Abstract

BackgroundUrinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs.ResultsThe overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor’s association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions.ConclusionWhile our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI.Trial registrationClinical trial registration number: ClinicalTrials.govNCT01776021.

Highlights

  • Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs

  • Though we present no direct evidence that changes in the relative abundance of OTU41 are linked to recurrent UTIs (rUTIs) symptomatology, we did find that some OTU41-characteristic functions could suggest a relationship between OTU41 abundances and the regulation of a variety of key host functions, including the transport of tryptophan and cobalamin metabolism

  • Our work suggests that long-term daily cranberry consumption elicits no large-scale taxonomic or functional changes to the gut microbiome, yet was associated with a decreased level of Flavonifractor OTU41 in the gut compared to long-term consumption of a placebo

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Summary

Introduction

Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. UTIs are often recurrent, with 20–30% of women experiencing recurrent UTIs (rUTIs), even after appropriate antibiotic treatment [4, 5]. Since UTI treatment accounts for over 15% of all antibiotics prescribed in the U.S, UTIs contribute significantly to the total burden of drug resistance [6]. A better understanding of how to control rUTIs and curb UPEC colonization and infection without repeated use of antibiotics could improve patients’ lives and help slow the propagation of antibiotic resistance [9,10,11]

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