Characterization of soyasaponin metabolism by human gut microorganisms and bioavailability in humans
Soyasaponins have demonstrated health-promoting properties including plasma cholesterol-lowering, anti-carcinogenic and hepato-protective. Significant amounts of soyasaponins are found in soybeans and soy products. The role of soyasaponins in promoting improved health status has led to a need in understanding their bioavailability and metabolism in humans.;Metabolism of soyasaponin I (3-O-[alpha-L-rhamnopyranosyl-beta-D-galactopyranosyl-beta-D-glucuronopyranosyl]-olean-12-en-3beta,22beta,24-triol ) by human gut microflora was investigated to elucidate the metabolism of dietary soyasaponins in human intestine. In a static in vitro fecal fermentation model, disappearance of soyasaponin I displayed an apparent first-order kinetics over 48 h. Two soyasaponin degradation phenotypes were observed among the subjects: rapid degraders with k = 0.23 +/- 0.04 h -1, and slow with k = 0.07 +/- 0.02 h-1. Two primary gut metabolites of soyasaponin I were identified as soyasaponin III (3-O-[beta-D-galactopyranosyl-beta-D-glucuronopyranosyl]-olean-12-en-3beta,22beta,24-triol ) and soyasapogenol B (4-methoxyl-olean-12-en-3beta,22beta,24-triol ).;Bioavailability of dietary soyasaponins was assessed in a human feeding study. After a single oral dose of soy drink, no soyasaponins or soyasapogenols was detected in the 24 h urine. About 8.6% of ingested group B soyasaponins was recovered as the form of soyasapogenol B, a major gut metabolite of group B soyasaponins, over a 5-day feces collection, suggesting dietary soyasaponins could be metabolized to soyasapogenols by gut microflora in vivo and excreted in feces.;The cellular absorbability and transport kinetics of soyasaponins was evaluated using Caco-2 transfer model, a human colon carcinoma cell model. The apical-to-basolateral absorption of soyasaponin I and soyasapogenol B was low with Papp of 0.9 to 3.5 x 10-6 cm/sec and 0.3 to 0.6 x 10-6 cm/sec, respectively. Caco-2 cells were able to uptake soyasaponin I and soyasapogenol B from the apical membrane. The accumulation of soyasaponin I in Caco-2 cells displayed a saturable and concentration-independent kinetics, while soyasapogenol B accumulated in Caco-2 cells in a concentration dependent manner. Soyasaponin I was not cytotoxic to Caco-2 cells at ≤3 mM, while soyasapogenol B at ≥1 mM significantly decreased cell viability in the culture.;These findings suggest that ingested soyasaponins can be metabolized by human gut microorganisms to smaller and more hydrophobic molecules. Individuals may vary in their ability to metabolize soyasaponins in the gut. Dietary soyasaponins and its gut metabolite soyasapogenols may have very low absorbability in the human intestine.