Bacteroides fragilis toxin 2 damages human colonic mucosa in vitro. Gut 44:504–510

Background—Strains of Bacteroides fra-gilis producing a 20 kDa protein toxin (B fragilis toxin (BFT) or fragilysin) are associated with diarrhoea in animals and humans. Although in vitro results indicate that BFT damages intestinal epithelial cells in culture, the eVects of BFT on native human colon are not known. Aims—To examine the electrophysiologi-cal and morphological eVects of purified BFT-2 on human colonic mucosa in vitro. Methods—For resistance (R) measure-ments, colonic mucosa mounted in Ussing chambers was exposed to luminal or sero-sal BFT-2 (1.25–10 nM) and after four hours morphological damage was measured on haematoxylin and eosin stained sections using morphometry. F actin distribution was assessed using con-focal microscopy. Results—Serosal BFT-2 for four hours was four-, two-, seven-, and threefold more potent than luminal BFT-2 in decreasing resistance, increasing epithelial 3H-mannitol permeability, and damaging crypt and surface colonocytes, respec-tively (p<0.05). Confocal microscopy showed reduced colonocyte F actin stain-ing intensity after exposure to BFT-2. Conclusions—BFT-2 increases human co-lonic permeability and damages human colonic epithelial cells in vitro. These eVects may be important in the develop-ment of diarrhoea and intestinal inflam-mation caused by B fragilis in vivo