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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands.
authors.forename: J W A M
authors.initials: JW
authors.lastname: Bosmans
authors.affiliation: Department of Surgery, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands.
authors.forename: A C H M
authors.initials: AC
authors.lastname: Jongen
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: G M H
authors.initials: GM
authors.lastname: Birchenough
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: E E L
authors.initials: EE
authors.lastname: Nyström
authors.affiliation: Departments of Pathology and Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands.|Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M J J
authors.initials: MJ
authors.lastname: Gijbels
authors.affiliation: Department of Surgery, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands.|Paediatric Surgical Centre Amsterdam, Emma Children's Hospital/VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: J P M
authors.initials: JP
authors.lastname: Derikx
authors.affiliation: Department of Surgery, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands.
authors.forename: N D
authors.initials: ND
authors.lastname: Bouvy
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: G C
authors.initials: GC
authors.lastname: Hansson
mesh_terms: D000714:Anastomosis, Surgical; D057868:Anastomotic Leak / Q000517:prevention & control; D000818:Animals; D018988:Bacterial Translocation; D003106:Colon / Q000601:surgery; D003107:Colorectal Surgery; D015232:Dinoprostone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D005838:Genotype; D007413:Intestinal Mucosa; D051379:Mice; D008962:Models, Theoretical; D055262:Mucin-2 / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D050556:Fatty Acid-Binding Proteins; C524626:Muc2 protein, mouse; D055262:Mucin-2; D015232:Dinoprostone