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Urinary Microbiome and Cytokine Levels in Women With Interstitial Cystitis

Evidence for the existence of a biodiverse urinary microbiome that cannot be isolated by conventional culture has significant clinical implications for the diagnosis and treatment of several urinary tract conditions. Interstitial cystitis is a debilitating chronic condition characterized by suprapubic pain and urinary frequency. It occurs in 3 million to 8 million US women. Its etiology remains elusive. Treatment is variable and often unsatisfactory. Affected individuals have higher rates of psychiatric diagnoses and other chronic pain conditions. It has been suggested that there is an inflammatory component of interstitial cystitis, but little is known about the possible role played by the urinary microbiome and its effect on the immune response. The aims of this cross-sectional study were to investigate differences in the urinary microbiota and cytokine levels among women with interstitial cystitis compared with healthy women and to determine whether the presence of specific urinary microbiotic bacteria or cytokines was associated with worsening symptom severity or screening positive for psychiatric comorbidities. Women, 21 years or older, presenting to a pelvic floor clinic diagnosed as having interstitial cystitis were compared with age-matched women in a healthy control group from the same institution over a 6-month period. A catheterized urine sample was obtained from each patient, and symptom severity, quality of life, depression, and anxiety screening questionnaires were completed by participants. Urinary microbiomes were generated through bacterial ribosomal RNA sequencing; cytokine levels were analyzed using a standard immunoassay. Multiple regression analysis was used to determine relative associations, and nonparametric analyses were used for all comparisons. Between November 2013 and April 2014, 40 participants were enrolled: 20 patients and 20 women in the control group. Compared with the control group, the patient group had more disability, bothersome urinary symptoms, genitourinary pain, and sexual dysfunction and scored higher on depression and anxiety screens. Fewer distinct operational taxonomic units were found in the urine of patients comparedwith women in the control group (2 vs 3.5;P = 0.015), and patient urine was less likely to contain Lactobacillus acidophilus (1/14 [7%] compared with 7/18 [39%], P = 0.05). Patients with L acidophilus in their urine scored lower (better) on the Interstitial Cystitis Symptoms Index (1 vs 10; P = 0.005) and the Female Genitourinary Pain Index (0 vs 22.5; P = 0.03). Participants with interstitial cystitis had higher levels of macrophage-derived chemokine (13.32 vs 0; P = 0.037) and interleukin 4 (1.95 vs 1.17; P = 0.029). A positive correlation was found between interleukin 4 and more severe scores on the Interstitial Cystitis Symptoms Index (r = 0.406, P = 0.013). There was no association between the presence of Lactobacillus genera and cytokine levels. Compared with healthy women, the urinary microbiome of patients with interstitial cystitis was less diverse, was less likely to contain Lactobacillus species, and was associated with higher levels of proinflammatory cytokines. Whether these findings represent causality and whether the effect of alterations to the urinary microbiome is mediated through an inflammatory component are unknown. This study highlights the need to fully characterize a healthy urinary microbiome and to better understand the relationship between the microbiome and lower urinary tract symptoms. Future research examining the urinary microbiome may lead to development of targeted treatment strategies.