Gardnerella Exposures Alter Bladder Gene Expression and Augment Uropathogenic Escherichia coli Urinary Tract Infection in Mice

Abstract

The anaerobic actinobacterium Gardnerella was first isolated from the bladder by suprapubic aspiration more than 50 years ago. Since then, Gardnerella has been increasingly recognized as a common and often abundant member of the female urinary microbiome (urobiome). Some studies even suggest that the presence of Gardnerella is associated with urological disorders in women. We recently reported that inoculation of Gardnerella into the bladders of mice results in urothelial exfoliation. Here, we performed whole bladder RNA-seq in our mouse model to identify additional host pathways involved in the response to Gardnerella bladder exposure. The transcriptional response to Gardnerella reflected the urothelial turnover that is a consequence of exfoliation while also illustrating the activation of pathways involved in inflammation and immunity. Additional timed exposure experiments in mice provided further evidence of a potentially clinically relevant consequence of bladder exposure to Gardnerella—increased susceptibility to subsequent UTI caused by uropathogenic Escherichia coli. Together, these data provide a broader picture of the bladder’s response to Gardnerella and lay the groundwork for future studies examining the impact of Gardnerella on bladder health.

The Role of Metabolomics and Microbiology in Urinary Tract Infection

“…The quantitative nature of the microbial whole genome sequencing (WGS) method identifies traditional uropathogens in low numbers in samples characterized by infection. Gilbert et al [ 29 ] used mouse bladder RNA-Seq data to point out the shedding and differentiation of uroepithelial cells affected by Gardnerella exposure, promoting the persistence of uropathogenic E. coli (UPEC) in the bladder. Nonetheless, research is ongoing to fully understand the precise mechanisms driving the development and maintenance of the urinary microbiota.…”

Female reproductive tract-organ axes

“…Similar to this gut-bladder axis, vaginal dysbiosis may prompt a UTI via the vagina-bladder axis as a reservoir for uropathogens such as E. coli ( 6 ). Although G. vaginalis is a rare cause of symptomatic UTI, an in vitro study showed that G. vaginalis altered bladder gene expression and increased susceptibility to subsequent UTI caused by uropathogenic E. coli ( 141 ). Compared to women without BV, those with BV have a significantly increased risk of UTI, with an odds ratio of 13.75 ( 142 ), and a clinical trial showed that the efficacy of intravaginally administered L. crispatus probiotics reduced the recurrence of UTI ( 143 ).…”

“…Compared to women without BV, those with BV have a significantly increased risk of UTI, with an odds ratio of 13.75 ( 142 ), and a clinical trial showed that the efficacy of intravaginally administered L. crispatus probiotics reduced the recurrence of UTI ( 143 ). Furthermore, as G. vaginalis is often detected in the urinary microbiota ( 141 ), the urine microbiota may prompt BV via the vagina-bladder axis as a reservoir for G. vaginalis .…”