Cranberry metabolites with urinary anti-adhesion activity

The fruit of the American cranberry (Vaccinium macrocarpon Aiton, Ericaceae) is a comfood and a top selling dietary supplement in the U.S. Cranberry juice is traditionally used for the prevention of urinary tract infections (UTIs), many of which are caused by P-fimbriated Escherichia coli. Human urine produced after cranberry juice consumption can prevent E. coli adhesion, but the urinary metabolites responsible for this activity are currently not known. High-molecular weight components of cranberry juice, specifically proanthocyanidin oligomers (PACs), are currently believed to be responsible for the ability of cranberry juice to prevent UTIs. Cranberry PACs can prevent the adherence of P-fimbriated E. coli to uroepithelial cells in vitro and are hypothesized to act by a similar mechanism of action in vivo. Many questions exist, however, regarding the potential for PACs to be absorbed, metabolized, and excreted into urine. Adult female sows were therefore fed spray-dried cranberry juice powder (5 g/kg/d) and urine was collected via catheter. Urine fractions were tested for anti-adhesion activity using a human red blood cell (HRBC) anti-agglutination assay with uropathogenic P-fimbriated E. coli. Active urine fractions but not control urine or inactive fractions were found to contain complex mixtures of oligosaccharides but not PACs. An octasaccharide, consisting of a tetrameric, β-(1→4)-linked D-glucose backbone and possessing two D-xylose-L-arabinose side chains, was purified from the oligosaccharide mixture of active urine fractions in sufficient quantity to assign the full structure. Oligosaccharide mixtures of similar character were subsequently identified in cranberry products using methods adapted from those applied to urine samples. Cranberry oligosaccharides were enriched in large scale from three sources of cranberry material and were shown to have activity in both the HRBC anti-agglutination assay and a second anti-adhesion assay that used uropathogenic E. coli and uroepithelial cells. The results of these studies indicate that the compounds responsible for the anti-adhesion properties of urine after cranberry juice consumption are oligosaccharides that are structurally related to those found in cranberry. These findings overturn the current paradigm regarding the active components of cranberry juice that prevent UTIs and provide many new directions for future research