title: Stool-based biomarkers of interstitial cystitis/bladder pain syndrome.
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.
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1207 West Gregory Drive, Urbana, Illinois, USA.
authors.forename: A
authors.initials: A
authors.lastname: Braundmeier-Fleming
authors.affiliation: Applied Research Institute at University of Illinois at Urbana-Champaign, 1205 West Clark Street, Urbana, IL, USA.
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Russell
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue Chicago, IL, USA.
authors.forename: Megan Y
authors.initials: MY
authors.lastname: Nas
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL, USA.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Yaggie
authors.affiliation: Applied Research Institute at University of Illinois at Urbana-Champaign, 1205 West Clark Street, Urbana, IL, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Berry
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Bachrach
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Flury
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL, USA.
authors.forename: Darlene S
authors.initials: DS
authors.lastname: Marko
authors.affiliation: Applied Research Institute at University of Illinois at Urbana-Champaign, 1205 West Clark Street, Urbana, IL, USA.
authors.forename: Colleen B
authors.initials: CB
authors.lastname: Bushell
authors.affiliation: Applied Research Institute at University of Illinois at Urbana-Champaign, 1205 West Clark Street, Urbana, IL, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Welge
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1207 West Gregory Drive, Urbana, Illinois, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: White
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Schaeffer
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL, USA.|Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue Chicago, IL, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Klumpp
mesh_terms: D000328:Adult; D001419:Bacteria / Q000145:classification* / Q000235:genetics; D015415:Biomarkers / Q000032:analysis*; D016000:Cluster Analysis; D018856:Cystitis, Interstitial / Q000473:pathology*; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D005243:Feces / Q000737:chemistry* / Q000382:microbiology*; D005260:Female; D006801:Humans; D055442:Metabolome; D056186:Metagenomics; D008875:Middle Aged; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D011795:Surveys and Questionnaires; D001743:Urinary Bladder / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S