INVITRO STUDY ON THE EFFECTS OF FECAL COMPOSITION ON FECAPENTAENE KINETICS IN THE LARGE-BOWEL

Dietary factors have been shown to affect excretion of fecapentaenes, potent mutagens present in human feces. Apart from effects of the diet on the bacterial synthesis of fecapentaenes in the bowel, fecapentaen e excretion is likely to be indirectly influenced by the composition o f the bowel contents, in particular fecapentaene-binding or -solubiliz ing factors. In the present study, interactions between dietary fiber and fecapentaene-12 (FP-12), as well as the effects of bile acids and calcium on the solubility of FP-12 in aqueous solutions, have been inv estigated in vitro. The results demonstrated that FP-12 may strongly a dsorb to fiber, as indicated by reduced concentrations in the aqueous PBS phase when increasing amounts of fiber are added. This fecapentaen e-binding capacity of fiber may explain the positive correlations that have previously been found between excreted fecapentaene concentratio ns and fiber consumption in human population studies. Further, it was found that at concentrations physiologically occurring in feces, both cholic and deoxycholic acid as well as mixtures of bile acids may incr ease the aqueous solubility of FP-12. This solubilizing effect of bile acids can be reduced by adding calcium at physiological concentration s of 2.5 mg/ml. It is hypothesized that high dietary fiber intake may increase fecapentaene excretion as a result of this fecapentaene fiber adsorption, which in turn may result in diminished exposure of the hu man bowel epithelium to these putative initiators of colorectal cancer . In contrast, high concentrations of fecal bile acids may act as feca pentaene-solubilizing factors which increase fecapentaene bioavailabil ity, thereby possibly resulting in increased risk for colorectal cance r.