Phenotyping of IC/BPS Using Microbial Community States: Validation of a Novel Noninvasive Biomarker
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating pain condition characterized by chronic bladder pain in conjunction with urinary frequency, urgency, and other urinary complaints. This disorder, which is often highly resistant to treatment, substantially degrades physical and social activity and overall quality of life. While up to 7% of women in the U.S. have symptoms consistent with the diagnosis, most are never recognized and even those who are experience lengthy delays before receiving effective treatments. While testing for related conditions, such as urinary tract infection (UTI), can rule out other pathologies as causes of the pain, IC/BPS is a diagnosis of exclusion; no objective test recognizes IC/BPS or differentiates it from other pelvic pain-related or urinary conditions. Objective markers to identify the condition are urgently needed. Given the similarities of IC/BPS symptoms to those of UTI, a bacterial contribution to the condition has long been postulated. Early studies of the urinary microbiome, the microbial communities that live within and interact with human hosts, have suggested differences in the bacterial communities in urine of patients with IC/BPS; these analyses, however, have not proven clinically useful in the care of affected patients and provided little insight into how these differences might impact bladder health or contribute to IC/BPS development. In our initial work, a diligent exploration of the patterns of symptoms for IC/BPS patients revealed three distinct disease “phenotypes,” subgroups of affected patients with unique patterns of pain and urinary complaints. Armed with this perspective, our expansive investigation of the microbiome was able to identify characteristic bacterial and fungal communities associated with each IC/BPS phenotype that also correlated with distinct patterns of inflammation in the urine and blood. These data suggested that the umbrella of the IC/BPS diagnosis reflects several unique conditions that may have different mechanistic origins. The patterns of microbes associated with each condition and the associated inflammatory changes also suggested possible cellular pathways involved in the generation of painful and irritative bladder symptoms. Building on our original award, this proposal expands on our study of IC/BPS, a major PRMRP topic area, centering on two specific areas of encouragement. We will focus on validation of the microbial biomarkers identified in our original study to diagnose IC/BPS and to classify the associated phenotypes. Preliminary data also suggest such a test may have utility in predicting treatment responses to IC/BPS therapies, which we will also investigate. An objective basis for diagnosis and differentiation of distinct IC/BPS subtypes will greatly increase the likelihood of patients receiving an accurate diagnosis and timely, efficacious treatment. Objective testing distinguishing IC/BPS from other confounding conditions not only allows better early identification and improved treatment assignment for IC/BPS patients but could also ensure improved management for the confounding conditions as well by preventing misdiagnosis. We will also attempt to define some of the mechanisms underlying IC/BPS. The inflammatory patterns associated with certain bacteria and fungi implicates microbial recognition by the bladder in the origin of disease, which can be explored in in vitro systems. Once we establish the pathways whereby pertinent bacteria and fungi interact with bladder cells to incite that inappropriate inflammation, we can explore potential targeted, inhibitory strategies that may serve as the foundation for innovative treatments and novel disease prevention methods. Few effective strategies for disease management currently exist for IC/BPS. This study is designed to lead directly to novel, rationally designed, targeted therapies and better identification of those specific patient populations that would
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110644
Entities
People
- Anne Ackerman
Organizations
- United States Army
- University of California, Los Angeles