Urinary fungi associated with urinary symptom severity among women with interstitial cystitis/bladder pain syndrome (IC/BPS)

  • J. Curtis NickelEmail author
  • Alisa Stephens
  • J. Richard Landis
  • Chris Mullins
  • Adrie van Bokhoven
  • Jennifer T. Anger
  • A. Lenore Ackerman
  • Jayoung Kim
  • Siobhan Sutcliffe
  • Jaroslaw E. Krol
  • Bhaswati Sen
  • Jocelyn Hammond
  • Garth D. Ehrlich
  • The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network
Original Article



To correlate the presence of fungi with symptom flares, pain and urinary severity in a prospective, longitudinal study of women with IC/BPS enrolled in the MAPP Research Network.


Flare status, pelvic pain, urinary severity, and midstream urine were collected at baseline, 6 and 12 months from female IC/BPS participants with at least one flare and age-matched participants with no reported flares. Multilocus PCR coupled with electrospray ionization/mass spectrometry was used for identification of fungal species and genus. Associations between “mycobiome” (species/genus presence, relative abundance, Shannon’s/Chao1 diversity indices) and current flare status, pain, urinary severity were evaluated using generalized linear mixed models, permutational multivariate analysis of variance, Wilcoxon’s rank-sum test.


The most specific analysis detected 13 fungal species from 8 genera in 504 urine samples from 202 females. A more sensitive analysis detected 43 genera. No overall differences were observed in fungal species/genus composition or diversity by flare status or pain severity. Longitudinal analyses suggested greater fungal diversity (Chao1 Mean Ratio 3.8, 95% CI 1.3–11.2, p = 0.02) and a significantly greater likelihood of detecting any fungal species (OR = 5.26, 95% CI 1.1–25.8, p = 0.04) in high vs low urinary severity participants. Individual taxa analysis showed a trend toward increased presence and relative abundance of Candida (OR = 6.63, 95% CI 0.8–58.5, p = 0.088) and Malassezia (only identified in ‘high’ urinary severity phenotype) for high vs low urinary symptoms.


This analysis suggests the possibility that greater urinary symptom severity is associated with the urinary mycobiome urine in some females with IC/BPS.


Interstitial cystitis Bladder pain syndrome Mycobiome Fungal Flares 


Author contributions

JCN, AS: protocol development, data management, data analysis, and manuscript writing/editing. JRL: protocol development, data management, data analysis, and manuscript editing. CM: protocol/project development, data collection and management, data analysis, and manuscript writing/editing. AvanB, GDE: protocol development, data collection and management, data analysis, and manuscript writing/editing. JTA, ALA, JK: protocol development, data analysis, and manuscript editing. SS: protocol/project development, data collection and management, data analysis, and manuscript editing. JEK, BS, JH: data collection and management, data analysis, and manuscript editing.


The authors declare that this project was supported (including salary support) by peer reviewed research grants from the US National Institutes of Health: NIDDK: U01DK103271 (JCN, JEK, BS, JH, GDE), U01DK082316 (AS, JRL), U01DK082333 (AVB), U01DK103260 (JTA, ALA, JK), U01DK082315 (SS).

Compliance with ethical standards

Conflict of interest

CM is an employee of the NIH/NIDDK. The authors report no other potential conflict of interest.

Ethical responsibilities of the authors

The authors agree to the conditions outlined in the submission instructions.

Informed consent

Written informed general consent for specimen procurement and data analysis was obtained from all individual participants included in the study.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Research involving animals

This article does not contain any studies with animals performed by any of the authors.

Supplementary material

345_2019_2764_MOESM1_ESM.doc (40 kb)
Supplementary material 1 (DOC 40 kb)
345_2019_2764_MOESM2_ESM.rtf (85 kb)
Supplementary material 2 (RTF 85 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • J. Curtis Nickel
    • 1
    Email author
  • Alisa Stephens
    • 2
  • J. Richard Landis
    • 2
  • Chris Mullins
    • 3
  • Adrie van Bokhoven
    • 4
  • Jennifer T. Anger
    • 5
  • A. Lenore Ackerman
    • 5
  • Jayoung Kim
    • 5
  • Siobhan Sutcliffe
    • 6
  • Jaroslaw E. Krol
    • 7
  • Bhaswati Sen
    • 7
  • Jocelyn Hammond
    • 7
  • Garth D. Ehrlich
    • 7
  • The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network
  1. 1.Department of UrologyQueen’s University at Kingston, Kingston General HospitalKingstonCanada
  2. 2.Center for Clinical Epidemiology and BiostatisticsUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.National Institutes of Health/NIDDKBethesdaUSA
  4. 4.Department of PathologyUniversity of ColoradoAuroraUSA
  5. 5.Division of UrologyCedars-Sinai Medical CenterBeverly HillsUSA
  6. 6.Department of SurgeryWashington University School of MedicineSt. LouisUSA
  7. 7.Department of Microbiology and ImmunologyDrexel College of MedicinePhiladelphiaUSA

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