Abstract
Interstitial cystitis/bladder pain syndrome (IC) is associated with significant morbidity, yet underlying mechanisms and diagnostic biomarkers remain unknown. Pelvic organs exhibit neural crosstalk by convergence of visceral sensory pathways, and rodent studies demonstrate distinct bacterial pain phenotypes, suggesting that the microbiome modulates pelvic pain in IC. Stool samples were obtained from female IC patients and healthy controls, and symptom severity was determined by questionnaire. Operational taxonomic units (OTUs) were identified by16S rDNA sequence analysis. Machine learning by Extended Random Forest (ERF) identified OTUs associated with symptom scores. Quantitative PCR of stool DNA with species-specific primer pairs demonstrated significantly reduced levels of E. sinensis, C. aerofaciens, F. prausnitzii, O. splanchnicus, and L. longoviformis in microbiota of IC patients. These species, deficient in IC pelvic pain (DIPP), were further evaluated by Receiver-operator characteristic (ROC) analyses, and DIPP species emerged as potential IC biomarkers. Stool metabolomic studies identified glyceraldehyde as significantly elevated in IC. Metabolomic pathway analysis identified lipid pathways, consistent with predicted metagenome functionality. Together, these findings suggest that DIPP species and metabolites may serve as candidates for novel IC biomarkers in stool. Functional changes in the IC microbiome may also serve as therapeutic targets for treating chronic pelvic pain.
Highlights
Patients with urologic chronic pelvic pain syndromes (UCPPS) suffer chronic pelvic pain and dramatically lower quality of life, yet diagnostic markers and effective therapies remain elusive for these costly syndromes[1]
Female healthy controls and patients were recruited from Multi-Disciplinary Approaches to Chronic Pelvic Pain (MAPP) participants at Northwestern and through separate advertising to yield a cohort of average age of 35 years
Study participants exhibited racial skewing such that all Interstitial cystitis/bladder pain syndrome (IC) patients were Caucasian, and three IC patients were on disability due to IC
Summary
Patients with urologic chronic pelvic pain syndromes (UCPPS) suffer chronic pelvic pain and dramatically lower quality of life, yet diagnostic markers and effective therapies remain elusive for these costly syndromes[1]. HPA axis dysfunction has been implicated in female and male patients and cats with feline IC9–13, and may be common among UCPPS, but mechanisms that integrate pelvic pain, voiding dysfunction, HPA activity, and depression are lacking Because of these long-standing questions, NIDDK has launched its flagship urology study, the Multi-Disciplinary Approaches to Chronic Pelvic Pain (MAPP) Research Network with the most comprehensive studies to date of UCPPS including clinical characterization and epidemiologic and mechanistic studies[14,15]. Individual species within the microbiome have recently been associated with driving disease through altered innate metabolism or altered pharmaceutical metabolism[18] Despite these advances, it remains unclear whether microbiota contribute to pain syndromes generally and to UCPPS in particular. We observed significant differences between microbiota of patients and controls, including specific species, thereby potentially identifying novel biomarkers and potential therapeutic targets for IC
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