Nutritional supplementation with transforming growth factor-beta inhibits intestinal adaptation after massive small bowel resection in a rat

Transforming growth factor beta (TGF-beta) has been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal and epithelial-immune cell interaction. In the present study, we evaluated the effect of TGF-beta 2-enriched polymeric diet (Modulen) on enterocyte turnover in a rat model of short bowel syndrome (SBS). Male rats were divided into four groups: Sham rats and Sham-TGF-beta rats underwent bowel transection, and were treated with TGF-beta from the 4th postoperative day, SBS rats underwent a 75% bowel resection, and SBS-TGF-beta rats underwent bowel resection and were treated with TGF-beta-enriched diet similar to Group B. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Real-time PCR was used to determine Bax and Bcl-2 mRNA expression. Treatment of SBS animals with TGF-beta 2 supplemented diet led to a significant decrease (vs. SBS rats) in bowel weight in ileum (18%, P < 0.05), mucosal DNA content in jejunum (threefold decrease, P < 0.05) and ileum (2.5-fold decrease, P < 0.05), and mucosal protein in jejunum (twofold decrease, P < 0.05) compared to SBS-untreated animals (Group B). Treatment with TGF-beta resulted in a mild decrease in enterocyte proliferation in jejunum (25%, P < 0.05) and ileum (18%, P < 0.05). A decreased cell apoptosis in the SBS-TGF-beta group was accompanied by a decreased Bax and increased Bcl-2 mRNA expression. In a rat model of SBS, dietary TGF-beta inhibits intestinal adaptation. Decreased enterocyte proliferation is responsible for this effect.