Metabolic Phenotyping Identifies Distinct Urinary Anti-Adhesion Phenotypes and Differential Responses to Cranberry Juice Intake in Healthy Women

Background: Cranberry products have been used by millions of women to prevent urinary tract infections (UTIs), although clinical trials have yielded inconsistent results. Objectives: This phenotyping trial aims to test the hypothesis that women’s urine differs in its anti-adhesion capabilities against P-type Escherichia coli (UPEC), potentially influenced by variations in their urine metabolome, and that women’s urinary anti-adhesion activity responds differently to cranberry juice intake. Methods: A total of 152 healthy women (aged 21–65) avoided any cranberry products for 10 days and consumed 10 oz of pure cranberry juice daily for 4 days. Two baseline and one post-consumption morning urine samples were collected on days 9, 10, and 15, respectively, to assess urinary anti-adhesion capacity using an optimized fluorometric method, and the results were expressed as anti-adhesion indices (AAI). Metabolites in 18 baseline urine samples with high AAI (133–164) and 18 baseline urine samples with low AAI (80–128) were explored using untargeted metabolomics on UHPLC-Orbitrap-MS/MS. Results: The baseline urinary AAI against P-type UPEC ranged from 84 to 170 in the women. Seventy-seven women (51%) were assigned to the “UTI-susceptible” phenotype due to a baseline AAI below the 50th percentile (AAI = 131). The rest (n = 75) were “UTI-nonsusceptible.” The metabolome differed in urine with high or low AAI, and 165 urinary metabolites were found to differentiate between UTI-susceptible and nonsusceptible phenotypes. After four days of cranberry juice consumption, 34.2% of susceptible women and 18.9% of nonsusceptible women were assigned to the “positive responders” phenotype due to positive AAI changes above 10. The rest were “non-positive responders.” Conclusions: Healthy women differed in their urinary anti-adhesion capacities against UTIs and responded differently to cranberry juice consumption. This study suggests that women need personalized recommendations on whether to use cranberry products to prevent UTIs based on their individual metabolic phenotype.