Initial evaluation of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic condition defined by often debilitating bladder pain, is directed by suspicion for the presence of Hunner lesions, inflammatory lesions of the bladder mucosa, as patients with these lesions typically respond to different treatments than those without. While more common in older patients, no clinical features can predict the presence of Hunner lesions. We therefore explored if characterization of the urobiome in IC/BPS patients could improve sensitivity of Hunner lesion screening.

We obtained DNA samples, demographic information, and symptom information regarding participants from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Study Trans-MAPP EP Study who were diagnosed with IC/BPS and had previously undergone a cystoscopy to evaluate for Hunner lesions. 16S next-generation sequencing (NGS) was used to characterize urinary microbial populations; validated questionnaires (female GenitoUrinary Pain Index, OAB questionnaire, O’Leary-Sant Indices) were used to quantify symptom type and severity. Microbiome Multivariable Associations with Linear Models (MaAsLin2) and linear discriminant analysis effect size (LEfSe) analyses were employed to identify microbiota features associated with the presence or absence of Hunner lesions, along with the clinical importance of these features and the degree to which they present utility as potential biomarkers for the presence or absence of these lesions.

IC/BPS participants exhibited two strikingly different urotypes. In one urotype, the Actinobacteriota (specifically Cellulosimicrobium cellulans) were the dominant taxa and were associated with the presence of Hunner lesions. In the other urotype, Proteobacteria (specifically Pseudomonas spp.) were the dominant taxa and were invariably associated with the absence of Hunner lesions. While Pseudomonas was largely absent from Hunner lesions participants, roughly half of the participants without these inflammatory lesions exhibited a similar urobiome as participants with Hunner lesions, with predominant Cellulosimicrobium.

A Cellulosimicrobium-dominant urobiome was invariably associated with Hunner lesions. While in Hunner lesion-negative subjects the urobiome shared numerous components with local vaginal and rectal microbiota, in Hunner lesion subjects, there were striking differences between the urobiome and the microbial populations of the neighboring vagina and rectum, suggesting a selective pressure enriching for an alternative microbiome in the bladder in Hunner lesion subjects. Most interesting is the similarity between a subset of Hunner lesion-negative subjects and the Hunner lesion-positive individuals. While it is unclear, this population may represent either a population “at-risk” for Hunner lesions or subjects with Hunner lesions who had no active lesions at the time of cystoscopy or individuals in whom their lesions were not recognized at Hunner lesions. Since there are no symptomatic differences between Hunner lesion-positive and -negative IC/BPS subjects, if this Hunner lesion-negative group bearing Cellulosimicrobium represents a group with the possibility of progression to more active Hunner lesion disease (either at-risk, between lesions, or misdiagnosed as negative), microbial biomarkers capable of identifying this group without cystoscopy might prompt either a change in treatment or more rigorous screening procedures, particularly with symptomatic exacerbations.

Our study suggests the possibility of using urinary microbial biomarkers to determine which patients should undergo screening for Hunner lesions, improving the early recognition of Hunner lesions and subjects at-risk for lesions, improving appropriate care.

Continence 12S (2024) 101589
DOI: 10.1016/j.cont.2024.101589