} and Jongen, {A. C.H.M.} and Birchenough, {G. M.H.} and Nystr{\"o}m, {E. E.L.} and Gijbels, {M. J.J.} and Derikx, {J. P.M.} and Bouvy, {N. D.} and Hansson, {G. C.}",
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Bosmans, JWAM, Jongen, ACHM, Birchenough, GMH, Nyström, EEL, Gijbels, MJJ, Derikx, JPM, Bouvy, ND & Hansson, GC 2017, 'Functional mucous layer and healing of proximal colonic anastomoses in an experimental model' British Journal of Surgery, vol. 104, no. 5, pp. 619-630. https://doi.org/10.1002/bjs.10456

Functional mucous layer and healing of proximal colonic anastomoses in an experimental model. / Bosmans, J. W.A.M.; Jongen, A. C.H.M.; Birchenough, G. M.H.; Nyström, E. E.L.; Gijbels, M. J.J.; Derikx, J. P.M.; Bouvy, N. D.; Hansson, G. C.

In: British Journal of Surgery, Vol. 104, No. 5, 01.04.2017, p. 619-630.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Functional mucous layer and healing of proximal colonic anastomoses in an experimental model

AU - Bosmans, J. W.A.M.

AU - Jongen, A. C.H.M.

AU - Birchenough, G. M.H.

AU - Nyström, E. E.L.

AU - Gijbels, M. J.J.

AU - Derikx, J. P.M.

AU - Bouvy, N. D.

AU - Hansson, G. C.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background: Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model. Methods: Mice of different Muc2 genotypes were used in a proximal colonic AL model. Tissues were scored histologically for inflammation, bacterial translocation was determined by quantitative PCR of bacterial 16S ribosomal DNA, and epithelial cell damage was determined by assessing serum levels of intestinal fatty acid-binding protein. Results: Of 22 Muc2-deficient (Muc2−/−) mice, 20 developed AL, compared with seven of 22 control animals (P < 0·001). Control mice showed normal healing, whereas Muc2−/− mice had more inflammation with less collagen deposition and neoangiogenesis. A tendency towards higher bacterial translocation was seen in mesenteric lymph nodes and spleen in Muc2−/− mice. Intestinal fatty acid-binding protein levels were significantly higher in Muc2−/− mice compared with controls (P = 0·011). Conclusion: A functional mucous layer facilitates the healing of colonic anastomoses. Clinical relevance Colorectal anastomotic leakage remains the most dreaded complication after colorectal surgery. It is known that the aetiology of anastomotic leakage is multifactorial, and a role is suggested for the interaction between intraluminal content and mucosa. In this murine model of proximal colonic anastomotic leakage, the authors investigated the mucous layer at the intestinal mucosa, as the first line of defence, and found that a normal, functioning mucous layer is essential in the healing process of colonic anastomoses. Further research on anastomotic healing should focus on positively influencing the mucous layer to promote better postoperative recovery.

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