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THE RELATIONSHIP BETWEEN THE URINARY MICROBIOME AND CENTRAL SENSITIZATION IN WOMEN WITH OVERACTIVE BLADDER

Login to Access Video or Poster Abstract: MP31-03
Sources of Funding: NIDDK of the NIH award number K23DK103910; SUFU Foundation research fund; NCATS under CTSA award number UL1TR000445; the Vanderbilt Office of Clinical and Translational Scientist Development

Introduction

Differences in pain perception and urinary microbiota have been linked to the presence of lower urinary tract symptoms (LUTS) and their severity. We aimed to characterize the relationship between the urinary microbiome and the presence or absence of overactive bladder (OAB) and elevated central sensitization (CS).

Methods

Women undergoing third-line therapy for OAB and healthy controls were recruited to undergo clinical assessment, quantitative sensory testing, and urine sample collection. Temporal summation to evoked, thermal cutaneous pain was performed with a Medoc Thermal Sensory Analyzer at .4 Hz, a frequency known to elicit C-fiber mediated wind-up in the dorsal horn of the spinal cord. Subjects were asked to rate their pain (0 – 100 VAS) during each of a sequence of 10 brief (.5 second) heat pulses to 49°C. Temporal summation was defined as the difference in pain rating between the maximum and first pain ratings. An individual with a difference in pain ratings or a first pain rating greater than 1 SD above controls after normalization was designated as demonstrating CS. Mid-stream urine samples collected from each patient were subjected to metagenomic sequencing targeting the V3-V4 region of the 16S-rRNA gene. Relative bacterial abundances were compared using the QIIME and the Wald test statistic in the MGLM package among women with and without OAB and CS.

Results

23 patients comprised the study cohort. 6/10 (60%) subjects with OAB demonstrated CS, 2/8 (25%) subjects demonstrating CS did not have OAB. Bacterial abundance differed significantly between patients with and without OAB (Wald test statistic 316, p<0.01) and CS (Wald test statistic 80, p<0.01). Relative bacterial abundances were similar in patients with OAB and CS (Table). Relative to those without OAB and CS, Enterobacteriaceae, Chitinophagaceae and Burkholderiaceae were more abundant in subjects with OAB and CS and Lactobacillaceae and Prevotellaceae less abundant.

Conclusions

C-fiber activation related to elevated CS and alterations in the urinary microbiome may represent a combined mechanism of action for the development of refractory LUTS in some patients that warrants further study.

Funding

NIDDK of the NIH award number K23DK103910; SUFU Foundation research fund; NCATS under CTSA award number UL1TR000445; the Vanderbilt Office of Clinical and Translational Scientist Development

Authors
Joshua Cohn
Elizabeth Timbrook Brown
Yan Guo
Casey Kowalik
Melissa Kaufman
Roger Dmochowski
Stephen Bruehl
Charles Robb Flynn
W. Stuart Reynolds
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