The Urethral Microbiota of Men with and without Idiopathic Urethritis.

Nongonococcal urethritis (NGU) is a common genital tract syndrome in men, and up to 50% of cases are considered idiopathic, i.e., no etiological agent is identified. This poses challenges for clinicians in the diagnosis and treatment of NGU and often results in antibiotic misuse and overuse. Therefore, to identify potential infectious causes of urethritis and inform clinical management of urethritis cases, we characterized and compared the urethral microbiota of men with and without idiopathic urethritis. Participants were derived from a case-control study that examined viral and bacterial pathogens and sexual practices associated with NGU. Men with NGU who tested negative for established causes of NGU (Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenoviruses, herpes simplex virus [HSV]-1, and/or HSV-2) were classified as idiopathic cases, and the controls were men reporting no current urethral symptoms. Men provided a urine sample that was used to characterize the urethral microbiota using 16S rRNA gene sequencing. Bacterial taxa associated with idiopathic urethritis were identified using analysis of compositions of microbiomes with bias correction. When stratified by sex of sexual partner, we found that the abundance of Haemophilus influenzae was significantly increased in men who have sex with men with idiopathic urethritis, and the abundance of Corynebacterium was significantly increased in men who have sex with women with idiopathic urethritis. Other taxa, including Ureaplasma, Staphylococcus haemolyticus, Streptococcus pyogenes, Escherichia, and Streptococcus pneumoniae/pseudopneumoniae, dominated the urethral microbiota of idiopathic urethritis cases but not controls, suggesting that these organisms may also contribute to urethritis. Importantly, the taxa we identified represent biologically plausible causes of urethritis and should be prioritized for future study. IMPORTANCE Nongonococcal urethritis (NGU) is the commonest genital tract syndrome in men and is nearly universally presumptively treated with an antibiotic. Common causes of NGU include Chlamydia trachomatis and Mycoplasma genitalium, but in more than 50% of cases, an infectious cause is not identified. In this case-control study, we found that the urethral microbiota composition differed between men with and without idiopathic urethritis and differed by sex of sexual partner. We identified specific bacterial taxa that were associated with idiopathic urethritis, including Haemophilus influenzae and Corynebacterium. These data, together with the finding that key bacterial taxa were found to dominate the urethral microbiota of cases but not controls, suggest that a range of bacteria contribute to urethritis and that these organisms may be influenced by sexual practices. Through identifying the infectious causes of urethritis, we can inform appropriate targeted diagnostic and treatment practices and importantly reduce misuse and overuse of antibiotics.

Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment.

Bacterial vaginosis (BV) is the most common vaginal dysbiosis to affect women globally, yet an unacceptably high proportion of women experience BV recurrence within 6 months of recommended antibiotic therapy. The low rate of sustained cure highlights our limited understanding of the pathogenesis of BV recurrence, which has been attributed to possible persistence and re-emergence of BV-associated bacteria (BVAB) or a BV-associated biofilm following antimicrobials and/or reinfection occurring from sexual partners.There is a robust body of evidence to support the exchange of bacteria between partners during sexual activity, and while the hypothesis that women treated for BV are subsequently reinfected with BVAB following sex with an untreated sexual partner is not new, failure of past partner treatment trials has eroded confidence in this concept. If reinfection is a key driver of recurrence, current antimicrobial regimens directed to women alone are unlikely to achieve a high level of sustained cure, and the approach of partner treatment to reduce reinfection is justified. In this manuscript, we present the molecular and epidemiological evidence that underlies the hypothesis that BV is sexually transmitted, and summarise why research that continues to consider sexual partnerships is necessary. We also outline the significant barriers and challenges that we have identified while undertaking partner treatment studies, and we discuss the factors that impact on our ability to determine their effectiveness.Ultimately, the pathogenesis of BV recurrence is likely to be multifaceted and not attributable to a single mechanism in all women. If we are to achieve sustained cure for women, it is likely that combined and individualised approaches to eradicate BVAB, support an optimal vaginal microbiome, and prevent reinfection from partners will be required.

Urethral Microbiota in Men: Association of Haemophilus influenzae and Mycoplasma penetrans With Nongonococcal Urethritis.

BACKGROUND: Nongonococcal urethritis (NGU) is a common syndrome with no known etiology in ≤50% of cases. We estimated associations between urethral bacteria and NGU in men who have sex with men (MSM) and men who have sex with women (MSW). METHODS: Urine was collected from NGU cases (129 MSM, 121 MSW) and controls (70 MSM, 114 MSW) attending a Seattle STD clinic. Cases had ≥5 polymorphonuclear leukocytes on Gram stain plus symptoms or discharge; controls had <5 PMNs, no symptoms, no discharge. NGU was considered idiopathic when Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenovirus, and herpes simplex virus were absent. The urethral microbiota was characterized using 16S rRNA gene sequencing. Compositional lasso analysis was conducted to identify associations between bacterial taxa and NGU and to select bacteria for targeted qPCR. RESULTS: Among NGU cases, 45.2% were idiopathic. Based on compositional lasso analysis, we selected Haemophilus influenzae (HI) and Mycoplasma penetrans (MP) for targeted qPCR. Compared with 182 men without NGU, the 249 men with NGU were more likely to have HI (14% vs 2%) and MP (21% vs 1%) (both P ≤ .001). In stratified analyses, detection of HI was associated with NGU among MSM (12% vs 3%, P = .036) and MSW (17% vs 1%, P < .001), but MP was associated with NGU only among MSM (13% vs 1%, P = .004). Associations were stronger in men with idiopathic NGU. CONCLUSIONS: HI and MP are potential causes of male urethritis. MP was more often detected among MSM than MSW with urethritis.

Bacterial communities associated to the urethra of healthy gilts and pregnant sows undergoing different reproductive protocols.

Nowadays, it is known that the urogenital microbiota plays a key role in the urinary health of mammalians. Despite the urinary infections affect the health and the welfare of breeding sows, the urethral microbiota of healthy sows remains unknown. Therefore, this work evaluates the urethral bacterial communities of healthy gilts and sows to determine the presence of Enterobacteriaceae populations, and the structure of this microbiota in gilts (G) and pregnant (P) sows. Samples were collected by scraping the urethral mucosa of G (n = 9) and P sows, which included natural mating (NM, n = 9) and artificial inseminated (AI, n = 7) sows. Samples were analyzed by culture-dependent techniques and 16S-rRNA gene high-throughput-sequencing. All females were positive for Enterobacteriaceae culture, without significant differences (Kruskal-Wallis) between G and P groups (median values: 2.78 and 3.09 log CFU/mL, respectively; P = 0.497). Also, the rate of Enterobacteriaceae/total mesophilic microorganisms was individually calculated, without significant differences between G and P sows (median values: 0.61 and 0.66, respectively; P = 0.497). When analyzing the bacterial communities, it was found similar richness in G, NM, and AI; however, diversity was lower in P sows than G (Mann Whitney/Kruskal-Wallis test, P < 0.01). The dominating phyla that constituted a "core microbiome" included Firmicutes, Proteobacteria, Cyanobacteria, Actinobacteria, and Bacteroidetes, which were common for all the studied females. The relative abundance for phyla, families, and genera was estimated, and Firmicutes was significantly higher in NM than AI sows (P = 0.02, Mann-Whitney/Kruskal Wallis test for univariate statistical comparisons); Pseudomonadaceae and Enterobacteriaceae were higher in AI than in NM (Mann-Whitney/Kruskal-Wallis, P < 0.05). Lactobacillus and Pseudomonas were among the dominant genera; however, only Pseudomonas sp. was significantly higher in AI than NM (Mann-Whitney/Kruskal-Wallis, P = 0.006). The results represent the first evidence about the existence of a urethral microbiota that includes Enterobacteriaceae, as well as the patterns of this microbiota in G and P sows. The knowledge of this urethral microbiota might allow for future research to develop innovative protocols to restore and/or preserve the healthy ecology of the urinary microbiome to prevent diseases ensuring the welfare of breeding sows.

[Evaluation of the composition of the microbiota of the urethra in men with sexually transmitted infections].

OBJECTIVE: to conduct a comparative study of the composition of the microbiota of the urethra in men with sexually transmitted infections (STIs), and healthy men. MATERIAL AND METHODS: The study included 103 men aged 18 to 45 years: 42 men with urethritis caused by STIs and 61 clinically healthy men. Identification of pathogenic and conditionally pathogenic microorganisms in scrapings from the urethra was performed by PCR in real time (test system Androflor (DNA-Technology, Moscow). RESULTS: In the analysis of the total bacterial mass, it was found that the bacterial contamination of the urethral biotope in patients with STI was significantly higher than in the group of healthy men (5.8 Lg10 and 4.7 Lg10, respectively), with the highest level of bacterial contamination was detected in patients infected with N. gonorrhoeae (6.4 Lg10). Patients with STIs had significantly lower levels of relative Staphylococcus spp., Streptococcus spp., Corynebacterium spp. and their amounts in General compared to clinically healthy men: according to ROC analysis, the best diagnostic indicator (0.93+/-0.04, p<0.001), distinguishing a group of healthy individuals from patients with STI, was the amount of Staphylococcus spp., Streptococcus spp. and Corynebacterium spp. ("Amount Of Normoflor"). In patients infected with C. trachomatis, compared with clinically healthy men, the relative number was significantly higher of Bacteroides spp. / Porphyromonas spp. / Prevotella spp., Peptostreptococcus spp. / Parvimonas spp.; in patients infected with N. gonorrhoeae - Anaerococcus spp. and in patients infected with M. genitalium - Megasphaera spp. / Veillonella spp. / Dialister spp., Anaerococcus spp., Peptostreptococcus spp. / Parvimonas spp. and Eubacterium spp. CONCLUSION: An increase in the total bacterial contamination of the urethra in STI was found, most pronounced in infection with Neisseria gonorrhoeae. The best diagnostic indicator that distinguishes normal microbiota from the microbiota of patients with STIs is the sum of Staphylococcus spp., Streptococcus spp. and Corynebacterium spp. In patients with clinical signs of an inflammatory reaction and the presence of STIs, a decrease in the normoflora in all types of STIs and an increase in obligate anaerobic bacteria - Megasphaera spp. / Veillonella spp. / Dialister spp., Bacteroides spp. / Porphyromonas spp. / Prevotella spp., Anaerococcus spp., Peptostreptococcus spp. / Parvimonas spp. and Eubacterium spp.