New growth factor therapies aimed at improving intestinal adaptation in short bowel syndrome

Abstract

Short bowel syndrome (SBS) is used to describe a condition of malabsorption and malnutrition resulting from the loss of absorptive area following massive small bowel resection. The key to improved clinical outcome after massive small bowel resection is the ability of the residual bowel to adapt. Although still in experimental stages, a major goal in the management of SBS may be the augmented use of growth factors to promote increased adaptation. A number of growth factors have been implicated in promoting the adaptation process. The best-described growth factors are reviewed: glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF), and growth hormone (GH). This article reviews the ability of recombinant GLP-2, EGF and GH to modulate structural and functional aspects of intestinal adaptation following small bowel resection. Although these growth factors have shown promise, small sample size, inconsistent measurement parameters and uncontrolled study designs have hampered the acquisition of strong data advocating the use of growth factor treatment for SBS. Multicenter trials using well-defined outcome measures to assess clinical efficacy are needed to direct the clinical indications, timing and duration of therapy and assess potential risks associated with growth factor therapies.

Gastric Pentadecapeptide BPC 157 and Short Bowel Syndrome in Rats

“…Also, standard peptide growth factors do not induce weight gain [9][10][11][12][13][14][15][16] and might only decrease (but not eliminate) weight loss [9][10][11][12][13][14][15][16]. Additional adaptive intestine increase produced by standard peptide growth factors was exhibited in one layer, but not in others [9][10][11][12][13][14][15][16], unlike after common adaptive theory [3]. Unfortunately, standard peptide growth factors exhibit imperfect activity and require a special application route (e.g., subcutaneous pump) [9,16].…”

“…It is possible that improved anastomosis healing [1,2] in rats with massive resection of small intestine may additionally improve with appropriate treatment by standard peptide growth factors [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Postsurgically, additional therapeutic success with improved anastomosis healing [1,2] will comprise constant weight regain, improved adaptation (e.g., in whole wall), and more appropriate application route (e.g., parenteral or peroral).…”

“…Postsurgically, additional therapeutic success with improved anastomosis healing [1,2] will comprise constant weight regain, improved adaptation (e.g., in whole wall), and more appropriate application route (e.g., parenteral or peroral). This could be important, as standard peptide growth factors sometimes have not even been tested for healing of small intestine anastomosis, as is the case for epidermal growth factor (EGF) [3,10]. Also, standard peptide growth factors do not induce weight gain [9][10][11][12][13][14][15][16] and might only decrease (but not eliminate) weight loss [9][10][11][12][13][14][15][16].…”

“…In addition, BPC 157 generally improved intestinal adaptation as a result of its adaptive effects, i.e., on villus height, crypt depth, and muscle thickness [and inner (circular) and/or outer (longitudinal) muscular layer], which particularly deserves to be substantiated to avoid the current methodological pitfalls inherent to all standard peptide factor intestinal adaptation studies that investigated postsurgical adaptation of some (but not all) intestinal layers without reference to normal rat intestinal layers [3][4][5][9][10][11][12][13][14][15][16]. To resolve this problem, one has to determine the range of initial increase from preoperative level, the relation between normal and adapted tissue, and the variation of the whole wall so that the rate, extent, and significance of subsequent adaptive increase of each layer postsurgically can be carefully determined.…”

Peptide YY induces enterocyte proliferation in a rat model with total enteral nutrition after distal bowel resection

“…An inadequate intestinal surface area following massive intestinal resection results in intestinal proliferation to expand the mucosal surface area of the remaining intestine in response to many neurohormonal factors [20][21][22]. Animal models evaluating the proliferative response after intestinal resection have demonstrated that sustained increases in intestinal mucosal wet weight, DNA and protein content, and intestinal villus height and crypt depth are observed [23].…”