Gardnerella vaginalis in Recurrent Urinary Tract Infection Is Associated with Dysbiosis of the Bladder Microbiome

Abstract

Recent studies on the urine microbiome have highlighted the importance of the gut-vagina-bladder axis in recurrent urinary tract infection (rUTI). In particular, the role of Gardnerella as a covert pathogen that activates E. coli in animal experiments has been reported. Herein, we conducted a human bladder microbiome study to investigate the effect of Gardnerella on rUTI. Urine 16S ribosomal RNA gene sequencing via transurethral catheterization was conducted in the normal control group (NC) (n = 18) and rUTI group (n = 78). The positive detection rate of Gardnerella species did not differ between the NC and rUTI groups (22.2% vs. 18.0%, p = 0.677). In addition, the Gardnerella-positive NC and Gardnerella-positive rUTI groups showed similar levels of microbiome diversity. The Gardnerella-positive group was categorized into three subgroups: the Escherichia-dominant group, Gardnerella-dominant group, and Lactobacillus-dominant group. All of the Escherichia-dominant groups were associated with rUTI. The Gardnerella-dominant or Lactobacillus-dominant groups expressed rUTI with symptoms when risk factors such as the degree of Gardnerella proliferation or causative agents of bacterial vaginosis were present. The presence of Gardnerella in the urine is considered to be related to rUTI depending on other risk factors. New guideline recommendations regarding antibiotic selection based on a novel method to detect the cause of rUTI may be required to reduce antibiotic resistance.

Keywords: 16S rRNA next-generation sequencing; Gardnerella; bladder; microbiome; recurrent cystitis; urinary tract infection.

Figure 1

Relative abundance of urinary microbiota in Gardnerella (+) normal control group and Gardnerella (+) recurrent UTI group.

Figure 2

(A) Alpha diversity and (B) principal coordinate analysis based on weighted UniFrac distances in Gardnerella (+) normal control group and Gardnerella (+) recurrent UTI group.

Figure 3

Gardnerella (+) urinary microbiota revealed three distinct subgroups by (A) K-medoids clustering and (B) hierarchical clustering in R program version 4.1.2 (The R Foundation for Statistical Computing, Vienna, Austria; https://svn.r-project.org/R-packages/trunk/cluster, accessed on 17 March 2021), (C) bar plot, (D) pie chart.

Figure 3

Gardnerella (+) urinary microbiota revealed three distinct subgroups by (A) K-medoids clustering and (B) hierarchical clustering in R program version 4.1.2 (The R Foundation for Statistical Computing, Vienna, Austria; https://svn.r-project.org/R-packages/trunk/cluster, accessed on 17 March 2021), (C) bar plot, (D) pie chart.

Figure 4

Relative abundance of Gardnerella in (A) Gardnerella-dominant subgroup and (B) Lactobacillus-dominant subgroup.