Suppression of human fecal 7α-hydroxysteroid dehydrogenase by a short-term low cholesterol diet

Abstract

Fourteen healthy human volunteers were placed on short-term (1–4 weeks) isocaloric dietary regimes on an outpatient basis. Each diet consisted of approx. 2200 calories and contained 17% protein, 35% fat, 48% carbohydrate and varied only in mg/day cholesterol intake and polyunsaturated/saturated (P/S) fatty acid ratio. Diets A, B, C and D consisted of a daily cholesterol intake of 100 mg cholesterol (chicken and/or fish based P/S = 2.0), 500 mg cholesterol (fish and/or chicken based P/S = 0.17), 500 mg cholesterol (beef based P/S = 0.35) and 1000 mg cholesterol (beef based P/S = 0.10). When both NAD- and NADP-dependent bile salt dehydrogenases in mixed fecal cultures were measured before and after weekly dietary sequences: A alone ( n = 2), B alone ( n = 2), C alone ( n = 2), A-D ( n = 5), A-D-D-D ( n = 2), B-A ( n = 2), and D-A ( n = 4), the NAD-dependent 7α-hydroxysteroid dehydrogenase (HSDH) activity was shown to be significantly depressed or eliminated after one week of diet A, and returned when subjects were taken off diet A or placed on another diet. No clear effect on 7α-HSDH was measurable by diets B, C or D. No dietary effect was seen on 3α-, 12α-HSDH or the NADP-component of 7α-HSDH. On serial dilution of fecal microorganisms and growth of the bacterial populations to stationary phase, NAD-dependent 7α-HSDH consistently increased on dilution, while NADP-dependent 7α-HSDH and NADP-dependent 12α-HSDH decreased and vanished on dilution. When NAD-dependent 7α-HSDH was eliminated by diet A, it could be restored by diluting fecal bacterial populations, simultaneously decreasing and eliminating NADP-7α-HSDH and NADP-12α-HSDH. The results suggest that these three enzymes may be markers for ecologically related fecal sub-populations. The dietary suppression of NAD-dependent 7α-HSDH has been interpreted as a transient suppression of that subpopulation carrying this enzyme.