Analysis of Gut Microbiome Reveals Significant Differences Between Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls
Daniel Shoskes*, Jessica Altemus, Alan Polackwich, Barbara Tucky, Hannah Wang, Charis Eng, Cleveland, OH
Introduction and Objectives
Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CPPS) is a common disorder with heterogeneous etiologies and clinical features including GI, psychiatric and neurologic symptoms. The gut microbiome is a metabolically active ecosystem linked to systemic conditions including autoimmunity, GI disorders and alterations in mood and stress (gut-brain axis). We hypothesize that the gut microbiome will show alterations between CPPS patients and controls
Methods
We identified CPPS patients (NIH category III) and controls who were either asymptomatic or only had Lower Urinary Tract Symptoms. After rectal exam, the soiled glove tip was immersed in sterile saline and stored on ice. Symptom severity was measured with the NIH-Chronic Prostatitis Symptom Index (CPSI) and clinical phenotype with UPOINT. Total DNA was extracted from the pellet of samples from cases and controls, and from the pellet of clean glove tip-containing saline. MiSeq-sequencing of bacterial-specific 16S-rDNA-capture was performed. Taxonomic and functional bioinformatic analyses were performed using principal coordinate analysis (PCoA), QIIME, LEfSe, and PiCRUSt algorithms
Results
There were 25 patients and 24 controls with complete data. Mean ages were similar (CPPS 52.3 vs control 57.0 years, p=0.27). For patients, median symptom duration was 48 months, mean CPSI was 26.0 and mean number of UPOINT domains was 3.6. 3D Unifrac PCoA revealed tighter clustering of controls in a space distinct from the wider clustering of cases (corrected P=0.001; a-diversity P=0.001). Compared to controls, 5 operational taxanomic units were over-represented, eg, Varibaculum, and 80 under-represented, eg, Prevotella, in cases. There was a trend in microbiomic differences with the neurologic/systemic phenotype for CPPS patients (p=0.2). Finally, in silico characterization by PiCRUSt showed specific pathways, such as ribosomes and pyrimidine transporters, and purine and thiamine metabolism, were under-expressed in patients
Conclusions
CPPS patients have significantly lower alpha diversity of gut microbiome which cluster differently from controls, and higher counts of Varibaculum, with separation sufficient to serve as a potential biomarker. The gut microbiome may serve as both biomarker of disease and potential target for therapy in CPPS.
Now published
Social Problem Solving, Perceived Stress and Daily Stressful Events in Chronic Prostatitis
Meghan M. Colosimo*, Christine Maguth Nezu, Arthur M. Nezu, Philadelphia, PA, Frank M. Nezu, Columbia, MD, Jennifer Y. Fariello, James F. Squadrito Jr., Bryn Mawr, PA, Stacey Lau, Melinda J. Webster, Philadelphia, PA
Introduction and Objectives
Nonbacterial chronic prostatitis (CP) is a prevalent urological condition characterized by persistent pain in the pelvic region, often co-occurring with lower urinary tract and sexual dysfunction symptoms and decreased life quality. The etiology of CP remains unknown and biomedical treatment options are often unsatisfactory in providing relief. It is important to consider how psychosocial factors inform our understanding of the distress associated with CP symptoms. Previous research indicates that stress is positively associated with CP symptoms, and two forms of stress were simultaneously examined: perceived stress and the experience of daily stressful events. This study adapts the contemporary diathesis stress model of social problem solving (SPS) to help explain the complex interaction of biological and psychosocial factors posited to dictate the development, course and prognosis of CP (1). SPS refers to the dynamic interplay between affective, cognitive and behavioral factors in the process of identifying/producing adaptive Methods for solving real life problems (1). Coping abilities of CP patients were observed by measuring SPS with the Social Problem Solving Inventory (SPSI-R: S). It was posited that SPS would predict CP symptoms above and beyond the variance already accounted for by both perceived stress (PS) and daily stress (DS).
Methods
61 males diagnosed with CP were administered a series of self-report measures: a) CP symptoms (NIH-CPSI), b) PS (Perceived Stress Scale), c) DS (Survey of Recent Life Experiences) and d) SPS (SPSI-R: S).
Results
CP symptoms were found to be significantly negatively correlated with total SPS (r = -.34, p = .007) and significantly positively correlated with PS (r = .38, p = .003) and DS (r = 34, p = .008). Hierarchical regression models significantly predicted CP symptoms and SPS was found to predict symptoms above and beyond PS and DS (Table 1).
Conclusions
SPS, PS and DS play a salient role in the frequency/severity of CP specific symptoms. Results suggest that Problem Solving Therapy (PST), an evidence based psychosocial intervention aimed at managing stress, may be a viable treatment option for refractory chronic pelvic pain. PST has been found to be effective in reducing both psychological distress and physical symptoms in a variety of chronically ill populations (1).
A Standardized Urological Examination for Women and Men with Urologic Chronic Pelvic Pain Syndromes: a MAPP Network site-specific study
Claire Yang*, Jane Miller, Adam Omidpanah, John Krieger, Seattle, WA
Introduction and Objectives
There have not been any physical examination findings reported to be specific to patients with urologic chronic pelvic pain syndromes (UCPPS). Our objective was to perform a standardized examination for both women and men with UCPPS.
Methods
Participants were enrolled in the MAPP Epidemiology Phenotyping Study. Our study included an expanded physical examination using the same technique in women and men, looking at 4 categories: a) extrapelvic, regional tenderness (including abdomen, flank, and back) b) pelvic floor and pelvic organ tenderness, c) pudendal nerve sensory function, and d) pelvic floor motor function. Comparisons of women and men were performed separately. Patients with UCPPS, positive controls with chronic fatigue syndrome and healthy, and pain free controls were enrolled.
Results
The examination was performed in 65 UCPPS cases (31 F, 34 M), 30 positive controls (15 F, 15 M), and 41 healthy controls (23 F, 18 M). There were no differences in pudendal nerve sensory function and pelvic floor motor function, when comparing cases with healthy controls, and cases with positive controls. Female and male cases were more likely to have tenderness than healthy controls in the following regions: right and left levator muscles, right and left obturator muscles, and right and left urogenital diaphragm. Female cases were more likely than healthy controls to have suprapubic, symphysis pubis, posterior superior iliac spine and bimanual examination tenderness. Positive controls also demonstrated tenderness in pelvic and extrapelvic regions, but less frequently than in cases, and more so in women than in men.
Conclusions
This extended examination revealed that pelvic and extrapelvic tenderness was found most frequently in UCPPS cases than in healthy and positive controls. Female positive controls also demonstrated tenderness. This examination can be used with female and male patients with UCPPS, and may prove helpful for phenotyping them.
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Evaluation of Candidate Urinary Biomarkers for Urologic Chronic Pelvic Pain Syndrome (UCPPS)
Adam Curatolo, Adelle Dagher, Monisha Sachdev, Boston, MA, Alisa J. Stephens-Shields, Philadelphia, PA, Andrew El-Hayek, Boston, MA, Chris Mullins, Bethesda, MD, J. Richard Landis, Philadelphia, PA, Adrie van Bokhoven, Aurora, CO, Roopali Roy, Jiang Yang, John Froehlich, Andrew C. Briscoe, Boston, MA, Michel A. Pontari, Philaelphia, PA, David Zurakowski, Richard S. Lee, Marsha A. Moses*, Boston, MA
Introduction and Objectives
There are no clinically useful, diagnostic or prognostic biomarkers for UCPPS. Identification of such biomarkers could aid in the clinical management and improved understanding of UCPPS pathology and advance current treatment and development of novel therapies.
Methods
We analyzed baseline urine samples from the MAPP Research Network study participants with UCPPS (n=259), positive controls (chronic pain without pelvic pain, n=107), and healthy controls (n=125) for the presence of proteins suggested in the literature to be associated with UCPPS. MMP-2 (Matrix Metalloproteinase-2), MMP-9, MMP-9/NGAL ((Neutrophil gelatinase-associated lipocalin), VEGF (Vascular Endothelial Growth Factor), VEGF-R1 (VEGF Receptor 1) and NGAL alone were assayed in duplicate and quantitated using mono-specific ELISAs in a blinded manner. Duplicates were averaged for analysis. Log-transformed concentration and total protein-corrected levels were compared among the groups within sex by the Student's t-test, with p-values adjusted for multiple comparisons. Among cases of UCPPS, correlations of protein with symptom severity were assessed by linear regression.
Results
Males with UCCPS had significantly higher total protein-corrected levels of VEGF (p<0.0001), VEGF-R1 (p=0.004), and MMP-9 (p=0.001) than male healthy controls. These differences were not observed in women. In females, pain severity was significantly positively associated with total protein-corrected MMP-9/NGAL (p<0.0001) and VEGF (p=0.013) and urinary severity was significantly positively associated with MMP-2 (p=0.0074) and MMP-9/NGAL (p<0.0001). In male UCPPS patients, none of the proteins studied were significantly correlated with either pain or urinary severity after adjustment for multiple comparisons.
Conclusions
VEGF, VEGF-R1, and MMP-9 may serve as clinically useful diagnostic markers for UCPPS in males. In females, MMP-9/NGAL, MMP-2, and VEGF may inform prognosis within patients with UCPPS.
The Efficacy of Trigger Point Injections in the Treatment of Sexual Pain
Sonia Bahlani-Khanna*, New Hyde Park, NY, Alexandra King, Hempstead, NY, Robert Moldwin, New Hyde Park, NY
Introduction and Objectives
Chronic pelvic pain (CPP), including pelvic floor dysfunction (PFD) and Category III B prostatitis/ chronic pelvic pain (CP/CPPS), affects up to 40% of patients age 18-45 years. Patients often present with a combination of lower urinary tract symptoms with pelvic pain and sexual dysfunction. Sexual pain is found in up to 42% of women with CPP. No uniform treatment strategy exists for treating these patients. Often patients with PFD and CP/CPPS will have trigger points. These hyperirritable muscular foci can give rise to pain. Trigger points can be involved in the etiology of sexual pain in women and ejaculatory pain in men. Trigger point injections involve infiltration of the musculature with anesthetic solution (consisting of a mixture of lidocaine and marcaine), which can be both diagnostic and therapeutic for patients. These injections have been shown to be effective in treating patients with PFD and associated pain. The objective of this study was to further evaluate the role of trigger point injections in treatment of PFD and CP/CPPS, specifically in regards to sexual pain.
Methods
48 patients with PFD and CP/CPPS were identified via medical record review. Medical records with access to trigger point procedures and specific questions regarding post procedural symptomatology were reviewed. Results were recorded in a database. Categoric data were compared with the chi-square test; binary data were compared with the McNemar test. No data was considered censored. All analyses were performed using SPSS version 22.0.
Results
48 patients with PFD and CP/CPPS were included. Median age of patients was 47 years [43.1-52.5]. 36 (75%) of these patients are female and 12 (25%) patients are male. 31 patients (64.6%) that received trigger point injections reported improvement in quality of life measures, such as decreases in hesitancy, nocturia, and constipation (all p<0.0001). In total, 22/48 patients reported sexual pain. 12 of 19 female patients with sexual pain reported improvement in sexual pain, including dyspareunia post procedure (p<0.0001). 3 of 3 of male patients (100 %) with ejaculatory pain felt improvement in symptoms post-procedure (p=.25). 15/22 patients reported improvement in sexual pain including dyspareunia and ejaculatory pain (p<.0001).
Conclusions
The use of trigger point injections is associated with an overall improvement in quality of life measures and sexual pain in patients diagnosed with PFD and CP/CPPS. This is the first study to evaluate sexual pain in patients after trigger point injections.
Chronic Psychological Stress Leads To Bladder Hyperalgesia Via Stress Induced Sensitization Of C Fibers And Mechanorecptors
Yunliang Gao*, Rong Zhang, Huiyi Chang, Larissa Rodriguez, Los Angeles, CA
Introduction and Objectives
Patients affected by overactive bladder and painful bladder syndrome/interstitial cystitis report symptoms exacerbation when stressed. We have shown that anxiety prone animals exposed to chronic psychological water avoidance stress (WAS) develop sustained bladder hyperalgesia. The bladder cooling reflex (BCR) is a segmental reflex believed to be triggered by cold receptors in bladder wall with C fibers signaling. We aimed to evaluate the chronic stress induces changes in BCR and if C fiber sensitization contributes to stress-induced bladder hypersensitivity.
Methods
22 adult female Wistar-Kyoto rats equally divided to 10-day WAS or handled controls. On day 11, animals were evaluated by cystometrogram (CMG) as well as visceromotor reflex (VMR) for bladder sensitivity and pain to saline infusion. CMG and VMR were obtained during bladder infusion at room temperature (RT) and cold (4 degree C) with an open urethral outlet thus allowing the animal to void. CMG and VMR were also obtained during RT isotonic bladder distention (RT-IBD, 10-40 cmH2O) with urethral occlusion.
Results
During RT infusion, WAS rats had a significant decreases in pressure threshold (PT) and the ratio of VMR threshold/maximum intravesical pressure (IVPmax). VMR duration significantly increased in WAS. BCR induced a more dramatic significant decline in PT and the ratio of VMR threshold/IVPmax in WAS (Fig.1A). No significant differences were found in contraction duration, inter-contraction interval or the VMR area under the curve (AUC) and duration. At RT-IBD (Fig.1B-C), VMR latency in WAS significantly decreased compared to controls. At 20 cmH2O, VMR AUC in WAS significantly increased compared to controls.
Conclusions
Chronic psychological stress induces bladder hypersensitivity, which manifests as earlier voiding and VMR. Prolonged VMR duration in WAS correlates with increased bladder sensitivity during voiding. BCR evokes C fibers activation and suggests that stress induced bladder hypersensitivity in functional voiding disorders mediated in part by afferent sensitization. Earlier VMR appearance at RT-IBD suggests a role for mechanoreceptor sensitivity in stress-induced bladder hypersensitivity.
Chronic Psychological Stress Induces Changes In Bladder Contractility
Yunliang Gao*, Huiyi Chang, Rong Zhang, Larissa Rodriguez, Los Angeles, CA
Introduction and Objectives
Chronic psychological stress can impact lower urinary tract function. We aimed to evaluate if the voiding dysfunction and bladder hyperalgesia seen in the animals exposed to water avoidance stress (WAS) is partially due to changes in bladder contractility.
Methods
Eight adult female Wistar-Kyoto rats were divided to 10-day WAS protocol (n=4) or handled control (n=4). On day 11, the urinary bladder was harvested, cut into strips, and kept in oxygenated Krebs solution. The remaining of the bladder and urethra were fixed in 10% formalin for histological studies. The contraction amplitude of each strip induced by KCl (80 µM) was regarded as 100% contraction amplitude for normalization. Carbachol, a non-selective cholinergic muscarinic receptor agonist, was given to examine the contractility (10-7 to 3×10-4 M). Atropine (10-6 M), a muscarinic receptor antagonist was given after carbachol to verify the response. Hematoxylin and eosin stain was used to assess tissue structure.
Results
There were dose dependent responses to carbachol with maximum contractility observed at 10-5 M(Fig 1A). At maximum dose response, there was significantly higher contractility in the bladders of WAS rats than controls (27% higher). Atropine reversed the effect of carbachol on bladder contractility. The thickness and structure of the bladder wall and urethra did not show significantly changes between WAS rats and controls(Fig 1B-C).
Conclusions
Chronic psychological stress leads to changes in bladder contractility without changes in the structure of bladder and urethra. Expression or responsiveness of muscarinic receptors induced by stress play a role in the urinary frequency and voiding changes seen in animals exposed to WAS. Receptor characterization will be evaluated in future studies. These Results have significant implications in human lower urinary pathologies that have been shown to be exacerbated by affected by stress such as urinary frequency, overactive bladders, and interstitial cystitis.
Chronic Prostate Inflammation Predicts Symptom Progression in Chronic Prostatitis/Chronic Pelvic Pain Patients
J. Curtis Nickel*, Kington, Canada, Stephen Freedland, Durham, NC, Ramiro Castro-Santamaria, King of Prussia, PA, Daniel Moreira, Rochester, MN
Introduction and Objectives
This report examines the 4-year longitudinal association between histological prostate inflammation in a negative prostate biopsy and CP/CPPS, specifically the development of new CP/CPPS and progression of existing CP/CPPS, in the men randomized to placebo in REDUCE.
Methods
Patients were randomized to placebo in the REDUCE, a 4-year, phase III, placebo controlled prostate cancer reduction trial study to determine whether 0.5 mg dutasteride daily decreased the risk of biopsy detectable prostate cancer. All men underwent biopsy before study entry, and CPSI at multiple times points, allowing review of the relationship between histological prostate inflammation and prostatitis symptoms. Uni- and multivariable analyses of the association between acute and chronic inflammation detected on baseline negative biopsies and the incidence of CPPS-like symptoms (defined as a positive response to CPSI question 1a [perineal pain] and/or question 2b [ejaculatory pain], and a total pain subscore of at least 4) and progression of existing CP/CPPS (defined as an increase = 4 points from baseline total CPSI score in patients with a baseline categorization of CP/CPPS) using Cox models.
Results
Acute and chronic inflammation was detected in 641 (15.6%) and 3216 (78.3%) of the 4109 men in the study. Of the 4109 men in the study, 2816 had available CP/CPPS symptom status at baseline. A total 2626 (93.3%) men did not have history of baseline CP/CPPS. Of these, 2150 had follow-up data available and were included in the analysis of the development of CP/CPPS, of which 317 developed CP/CPPS like symptoms. Acute and chronic inflammations were not associated with the incidence of CP/CPPS like symptoms (p>0.1). A total of 190 (6.7%) men had CP/CPPS symptoms at baseline. Of these, 145 had follow-up data and were included in the analysis of the progression of CP/CPPS symptoms. After a median follow-up of 12 months, a total of 109 men with CP/CPPS symptoms developed symptomatic progression. Chronic, but not acute, inflammation was significantly associated with shorter time to CP/CPPS progression in both uni- or multivariable analyses (HR=1.74, p=0.029 and HR=1.95, p=0.018 respectively).
Conclusions
Our comprehensive longitudinal evaluation of REDUCE patients randomized to placebo for 4 years showed that histological inflammation in a negative prostate biopsy is not associated with an increased risk of developing CP/CPPS but chronic inflammation does predict increased risk of symptomatic progression in men who had identified CP/CPPS symptoms at baseline. Funding: Glaxo-Smith-Kline
Chronic Prostatitis/Chronic Pelvic Pain Syndrome Is Associated with Irritable Bowel Syndrome: A Population-based Study
Shyi-Chun Yii*, Chun-Hou Liao, New Taipei City, Taiwan, Shiu-dong Chung, New-Taipei City, Taiwan, Herng-Ching Lin, New Taipei City, Taiwan
Introduction and Objectives
To date, the associations between irritable bowel syndrome (IBS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) lack large-scale epidemiological evidence. This case-control study utilized a population-based dataset to examine the association by comparing the risk of prior IBS between subjects with CP/CPPS and matched controls in Taiwan.
Methods
The data were retrieved from the Longitudinal Health Insurance Database 2005 (LHID2005), which includes all the original medical claim data and registration files of 1,000,000 individuals, randomly sampled from the 2005 Registry for Beneficiaries (n= 25.68 million) of the Taiwan National Heath Insurance program. We identified patients who had received their first diagnosis of CP/CPPS (ICD-9CM code 601.1) in ambulatory care visits between January 2001 and December 2013. Only those who had received two or more CP/CPPS diagnoses with at least one being made by a certified urologist were included. We likewise selected matched controls (n=4870) from the LHID2005, matched on age with a stratification basis of ten-years (<30, 30-39, 40-49, 50-59, 60-69, and >69) and index year. IBS cases were identified by a diagnosis of ICD-9-CM code 564.1. Conditional logistic regressions (conditioned on the study matching factors of age (10-year basis) and index year) were conducted to examine associations of CP/CPPS with previously diagnosed IBS.
Results
After matching for age (10-year basis), there were significant differences in monthly income, geographical location, and urbanization level of the patient’s residence between cases and controls (all p<0.001). A total of 753 (7.7%) out of the 9740 sampled patients had IBS prior to the index date; IBS was found in 497 (10.2%) cases and in 256 (5.3%) controls (p<0.001). Conditional logistic regression analysis (conditioned on age (10-year basis) and index year) revealed that the odds ratio (OR) of prior IBS were 2.05 (95% CI=1.75-2.40, p<0.001) for cases than for controls. Furthermore, after adjusting for the patients’ monthly income, geographical location, urbanization level, and hypertension and CHD, the conditional logistic regression analysis indicated that cases were more likely to have prior IBS (OR=1.96, 95% CI=1.67-2.29) when compared to controls. We found that CP/CPPS was consistently and significantly associated with prior IBS regardless of age group.
Conclusions
We concluded that CP/CPPS is associated with previously diagnosed IBS. Urologists should be alert for the association between CP/CPPS and IBS in subjects suffering from IBS.
Mechanisms Of Stress-Induced Bladder Dysfunction: A Novel Role For Alterations In Urinary Bladder Permeability
Ehsan Mohammadi*, Niran Hadad, Robert Hurst, Beverley Greenwood-Van Meerveld, Oklahoma City, OK
Introduction and Objectives
Evidence suggests that symptoms of painful bladder syndrome (PBS) are exacerbated by stress. Our previous studies in rats found that chronic water avoidance stress (WAS) increases visceral pain, Our current hypothesis is that changes in urothelial permeability and alterations in tight junction protein expression may represent a novel mechanism for stress-induced bladder dysfunction.
Methods
Fasted, male F-344 rats were exposed to WAS (n=12) or sham-WAS (n=12) 1-hr daily for 7 days. Bladder tissue were harvested on day 8 and mounted into modified Ussing chambers. Permeability was assessed ectrophysiologically via transepithelial electrical resistance (TEER) and via the flux of a macromolecular marker (fluorescein isothiocynate-dextrin [FITC-4 KD). Bladder tissue was isolated for assessment of tight junction (TJ) protein via Western Blot and immunoflouresnce following WAS or Sham-WAS. Fecal pellet output was used to quantify autonomic output during the daily WAS paradigm to ensure that the rats did not habituate to the daily stress.
Results
Following WAS, bladder permeability was increased when compared to sham-treated controls as demonstrated by a significant decrease in TEER (2917±480 to 1215±134 O/cm2; P<0.001) and an increase in the macromolecular flux of FITC-4 (383±40 to 1077±67 pgFITC/min/cm2; P<0.001). TJ protein analysis revealed a 0.31 fold decrease in the expression of claudin 1 and an increase in claudin 2 expression (0.84 fold) over sham WAS controls. Fecal pellet production remained consistent confirming that the rats did not habituate to the chronic stress (Day 1: 7.3±0.6 vs. Day 7: 6.5±0.8 fecal pellets).
Conclusions
These data highlight a pivotal role for alterations in bladder permeability via a mechanism involving alterations in tight junction protein expression, in the bladder's response to chronic stress. This new data advance our understanding of the long term effects of stress on bladder function and support the concept that in patients with PBS the symptomology may be due increases in urothelial permeability.
The Urinary Microbiome Differs Significantly Between Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls as Well as Between Patients With Different Clinical Phenotypes
Daniel Shoskes*, Jessica Altemus, Alan Polackwich, Barbara Tucky, Hannah Wang, Charis Eng, Cleveland, OH
Introduction and Objectives
Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common disorder with heterogeneous etiologies and clinical features. There are currently no validated biomarkers. Several studies of the urinary microbiome have failed to find consistent differences between patients and controls and between different CP/CPPS phenotypes.
Methods
We identified 25 CP/CPPS patients (NIH category III definition) seen in clinic and 25 men who were either asymptomatic or only had Lower Urinary Tract Symptoms but no pain. Mid-stream urine was collected and stored on ice. Symptom severity was measured with the NIH-Chronic Prostatitis Symptom Index (CPSI) and clinical phenotype with UPOINT. Total DNA was extracted from the pellet of the collected urine from cases and controls. MiSeq-sequencing of bacterial-specific 16S-rDNA-capture was performed. Taxonomic and functional bioinformatic analyses were performed using principal coordinate analysis (PCoA), QIIME, LEfSe, and PiCRUSt algorithms
Results
There were 25 patients and 24 controls with evaluable data. Mean ages were similar (CP/CPPS 52.3 vs control 57.0 years, p=0.27). For patients, median duration was 48 months, mean CPSI was 26.0 and mean number of UPOINT domains was 3.6. Weighted 3D Unifrac PCoA revealed tighter clustering of controls in a space distinct from the wider clustering of cases (corrected P=0.001; a-diversity P=0.006). Compared to controls, 49 operational taxonomic units (OTU) were over-represented in patients, eg, Clostridia, and 18 under-represented, eg, Eichenella, resulting in predicted perturbations in functional pathways. Microbiomic differences were noted for symptom severity (CPSI < or > 26), duration (< or > 48 months), total positive UPOINT domains and presence of specific Psychosocial and Neurologic/Systemic domains (p=0.001-0.003). These associations were predicted to result in perturbations of several pathways, such as indole alkaloid synthesis, and flavone/flavonoid synthesis pathways
Conclusions
CP/CPPS patients have significantly higher alpha diversity of the urinary microbiome which cluster differently from controls, and higher counts of Clostridia compared with controls, with separation sufficient to serve as a potential biomarker. Significant microbiome differences occur with several clinical measures of severity and clinical phenotype resulting in predictive perturbations of functional pathways which could suggest metabolite-specific targeted treatment
Presence of urinary Ureaplasma urealyticum or Ureaplasma parvum is not associated with the occurrence of chronic prostatitis/chronic pelvic pain syndrome
Yu Seo, Gil Lee*, Cheonan, Korea, Republic of
Introduction and Objectives
Ureaplasmas are the smallest human parasites. Its slow growth in infected host cells allow for the possibility of being causal pathogen for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Therefore, we examined the presence of Ureaplasma urealyticum (UU) and Ureaplsma pavum (UP) in 696 urine samples from 669 men who attended a urology outpatient clinic with various reasons by using an automated sequencing method.
Methods
696 urine samples that are nonbacterial (from prostate and urine ordinary cultures) and nongonorrheal and nonchlamydial (based on PCR) were randomly selected from stored samples. Clinical information of individual subject is presented in Table 1. We amplified the UU/UP urease complex components with consensus primers. Finally, we read the genetic sequences and classified between the UU and UP from ureaplasma spp.
Results
The overall rates of UU and UP were 3.88% (27/696) and 6.46% (45/696), respectively. In univariate analysis, only UU infection significantly increases the likehood of urinary WBC count =5 only (odds ratio [OR]; 7.377, 95% confidence interval [CI]: 2.244-24.248, P=0.001) (Table 1). However, the presence of both UU and UP in urine do not increase the risk of having the CP/CPPS symptoms and signs. The mean NIH-CPSI scores in total of pain Items, urinary and quality of life items do not differ among the negative, UU positive, and UP positive groups (Table 2).
Conclusions
We find that only UU can induce asymptomatic pyuria. However, the presence of urinary UU or UP is not definitively associated with the occurrence of CP/CPPS.
