Fecal steroids in diarrhea. I. Acute shigellosis

Fecal bile acid and neutral sterol patterns of five healthy adult male volunteers, who were challenged by a virulent Shigella flexneri 2a (M42–43) strain and developed dysentery were studied. It was observed that cholic acid was increased from 1.9 ± 0.4% of total bile acid in the feces before infection to 14.5 ±2.1% during diarrhea (P < 0.001). Chenodeoxycholic acid also was increased from 3.2 ± 0.7 to 8.7 ± 3.2% in diarrhea but the difference was not significant statistically. Deoxycholic and lithocholic acids constituted 34.1 ± 4.1 and 40.5 ± 2.8%, respectively, of total bile acid in the normal controls as compared to 13.9 ± 2.5 and 24.8 ± 2.5% for the same subjects during diarrhea (P < 0.005). Total excretion of bile acids, expressed as mg/kg of body weight per day, were higher in diarrhea (5.4 ± 1.0) than that in controls (4.2 ± 1.0) but the difference was not statistically significant. In the neutral sterol fraction, unmodified cholesterol was increased during diarrhea (86.2 ± 8.7 versus 25.0 ± 4.8% of total cholesterol metabolites in controls, P < 0.001). Coprostanol was decreased in shigellosis (12.2 ± 8.2 versus 65.8 ± 4.7% in controls, P < 0.001). Epicoprostanol, coprostanone, and unidentified cholesterol metabolites also were reduced in shigellosis. The effect of diarrhea on the plant sterols was not as consistent. However, unidentified plant sterols were reduced significantly in shigellosis stools. Total excretion of cholesterol metabolites and plant sterols, when expressed as mg/kg of body weight per day, were 6.8 ± 1.7 and 0.6 ± 0.2, respectively, in shigellosis. These values were not significantly different from the corresponding values for controls (10.3 ± 3.0 and 0.8 ± 0.2). One subject's stool samples were studied during infection for the sequence of bile acid alteration. A progressive reduction of bacterial activity upon fecal steroids was evident following the initial diarrheal episode. The production of coprostanol was correlated with 7α-dehydroxylation of cholic acid (r = 0.937, P < 0.001) and chenodeoxycholic acid (r = 0.755, P < 0.01).