title: Comparison of three different application routes of butyrate to improve colonic anastomotic strength in rats.
abstract: BACKGROUND
  Despite extensive research, anastomotic leakage (AL) remains one of the most dreaded complications after colorectal surgery. Since butyrate enemas are known to enhance anastomotic healing, several administration routes have been explored in this study.
  
  
  METHODS
  Three intraluminal approaches involving butyrate were investigated: (1) butyrin-elucidating patch, (2) a single injection of hyaluronan-butyrate (HA-But) prior to construction of the proximal anastomosis and (3) rectal hyaluronan-butyrate (HA-But) enemas designed for distal anastomoses. The main outcome was AL and secondary outcomes were bursting pressure, histological analysis of the anastomosis, zymography to detect MMP activity and qPCR for gene expression of MMP2, MMP9, MUC2 and TFF3.
  
  
  RESULTS
  Neither the patches nor the injections led to a reduction of AL in experiments 1 and 2. In experiment 3, a significant reduction of AL was accomplished with the (HA-But) enema compared to the control group together with a higher bursting pressure. Histological analysis detected only an increased inflammation in experiment 2 in the hyaluronan injection group compared to the control group. No other differences were found regarding wound healing. Zymography identified a decreased proenzyme of MMP9 when HA-But was administered as a rectal enema. qPCR did not show any significant differences between groups in any experiment.
  
  
  CONCLUSIONS
  Butyrate enemas are effective in the enhancement of colonic anastomosis. Enhanced butyrate-based approaches designed to reduce AL in animal models for both proximal and distal anastomoses were not more effective than were butyrate enemas alone. Further research should focus on how exogenous butyrate can improve anastomotic healing after gastrointestinal surgery.
authors.affiliation: Department of General Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands. ac.bosmans@maastrichtuniversity.nl.|NUTRIM School for Nutrition and Translation Research in Metabolism, Maastricht University, Maastricht, the Netherlands. ac.bosmans@maastrichtuniversity.nl.
authors.forename: J W A M
authors.initials: JW
authors.lastname: Bosmans
authors.affiliation: Department of General Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.|NUTRIM School for Nutrition and Translation Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: A C H M
authors.initials: AC
authors.lastname: Jongen
authors.affiliation: Department of General Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.
authors.forename: B T C
authors.initials: BT
authors.lastname: Boonen
authors.affiliation: Department of General Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.|NUTRIM School for Nutrition and Translation Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van Rijn
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Scognamiglio
authors.affiliation: SIGEA Srl, AREA Science Park, Trieste, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Stucchi
authors.affiliation: Departments of Pathology and Molecular Genetics, CARIM, Maastricht University, Maastricht, The Netherlands.|Department of Medical Biochemistry, Academic Medical Center, Maastricht, the Netherlands.
authors.forename: M J J
authors.initials: MJ
authors.lastname: Gijbels
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Marsich
authors.affiliation: Department of General Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.|NUTRIM School for Nutrition and Translation Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: N D
authors.initials: ND
authors.lastname: Bouvy
mesh_terms: D000714:Anastomosis, Surgical; D057868:Anastomotic Leak / Q000473:pathology; D000818:Animals; D020148:Butyric Acid / Q000008:administration & dosage* / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000601:surgery*; D004333:Drug Administration Routes; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011312:Pressure; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D020148:Butyric Acid; D003094:Collagen; D020782:Matrix Metalloproteinases
keywords: Anastomoses; Anastomotic healing; Animal study; Butyrate; Colorectal anastomotic leakage