We report a detailed cultivation independent comparison of urine microbiomes in men with and without STI. Large-scale Sanger sequencing of near full-length 16S rRNA alleles was utilized so the data set would be a robust resource for future comparisons.
Our data support an expanded view of the association of the urogenital microbial communities in health and disease. First, the bacterial communities in urine are complex and a single, characteristic microbial community was not apparent. Urogenital genera overlap to some degree microbial communities found in the superficial skin 
, colon 
, vagina 
. A variety of taxa identified on the penile coronal sulcus in a recent study were also observed 
. However, our data suggest the overall composition of urine and coronal sulcus microbiomes differ. The sulcus is dominated by Pseudomonadaceae spp. 
whereas sequences corresponding to this family were rare in urine. Second multiple BV-associated anaerobic taxa, such as Sneathia spp.
, which appear to be minor components of sulcus microbiomes in uncircumcised men were dominant components of urine microbiomes. Finally, Lactobacillus
spp. were abundant in some urines but were not reported in sulcus specimens. Caveats of these comparisons include subject populations (African men versus an ethnically diverse population of American men). The power of our study was also too low to assess differences in microbiomes associated with race or ethnicity. Finally this study and the survey in question employed different PCR primers, PCR amplification conditions and 16S rRNA sequencing, all of which limit the utility of direct comparisons of the data sets.
A second key finding is the association of STI with a cluster of organisms not previously linked to the male urogenital tract: Sneathia
, to name a few 
. These organisms have previously been identified in the coronal sulcus of uncircumcised men, and became less frequent following circumcision to reduce risk of sexually transmitted human immunodeficiency virus infection 
. Some of these organisms are also commonly observed in the vaginal microbial communities of asymptomatic women 
, as well as women with bacterial vaginosis 
and upper genital tract pathology 
. Similar anaerobic communities in female genital tract are associated with increased risk for STI 
. These observations suggest the hypothesis that establishment of BV-like communities in the male urethra is similarly associated with STI risk. However, present data are clearly inadequate to differentiate if the STI-associated communities precede, are co-transmitted with or are established subsequent to STI.
An limitation of this study is that urine can sample multiple body compartments and that these specimens were used as a proxy for urethral swabs because the latter technique is contraindicated in STI negative men. Urethral swabs and urine are equally suitable specimens for PCR-based detection of a variety of sexually transmitted pathogens 
. Comparisons of paired first-catch urine and urethral swabs support that interpretation that the microbiomes sampled by with these specimen types are highly similar (Q Dong et al.
, manuscript in preparation). Thus we assume here that urine specimens primarily contain bacteria associated with the urethral epithelium, and lower numbers of organisms from the bladder and urethral meatus. Incidence of upper urinary tract infection is low in our study population which suggests bladder flora were infrequent. Thus, although male urine may not exclusively sample urethral flora, we believe it provides as good of a measure of this flora as is practical and ethical in individuals not suspected to have STI.
In conclusion, our data provide the first glimpse into the urogenital microbiome in men with STI. Caution is clearly warranted in interpreting associations between characteristic microbiomes and STI; we cannot exclude other possible explanations for the patterns observed, such as long-term effects of undocumented antibiotic use 
. Considering these and similar caveats we believe the data suggest the hypothesis that establishment characteristic microbiomes might be related to risk for subsequent STI. Longitudinal studies of urine microbiomes prior to and post STI will be necessary to test this and we believe such studies could elucidate inter-species microbial interactions relevant to a variety of poorly understood urogenital syndromes.