Project Grant 20226701736240

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THE AMERICAN CRANBERRIES, ESPECIALLY CRANBERRY JUICE, HAVE BEEN USED FOR CENTURIES AS A FOLK MEDICINE TO PREVENT URINARY TRACT INFECTIONS (UTI), WHICH AFFECT 50% OF WOMEN IN THEIR LIFETIME. OVER 30 CLINICAL TRIALS HAVE BEEN CONDUCTED IN THE LAST 20 YEARS TO VERIFY THE UTI PREVENTATIVELY ACTIVITY OF CRANBERRY JUICES, BUT THE RESULTS WERE CONTRADICTORY. ABOUT 90% OF UTI ARE INITIATED BY THE ADHESION OF UROPATHOGENIC E. COLI (UPEC) ON URINARY TRACT EPITHELIA. IT WAS REPORTED THAT HUMAN URINE AFTER CONSUMPTION OF CRANBERRY JUICE INHIBITED THE ADHESION OF UPEC. THE A-TYPE PROANTHOCYANIDINS AND XYLOGLUCANS ARE THE PRESUMED BIOACTIVES IN CRANBERRIES, HOWEVER, THIS IS UNLIKELY BECAUSE THESE TWO CLASSES OF COMPOUNDS HAVE EXTREMELY LOW BIOAVAILABILITY IN HUMAN BODY. PRELIMINARY RESEARCH SUGGESTED THAT WOMEN CAN BE EITHER RESISTANT OR SUSCEPTIBLE TO UTI DEPENDING ON THE INHERENT ANTI-ADHESION ACTIVITY IN THEIR URINE AGAINST UPEC BEFORE CONSUMING CRANBERRY JUICE. NOT ALL BUT A FRACTION OF UTI SUSCEPTIBLE WOMEN HAD INCREASED URINARY ANTI-ADHESION ACTIVITY AFTER CONSUMING CRANBERRY JUICES. THESE WOMEN ARE CLASSIFIED AS RESPONDERS AND OTHERS ARE NON-RESPONDERS. THE VARIATION OF GUT MICROBIOME IS A PROBABLE MECHANISM FOR METABOLIC POLYMORPHISMS AND DISPARITY IN UTI PREVENTION. THE OBJECTIVE OF THIS TRIALS IS TO IDENTIFY GUT MICROBES AND ANTI-ADHESIVE URINARY BIOMARKERS WHICH SIGNIFICANTLY CONTRIBUTE TO THE ANTI-ADHESION OF UPEC.