The antiadhesive activity of cranberry phytocomplex studied by metabolomics: Intestinal PAC-A metabolites but not intact PAC-A are identified as markers in active urines against uropathogenic Escherichia coil

Cranberry procyanidins and quercetin derivatives are considered possible active compounds against urinary tract infections (UTIs). In this paper a small group (n = 6) of healthy subjects consumed a product containing 360 mg of cranberry extract (42.6% w/w of PAC-A and 14.6% w/w of PAC-B) and 200 mg of quercetin. Urine samples were collected after 2,4,6,8, and 24 h. The changes in antiadhesive properties against urophatogenic E. coli of the urinary output were determined in vitro and modification to urinary metabolome were studied by LC MS. Significant antiadhesive properties of urine samples were observed, with the greatest effect 6-8 h after oral administration, confirming the possible usefulness of cranberry containing products in urinary tract infections (UTI). Metabolomic analysis revealed that valeric acid and valerolactone derivatives that were detected in 6 and 8 h sample, while 4-hydroxy-5-(phenyl)-valeric acid-O-glucuronide and 5-(3',4'-dihydroxypheny1)-y-valerolactone at 6 h and 4-hydroxy-5-(phenyl)-valeric acid-O-sulphate, 3-hydroxyphenyl-valeric acid, 5-(4'-hydroxypheny1)-gamma-valerolactone-4'-O-glucuronide and 4-hydroxy-5-(3'-hydroxypheny1)-valeric acid-3'-O-sulphate were the most abundant at 8 h. The present study shows that the antiadhesive properties of urine sample after cranberry consumption are not ascribable to the direct effect of PAC-A, because their levels in urinary output are in the range of ng/mL. On the other hand, significant metabolites that were detected are mainly metabolites of intestinal action on polyphenols and PACs, as well as glucuronidated and sulphated quercetin, suggesting an important role of intestinal modification of phytoconstituents in the cranberry extract mechanism of action.