Exploring recurrent urinary tract infection: paired microbiota and culture-based profiling reveals stable dysbiosis and multidrug-resistant, virulence-enriched uropathogens
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Objectives
Recurrent urinary tract infection (rUTI) is increasingly complicated by antimicrobial resistance (AMR), yet urinary microbiome dysbiosis and isolate-level resistance-virulence are rarely examined together across different treatment states. In this study we characterized both within the same sample in rUTI and in healthy controls.
Methods
Cross-sectional cohort, mid-stream urine was collected from women with untreated, treated and prophylaxis rUTI and age-matched healthy controls at four centres in South India. Of 80 samples collected, 75 were analysed (26 controls, 20 untreated, 20 treated, 9 prophylaxis) by 16S rRNA V3-V4 sequencing; in addition, 105 culturable isolates from the same samples were identified and tested for antimicrobial susceptibility (VITEK 2) and phenotypic virulence.
Results
rUTI groups showed approximately half the alpha diversity of controls (median Shannon 1.07-1.18 vs 2.17; Kruskal-Wallis p = 0.041). Community structure differed from controls in every rUTI sub-group (PERMANOVA R 2 = 0.091, p = 0.004; pairwise FDR = 0.008) but not among sub-groups. Mean Lactobacillus relative abundance fell from 29.2% in controls to ≤13.2% in rUTI groups, while Escherichia - Shigella rose from 7.2% to 25.0-43.0%. Control-referenced dysbiosis z-scores were elevated in all rUTI groups (community distance: FDR ≤ 0.003; uropathogen: Lactobacillus index: FDR < 0.001 for treated and prophylaxis groups). Among isolates, Escherichia coli predominated (35/105; 16/35, 45.7% multidrug-resistant), followed by Klebsiella spp. (32% multidrug-resistant); carbapenem susceptibility was largely retained, and multidrug-resistant E. coli co-carried more virulence traits.
Conclusions
rUTI is associated with a stable dysbiotic state that treatment does not restore, combining Lactobacillus loss and uropathogen dominance with a multidrug-resistant culturable reservoir that co-accumulates virulence traits. Reading the community and its isolates together may support microbiome-sparing, resistance-aware management of rUTI.
