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Urinary Microbiome and Cytokine Levels in Women With Interstitial Cystitis

Abernethy, Melinda G. MD; Rosenfeld, Amy PhD; White, James R. PhD; Mueller, Margaret G. MD; Lewicky-Gaupp, Christina MD; Kenton, Kimberly MD

doi: 10.1097/AOG.0000000000001892
Contents: Original Research
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OBJECTIVE: To investigate differences in the urinary microbiome and cytokine levels between women with and without interstitial cystitis and to correlate differences with scores on standardized symptom severity scales and depression and anxiety screening tools.

METHODS: Our cross-sectional study compared women presenting to a pelvic floor clinic and diagnosed with interstitial cystitis over a 6-month period with age-matched women in a control group from the same institution. Participants provided a catheterized urine sample and completed symptom severity, quality-of-life, depression, and anxiety screening questionnaires. Urinary microbiomes generated through bacterial ribosomal RNA sequencing and cytokine levels were analyzed using a standard immunoassay. Nonparametric analyses were used for all comparisons.

RESULTS: Participants with interstitial cystitis reported more disability, bothersome urinary symptoms, genitourinary pain, and sexual dysfunction and scored higher on depression and anxiety screens compared with women in the control group. The urine of participants with interstitial cystitis contained fewer distinct operational taxonomic units (2 [median range 2–7, interquartile range 1] compared with 3.5 [median, range 2–22, interquartile range 5.25], P=.015) and was less likely to contain Lactobacillus acidophilus (1/14 [7%] compared with 7/18 [39%], P=.05) compared with women in the control group. L acidophilus was associated with less severe scores on the Interstitial Cystitis Symptoms Index (1 [median, range 0–17, interquartile range 5] compared with 10 [median, range 0–14, interquartile range 11], P=.005) and the Genitourinary Pain Index (0 [median, range 0–42, interquartile range 22] compared with 22.5 [median, range 0–40, interquartile range 28], P=.03). Participants with interstitial cystitis demonstrated higher levels of macrophage-derived chemokine (13.32 [median, range 8.93–17.05, interquartile range 15.86] compared with 0 [median, range 8.93–22.67, interquartile range 10.35], P=.037) and interleukin-4 (1.95 [median, range 1.31–997, interquartile range 11.84] compared with 1.17 [median, range 0.44–3.26, interquartile range 1.51], P=.029). There was a positive correlation between interleukin-4 and more severe scores on the Interstitial Cystitis Symptoms Index (r=0.406, P=.013). No associations between the presence of lactobacillus species and cytokine levels were observed.

CONCLUSION: The urinary microbiome of participants with interstitial cystitis was less diverse, less likely to contain Lactobacillus species, and associated with higher levels of proinflammatory cytokines. It is unknown whether this represents causality and whether the effect of alterations to the urinary microbiome is mediated through an inflammatory response.

Supplemental Digital Content is Available in the Text.The urinary microbiome of women with interstitial cystitis is less diverse and less likely to include lactobacillus species compared with women in a control group.

Northwestern Feinberg School of Medicine, Chicago, Illinois; Columbia University, New York, New York; and Resphera Biosciences, Baltimore, Maryland.

Corresponding author: Melinda G. Abernethy, MD, Johns Hopkins Department of Gynecology and Obstetrics, 4940 Eastern Avenue, 301 Building, 3rd Floor, Baltimore, MD 21224; email: maberne1@jhmi.edu.

Supported by an American Urogynecologic Society Foundation and International Continence Society–Interstitial Cystitis Research grant to Melinda G. Abernethy, MD.

Presented at the 36th Annual Scientific Meeting of the American Urogynecologic Society, October 13–17, 2015, Seattle, Washington.

Financial Disclosure Dr. White is the founder and owner of Resphera Biosciences in Baltimore, Maryland. He served as a guidelines methodology consultant to the American Urological Association in 2015. Dr. White performed the species-level taxonomic assignments utilizing Resphera technology. The other authors did not report any potential conflicts of interest.

Each author has indicated that he or she has met the journal's requirements for authorship.

© 2017 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.