Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis.

BACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis. METHOD: BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. RESULTS: Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis. CONCLUSION: C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.

A review of urinary bladder microbiome in patients with bladder cancer and its implications in bladder pathogenesis.

PURPOSE: The recent discovery of the urinary microbiome has led to an emerging field of investigation about the potential role of microorganisms in the pathogenesis of urinary bladder cancer. Few preliminary data have been reported so far implicating urobiome as causative and prognostic factor of bladder tumorigenesis. In the present study, a review of the current evidence is presented about microbiome composition among patients with bladder cancer and healthy individuals as well as possible implications of microbiome on urothelial carcinoma of the bladder. METHODS: A literature review was conducted using PubMed/MEDLINE, Scopus, and the Cochrane library until December 2023. Search algorithm was constructed using the following terms and their associated Mesh terms and Boolean operators: "urinary microbiome" and "urinary microbiota". Studies written in English language, identifying, and comparing urinary microbiome among bladder cancer patients and healthy control group were included in the review. RESULTS: A total of 2,356 reports were identified. From this total 16 articles complied with the inclusion criteria were selected for analysis. These articles represent a total of about 486 bladder cancer patients. CONCLUSION: Recent studies revealed the colonization of the urinary tract and the bladder by micro-organisms using both enhanced culture- and molecular-based techniques for microbial characterization. However, several limitations exist in the literature decreasing the reliability of the current reports. As a result, urinary microbiome consist an ambitious era in bladder cancer research with an increasing number of evidence about its potential pathogenetic, prognostic and therapeutic role.

Comparison of the urinary microbiome in men who have sex with men with and without Chlamydia trachomatis infection.

PURPOSE: The urinary tract is colonized by microbial communities that impact urinary health. Previous studies have suggested that the bacterial composition of the male urinary microbiota is related to STIs. This study assessed the bacterial composition of the urinary microbiome in South African MSM with and without C. trachomatis. METHODS: This study used urine samples from MSM attending care at the King Edward VIII hospital and the Aurum Institute in Durban, South Africa. A total of 200 samples were tested for C. trachomatis infection using the Applied Biosystems™ TaqMan® Assays. Urinary microbiomes of 23 samples were characterized using 16 S rRNA (V3 and V4) gene sequencing on the Illumina MiSeq platform. RESULTS: Bacterial taxonomic analysis showed a high abundance of Streptococcus, Corynebacterium, and Staphylococcus in all the sequenced samples. Moreover, Prevotella and Lactobacillus were detected in urine samples of MSM. Alpha diversity metrics showed a slight increase in microbial diversity in C. trachomatis positive samples; however, this was not significant (ANOVA, P > 0.05). Principal coordinates analysis (PCoA) showed that the microbiome of C. trachomatis infected MSM was not clearly different from those uninfected. Distinct bacterial communities were not detected between positive and negative samples (PERMANOVA F1,22= 1.0284, R2 = 0.047%, P = 0.385). CONCLUSION: Most microbiome studies on MSM to date have focused on the gut microenvironment. Few studies, however, have provided data regarding the normal composition of the male urethral microbiomes or if these microbiomes are associated with male STIs. This study adds to the growing body of knowledge highlighting the urinary microbiome in MSM.

Evaluation of the vaginal and urinary microbiota of healthy cycling bitches.

BACKGROUND: While the urogenital microbiota has recently been characterized in healthy male and female dogs, the influence of sex hormones on the urogenital microbiome of bitches is still unknown. A deeper understanding of the cyclic changes in urinary and vaginal microbiota would allow us to compare the bacterial populations in healthy dogs and assess the impact of the microbiome on various urogenital diseases. Therefore, the aim of this study was to characterize and compare the urogenital microbiota during different phases of the estrous cycle in healthy female dogs. DNA extraction, 16 S rDNA library preparation, sequencing and informatic analysis were performed to determine the vaginal and urinary microbiota in 10 healthy beagle dogs at each phase of the estrous cycle. RESULTS: There were no significant differences in alpha and beta diversity of the urinary microbiota across the different cycle phases. Similarly, alpha diversity, richness and evenness of vaginal bacterial populations were not significantly different across the cycle phases. However, there were significant differences in vaginal beta diversity between the different cycle phases, except for between anestrus and diestrus. CONCLUSION: This study strongly suggests that estrogen influences the abundance of the vaginal microbiota in healthy female dogs, but does not appear to affect the urinary microbiome. Furthermore, our data facilitate a deeper understanding of the native urinary and vaginal microbiota in healthy female dogs.

Dysbiosis in Human Urinary Microbiota May Differentiate Patients with a Bladder Cancer.

Recent interest in noninvasive diagnostic approaches has highlighted the potential of urinary microbiota as a novel biomarker for bladder cancer. This study investigated the urinary microbiota of 30 bladder cancer patients and 32 healthy controls using a specific NGS protocol that sequences eight hypervariable regions of the 16S rRNA gene, providing detailed insights into urinary microbiota composition. The relative abundance of microbial compositions in urine samples from cancer patients and healthy controls was analyzed across various taxonomic levels. No notable differences were highlighted at the phylum, class, order, and family levels. At the genus level, 53% of detected genera were represented in either cancer patients or healthy controls. Microbial diversity was significantly lower in cancer patients. The differential analysis identified five genera, Rhodanobacter, Cutibacterium, Alloscardovia, Moryella, and Anaeroglobus, that were significantly more abundant in cancer patients. Notably, Rhodanobacter was present in 20 cancer samples but absent in healthy controls. Conversely, 40 genera, including Lactobacillus, Propionibacterium, and Bifidobacterium, exhibited reduced abundance in cancer patients. These findings suggest that some genera may serve as potential biomarkers for bladder cancer, highlighting the need for further research to explore their roles in disease pathogenesis and their potential applications in diagnostics and therapeutics.

Evolution of the urinary microbiota in spinal cord injury patients with decubitus ulcer: A snapshot study.

Current microbiome investigations of patients with pressure ulcers (PU) are mainly based on wound swabs and/or biopsy sequencing, leaving the colonization scenario unclear. Urinary microbiota has been never studied. As a part of the prospective ESCAFLOR study, we studied urinary microbiota of spinal cord injury (SCI) patients with PU without any urinary tract infection at the inclusion, collected at two times (at admission [D0] and after 28 days [D28]) during the patient's care, investigated by 16S rDNA metagenomics next generation sequencing. Subgroup analyses were carried out between patients with wounds showing improved evolution versus stagnated/worsened wounds at D28. Analysis was done using EPISEQ® 16S and R software. Among the 12 studied patients, the urinary microbiota of patients with improved wound evolution at D28 (n = 6) presented a significant decrease of microbial diversity. This modification was associated with the presence of Proteobacteria phylum and an increase of Escherichia-Shigella (p = 0.005), as well as the presence of probiotic anaerobic bacteria Lactobacillus and Bifidobacterium. In contrast, Proteus abundance was significantly increased in urine of patients with stagnated/worsened wound evolution (n = 6) (p = 0.003). This study proposes urinary microbiota as a complementary factor indirectly associated with the wound evolution and patient cure. It opens new perspectives for further investigations based on multiple body microbiome comparison to describe the complete scenario of the transmission dynamics of wound-colonizing microorganisms.

Urinary microbiota and bladder cancer: A systematic review and a focus on uropathogens.

The higher incidence of bladder cancer in men has long been attributed to environmental factors, including smoking. The fact that the sex ratio of bladder cancer remains consistently weighted toward men despite the remarkable increase in the prevalence of smoking among women suggests that other risk factors influence the incidence rates of bladder cancer. These factors may include the urinary microbiota. In this study, we provide a review of recent literature regarding the association between bladder cancer and changes in the urinary microbiota, with a focus on the potential role of uropathogens in the microbiota and sex in bladder cancer. Four databases were systematically searched up to 31 March 2021 to identify human case-controlled studies that evaluated the relationship between urinary microbiota and bladder cancer. We combined bacterial taxa that were significantly higher or lower in the bladder cancer group in each study in the urine (voided and catheterized) and tissue samples. Findings from sixteen eligible studies were analyzed. The total sample size of the included studies was 708 participants, including 449 (63.4 %) bladder cancer patients and 259 (36.6 %) participants in the control group. When considering only the taxa that have been reported in at least two different studies, we observed that with regards to neoplastic tissues, no increased taxa were reported, while Lactobacillus (2/5 of the studies on tissue samples) was increased in nonneoplastic-tissue compared to neoplastic-tissues at the genus level. In catheterized urine, Veillonella (2/3 of the studies on catheterized urine) was increased in bladder cancer patients compared to the control groups at the genus level. In voided urine, Acinetobacter, Actinomyces, Aeromonas, Anaerococcus, Pseudomonas, and Tepidomonas were increased in the bladder cancer patients, while Lactobacillus, Roseomonas, Veillonella were increased in the control groups. Regarding gender, the genus Actinotignum was increased in female participants while Streptococcus was increased in male participants at the genus level. Regarding potential uropathogens in the urinary microbiota, Escherichia-Shigella provided conflicting results, with both showing higher and lower levels in the bladder cancer groups. However, the family Enterobacteriaceae was lower in the bladder cancer groups than in the control groups. In conclusion, there is no consensus on what taxa of the urinary microbiota are associated with bladder cancer according to the sample type. Findings on the potential role of uropathogens in the urinary microbiota in bladder cancer remain inconsistent. Due to the limited number of studies, further studies on urinary microbiota and bladder cancer are needed to address this issue. Given that all publications concerning the urinary microbiota and bladder cancer have been performed using 16S rRNA gene sequencing, we propose that polyphasic approaches, including culture-dependent techniques, may allow for a more comprehensive investigation of the urinary microbiota associated with bladder cancer.

The impact of urine collection method on canine urinary microbiota detection: a cross-sectional study.

BACKGROUND: The urinary tract harbors unique microbial communities that play important roles in urogenital health and disease. Dogs naturally suffer from several of the same urological disorders as humans (e.g., urinary tract infections, neoplasia, urolithiasis) and represent a valuable translational model for studying the role of urinary microbiota in various disease states. Urine collection technique represents a critical component of urinary microbiota research study design. However, the impact of collection method on the characterization of the canine urinary microbiota remains unknown. Therefore, the objective of this study was to determine whether urine collection technique alters the microbial populations detected in canine urine samples. Urine was collected from asymptomatic dogs by both cystocentesis and midstream voiding. Microbial DNA was isolated from each sample and submitted for amplicon sequencing of the V4 region of the bacterial 16 S rRNA gene, followed by analyses to compare microbial diversity and composition between urine collection techniques. RESULTS: Samples collected via midstream voiding exhibited significantly higher sequence read counts (P = .036) and observed richness (P = .0024) than cystocentesis urine. Bray Curtis and Unweighted UniFrac measures of beta diversity showed distinct differences in microbial composition by collection method (P = .0050, R2 = 0.06 and P = .010, R2 = 0.07, respectively). Seven taxa were identified as differentially abundant between groups. Pasteurellaceae, Haemophilus, Friedmanniella, two variants of Streptococcus, and Fusobacterium were over-represented in voided urine, while a greater abundance of Burkholderia-Caballeronia-Paraburkholderia characterized cystocentesis samples. Analyses were performed at five thresholds for minimum sequence depth and using three data normalization strategies to validate results; patterns of alpha and beta diversity remained consistent regardless of minimum read count requirements or normalization method. CONCLUSION: Microbial composition differs in canine urine samples collected via cystocentesis as compared to those collected via midstream voiding. Future researchers should select a single urine collection method based on the biological question of interest when designing canine urinary microbiota studies. Additionally, the authors suggest caution when interpreting results across studies that did not utilize identical urine collection methods.

Uncovering the role of urinary microbiota in urological tumors: a systematic review of literature.

PURPOSE: Urinary microbiota has been found to play a key role in numerous urological diseases. The aim of this systematic review is to depict the role of urinary microbiota in the pathogenesis, diagnosis, prognosis, and treatment of urological tumors, including bladder cancer (BCa), prostate cancer (PCa) and renal cell carcinoma (RCC). METHODS: A systematic PubMed and Scopus search was undergone from inception through June 2021 for studies investigating urinary microbiota alterations in urological tumors. Study selection followed the PRISMA statement. Phylum, family, genus and species of each bacterium in cancer patients and controls were recorded. RESULTS: Twenty-one studies with 1194 patients (748 cancer patients and 446 controls) were included in our final analysis. Certain bacterial phylum, family, genus, and species were more predominant in each of BCa, PCa and RCC patients compared to controls. Abundance and specificity of urinary microbiota were prognosticators for: (1) recurrence, distinguishing recurrent from non-recurrent BCa, (2) disease stage, distinguishing non-muscle invasive from muscle invasive BCa, and (3) disease grade, distinguishing high- vs. low-grade PCa and BCa. Dietary, environmental and geographic patterns influenced urinary microbiota. Urinary microbiota of benign prostatic hyperplasia was different from PCa. CONCLUSION: Urological cancer patients have an altered urinary microbiota compared to controls. This may predict recurrence, disease stage and disease grade of these tumors. Further prospective studies are needed to depict a potential influence on therapeutic outcomes.

A Perspective of the Urinary Microbiome in Lower Urinary Tract Infections - A Review.

PURPOSE OF REVIEW: Greater availability of sequencing methods has broadened the knowledge of the urinary microbiome in an environment previously believed to be sterile. This review discusses internal and external influences that promote either a balance or a dysbiosis of the urinary tract and the future perspectives in understanding lower urinary tract infections. RECENT FINDINGS: Efforts have been made to identify a "core" urinary microbiome in which Firmicutes and Bacteroidetes account for most of the bacterial representations. A shift to a Proteobacteria-dominant representation shapes the fingerprint of the infectious urinary microbiome; furthermore, the virome and the mycobiome are important modulators of the urinary microbiome, which have been recently explored to determine their role in the health-disease process of the lower urinary tract. A disturbance of bacterial representation and diversity triggers a transition from health to disease; conversely, a functional cooperative interplay between the host and microbiome allows for basic metabolic and immune functions to take place.

Assessment of the Urinary Microbiota of MSM Using Urine Culturomics Reveals a Diverse Microbial Environment.

BACKGROUND: The urinary tract is not sterile and is populated by microbial communities that influence urinary health. Men who have sex with men (MSM) are understudied yet have increased risk factors for genitourinary infections. Our objective was to interrogate the composition of MSM urinary microbiota. METHODS: Midstream urine specimens (n = 129) were collected from MSM (n = 63) and men seen for routine care (clinical cohort, n = 30). Demographics and sexual/medical history were documented. Specimens underwent culture using standard-of-care and enhanced methods designed to isolate fastidious and anaerobic microorganisms. Isolates were identified by MALDI-TOF mass spectrometry or 16S rRNA gene sequencing. RESULTS: The MSM cohort was younger (mean (SD), 35.4 (11.26) years) compared to the clinical cohort (62.7 (15.95) years). Organism recovery was significantly increased using enhanced vs standard culture for the MSM (mean of 9.1 vs 0.6 species/sample [P < 0.001]) and clinical (7.8 vs 0.9 species/sample [P < 0.001]) cohorts. The microbial composition of MSM urine specimens was dominated by Gram-positive and anaerobic microbes and clustered distinctly from that of clinical urine specimens. Composition of microbial species recovered within the same subject was dynamic between urine specimens but more similar relative to inter-individual comparisons. Principal coordinate analysis showed no correlation between urinary microbiota composition and age, recent antibiotic use, sexually transmitted infection/HIV status, or sexual practices. CONCLUSIONS: Enhanced culture recovered a large diversity of microbial species from MSM urine specimens, especially taxa typically associated with mucosal surfaces. These findings may increase understanding of urologic disease in MSM and improve diagnostic methods for detection of genitourinary infections.

The controversial association of gut and urinary microbiota with kidney stone formation.

Nephrolithiasis (kidney stones) is one of the most common chronic kidney diseases that are typically more common among adult men comparing to adult women. The prevalence of this disease is increasing which is influenced by genetic and environmental factors. Kidney stones are mainly composed of calcium oxalate and urinary oxalate which is considered a dangerous factor in their formation. Besides diverse leading reasons in the progression of nephrolithiasis, the gut and urinary microbiome has been recognized as a major player in the development or prevention of it. These microbes produce metabolites that have diverse effects on host biological functions. Therefore, Changes in the composition and structure of the microbiome (dysbiosis) have been implicated in various diseases. The present review focuses on the roles of gut and urinary in kidney stone formation.

Dynamics of the urinary microbiome in pregnancy and the coincidental predictive value of the microbiota for IVF/IVF-ICSI outcome.

RESEARCH QUESTION: What is the impact of clinical pregnancy on the composition of the urinary microbiota? DESIGN: Eighty-five women receiving IVF, without or with intracytoplasmic sperm injection (ICSI) treatment were enrolled in a prospective observational study performed in 2008. Approximately 14 weeks before the start of hormonal treatment and embryo transfer, a midstream urine sample was obtained, followed by an additional sample 16 weeks after embryo transfer. The microbial composition was determined by polymerase chain reaction of the V1-V3 regions of the 16S rRNA bacterial gene. Clinical pregnancy data were collected after the first IVF/IVF-ICSI cycle and 1 year later. RESULTS: A significant decrease in the abundance of Lactobacillus species as well as a significant increase in that of Staphylococcus species was observed in women who became pregnant after IVF/IVF-ICSI treatment (both P < 0.0001). In addition, based on the composition of the pretreatment microbiome it was possible to identify women with a lower likelihood of achieving clinical pregnancy after IVF/IVF-ICSI treatment. The resulting prediction model was validated in another 27 women who did not become pregnant during the first cycle and received additional IVF/IVF-ICSI cycle(s) or frozen embryo transfer(s). The model predicted the women with no clinical pregnancy after IVF/IVF-ICSI treatment with a sensitivity of 0.42 and a specificity of 1.00. CONCLUSIONS: The data primarily showed that clinical pregnancy results in significant changes in the abundance and diversity of the urinary microbiota. Coincidentally, it was discovered that the urinary microbiome composition before IVF/IVF-ICSI treatment can potentially be used as a predictor of clinical pregnancy.

Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women.

AIMS: Clinical profiles of women with recurrent urinary tract infection (RUTI) are correlated with their urinary microbes. METHODS: This IRB-approved, cross-sectional study enrolled adult women with RUTI. Urine samples (catheterized and voided) underwent culture by expanded quantitative urine culture (EQUC) and standard urine culture (SUC) methods. A validated symptom questionnaire, relevant clinical variables, and EQUC were used to identify symptom clusters and detect associations with specific urinary microbes. RESULTS: Most (36/43) participants were postmenopausal; the average age was 67 years. 51% reported vaginal estrogen use; 51% reported sexual activity. Although single symptoms were not associated with specific urinary microbes, EQUC results were correlated with five distinct clinical profile clusters: Group A: odor, cloudiness, and current vaginal estrogen use (no culture result association). Group B: frequency, low back pain, incomplete emptying, and vaginal estrogen (significantly increased proportion of Lactobacillus-positive cultures). Group C: pain/burning, odor, cloudiness, and urgency (high proportions of UTI-associated microbe-positive cultures). Group D: frequency, urgency, pain/burning, and current vaginal estrogen use (increased number of no growth cultures). Group E: frequency, urgency, pain/burning, odor, overactive bladder, and sexually active (significantly increased proportion of Klebsiella-positive cultures). CONCLUSIONS: Distinct clinical profiles are associated with specific urinary microbes in women with RUTI. Refined assessments of clinical profiles may provide useful insights that could inform diagnostic and therapeutic considerations.

The urobiome of continent adult women: a cross-sectional study.

OBJECTIVE: To characterise the bladder microbiota of continent adult women. DESIGN: Cross-sectional study of adult women who contributed catheterised urine samples, completed validated symptom questionnaires, and provided demographic data. SETTING: US academic medical centre. POPULATION: Well-characterised continent adult women. METHODS: Participants contributed symptoms questionnaires, demographic data, and catheterised urine samples that were analysed by enhanced urine culture methodology and 16S rRNA gene sequencing. MAIN OUTCOME MEASURES: Associations between demographics and microbial community state structures (urotypes, defined by the dominant taxon of each specimen). RESULTS: The bladder microbiota (urobiome) of a control group of 224 continent women were characterised, demonstrating variability in terms of urotype. The most common urotype was Lactobacillus (19%), which did not differ with any demographic. In contrast, the Gardnerella (P < 0.001) and Escherichia (P = 0.005) urotypes were more common in younger and older women, respectively. CONCLUSIONS: For urobiome research, enhanced culture methods and/or DNA sequencing are the preferred techniques for bacterial detection. The interpretation of clinical tests, such as the standard urine culture, should incorporate the knowledge that some women have Gardnerella or Escherichia urotypes without evidence of any clinical disorder. Clinical care strategies should preserve or restore the beneficial effects of the native urobiome, as disruption of that microbial community could result in unintended vulnerability to uropathogen invasion or opportunistic pathogen overgrowth. Longitudinal studies of urobiome responses to therapies should be encouraged. TWEETABLE ABSTRACT: In continent adult women bladder microbiome composition differs by age, with relevance for clinical practice.

Relationship between alterations of urinary microbiota and cultured negative lower urinary tract symptoms in female type 2 diabetes patients.

BACKGROUND: Lower urinary tract symptoms (LUTS) is the most common complication of diabetes. However, the underlying pathogenesis of cultured negative LUTS (cn-LUTS) in diabetic patients has not been well understood. Numerous evidence indicates that urinary dysbiosis is related to urologic disorders. We aim to study alterations of the urinary microbiota of cn-LUTS in type 2 diabetes (T2D) patients. METHODS: Female T2D patients and controls were recruited and requested to finish the American Urological Association Symptom Index. Mid-stream urine was collected for culturing and extracting DNA. Microbial diversity and composition were analyzed by targeting to 16S rDNA. Linear discriminant analysis effect size (LEfSe) was carried out to identify significantly different bacteria. RESULTS: 32 female T2D patients and 26 controls were enrolled. No significant differences in alpha diversity were observed between patients and controls. However, statistically decreased richness (ACE index and Chao 1 index, 85.52(13.75, 204.84) vs. 129.82(63.89, 280.30) and 83.86(11.00, 210.77) vs. 125.19(62.00, 251.77), P = 0.005; Observed Species, 76(10, 175) vs. 98(54, 234), P = 0.011) and decreased species diversity (Shannon index, 1.37(0.04, 3.48) vs. 2.09(0.98, 3.43), P = 0.033; Simpson index, 0.46 (0.06, 0.99) vs. 0.23(0.07, 0.64), P = 0.029) were shown in moderate-to-severe LUTS group and high Hemoglobin A1c group, respectively. A significant difference of beta diversity was found between T2D patients and controls and T2D patients with different severity of cn-LUTS as well as the different level of Hemoglobin A1c. LEfSe revealed that 10 genera (e.g., Escherichia-Shigella and Klebsiella) were increased and 7 genera were decreasing in T2D patients, 3 genera (e.g., Escherichia-Shigella and Campylobacter) were increased and 16 genera (e.g., Prevotella) were reduced in moderate-to-severe LUTS group, 2 genera (Escherichia-Shigella and Lactobacillus) were over-represented and 10 genera (e.g., Prevotella) were under-represented in high Hemoglobin A1c group. Finally, Hemoglobin A1c was found positively correlated with the total score of the American Urological Association Symptom Index (r = 0.509, P = 0.003). CONCLUSIONS: Urinary dysbiosis may be related to cn-LUTS in female T2D patients. A better understanding of urinary microbiota in the development and progression of cn-LUTS in female T2D patients was necessary. The severity of cn-LUTS was correlated to hyperglycemia and chronic hyperglycemia might induce or promote cn-LUTS by influencing urinary microbiota.

The bladder microbiota is not significantly altered by intravesical BCG therapy.

INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, n = 32) or benign prostatic hyperplasia (control group, n = 41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.

Impact of coexisting type 2 diabetes mellitus on the urinary microbiota of kidney stone patients.

Objectives: Type 2 diabetes mellitus (T2DM) commonly complicates kidney stone disease (KSD). Our objective is to investigate the variations in the urinary microbiota between individuals with KSD alone and those with KSD plus T2DM. This exploration could have implications for disease diagnosis and treatment strategies. Methods: During lithotripsy, a ureterscope was employed, and 1 mL of urine was collected from the renal pelvis after bladder disinfection. Sequencing targeting the V3-V4 hypervariable region was performed using the 16S rRNA and Illumina Novaseq platform. Results: The Shannon index showed a significant decrease in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.041). Principal Coordinate Analysis (PCoA) demonstrated a distinct bacterial community in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.027). The abundance of Sphingomonas, Corynebacterium, and Lactobacillus was significantly higher in the KSD plus T2DM group than in the KSD-only group (false discovery rate < 0.05). Furthermore, Enhydrobacter, Chryseobacterium, and Allobaculum were positively correlated with fasting blood glucose and HbA1c values (P < 0.05). Conclusions: The urinary microbiota in the renal pelvis exhibits differences between patients with KSD plus T2DM and those with KSD alone. Further studies employing animal models are necessary to validate these distinctions, potentially paving the way for therapeutic developments based on the urinary microbiota.

Gut and Urinary Microbiota in Cats with Kidney Stones.

Upper urinary tract urolithiasis is an emerging disease in cats, with 98% of kidney stones composed of calcium oxalate. In humans, disturbances in the intestinal and urinary microbiota are suspected to contribute to the formation of calcium oxalate stones. We hypothesized that similar mechanisms may be at play in cats. This study examines the intestinal and urinary microbiota of nine cats with kidney stones compared to nine healthy cats before, during, and after treatment with the antibiotic cefovecin, a cephalosporin. Initially, cats with kidney stones displayed a less diverse intestinal microbiota. Antibiotic treatment reduced microbiota diversity in both groups. The absence of specific intestinal bacteria could lead to a loss of the functions these bacteria perform, such as oxalate degradation, which may contribute to the formation of calcium oxalate stones. This study confirms the presence of a distinct urobiome in cats with kidney stones, characterized by greater richness and diversity compared to healthy cats. These findings highlight the potential of microbiota modulation as a strategy to prevent renal lithiasis in cats.