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Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections

Straub, Timothy J. and Chou, Wen-Chi and Manson, Abigail L. and Schreiber, Henry L., IV and Walker, Bruce J. and Desjardins, Christopher A. and Chapman, Sinéad B. and Kaspar, Kerrie L. and Kahsai, Orsalem J. and Traylor, Elizabeth and Dodson, Karen W. and Hullar, Meredith A. J. and Hultgren, Scott J. and Khoo, Christina and Earl, Ashlee M. (2021) Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections. BMC Microbiology, 21 . Art. No. 53. ISSN 1471-2180. PMCID PMC7890861. https://resolver.caltech.edu/CaltechAUTHORS:20210224-074035877

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Abstract

Background: 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. 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. Results: The 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. Conclusion: While 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 registration: Clinical trial registration number: ClinicalTrials.govNCT01776021.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1186/s12866-021-02106-4DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890861PubMed CentralArticle
https://clinicaltrials.gov/ct2/show/NCT01776021Related ItemTrial registration
https://www.ncbi.nlm.nih.gov/bioproject/PRJNA528960PubMed Central16S rRNA and WMS sequencing reads
ORCID:
AuthorORCID
Manson, Abigail L.0000-0002-3800-0714
Schreiber, Henry L., IV0000-0002-4501-9886
Earl, Ashlee M.0000-0001-7857-9145
Additional Information:© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Received 16 September 2020; Accepted 28 January 2021; Published 18 February 2021. We would like to thank Colin Worby, Rauf Salamzade, and Andrew Kau, as well as other members of the Earl and Hultgren labs, for helpful discussions, and Whitney Howe for additional project management. We would also like to thank Anthony Fodor for critical reading of the manuscript. This project has been funded in part by Ocean Spray (Lakeville-Middleboro, MA), with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No.:HHSN272200900018C and Grant Number U19AI110818 to the Broad Institute, with federal funds from the National Institute of Allergy and Infectious Disease, National Institutes of Health, Department of Health and Human Services, under Grant Number U01AI095542 to Washington University in St. Louis, and with federal funds from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, under Grant Number R01DK121822 to Washington University in St. Louis. Availability of data and materials: The 16S rRNA and WMS sequencing reads generated and analyzed during the current study are available in the NCBI SRA repository, under the BioProject PRJNA528960 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA528960). Additional data generated and analyzed during this study are included in this published article and its additional files. Timothy J. Straub and Wen-Chi Chou contributed equally to this work. Author Contributions: HLS, KWD, SJH, CK, and AME conceived of and designed the study. WC, SBC, KLK, OJK, ET, and MAJH processed samples and coordinated delivery to the Broad for sequencing. TJS, WC, ALM, HLS, BJW, and CAD processed and participated in analysis of sequencing data. KWD, SJH and AME provided project oversight. TJS, WC, ALM, HLS, and AME drafted the manuscript. All authors read and approved the final manuscript. Ethics approval and consent to participate: The clinical trial was approved by the institutional review boards at the Quorum Review IRB (Seattle, Washington) and the National Security Agency for Medicines and Health Products and an Ethical Research Committee (Committee for Personal Protection) (Saint-Denis, France). This study was reviewed and approved by MIT’s Committee on the Use of Humans as Experimental Subjects (Cambridge, Massachusetts), under protocol #1504007050. Informed consent was obtained for all participants. Consent for publication: Not applicable. Competing interests: KLK and CK are employees of Ocean Spray (Lakeville-Middleboro, MA). All other authors have no competing interests to declare.
Funders:
Funding AgencyGrant Number
Ocean SprayUNSPECIFIED
NIHHHSN272200900018C
NIHU19AI110818
NIHU01AI095542
NIHR01DK12182
Subject Keywords:Urinary tract infection (UTI), Microbiome, Metagenome, Flavonifractor, Cranberry
PubMed Central ID:PMC7890861
Record Number:CaltechAUTHORS:20210224-074035877
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210224-074035877
Official Citation:Straub, T.J., Chou, WC., Manson, A.L. et al. Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections. BMC Microbiol 21, 53 (2021). https://doi.org/10.1186/s12866-021-02106-4
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108162
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Feb 2021 20:32
Last Modified:24 Feb 2021 20:32

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