biostudies-literatureWorby CJDoris Duke Charitable FoundationNIDDK NIH HHSNIAID NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious DiseasesNIGMS NIH HHSU.S. Department of Health & Human Services | National Institutes of Health630-639https://www.ebi.ac.uk/biostudies/studies/S-EPMC9136705biostudies-literatureUnknown7(5)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.Nature microbiologyLongitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women.PMC9136705U01AI095542U19AI110818R01 DK121822T32 GM007067R01 AI1659152019083U01 AI095542T32 GM139774R37 AI048689U19 AI110818Bronson RASchreiber HLAzimzadeh PNChapman SBManson ALKlim ADodson KWObernuefemann CLPMunoz VLEarl AMStraub TJLai HHWalker BJPaharik AEvan Dijk LRKau ALBergeron KWorby CJChou WCHannan TJOlson BSDesjardins CAHooton TMHultgren SJPinkner JSfalseLongitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women.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.2022-01-01T00:00:00Z2022 May2026-04-08T10:05:38.041Z2025-04-19T22:48:21.606ZS-EPMC91367053550524810.1038/s41564-022-01107-x