Recurrent urinary tract infection and estrogen shape the taxonomic ecology and function of the postmenopausal urogenital microbiomeOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study examined how recurrent UTI history and estrogen therapy shape the urogenital microbiome of postmenopausal women. It used whole-genome metagenomic sequencing plus advanced culture. Clean-catch midstream urine sampled the urogenital tract. Sequencing profiled taxonomy, metabolic pathways with HUMAnN2, and antibiotic resistance genes with the GROOT pipeline. Targeted mass spectrometry quantified urinary estrogen conjugates, letting the team link estrogen levels to specific taxa. Culture built a biobank of isolates whose resistance phenotypes were compared with predicted resistance genes.
Who was studied?
The cohort was 75 postmenopausal women in three balanced groups of 25: no lifetime UTI history, rUTI history without active infection, and rUTI history with active symptomatic UTI. All were human volunteers. Groups were matched for race, BMI, smoking, estrogen therapy use, urine pH, and creatinine. The active-infection group was older, with a median age of 76 versus 67 and 68 years. Thirty-seven women used estrogen hormone therapy, spanning oral, patch, and vaginal modalities. Sequencing detected 276 bacterial, archaeal, and fungal species across 106 genera.
What were the most important findings?
The active-infection group was dominated by single uropathogens, with uropathogenic E. coli in 60% of cases, and had significantly lower alpha diversity. Bacteria made up 99.4% of detected microbes across four phyla led by Firmicutes at 44.7%. Antibiotic resistance genes were significantly enriched in both rUTI history groups versus no-UTI-history women (p = 0.0455 and p = 0.0302), even without active infection. 55 high-confidence resistance genes were detected. Estrogen therapy was strongly associated with urogenital Lactobacillus, especially with oral and patch modalities. Distinct taxa correlated with urinary estrogen in women with versus without rUTI history.
What are the greatest implications of this study?
Recurrent UTI history leaves a lasting imprint on the urogenital microbiome, including an enriched resistome that persists between infections. This may help explain why rUTI becomes hard to treat. The link between estrogen therapy and protective lactobacilli supports estrogen-based strategies for rUTI prevention, though vaginal therapy showed variable effects between individuals. This was a cross-sectional cohort of 75 women, and the identified taxa are putative biomarkers needing validation. The design cannot prove that resistance genes or lactobacilli causally alter rUTI susceptibility.