Cited by 188Gut microbiota and healthUrinary Tract Infections ManagementReproductive tract infections research

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Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women

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Worby, Colin J., Schreiber, Henry L., Straub, Timothy J., van Dijk, Lucas R., Bronson, Ryan A., Olson, Benjamin S., Pinkner, Jerome S., Obernuefemann, Chloe L. P., Muñoz, Vanessa L., Paharik, Alexandra E., Azimzadeh, Philippe N., Walker, Bruce J., Desjardins, Christopher A., Chou, Wen-Chi, Bergeron, Karla, Chapman, Sinéad B., Klim, Aleksandra, Manson, Abigail L., Hannan, Thomas J., Hooton, Thomas M., Kau, Andrew L., Lai, H. Henry, Dodson, Karen W., Hultgren, Scott J., Earl, Ashlee M.·2022·Nature Microbiology

DOI 10.1038/s41564-022-01107-xPMC PMC9136705

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Abstract

Recurrent urinary tract infections (rUTIs) are a major health burden worldwide, with history of infection being a significant risk factor. While the gut is a known reservoir for uropathogenic bacteria, the role of the microbiota in rUTI remains unclear. We conducted a year-long study of women with (n = 15) and without (n = 16) history of rUTI, from whom we collected urine, blood and monthly faecal samples for metagenomic and transcriptomic interrogation. During the study 24 UTIs were reported, with additional samples collected during and after infection. The gut microbiome of individuals with a history of rUTI was significantly depleted in microbial richness and butyrate-producing bacteria compared with controls, reminiscent of other inflammatory conditions. However, Escherichia coli gut and bladder populations were comparable between cohorts in both relative abundance and phylogroup. Transcriptional analysis of peripheral blood mononuclear cells revealed expression profiles indicative of differential systemic immunity between cohorts. Altogether, these results suggest that rUTI susceptibility is in part mediated through the gut-bladder axis, comprising gut dysbiosis and differential immune response to bacterial bladder colonization, manifesting in symptoms.

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Authors: Worby, C. J., Schreiber, H. L., Straub, T. J., van Dijk, L. R., Bronson, R. A., Olson, B. S., Pinkner, J. S., Obernuefemann, C. L. P., Muñoz, V. L., Paharik, A. E., Azimzadeh, P. N., Walker, B. J., Desjardins, C. A., Chou, W.-C., Bergeron, K., Chapman, S. B., Klim, A., Manson, A. L., Hannan, T. J., Hooton, T. M., Kau, A. L., Lai, H. H., Dodson, K. W., Hultgren, S. J., & Earl, A. M.
Affiliations: Broad Institute (US)
California Institute of Technology (US)
Washington University in St. Louis (US)
University of Miami (US)
Corresponding author: Hultgren, Scott J.
Earl, Ashlee M.
ORCID: Worby, Colin J.
Schreiber, Henry L.
Straub, Timothy J.
van Dijk, Lucas R.
Olson, Benjamin S.
Pinkner, Jerome S.
Paharik, Alexandra E.
Azimzadeh, Philippe N.
Desjardins, Christopher A.
Chapman, Sinéad B.
Manson, Abigail L.
Hannan, Thomas J.
Hooton, Thomas M.
Kau, Andrew L.
Lai, H. Henry
Dodson, Karen W.
Hultgren, Scott J.
Earl, Ashlee M.
Venue: Nature Microbiology
Publisher: Springer Science and Business Media LLC
Published: 2022-05-02
Volume: 7
Issue: 5
Pages: 630-639
ISSN: 2058-5276 (ISSN-L)
DOI: 10.1038/s41564-022-01107-x
PMC: PMC9136705
OpenAlex: W4225388682
Cited by: 188
References: 64
Citations by year: 2026: 48 · 2025: 46 · 2024: 48 · 2023: 34 · 2022: 11
FWCI: 11.35
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Microbiology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders: U.S. Department of Health & Human Services | National Institutes of Health (U01AI095542)
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (U19AI110818)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Urology › Urinary Tract Infections Management
Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
Keywords: recurrent urinary tract infection, gut dysbiosis, women, butyrate-producing bacteria, Escherichia coli, uropathogenic bacteria, peripheral blood mononuclear cells, systemic immunity, microbial richness, bladder colonization, multi-omics
MeSH terms: Gastrointestinal Microbiome, Escherichia coli, Escherichia coli Infections, Female, Humans, Leukocytes, Mononuclear, Male, Urinary Tract Infections, Dysbiosis

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Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women

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