Colonic fermentation to short-chain fatty acids is decreased in antibiotic-associated diarrhea

Abstract

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.