Heterogeneity in responses by primary adult human colonic epithelial cells to purified enterotoxin of Bacteroides fragilis

Background—Enterotoxigenic strains ofBacteroides fragilis (ETBF) have been implicated indiarrhoeal illness in livestock and children, but their role in adulthuman colonic disease is unknown.
Aims—To investigate responses by primary adulthuman colonic epithelial cells to purified B fragilistoxin (BFT).
Methods—BFT was purified from culture supernatantof a highly toxigenic strain of ETBF. Morphological changes to primarycolonic epithelial cells, in response to purified BFT, were studied in organ culture of colonic biopsy specimens from 15adults.
Results—BFT induced epithelial cell cytotoxicityin colonic biopsy specimens from 12/15 subjects. The BFT inducedmorphological changes were characterised by epithelial cell rounding,separation from adjacent cells, and detachment from the basementmembrane. In severely affected specimens, almost all the epithelialcells were affected. There was heterogeneity between subjects in the rate at which BFT induced epithelial cell cytotoxicity occurred. Furthermore, in colonic biopsy specimens from three subjects, exposureto BFT did not induce any significant morphological changes toepithelial cells.
Conclusion—BFT is capable of inducingcytotoxicity in primary adult human colonic epithelial cells. Such aneffect of ETBF derived BFT on epithelial cells in the colon in vivowould be expected to lead to mucosal inflammation and diarrhoea.Heterogeneity in responses by primary colonocytes probably reflects theoutcome of host-BFT interactions. Such interactions in vivo coulddetermine the occurrence of colonic disease in some individuals but not others.

Keywords:Bacteroides fragilis; enterotoxin; epithelial cells; apoptosis