The Urobiomes of Adult Women With Various Lower Urinary Tract Symptoms Status Differ: A Re-Analysis.

The discovery of the urinary microbiome (urobiome) has created opportunities for urinary health researchers who study a wide variety of human health conditions. This manuscript describes an analysis of catheterized urine samples obtained from 1,004 urobiome study participants with the goal of identifying the most abundant and/or prevalent (common) taxa in five clinically relevant cohorts: unaffected adult women (n=346, 34.6%), urgency urinary incontinence (UUI) (n=255, 25.5%), stress urinary incontinence (SUI) (n=50, 5.0%), urinary tract infection (UTI) (n=304, 30.4%), and interstitial cystitis/painful bladder syndrome (IC/PBS) (n=49, 4.9%). Urine was collected via transurethral catheter and assessed for microbes with the Expanded Quantitative Urine Culture (EQUC) technique. For this combined analytic cohort, the mean age was 59 ± 16; most were Caucasian (n=704, 70.2%), Black (n=137, 13.7%), or Hispanic (n=130, 13.0%), and the mean BMI was 30.4 ± 7.7. Whereas many control or IC/PBS cohort members were EQUC-negative (42.4% and 39.8%, respectively), members of the other 3 cohorts were extremely likely to have detectable microbes. The detected urobiomes of the controls and IC/PBS did not differ by alpha diversity or genus level composition and differed by only a few species. The other 3 cohorts differed significantly from the controls. As expected, Escherichia was both prevalent and highly abundant in the UTI cohort, but other taxa also were prevalent at more moderate abundances, including members of the genera Lactobacillus, Streptococcus, Staphylococcus, Corynebacterium, Actinomyces, and Aerococcus. Members of these genera were also prevalent and highly abundant in members of the UUI cohort, especially Streptococcus anginosus. Intriguingly, these taxa were also detected in controls but at vastly lower levels of both prevalence and abundance, suggesting the possibility that UUI-associated symptoms could be the result of an overabundance of typical urobiome constituents. Finally, prevalence and abundance of microbes in the SUI cohort were intermediate to those of the UUI and control cohorts. These observations can inform the next decade of urobiome research, with the goal of clarifying the mechanisms of urobiome community composition and function. There is tremendous potential to improve diagnosis, evaluation and treatment for individuals affected with a wide variety of urinary tract disorders.

The bacterial microbiota of Hunner lesion interstitial cystitis/bladder pain syndrome.

OBJECTIVE: To undertake the first comprehensive evaluation of the urinary microbiota associated with Hunner lesion (HL) interstitial cystitis/bladder pain syndrome (IC/BPS). Despite no previous identification of a distinct IC/BPS microbial urotype, HL IC/BPS, an inflammatory subtype of IC/BPS, was hypothesized most likely to be associated with a specific bacterial species or microbial pattern. PARTICIPANTS AND METHODS: The bacterial microbiota of midstream urine specimens from HL IC/BPS and age- and gender-matched IC/BPS patients without HL (non-HL IC/BPS) were examined using the pan-bacterial domain clinical-level molecular diagnostic Pacific Biosciences full-length 16S gene sequencing protocol, informatics pipeline and database. We characterized the differential presence, abundances, and diversity of species, as well as gender-specific differences between and among HL and non-HL IC/BPS patients. RESULTS: A total of 59 patients with IC/BPS were enrolled (29 HL, 30 non-HL; 43 women, 16 men) from a single centre and the microbiota in midstream urine specimens was available for comparison. The species abundance differentiation between the HL and non-HL groups (12 species) was not significantly different after Bonferroni adjustments for multiple comparisons. Similarly, the nine differentiating species noted between female HL and non-HL patients were not significantly different after similar statistical correction. However, four species abundances (out of the 10 species differences identified prior to correction) remained significantly different between male HL and non-HL subjects: Negativicoccus succinivorans, Porphyromonas somerae, Mobiluncus curtisii and Corynebacterium renale. Shannon diversity metrics showed significantly higher diversity among HL male patients than HL female patients (P = 0.045), but no significant diversity differences between HL and non-HL patients overall. CONCLUSIONS: We were not able to identify a unique pathogenic urinary microbiota that differentiates all HL from all non-HL IC/BPS. It is likely that the male-specific differences resulted from colonization/contamination remote from the bladder. We were not able to show that bacteria play an important role in patients with HL IC/BPS.

Bladder infection with uropathogenic Escherichia coli increases the excitability of afferent neurons.

Urinary tract infections (UTIs) cause bladder hyperactivity and pelvic pain, but the underlying causes of these symptoms remain unknown. We investigated whether afferent sensitization contributes to the bladder overactivity and pain observed in mice suffering from experimentally induced bacterial cystitis. Inoculation of mouse bladders with the uropathogenic Escherichia coli strain UTI89 caused pelvic allodynia, increased voiding frequency, and prompted an acute inflammatory process marked by leukocytic infiltration and edema of the mucosa. Compared with controls, isolated bladder sensory neurons from UTI-treated mice exhibited a depolarized resting membrane potential, lower action potential threshold and rheobase, and increased firing in response to suprathreshold stimulation. To determine whether bacterial virulence factors can contribute to the sensitization of bladder afferents, neurons isolated from naïve mice were incubated with supernatants collected from bacterial cultures with or depleted of lipopolysaccharide (LPS). Supernatants containing LPS prompted the sensitization of bladder sensory neurons with both tetrodotoxin (TTX)-resistant and TTX-sensitive action potentials. However, bladder sensory neurons with TTX-sensitive action potentials were not affected by bacterial supernatants depleted of LPS. Unexpectedly, ultrapure LPS increased the excitability only of bladder sensory neurons with TTX-resistant action potentials, but the supplementation of supernatants depleted of LPS with ultrapure LPS resulted in the sensitization of both population of bladder sensory neurons. In summary, the results of our study indicate that multiple virulence factors released from UTI89 act on bladder sensory neurons to prompt their sensitization. These sensitized bladder sensory neurons mediate, at least in part, the bladder hyperactivity and pelvic pain seen in mice inoculated with UTI89.NEW & NOTEWORTHY Urinary tract infection (UTI) produced by uropathogenic Escherichia coli (UPEC) promotes sensitization of bladder afferent sensory neurons with tetrodotoxin-resistant and tetrodotoxin-sensitive action potentials. Lipopolysaccharide and other virulence factors produced by UPEC contribute to the sensitization of bladder afferents in UTI. In conclusion, sensitized afferents contribute to the voiding symptoms and pelvic pain present in mice bladder inoculated with UPEC.

Cultivable Bacteria in Urine of Women With Interstitial Cystitis: (Not) What We Expected.

OBJECTIVE: Multiple studies show cultivatable bacteria in urine of most women. The existence of these bacteria challenges interstitial cystitis (IC)/painful bladder syndrome (PBS) diagnosis, which presumes a sterile bladder. The aims of this study were (1) to compare the female bladder microbiomes in women with IC/PBS and unaffected controls and (2) to correlate baseline bladder microbiome composition with symptoms. METHODS: This cross-sectional study enrolled 49 IC/PBS and 40 controls. All provided catheterized urine samples and completed validated questionnaires. A subset of the IC/PBS cohort provided voided and catheterized urine samples. All samples from both cohorts were assessed by the expanded quantitative urine culture (EQUC) protocol; a subset was assessed by 16S rRNA gene sequencing. RESULTS: Of the IC/PBS cohort, 49.0% (24/49) were EQUC positive; in these EQUC-positive samples, the most common urotypes were Lactobacillus (45.8%) and Streptococcus (33.3%). Of the controls, 40.0% were EQUC positive; of these EQUC-positive samples, the most common urotype was Lactobacillus (50.0%). The urotype distribution was significantly different (P < 0.05), as 16% of the IC/PBS cohort, but 0% of controls, were Streptococcus urotype (P < 0.01). Symptom-free IC/PBS participants were less likely to be EQUC positive (12.5%) than IC/PBS participants with moderate or severe symptoms (68.8% and 46.2%) and the control cohort (60%; P < 0.05). CONCLUSION: Lactobacillus was the most common urotype. However, the presence of Lactobacillus did not differ between cohorts, and it did not impact IC/PBS symptom severity. Bacteria were not isolated from most participants with active IC/PBS symptoms. These findings suggest that bacteria may not be an etiology for IC/PBS.

Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infection and the potential role of the urinary microbiome.

Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections carry significant burden for those affected. As women enter the menopause, other factors may influence how these conditions manifest. The urinary microbiome has shown that the urine contains extensive numbers of bacteria. There is some evidence to suggest that it is altered depending on the menopausal state of the individual. It is possible that this alteration may go on to influence how the disease course of interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections runs in the post-menopausal group. The review will explore these two conditions and the potential role of the urinary microbiome.

Urinary microbiome in uncomplicated and interstitial cystitis: is there any similarity?

PURPOSE: Acute/uncomplicated cystitis is the most common bacterial infection causing inflammation in the bladder tissues and predominantly diagnosed in women. Interstitial cystitis may too, cause inflammation in the bladder but its etiology has been elusive. Even though the site and symptoms of both diseases are largely shared, state of the urinary microbiome in these disorders have not been comparatively evaluated before. The purpose of this review is to assess and qualitatively compare structure and composition of the urinary microbiome in acute/uncomplicated cystitis and interstitial cystitis. METHODS AND RESULTS: The available literature in MEDLINE are extensively searched using keywords and screened. Pertinent evidence is carefully assessed and synthesized. We included the original studies with a cohort of medically stable, non-pregnant women with otherwise functionally normal urinary tract and excluded the original articles if the infection in a patient's cohort is accompanied by urinary syndromes such as incontinence and overactive bladder syndrome. A total of six original papers reporting on the urinary microbiome in acute cystitis and nine papers on the interstitial cystitis met the selection criteria. CONCLUSION: The evidence we have gleaned from the literature on the urinary microbiome associated with the acute and interstitial cystitis does not point to convergence of microbiome similarities between the two diseases. More studies with direct sampling of the bladder tissues besides sampling bladder surfaces are warranted for accurate comparison of microbiome similarity between the two conditions. The future research on interstitial cystitis microbiome should include stratified cohorts with prospective design.

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

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

A new look at the etiology of interstitial cystitis/bladder pain syndrome: extraordinary cultivations.

PURPOSE: So far, studies have not clearly identified infectious agents as an etiological factor for interstitial cystitis (IC). Specific microbiological diagnosis for detecting the pathogen with higher sensitivity in IC may decrease the treatment costs and increase psychosocial health of the patients. METHODS: A prospective clinical study was performed in 26 IC patients and 20 controls between April and September 2017. All participants were asked to give mid-stream urine sample for routine urine cultures. Followed by the negative results, symptomatic 26 patients were evaluated for L-form pathogen existence by extraordinary cultivation methods. Biopsy samples were taken from 19 patients with ulcerative lesions in the bladder while collecting sterile urine samples from all 26 patients. PG broth, 5% sheep blood agar, EMB, Sabouraud's dextrose, LEM, and GYPA were used. Followed by the 1st day inoculations, all inoculated PG broths were subcultured into the same solid media at the 2nd and 10th days in case of any growth after incubation of 24 h under 35-37 °C. The "O'Leary Sant Symptom and Problem Index" score forms were used to evaluate response to the appropriate treatment for those patients with documented pathogens. RESULTS: Bacterial isolations were yielded from samples of 13 IC patients in PG broth. Eight (61.5%) P. aeruginosa, 2 (15.4%) K. pneumoniae, 2 (15.4%) C. mucifaciens, and 1 (7.7%) E. faecalis were isolated. Antibiotic susceptibility tests were performed. Somehow, the median symptom index and problem scores of those 13 IC patients were lower after the appropriate antibiotic treatment (p < 0.05). CONCLUSIONS: Extraordinary mediums with longer incubation periods may reveal a causative pathogen in the etiology of IC. Future culture techniques may have some value, because still some of IC/BPS patients are describing symptomatic relief by a group of antibiotics.

Female lower urinary tract microbiota do not associate with IC/PBS symptoms: a case-controlled study.

INTRODUCTION AND HYPOTHESIS: The current etiology of interstitial cystitis/painful bladder syndrome (IC/PBS) is poorly understood and multifactorial. Recent studies suggest the female urinary microbiota (FUM) contribute to IC/PBS symptoms. This study was designed to determine if the FUM, analyzed using mid-stream voided urine samples, differs between IC/PBS patients and controls. METHODS: This prospective case-controlled study compared the voided FUM of women with symptoms of urinary frequency, urgency, and bladder pain for > 6 months with the voided FUM of healthy female controls without pain. Bacterial identification was performed using 16S rRNA gene sequencing and EQUC, a validated enhanced urine culture approach. Urotype was defined by a genus present at > 50% relative abundance. If no genus was present above this threshold, the urotype was classified as 'mixed.' Group comparisons were performed for urotype and diversity measures. RESULTS: A mid-stream voided specimen was collected from 21 IC/PBS patients and 20 asymptomatic controls. The two groups had similar demographics. Urotypes did not differ between cohorts as assessed by either EQUC or 16S rRNA gene sequencing. We detected no significant differences between cohorts by alpha diversity. Cohorts also were not distinct using principle component analysis or hierarchical clustering. Detection by EQUC of bacterial species considered uropathogenic was high in both cohorts, but detection of these uropathogenic species did not differ between groups (p = 0.10). CONCLUSIONS: Enhanced culture and DNA sequencing methods provide evidence that IC/PBS symptoms may not be related to differences in the FUM, at least not its bacterial components. Future larger studies are needed to confirm this preliminary finding.

The Vaginal and Urinary Microbiomes in Premenopausal Women With Interstitial Cystitis/Bladder Pain Syndrome as Compared to Unaffected Controls: A Pilot Cross-Sectional Study.

Interstitial cystitis/bladder pain syndrome (ICBPS) may be related to an altered genitourinary microbiome. Our aim was to compare the vaginal and urinary microbiomes between premenopausal women with ICBPS and unaffected controls. This cross-sectional study screened premenopausal women with an O'Leary-Sant questionnaire (ICBPS if score ≥6 on either index; controls <6 on both). Women completed questionnaires on health characteristics, pelvic floor symptoms (OABq, PFDI-20), body image (mBIS), and sexual function (PISQ-IR). Bacterial genomic DNA was isolated from vaginal and clean-catch urinary specimens; the bacterial 16 rRNA gene was sequenced and analyzed using the QIIME pipeline. We performed UniFrac analysis (ß-diversity) and generated Chao1 estimator (richness) and Simpson index (richness and evenness) values. We analyzed 23 ICBPS and 18 non-ICBPS patients. ICBPS patients had increased vaginal deliveries, BMI, and public insurance as well as worsened OAB-q, PFDI-20, mBIS, and PISQ-IR domain scores. Lactobacilli was the most abundant genus in both cohorts, and anaerobic or fastidious predominance was similar between groups (p = 0.99). For both the urine and vagina specimens, Chao1 and Simpson indices were similar between ICBPS and unaffected women. Weighted and unweighted UniFrac analyses showed no differences between groups. A significant correlation existed between the urinary and vaginal Simpson indices in ICBPS women, but not in unaffected women. Premenopausal women with ICBPS, despite worsened socioeconomic indicators and pelvic floor function, were not found to have significantly different urinary and vaginal microbiomes compared to women without ICBPS.

The Urinary Tract Microbiome: The Answer to All Our Open Questions?

CONTEXT: The dogma of a sterile urinary tract persisted for over a century. With the advances in new high-throughput sequencing technologies and modified culture protocols for microbiome research, we have discovered a variable microbial spectrum in the urinary tract. Its relevance for health and disease is now under investigation. OBJECTIVE: To present the latest insights into the role of the urinary tract microbiome in functional disorders. EVIDENCE ACQUISITION: Medline, PubMed, the Cochrane database, and Embase were screened for randomised controlled trials, clinical trials, and reviews on the urinary tract microbiome. EVIDENCE SYNTHESIS: The urinary tract is not sterile. Every individual harbours a complex microbial network in the urinary tract that is exposed to internal and external factors. Any imbalance in this network is likely to contribute to the development of lower urinary tract symptoms. Functional disorders such as interstitial cystitis, urinary urge incontinence, and chronic prostatitis/chronic pelvic pain syndrome, none of which include a bacterial origin for diagnosis, show features of an altered microbiome with specific dominating urotypes in contrast to urine from asymptomatic healthy individuals. The growing insights into the impact of the urinary microbiome on these entities may help in gaining a deeper understanding of the condition and may provide guidance for optimised management. CONCLUSIONS: The urinary tract is not sterile. The discovery of the urinary microbiome suggests that any imbalance may have a relevant role in the development of symptoms in functional disorders. PATIENT SUMMARY: The urinary tract is naturally colonised with a specific microbial spectrum for which impairment may cause bothersome symptoms.

Assessment of the Lower Urinary Tract Microbiota during Symptom Flare in Women with Urologic Chronic Pelvic Pain Syndrome: A MAPP Network Study.

PURPOSE: We compared culture independent assessment of microbiota of the lower urinary tract in standard culture negative female patients with urological chronic pelvic pain syndrome who reported symptom flare vs those who did not report a flare. MATERIALS AND METHODS: Initial stream (VB1) and midstream (VB2) urine specimens (233 patients with urological chronic pelvic pain syndrome) were analyzed with Ibis T-5000 Universal Biosensor system technology for comprehensive identification of microorganism species. Differences between flare and nonflare groups for presence or number of different species within a higher level group (richness) were examined by permutational multivariate analysis of variance and logistic regression. RESULTS: Overall 81 species (35 genera) were detected in VB1 and 73 (33) in VB2. Mean (SD) VB1 and VB2 species count per person was 2.6 (1.5) and 2.4 (1.5) for 86 flare cases and 2.8 (1.3) and 2.5 (1.5) for 127 nonflare cases, respectively. Overall the species composition did not significantly differ between flare and nonflare cases at any level (p=0.14 species, p=0.95 genus in VB1 and VB2, respectively) in multivariate analysis for richness. Univariate analysis, unadjusted as well as adjusted, confirmed a significantly greater prevalence of fungi (Candida and Saccharomyces) in the flare group (15.7%) compared to the nonflare group in VB2 (3.9%) (p=0.01). When adjusted for antibiotic use and menstrual phase, women who reported a flare remained more likely to have fungi present in VB2 specimens (OR 8.3, CI 1.7-39.4). CONCLUSIONS: Among women with urological chronic pelvic pain syndrome the prevalence of fungi (Candida and Saccharomyces sp.) was significantly greater in those who reported a flare compared to those who did not.

[About the causes of inveterate cystitis in young women].

16 female patients,aged 28.6 +/- 3.2 years, with recrudescent inveterate cystitis were examined for the purpose of improvement of treatment of chronic cystitis. The examined patients noted relapse of disease after sex intercourse. Spectrum of diagnosed uropathogens in female patients corresponds to the structure of bacterio from urina taken after prostate milking and prostatic fluid of patients' intercourse partners. The given uropathogens also corresponds to the structure of contagium of urinary tract in young men. Connection between urogenital biotope and biotope of prostate as a vessel of persistence infection is related. Recrudescent inveterate cystitis in young women may be result from latent inveterate bacteritic prostatitis in their intercourse partners. Effectiveness of treatment and prophylaxis of recrudescence of inveterate cystitis in young women depends on timely diagnostics, treatment, and prophylaxis of inveterate bacteritic prostatitis in their intercourse partners.

Alterations of microbiota in urine from women with interstitial cystitis.

BACKGROUND: Interstitial Cystitis (IC) is a chronic inflammatory condition of the bladder with unknown etiology. The aim of this study was to characterize the microbial community present in the urine from IC female patients by 454 high throughput sequencing of the 16S variable regions V1V2 and V6. The taxonomical composition, richness and diversity of the IC microbiota were determined and compared to the microbial profile of asymptomatic healthy female (HF) urine. RESULTS: The composition and distribution of bacterial sequences differed between the urine microbiota of IC patients and HFs. Reduced sequence richness and diversity were found in IC patient urine, and a significant difference in the community structure of IC urine in relation to HF urine was observed. More than 90% of the IC sequence reads were identified as belonging to the bacterial genus Lactobacillus, a marked increase compared to 60% in HF urine. CONCLUSION: The 16S rDNA sequence data demonstrates a shift in the composition of the bacterial community in IC urine. The reduced microbial diversity and richness is accompanied by a higher abundance of the bacterial genus Lactobacillus, compared to HF urine. This study demonstrates that high throughput sequencing analysis of urine microbiota in IC patients is a powerful tool towards a better understanding of this enigmatic disease.

Evidence of bladder oversensitivity in the absence of an infection in premenopausal women with a history of recurrent urinary tract infections.

UNLABELLED: Study Type - Prevalence (case control) Level of Evidence 4. What's known on the subject? and What does the study add? Urinary tract infections (UTIs) have been implicated in the aetiology of interstitial cystitis/painful bladder syndrome (IC/PBS). Prior studies have described symptoms and laboratory tests suggestive of UTI at the onset of IC/PBS as well as a significant history of childhood recurrent UTIs. However, the mechanism by which recurrent UTIs contribute to the development of IC/PBS is not clear. Our study shows that women with recurrent UTI suffer from bladder oversensitivity. Our findings have useful clinical implications. Women with bladder oversensitivity complain of urinary frequency which is often misdiagnosed as an infection and treated with unnecessary antibiotics. Additionally, there are no effective therapies for bladder oversensitivity. Therefore, women with recurrent UTI should undergo prompt evaluation and treatment of episodes of infection to prevent the development of bladder oversensitivity. Our findings also provide a possible mechanism for the development of IC/PBS. Whether women with recurrent UTI are at increased risk for developing IC/PBS in the future will need to be confirmed in future studies. OBJECTIVE: • To compare the mean voided volume and bladder sensation during filling cystometry in women with a history of recurrent urinary tract infection (UTI) and controls. PATIENTS AND METHODS: • This was a case-control study including adult women seen in the urogynaecology clinic. • The cases were 49 women with at least three documented positive urine cultures >105 colonies/mL in the previous 12 months and no active infection at the time of data collection. • Controls were 53 women with stress urinary incontinence and no history of recurrent UTI or coexistent urge urinary incontinence. • We compared bladder diary variables and filling cystometry data in the absence of an active infection. RESULTS: • There was no significant difference in the median age, parity and body mass index of women with a history of recurrent UTI and controls. • The median number of voids per day and median number of voids per litre of fluid intake was significantly greater in women with recurrent UTI than controls (12 vs 7 voids/day and 6 vs 4 voids/L, P= 0.005 and P= 0.004 respectively). • The median average voided volume was significantly lower in women with recurrent UTI than controls (155 vs 195 mL, P= 0.008). • On filling cystometry, median volumes of strong desire to void and maximum cystometric capacity were significantly lower in women with recurrent UTI than controls (all P < 0.05). CONCLUSION: • In the absence of an infection, premenopausal women with a history of recurrent UTI have significantly greater urinary frequency, lower average voided volume and a lower threshold of bladder sensitivity than controls.

[Bacterial mixed infection in women with chronic recurrent cystitis].

AIM: To study microbial repertoire of urine in healthy women and patients with chronic recurrent cystitis (CRC) including facultative anaerobic (FA) and non-clostridial anaerobic (NCA) bacteria. MATERIALS AND METHODS. Triple bacteriological study of urine was performed in three groups of women: group I--22 healthy virgin women aged 18- 25 years, group II--24 women aged 18 - 25 years with regular sexual contacts, group III--72 women aged 20 - 60 years with CRC, before antibacterial therapy. Bacteriological method was used to study qualitative and quantitative composition of urine microflora. RESULTS: In all subjects from groups I and II aerobic-anaerobic associations with predomination of coagulase-negative staphylococci (CNS), corynebacteria, peptococci, and peptostreptococci were isolated from urine. Quantity of isolated NCA bacteria was significantly higher than that of FA. In etiologic structure of CRC, NCA bacteria, enterobacteria, and CNS predominated. Spectrum of NCA bacteria isolated from patients with CRC was wider and level of bacteriuria--higher (p < 0.05) compared to groups I and II. Bacteria were identified in aerobic-anaerobic associations. In 85.7% of cases following NCA were identified in biopsy samples: Propionibacterium sp. (41.8%), Peptococcus sp. (35.7%), Eubacterium sp. (28.6%), Peptostreptococcus sp. (14.3%), and Bacteroides sp. (14.3%). Aerobic-anaerobic associations were observed in 7.1% of samples. CONCLUSION: Urine of healthy women is not sterile. Aerobic-anaerobic mixed infections were detected in patients with CRC that should take into account during diagnostics and treatment of this disease.

The natural history of urinary tract infection in women.

Many women who suffer from the symptoms of urinary tract infection have a negative urine culture when conventional methods are used. Their condition is described as 'urethral' (or 'dysuria/frequency') syndrome' (US). As they may be indistinguishable clinically from those with positive cultures antibiotics are often prescribed. Their symptoms are usually recurrent and they may receive many courses of treatment. Some women are said to have 'interstitial cystitis' (IC); they have a long history of symptoms and antibacterial treatment. The urine contains white blood cells (pyuria) and biopsy of the bladder wall shows the histological changes of chronic inflammation. Additional culture techniques applied to urine from these two groups of patients consistently yield bacteria, most commonly lactobacilli in those with US. From the urine of women with IC, lactobacilli and some other 'fastidious' bacteria are isolated from catheter specimens and also from bladder wall biopsies. These bacteria are known to be constituents of the mixed commensal flora of the distal one-third of the urethra. It is proposed that these two syndromes are different stages in the natural history of UTI, and that antibacterial agents, by selection of resistant bacteria in the urethral commensal flora, are an important aetiological factor. It is possible that these bacteria may invade the paraurethral glands via their ducts - a situation analogous to invasion of the prostate in men. There is a considerable body of evidence supporting this hypothesis, but as it all emanates from one centre it needs to be confirmed elsewhere. Acceptance would bring great clinical benefit and considerable financial savings. A laboratory protocol which requires only small additional expenditure, and a clinical management regimen are proposed. At present, much antibacterial treatment is prescribed and many patients undergo radiological and invasive investigations such as cystoscopy and urethral dilatation, the latter incurring the risk of post-instrumentation UTI. There is evidence that 'US' responds gradually if antibiotics are withheld. 'IC' is a more difficult problem because bacteria may have invaded the bladder wall. Carefully targeted antibacterial treatment given for at least 10-14 days might be effective, but there are no data on this. Rational management of 'US' might prevent the development of 'IC'. A recent thorough review of published work on this condition states that the aetiology is still unknown. It appears, however, that no attempt has been made in any recent studies to use urine culture techniques capable of detecting bacteria other than the recognised aerobic pathogens.

Decreased nanobacteria levels and symptoms of nanobacteria-associated interstitial cystitis/painful bladder syndrome after tetracycline treatment.

INTRODUCTION AND HYPOTHESIS: This study was designed to detect whether nanobacteria (NB) reside in urine and bladder tissue samples of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) and whether antibiotic therapy targeting these organisms is effective in reducing NB levels and IC/PBS symptoms. METHODS: Twenty-seven IC/PBS patients underwent cystoscopy. Bladder biopsies and urine samples were obtained and cultured for NB, which were identified by indirect immunofluorescent staining and transmission electron microscopy. RESULTS: Eleven bladder samples showed growth of microbes that were identified to be similar to NB. Homologous study of the 16S ribosomal RNA gene suggested that the NB could be the pathogen. For enrolled 11 patients, NB levels decreased dramatically after tetracycline treatment, and they reported significant reduction in the severity of IC/PBS symptoms. CONCLUSIONS: A high prevalence of NB was observed in female IC/PBS, and anti-NB treatment effectively improved the symptoms, which suggest that NB may cause some cases of IC/PBS.

The painful bladder: urinary tract infection and interstitial cystitis in women.

Irritative voiding symptoms in women are most often due to uncomplicated urinary tract infection. A cost-effective approach to the treatment of urinary tract infections is a reasonable first step. However, in patients who have persistent or frequently recurrent symptoms, a more thorough evaluation is warranted. These women may be found to have interstitial cystitis, requiring further evaluation. While interstitial cystitis remains a difficult disease to treat, a multi-modality therapy provides excellent symptom relief.

Interstitial cystitis and infectious agents.

Interstitial cystitis (IC) is a syndrome consisting of severe refractory bladder symptoms of unknown etiology. The disease tends to affect Caucasian women with a mean age of 40 years, with 25% of patients under the age of 30. Few population based epidemiological studies of IC have been performed. We analyzed a case of interstitial cystitis in a 42-year-old non-smoker woman. In two biopsy samples the presence of viral DNA of human polyomavirus BK (BKV), human herpes virus type 1 and type 2 (HHV- 1 and HHV-2), adenovirus, human papillomavirus (HPV) and bacterial DNA (Chlamydia trachomatis and Mycoplasma genitalium) were evaluated by means of polymerase chain reaction (PCR). Both samples resulted positive only for BKV and HPV DNA. HPV genotyping revealed the presence of HPV-66 that is associated with a high risk of cancer development. Thus the finding of a viral co-infection could support the hypothesis of the multi-factorial origin of this pathology.