PD01-02: Comparative Analysis of the Microbiome of Interstitial Cystitis/Bladder Pain Syndrome, Cystitis and Asymptomatic Healthy Controls: The Key to Interpretation of Next Generation Sequencing Urine Reports



Authors: J. Curtis Nickel, Craig D. Tipton, Caleb D. Phillips, Rick Martin, E. David Crawford

Introduction: Urine specimens from patients diagnosed with interstitial cystitis/bladder pain syndrome (IC/BPS) are being submitted for next generation sequencing (NGS) analyses to determine potentially treatable infection missed by standard culture.  These complex NGS reports have been difficult to interpret for patients diagnosed with IC/BPS.  We present a comparative analysis of clinical NGS urine specimens from a large urinary microbiome data base (MicroGenDX, n=71,737) which includes female patients with a physician diagnosis of IC/BPS, cystitis, and a smaller cohort of asymptomatic healthy control volunteers.

Methods: The microbiome of female subjects with IC/BPS (n=565) were compared to subjects with acute cystitis (n=975), chronic cystitis (n=1,629) and healthy controls with no urological pain or infection (n=106). Differences in each group’s microbiome were investigated from the perspectives of differential taxa abundance, beta and alpha diversity, using ANCOM, Permanova (ADONIS) and ANOVA, respectively.

Results: Overall 351 genera were detected with 56 genera found to be differentially abundant across the diagnoses, including the top five most abundant genera identified; Escherichia, Lactobacillus, Klebsiella, Enterococcus and Streptococcus.  Alpha diversity was higher in the healthy control group compared to the other diagnoses (ANOVA; p = 0.0039; Figure 1a).  Similarly, microbiome composition was associated to diagnostic group, though with considerable overlap (Permanova; p = 0.001; Figure 1b). Pairwise testing suggests that healthy controls and acute cystitis are the most distinct groups with IC/BPS overlapping both (with more similarities to healthy controls than acute cystitis).

Conclusions: The microbiome of IC/BPS patients is divergent from healthy controls and acute/chronic cystitis but is taxonomically more similar to a healthy cohort than to those with a diagnosis of cystitis.  However, the altered microbiome state of the subset of IC/BPS patients resembling that of cystitis patients suggests the need for outcome research regarding NGS directed antimicrobial therapy in selected patients with IC/BPS.

Source of Funding: MicroGenDX

Therapeutic Area
Female UrologyInfection/Inflammation