Alteration in human defensin-5 expression following gastric bypass surgery

Abstract

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. Our aim was to study changes in jejunal mucosal immunoreactivity of human defensin (HD)-5, which is an antimicrobial peptide normally produced by Paneth cells.

Methods: Mucosal samples were obtained from 18 female patients (24 – 54 yrs), 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 peri-operative jejunal samples but colonies of bacteria normally present in the pharynx were identified during culture of all post-operative jejunal biopsies (1 - >100 colonies). Paneth cell numbers per crypt were unchanged after gastric bypass [4.16(0.71) v 4.24(0.78)]. However, following surgery, there was an increase in: HD-5-positive intermediate cells per crypt [0.25(0.41) v 1.12(0.66), p<0.01), HD-5 staining enterocytes per crypt [0.03(0.09) v 1.38(1.10), p<0.01], HD-5 staining material in the crypt lumen [crypt lumens: 5.0(10.9)% v 68.1(27.9)%, p<0.01] and HD-5 immunoreactivity coating the luminal surface of villus enterocytes [villi sampled: 15.0(31.0) % v 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.