Effect of Escherichia coli on fluid transport across canine small bowel. Mechanism and time course with enterotoxin and whole bacterial cells

Recent studies have suggested that noninvasive, enterotoxigenic E.coli strains cause a major portion of severe acute diarrheal disease, both in developing nations and in the United States. In recent studies about 50% of the adults hospitalized in Calcutta with acute 'undifferentiated' cholera like diarrhea had small bowel colonization by homogeneous isolates of E.coli which were not of previously recognized enteropathogenic serotypes. Cell free culture filtrates of these strains contain a partly heat labile enterotoxin which causes fluid accumulation in ligated segments of rabbit small bowel. In canine jejunum, crude E.coli enterotoxin (ECT) induces outpouring of isotonic fluid similar in composition to that induced by cholera enterotoxin (CT), but following a very different time course. Earlier studies have suggested that the mechanism of action of ECT may be similar to that of CT, in that ECT does not alter the rate of jejunal fluid accumulation after a maximum secretory rate has been induced by CT. Further studies have indicated that ECT has an effect qualitatively similar to that of CT in stimulating adenyl cyclase in rabbit ileal mucosa and in rat lipocytes. An E.coli strain isolated from a patient with severe cholera like diarrhea elaborates a partly heat labile enterotoxin shown to cause prompt adenyl cyclase stimulation and isotonic fluid secretion by canine jejunum. Both responses disappear upon removal of the enterotoxin. The duration of action of a submaximal dose of this E.coli enterotoxin was brief, despite sustained exposure to the jejunum, suggesting inactivation of the enterotoxin by its interaction with the mucosa. Inoculation of whole bacterial cultures of this E.coli strain into canine duodenum was followed by bacterial survival and induction of net secretion after 4-7 h. The onset of fluid production was associated with increasing gut mucosal adenyl cylase activity. Washed bacterial cells could also produce fluid secretion. In vivo multiplication of this enterotoxin producing E.coli was demonstrated 6-12 h after intraduodenal inoculation of approximately 10⁶ organisms. This was associated with fluid secretion. Intestinal fluid production occurred without microscopic pathology in the mucosa.