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

L Sanfilippo,^a T J Baldwin,^b M G Menozzi,^c S P Borriello,^b Y R Mahida^a

^a Division of Gastroenterology, ^b Institute of Infections and Immunity, University of Nottingham, UK, ^c Istituto di Microbiologia, University of Parma, Italy

Correspondence to: Dr Y R Mahida,Division of Gastroenterology, University Hospital,Queen's Medical Centre, Nottingham NG7 2UH, UK.

Accepted for publication 4 June 1998

BackgroundEnterotoxigenic strains of Bacteroides fragilis (ETBF) have been implicated in diarrhoeal illness in livestock and children, but their role in adult human colonic disease is unknown.
AimsTo investigate responses by primary adult human colonic epithelial cells to purified B fragilis toxin (BFT).
MethodsBFT was purified from culture supernatant of a highly toxigenic strain of ETBF. Morphological changes to primary colonic epithelial cells, in response to purified BFT, were studied in organ culture of colonic biopsy specimens from 15 adults.
ResultsBFT induced epithelial cell cytotoxicity in colonic biopsy specimens from 12/15 subjects. The BFT induced morphological changes were characterised by epithelial cell rounding, separation from adjacent cells, and detachment from the basement membrane. In severely affected specimens, almost all the epithelial cells 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, exposure to BFT did not induce any significant morphological changes to epithelial cells.
ConclusionBFT is capable of inducing cytotoxicity in primary adult human colonic epithelial cells. Such an effect of ETBF derived BFT on epithelial cells in the colon in vivo would be expected to lead to mucosal inflammation and diarrhoea. Heterogeneity in responses by primary colonocytes probably reflects the outcome of host-BFT interactions. Such interactions in vivo could determine the occurrence of colonic disease in some individuals but not others.
(GUT 1998;43:651-655)

Keywords: Bacteroides fragilis;  enterotoxin;  epithelial cells;  apoptosis