Bile acids, diarrhea, and antibiotics: data, speculation, and a unifying hypothesis

Abstract

The primary bile acid, chenodeoxycholic acid, and the secondary bile acid, deoxycholic acid, when present at a concentration of greater than 3 mM, induce salt and water secretion from the human colon and cause a marked increase in the permeability of the human colon to molecules of a molecular weight of 200-500 daltons. Scanning electron microscopy indicates that this action may be associated with tissue damage in some species. In the healthy individual, the primary bile acids, cholic and chenodeoxycholic acid, are dehydroxylated in the colon and are simultaneously precipitated from solution; at pH less than 7, deoxycholic and lithocholic acid are insoluble. In patients with bile acid diarrhea resulting from bile acid malabsorption, dehydroxylation is decreased, and the concentration of bile acids in the colon is markedly elevated. The major secretory bile acid in solution is chenodeoxycholic acid. Administration of cholestyramine, a resin that binds bile acid, reduces the elevated concentration of chenodeoxycholic acid and abolishes the diarrhea. These facts can be used to develop a unifying hypothesis which proposes that elevated concentrations of primary bile acids in the colon play a role in diarrhea and pseudomembranous colitis induced by clindamycin.