Urinary Microbiota Research Articles

Microbiota in 2016: Associating infection and incontinence with the female urinary microbiota.

The discovery and confirmation of the female urinary microbiota in 2012 provided opportunities to improve insight into lower urinary tract disorders in women, including UTI and urgency urinary incontinence. Now, research in 2016 has shown that expanded culture techniques enable improved uropathogen detection and confirm that bacteria detected by culture-independent methods are alive.

The female urinary microbiota, urinary health and common urinary disorders.

This review provides the clinical context and updated information regarding the female urinary microbiota (FUM), a resident microbial community within the female bladder of many adult women. Microbial communities have variability and distinct characteristics in health, as well as during community disruption (dysbiosis). Information concerning characteristics of the FUM in health and disease is emerging. Sufficient data confirms that the microbes that compose the FUM are not contaminants and are cultivatable under appropriate conditions. Common clinical conditions, including urinary tract infection (UTI) and urgency urinary incontinence (UUI), a common form of urinary incontinence (UI), may be usefully reconsidered to determine the role of the FUM. Knowledge of FUM characteristics may help advance prevention, diagnosis and treatment of these conditions and other common lower urinary disorders in women. The FUM appears related to UTI and UUI in adult women. The specific role of the FUM remains to be clarified and requires significant additional work in describing FUM variability and resilience in health. Unique aspects of the FUM prompt re-evaluation of existing nomenclature to more appropriately define health and disease; the concept of dysbiosis may be useful for understanding the interaction of the FUM with other aspects of lower urinary tract physiology, including urothelial signaling. Clinicians, through their clinical laboratories, can adopt enhanced urine culture techniques that more fully describe the living microbes within the FUM. This additional information may provide clinicians and their patients an opportunity to impact clinical care without antibiotic use, if the FUM can be appropriately modified to improve treatment precision for UTI and UUI.

Dysbiosis of urinary microbiota is positively correlated with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) may be associated with altered urinary microbiota in female patients. We investigated alterations of urinary microbiota in Chinese female T2DM patients, and explored the associations between urinary microbiota and a patient’s fasting blood glucose (FBG), urine glucose (UGLU), age, menstrual status, and body mass index (BMI). Midstream urine was collected from 70 female T2DM patients and 70 healthy females. Microbial diversity and composition were analyzed using the Illumina MiSeq sequencing platform by targeting the hypervariable V3-V4 regions of the 16S rRNA gene. We found that bacterial diversity was decreased in T2DM patients. Increased Actinobacteria phylum was positively correlated with FBG, UGLU, and BMI; Lactobacillus abundance decreased with age and menopause; and increased Lactobacillus correlated positively with FBG and UGLU. Decreased Akkermansia muciniphila was associated with FBG and UGLU. Escherichia coli abundance did not differ between the two cohorts. Carbohydrate and amino acid metabolism was reduced in T2DM patients, which were associated with bacterial richness indices such as Chao1 and ACE. Detailed microbiota analysis of well-characterized T2DM patients and healthy controls indicate that Chinese T2DM female patients exhibit dysbiosis of urinary microbiota.

Draft Genome Sequence of a Urinary Isolate of Lactobacillus crispatus.

While Lactobacillus crispatus contributes to the stability of normal vaginal microbiota, its role in urinary health remains unclear. As part of an on-going attempt to characterize the female urinary microbiota, we report the genome sequence of an L. crispatus strain isolated from a woman displaying no lower urinary tract symptoms.

Seven Bacteriophages Isolated from the Female Urinary Microbiota.

Recent research has debunked the myth that urine is sterile, having uncovered bacteria within the bladders of healthy individuals. However, the identity, diversity, and putative roles of bacteriophages in the bladder are unknown. We report the draft genome sequences of seven bacteriophages isolated from microbial communities from adult female bladders.

Rosalind Mary Maskell

“The work of Rosalind Maskell is unknown to many; yet, clearly ahead of her time, she performed scientifically rigorous studies that provided compelling evidence to disprove the dogma that urine...

The urinary microbiota: a paradigm shift for bladder disorders?

A resident microbial community [the female urinary microbiota (FUM)] exists within the female bladder of many adult women. Information about the FUM is likely to modify the diagnosis, prevention and treatment of adult women with urinary disorders. This review highlights key findings from recent literature relevant to adult, nonpregnant women. Similar to other human microbial communities, the FUM varies in its characteristics, including organism diversity and predominant organism identity. Recent literature reveals previously undetected organisms and community characteristics that appear associated with certain urinary symptoms, including urinary tract infection and urgency urinary incontinence. The role of individual organisms may range from beneficial to pathogenic and may vary on the basis of an individual's FUM characteristics. The simple dichotomy of 'infected' or 'sterile' no longer sufficiently captures the microbiological complexity of the female bladder. Deeper understanding of the FUM should yield better methods to restore the microbiota to a healthy state, providing symptom relief. Opportunities to modify the FUM without antibiotic use are exciting possibilities for future research; stand-alone antibiotic use may be reevaluated to improve treatment precision. Long-standing nomenclature for conditions such as asymptomatic bacteriuria and urinary tract infection will likely require modification.

Urinary incontinence: Making sense of the urinary microbiota in clinical urology.

Some urologists might be surprised that the urinary tract is not sterile, and bacteria might have important roles in a number of urological conditions such as urge incontinence. This paradigm shift, which has been further illustrated by data from a recent study, has implications for how urologists diagnose disease and treat patients.

Urinary Microbiota Associated with Preterm Birth: Results from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study.

Preterm birth (PTB) is the leading cause of infant morbidity and mortality. Genitourinary infection is implicated in the initiation of spontaneous PTB; however, examination of the urinary microbiota in relation to preterm delivery using next-generation sequencing technologies is lacking. In a case-control study nested within the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study, we examined associations between the urinary microbiota and PTB. A total of 49 cases (delivery < 37 weeks gestation) and 48 controls (delivery ≥ 37 weeks gestation) balanced on health insurance type were included in the present analysis. Illumina sequencing of the 16S rRNA gene V4 region was performed on urine samples collected during the second trimester. We observed no difference in taxa richness, evenness, or community composition between cases and controls or for gestational age modeled as a continuous variable. Operational taxonomic units (OTUs) classified to Prevotella, Sutterella, L. iners, Blautia, Kocuria, Lachnospiraceae, and S.marcescens were enriched among cases (FDR corrected p≤ 0.05). A urinary microbiota clustering partition dominated by S. marcescens was also associated with PTB (OR = 3.97, 95% CI: 1.19–13.24). These data suggest a limited role for the urinary microbiota in PTB when measured during the second trimester by 16S rRNA gene sequencing. The enrichment among cases in several organisms previously reported to be associated with genitourinary pathology requires confirmation in future studies to rule out the potential for false positive findings.

Urinary microbiome of kidney transplant patients reveals dysbiosis with potential for antibiotic resistance

Recent studies have established that a complex community of microbes colonize the human urinary tract; however, their role in kidney transplant patients treated with prophylactic antibiotics remains poorly investigated. Our aim was to investigate the urinary microbiome of kidney transplant recipients. Urine samples from 21 patients after kidney transplantation and 8 healthy controls were collected. All patients received prophylactic treatment with the antibiotic combination trimethoprim-sulfamethoxazole. Metagenomic DNA was isolated from urine samples, sequenced using shotgun sequencing approach on Illumina HiSeq 2000 platform, and analyzed for microbial taxonomic and functional annotations. Our results demonstrate that the urine microbiome of kidney transplants was markedly different at all taxonomic levels from phyla to species, had decreased microbial diversity, and increased abundance of potentially pathogenic species compared with healthy controls. Specifically, at the phylum level, we detected a significant decrease in Actinobacteria and increase in Firmicutes due to increases in Enterococcus faecalis. In addition, there was an increase in the Proteobacteria due to increases in Escherichia coli. Analysis of predicted functions of the urinary metagenome revealed increased abundance of enzymes in the folate pathway including dihydrofolate synthase that are not inhibited by trimethoprim-sulfamethoxazole, but can augment folate metabolism. This report characterizes the urinary microbiome of kidney transplants using shotgun metagenomics approach. Our results indicate that the urinary microbiota may be modified in the context of prophylactic antibiotics, indicating that a therapeutic intervention may shift the urinary microbiota to select bacterial species with increased resistance to antibiotics. The evaluation and development of optimal prophylactic regimens that do not promote antibiotic resistance is an important future goal.

Comprehensive Molecular Characterization of Bacterial Communities in Feces of Pet Birds Using 16S Marker Sequencing.

Birds and other animals live and evolve in close contact with millions of microorganisms (microbiota). While the avian microbiota has been well characterized in domestic poultry, the microbiota of other bird species has been less investigated. The aim of this study was to describe the fecal bacterial communities of pet birds. Pooled fecal samples from 22 flocks representing over 150 individual birds of three different species (Melopsittacus undulatus or budgerigars, Nymphicus hollandicus or cockatiels, and Serinus canaria or domestic canaries) were used for analysis using the 16S rRNA gene sequencing in the MiSeq platform (Illumina). Firmicutes was the most abundant phylum (median 88.4%; range 12.9-98.4%) followed by other low-abundant phyla such as Proteobacteria (median 2.3%; 0.1-85.3%) and Actinobacteria (median 1.7%; 0-18.3%). Lactobacillaceae (mostly Lactobacillus spp.) was the most abundant family (median 78.1%; 1.4-97.5%), especially in budgerigars and canaries, and it deserves attention because of the ascribed beneficial properties of lactic acid bacteria. Importantly, feces from birds contain intestinal, urinary, and reproductive-associated microbiota thus posing a serious problem to study one anatomical region at a time. Other groups of interest include the family Clostridiaceae that showed very low abundance (overall median <0.1%) with the exception of two samples from cockatiels (14 and 45.9%) and one sample from budgerigars (19.9%). Analysis of UniFrac metrics showed that overall, the microbial communities from the 22 flocks tended to cluster together for each bird species, meaning each species shed distinctive bacterial communities in feces. This descriptive analysis provides insight into the fecal microbiota of pet birds.

Evaluation of the urinary microbiota of women with uncomplicated stress urinary incontinence

Female urinary microbiota are associated with urgency urinary incontinence and response to medication. The urinary microbiota of women with stress urinary incontinence has not been described. We sought to study the cross-sectional relationships between urinary microbiota features and demographic and clinical characteristics of women undergoing stress urinary incontinence surgery. Preoperative urine specimens were collected from women without urinary tract infection and were available from 197 women (174 voided, 23 catheterized) enrolled in a multicenter prospective randomized trial, the Value of Urodynamic Evaluation study. Demographic and clinical variables were obtained including stress and urgency urinary incontinence symptoms, menopausal status, and hormone use. The bacterial composition of the urine was qualitatively assessed by sequencing the bacterial 16S ribosomal RNA gene. Phylogenetic relatedness and microbial alpha diversity were compared to demographics and symptoms using generalized estimating equation models. The majority of 197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was significantly associated with higher body mass index (P= .02); increased Medical, Epidemiologic, and Social Aspects of Aging urge index score (P= .04); and hormonal status (P < .001). No associations were detected with stress urinary incontinence symptoms. Increased diversity was also associated with a concomitant lower frequency of Lactobacillus in hormone-negative women. Women undergoing stress urinary incontinence surgery have detectable urinary microbiota. This cross-sectional analysis revealed that increased diversity of the microbiota was associated with urgency urinary incontinence symptoms, hormonal status, and body mass index. In contrast, the female urinary microbiota were not associated with stress urinary incontinence symptoms.

The New World of the Urinary Microbiota in Women

Obstet Gynecol Surv 2016;71(3):151–153 The objective of this clinical opinion is to describe the limitations of current tests used to detect bacteria in the female urinary tract and inform practicing clinicians about emerging new techniques that can identify previously undetected organisms in the bladder. The authors describe the new techniques for assessment of urinary bacterial content and explain how their use has major implications for diagnosis and treatment of many urinary and other disorders.

The human urinary microbiome and how it relates to urogynecology.

Recent studies applying molecular techniques have demonstrated the presence of a urinary microbiota not detected by standard microbiological techniques. These have been found in the urine of healthy individuals and in those suffering from clinical symptoms. The present article reviews the findings of these studies to date, describing the molecular techniques, and specifically outlining any differences in microbiomes in relation to urogynecological disease. Further, the role of commensal bacteria in the lower urinary tract is considered. An extensive literature search was conducted to identify articles on the microbiome of the female urinary tract in health and disease. We searched the electronic meta-databases Ovid MEDLINE® 1946-2015 and Embase 1974-2015. The keywords "microbiome, microbiota, bacterial colonization, microbiology, commensal bacteria, and bacteriuria" were searched in combination with "lower urinary tract symptoms, urogenital symptoms, urinary tract infection, overactive bladder and urinary incontinence." A total of 426 papers were retrieved; 33 were included in this paper. The microbiome of the female lower urinary tract shows variance between individuals and between age groups. There are significant differences between the microbiota in the lower urinary tract of individuals with urological symptoms and those without, relating to type and proportion of commensal Lactobacillus spp. There is only weak evidence to suggest that Lactobacillus might be applied as a therapeutic measure. It is still unclear what role microbiota plays in female urinary tract health. The discovery of bacteria in the urine of healthy individuals may have implications for future therapies for lower urinary tract symptoms.

Incontinence medication response relates to the female urinary microbiota.

Many adult women have resident urinary bacteria (urinary microbiome/microbiota). In adult women affected by urinary urgency incontinence (UUI), the etiologic and/or therapeutic role of the urinary microbiome/microbiota remains unknown. We hypothesized that microbiome/microbiota characteristics would relate to clinically relevant treatment response to UUI medication per os. Adult women initiating medication treatment orally for UUI and a comparator group of unaffected women were recruited in a tertiary care health-care system. All participants provided baseline clinical data and urine samples. Women with UUI were given 5mg solifenacin, with potential dose escalation to 10mg for inadequate UUI symptom control at 4weeks. Additional data and urine samples were collected from women with UUI at 4 and 12weeks. The samples were assessed using 16S ribosomal RNA (rRNA) gene sequencing and enhanced quantitative urine culturing. The primary outcome was treatment response as measured by the validated Patient Global Symptom Control (PGSC) questionnaire. Clinically relevant UUI symptom control was defined as a 4 or 5 score on the PGSC. Diversity and composition of the urinary microbiome/microbiota of women with and without UUI differed at baseline. Women with UUI had more bacteria and a more diverse microbiome/microbiota. The clinical response to solifenacin in UUI participants was related to baseline microbiome/microbiota, with responders more likely to have fewer bacteria and a less diverse community at baseline. Nonresponders had a more diverse community that often included bacteria not typically found in responders. Knowledge of an individual's urinary microbiome/microbiota may help refine UUI treatment. Complementary tools, DNA sequencing, and expanded urine culture provide information about bacteria that appear to be related to UUI incontinence status and treatment response in this population of adult women.

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

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. 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. 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 andnonflare 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). 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.

The female urinary microbiome in urgency urinary incontinence

The purpose of this study was to characterize the urinary microbiota in women who are planning treatment for urgency urinary incontinence and to describe clinical associations with urinary symptoms, urinary tract infection, and treatment outcomes. Catheterized urine samples were collected from multisite randomized trial participants who had no clinical evidence of urinary tract infection; 16S ribosomal RNA gene sequencing was used to dichotomize participants as either DNA sequence-positive or sequence-negative. Associations with demographics, urinary symptoms, urinary tract infection risk, and treatment outcomes were determined. In sequence-positive samples, microbiotas were characterized on the basis of their dominant microorganisms. More than one-half (51.1%; 93/182) of the participants' urine samples were sequence-positive. Sequence-positive participants were younger (55.8 vs 61.3 years old; P = .0007), had a higher body mass index (33.7 vs 30.1 kg/m(2); P = .0009), had a higher mean baseline daily urgency urinary incontinence episodes (5.7 vs 4.2 episodes; P < .0001), responded better to treatment (decrease in urgency urinary incontinence episodes, -4.4 vs -3.3; P = .0013), and were less likely to experience urinary tract infection (9% vs 27%; P = .0011). In sequence-positive samples, 8 major bacterial clusters were identified; 7 clusters were dominated not only by a single genus, most commonly Lactobacillus (45%) or Gardnerella (17%), but also by other taxa (25%). The remaining cluster had no dominant genus (13%). DNA sequencing confirmed urinary bacterial DNA in many women with urgency urinary incontinence who had no signs of infection. Sequence status was associated with baseline urgency urinary incontinence episodes, treatment response, and posttreatment urinary tract infection risk.

The new world of the urinary microbiota in women

Emerging evidence challenges the long-held paradigm that the healthy bladder is sterile. These discoveries may provide new opportunities to address important women's health conditions, which include preterm labor and delivery, urinary tract infections, and common forms of urinary incontinence. Traditional tools for urinary bacterial assessment, which includes urinary dipsticks and standard urine cultures, have significant limitations that restrict the information that is available to clinicians. For example, the standard urine culture does not detect slow-growing bacteria that die in the presence of oxygen. Two new, complementary tools, however, can detect these and other organisms, which permits a more complete characterization of bacterial communities within the female bladder. Obstetrician-gynecologists should become familiar with these new approaches (expanded quantitative urine culture and 16S ribosomal RNA gene sequencing) that can detect previously unrecognized organisms. These advances are making it possible to answer previously intractable scientific and clinical questions. Traditional nomenclature used to describe the bacterial status in the bladder is quite dated and unsuited for the emerging information about the bacterial milieu of the female urinary tract. In the context of the sterile bladder paradigm, clinicians have learned about "uropathogens," "asymptomatic bacteriuria," and "urinary tract infection." Given that the lower urinary tract is not sterile, these terms should be reevaluated. Clinicians can already benefit from the emerging knowledge regarding urinary organisms that have previously gone undetected or unappreciated. For example, in some subpopulations of women with urinary symptoms, existing data suggest that the urinary bacterial community may be associated with women's health conditions of interest. This Clinical Opinion highlights the inadequacies of the current tools for urinary bacterial assessment, describes the new assessment tools, explains the current interpretation of the resulting data, and proposes potential clinical uses and relevance. A new world is opening to our view that will give us the opportunity to better understand urinary bacteria and the bladder in which they live. This new knowledge has significant potential to improve patient care in obstetrics and gynecology.

THE DYNAMICS OF THE MICROBIOTA OF URINE IN PATIENTS WITH ACUTE OBSTRUCTIVE PYELONEPHRITIS IN PERIODS OF OBSERVATION.

The dynamics of the microbiota of urine in patients with acute obstructive pyelonephritis in periods of observation. Abstract. Analysis of urine culture in 72 patients with acute obstructive pyelonephritis within 6 months. When hospitalization was performed urine culture before and after the elimination of the upper urinary tract obstruction (VMP). Over the next 5 days the patients received empirical antibiotic therapy until the results of the microbiological examination of urine, after which all patients were divided into two groups. 1 group of patients consisted of 38 people who received antibiotic therapy based on antibiotic susceptibility obschedokazannyh pathogens (E.coli, Proteus sp., Klebsiella sp., Enterococcus sp., Etc.), The 2 group of patients included 34 men treated with antibacterial treatment based antibiotic susceptibility of microorganisms isolated from urine. After the completion of antibiotic therapy, all patients underwent clinical and laboratory and bacteriological monitoring of urine through the 1,3 and 6 months follow-up.

The microbiome of the urinary tract--a role beyond infection.

Urologists rarely need to consider bacteria beyond their role in infectious disease. However, emerging evidence shows that the microorganisms inhabiting many sites of the body, including the urinary tract--which has long been assumed sterile in healthy individuals--might have a role in maintaining urinary health. Studies of the urinary microbiota have identified remarkable differences between healthy populations and those with urologic diseases. Microorganisms at sites distal to the kidney, bladder and urethra are likely to have a profound effect on urologic health, both positive and negative, owing to their metabolic output and other contributions. Connections between the gut microbiota and renal stone formation have already been discovered. In addition, bacteria are also used in the prevention of bladder cancer recurrence. In the future, urologists will need to consider possible influences of the microbiome in diagnosis and treatment of certain urological conditions. New insights might provide an opportunity to predict the risk of developing certain urological diseases and could enable the development of innovative therapeutic strategies.