Background:Although soy isoflavonoids have a number of healthpromoting benefits, information concerning the sites of their absorption and metabolism in humans remains limited. Isoflavonoid absorption from the gut requires deconjugation of glucosides to aglycones. Objective: The objective was to investigate the role of the small intestine in isoflavonoid absorption and metabolism in humans. Design: Human subjects with fully functional gastrointestinal tracts (n ҃ 6) and ileostomy subjects (n ҃ 6) were fed a single soy meal containing 64.8 mg isoflavonoid aglycone equivalents (95% as glucosides). Metabolism of isoflavonoids in the upper gastrointestinal tract was examined by analyzing ileal effluent from ileostomy subjects, and absorption was assessed indirectly by quantifying isoflavonoids and several metabolites in 24-h urine pools. Results: Chyme contained 36.7% of ingested isoflavonoid aglycone equivalents, primarily (95.8%) as aglycones. Qualitative profiles (x Ȁ SEM) of isoflavonoid excretion in urine (daidzein glycitein genistein) and the quantity of isoflavonoid equivalents were not significantly different between the control (18.4 Ȁ 2.2 mg) and ileostomy (13.5 Ȁ 3.2 mg) subjects. Dihydrodaidzein was present in the urine of all subjects, although the amount excreted by ileostomy subjects was less than that excreted by the control subjects. The percentage of producers and mean quantities of dihydrogenistein, equol, and O-desmethylangolensin in the urine of ileostomy subjects also were lower than those of control subjects. Conclusions: Ileostomy subjects efficiently deglycosylate isoflavonoid glucosides in the small intestine and appear to absorb aglycones with an efficiency comparable with that of control subjects. However, the production of microbial metabolites of isoflavonoids is limited in ileostomy subjects.Am J Clin Nutr 2007;85: 1050 -6.