American Cranberries to Prevent UTIs in Susceptible Women

To Determine the Metabolic Polymorphisms of American Cranberries to Prevent UTIs in Susceptible Women Using an Integrated Metabolome-Microbiome Approach

The investigators pre-preliminary study showed that the urine from a portion of study participants had anti-adhesion activity. The investigators propose that UTI susceptible women can be divided into responders and non-responders depending on whether cranberry intake increase anti-adhesion activity of their urine. The overall objectives are to identify gut microbes and anti-adhesive urinary biomarkers which significantly contribute to the anti-adhesion of E. coli.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Other: Cranberry juice; Other: Placebo juice

Detailed Description

The American cranberries (Vaccinium macrocarpon) have been consumed for centuries to prevent urinary tract infections (UTI), which affect 50% of women in their lifetime. However, NIH-funded clinical trials of cranberries on UTI in the last 20 years yielded conflicting results but the reasons are unknown. About 90% of UTI are initiated by adhesion of uropathogenic E. coli on urinary tract epithelia. It was reported that human urine after cranberry intake inhibited the adhesion of E. coli. A-type procyanidins and xyloglucans are the presumed bioactives in cranberries; however, none of these compounds are absorbable in small intestine. They are degraded by microbes in colon.The pre-preliminary study showed that the urine from a portion of study participants had anti-adhesion activity, suggesting there are polymorphisms in human's ability to metabolize cranberry bioactives. Based on these observations, the investigators formulate a novel hypothesis that not all, but a fraction of women harbor specific gut microbes with the ability to catabolize cranberry bioactives to anti-adhesion metabolites in the urine; therefore, the variation of gut microbiome is the underlying mechanism for metabolic polymorphisms and disparity in UTI prevention. The investigators propose that UTI susceptible women can be divided into responders and non-responders depending on whether cranberry intake increase anti-adhesion activity of their urine. The overall objectives are to identify gut microbes and anti-adhesive urinary biomarkers which significantly contribute to the anti-adhesion of E. coli. The expected result will be to generate strong preliminary data showing the differences of gut microbiome between responders and non-responders in additional to correlations between gut microbes and candidate anti-adhesion biomarkers in the urine of UTI susceptible women.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liwei Gu, PhD; Phone Number: (352)2943730; Email: lgu@ufl.edu
• Study Contact Backup: Name: Yavuz Yagiz, PhD; Phone Number: (352)2943988; Email: yavuzy@ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • Recruiting
      • Food Science and Human Nutrition Department at University of Florida
      • Contact: Yavuz Yagiz, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy women participants
• BMI 18.5-29.9 kg/m2
• At least 110 pounds in weight

Exclusion Criteria:

• BMI≥ 30 kg/m2
• Pregnancy and breast-feeding
• Smoking, frequent alcohol use
• History of any clinically important disorder that may interfere with interpretation of the results,
• Intake of medication that might influence the outcome of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Cranberry juice consumption; Participants will be provided cranberry juice to consume for 21 days	Other: Cranberry juice; Cranberry juice cocktail will be provided by Ocean Spray Cranberries, Inc.
Experimental: Placebo juice consumption; Participants will be provided placebo juice to consume for 21 days	Other: Placebo juice; Apple juice added with flavor and colorants will be provided by Ocean Spray Cranberries, Inc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the anti-adhesion activity	Compare the statistical difference between the changes from baseline in the an-adhesion activity uropathogenic E. coli in UTI-susceptible women after consuming the cranberry beverage for 3 weeks versus the change after consuming the control beverage for 3 weeks. Anti-adhesion activity in urine will be measured using a fluoresces-based micro-plate method. The anti-adhesion activities of urines will be expressed by its equivalence to myricetin level. The unit for urine anti-adhesion activities is µg myricetin/ mg creatinine.	Baseline and 21 days of each intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in urinary biomarkers	Compare the statistical difference between the change from baseline in the an-adhesion activity uropathogenic E. coli in UTI-susceptible women after consuming the cranberry beverage for 3 weeks versus the change after consuming the control beverage for 3 weeks. The Urinary biomarkers will be identified and measured using LC-Orbitrap-MS.	Baseline and 21 days of each intervention
Change in gut microbiomes	Compare the difference between the changes in gut microbiomes between responders and non-responders participants after consuming the cranberry beverage for 3 weeks versus the change after consuming the control beverage for 3 weeks. The gut microbiomes will be measured Genomic microbial DNA the extraction of genomic microbial DNA from fecal samples using DNA isolation kits and the 16S ribosomal RNA gene (V1-3 region) will be amplified and sequenced.	Baseline and 21 days of each intervention

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Study Director: Yavuz Yagiz, PhD, University of Florida; Principal Investigator: Liwei Gu, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2021
• Primary Completion (Estimated): August 20, 2025
• Study Completion (Estimated): August 20, 2025

Study Registration Dates

• First Submitted: October 15, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: UTI; Cranberry
• Other Study ID Numbers: IRB202002624

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No