Urinary Microbiome and Metabolome Differentiate Overactive Bladder From the Physiological State, and Reflect Recent Antibiotic Use and Treatment Response.
cross_sectional · Level IV
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- Also identified by DOI 10.1097/JU.0000000000004990.
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Abstract
To characterize and compare the bacterial urinary microbiome in individuals with and without overactive bladder (OAB), and secondarily compare its composition by phenotype, comorbidities, recent antibiotic exposure, and therapeutic response. We isolated DNA and metabolites from the urine of women without urologic diagnoses and with OAB. Bacterial profiles were generated with 16S rRNA sequencing, and metabolite profiles were generated with untargeted metabolomics. Alpha-diversity and beta-diversity, relative abundance, and microbe-metabolite co-occurrence interaction networks were identified by OAB status and patient characteristics. One hundred fifty-two participants were included, and bacteria were identified in all urine samples. Bacilliota was the most abundant phylum and <i>Lactobacillus</i>, <i>Escherichia</i>, and <i>Prevotella</i> the most abundant genera in individuals without urologic conditions. <i>Megasphaera</i> and <i>Scardovia</i> were the primary genera more abundant in individuals without OAB than those with OAB (each: log<sub>2</sub>-fold change [FC] -3.7 <i>P</i> < .001). <i>Escherichia</i> (log<sub>2</sub>-FC 5.9), <i>Enterococcus</i> (log<sub>2</sub>-FC 3.5), and <i>Proteus</i> (log<sub>2</sub>-FC 3.1) were the primary genera significantly more abundant in the urine of individuals with OAB than those without (<i>P</i> < .001). Beta diversity differed between individuals with and without OAB and by diabetes mellitus status (<i>P</i> < .05). Relative abundance of bacterial genera differed by OAB phenotype, diabetes mellitus status, recent antibiotic exposure, and response to OAB treatment (<i>P</i> < .05). Microbe-metabolite interaction networks demonstrated central microbes and metabolites in the healthy and OAB states. The study provides new understanding regarding the physiological bacterial composition of urine, and that in the context of OAB. Furthermore, microbiota differed by patient phenotype, comorbidities, recent antibiotic exposure, and therapeutic response. The results inform strategies of microbiological modulation to augment existing therapeutic strategies.