Alteration in human defensin-5 expression following gastric bypass surgery

Background: Roux-en-Y gastric bypass surgery provides a novel human model to investigate small bowel mucosal innate immunity, in which there is loss of gastric acid-mediated protection against orally-acquired microorganisms. Aim: To study changes in jejunal mucosal immunoreactivity of human defensin (HD)-5,an antimicrobial peptide normally produced by Paneth cells. Methods: Mucosal samples were obtained from 18 female patients ( 24 - 54 years), from the same segment of jejunum during and after gastric bypass surgery. Samples were used for bacterial culture and immunohistochemistry using anti-HD-5 antibody. The number of immunoreactive cells per crypt and villus were determined and expressed as mean (SD). Results: No bacteria were cultured from any of the perioperative jejunal samples but colonies of bacteria normally present in the pharynx were identified during culture of all postoperative jejunal biopsy specimens (1-> 100 colonies). Paneth cell numbers per crypt were unchanged after gastric bypass ( 4.16 (0.71) vs 4.24 (0.78)). However, following surgery, there was an increase in HD-5-positive intermediate cells per crypt (0.25 (0.41) vs 1.12 (0.66), p < 0.01), HD-5 staining enterocytes per crypt ( 0.03 ( 0.09) vs 1.38 ( 1.10), p < 0.01), HD-5 staining material in the crypt lumen (crypt lumens: 5.0% ( 10.9%) vs 68.1% ( 27.9%), p < 0.01) and HD-5 immunoreactivity coating the luminal surface of villus enterocytes ( villi sampled: 15.0% ( 31.0%) vs 67.5% ( 42.0%), p < 0.01). Conclusions: Bacteria normally resident in the pharynx were present in the proximal jejunal mucosa following Roux-en-Y gastric bypass surgery. After gastric bypass, there was increased secretion of HD-5 and an increase in HD-5 expressing intermediate cells and enterocytes in the crypt. The increase in HD-5 expression in the jejunal mucosa following gastric bypass surgery is likely to be secondary to exposure to orally-acquired microorganisms.