Occasional Survey

DIARRHOEA: THE FAILURE OF COLONIC SALVAGE

Humans swallow a great variety and often large amounts of chemicals as nutrients, incidental food additives and contaminants, drugs, and inhaled particles and chemicals, thus exposing the gastrointestinal tract to many potentially toxic substances. It serves as a barrier in many cases to protect other components of the body from such substances and infections. Fortunately, the gastrointestinal tract is remarkably robust and generally is able to withstand multiple daily assaults by the chemicals to which it is exposed. Some chemicals, however, can affect one or more aspects of the gastrointestinal tract to produce abnormal events that reflect toxicity. It is the purpose of this chapter to evaluate the mechanisms by which toxic chemicals produce their deleterious effects and to determine the consequences of the toxicity on integrity of gastrointestinal structure and function. Probably because of the intrinsic ability of the gastrointestinal tract to resist toxic chemicals, there is a paucity of data regarding gastrointestinal toxicology. It is therefore necessary in many cases to extrapolate toxic mechanisms from infectious processes, inflammatory conditions, ischemia, and other insults in addition to more conventional chemical sources of toxicity.

To elucidate the pathogenesis of antibiotic-associated diarrhea, colonic carbohydrate fermentation was investigated in three groups of subjects—a group of controls, a group of patients with antibiotic-associated diarrhea, and a group of patients receiving antibiotic therapy without diarrhea. Compared with controls, the colonic fermentation was markedly impaired in patients with antibiotic-associated diarrhea reflected by both very low concentrations (22.1 vs. 59.5 mmol/L; P < 0.01) and production rates of short-chain fatty acids. In the group of patients without diarrhea, the effect on the colonic fermentation was dependent on the antibiotic administered. Penicillin and pivampicillin PO did not reduce the concentrations (69.9 and 66.7 mmol/L, respectively) or production rates. Dicloxacillin, erythromycin, and combined IV treatment with ampicillin, netilmicin, and metronidazole reduced both concentrations (27.1, 38.2, and 18.8 mmol/L; P < 0.01) and production rates of short-chain fatty acids to levels seen in patients with diarrhea. l-Lactate and d-lactate concentrations were normal in all patients (< 5 mmol/L), but lactate production was reduced in the patients who had reduced production of short-chain fatty acids, including patients with diarrhea. Thus, antibiotic-associated diarrhea was always related to reduced fecal concentrations and production rates of short-chain fatty acids and production rates of lactate. These results suggest that the antibiotic-associated diarrhea might be secondary to impaired colonic fermentation in otherwise disposed subjects, resulting in accumulation of luminal carbohydrate and/or decreased short-chain fatty acid-stimulated sodium and water absorption.