Gut microbiome correlates of recurrent urinary tract infection: a longitudinal, multi-center study

Background Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic Escherichia coli (UPEC). Methods 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi -center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome pro fi les were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-speci fi c differences. Findings Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in E. coli abundance 7 - 14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to noncolonizing lineages. Interpretation The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARGenriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut E. coli among urinary tract colonized patients suggest that cross -habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics. Copyright (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Copyright (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).