Scholarlink

Background <p>Uropathogenic <i>Escherichia coli</i> (UPEC) is the principal causative agent of urinary tract infections (UTIs); however, urine samples from patients with recurrent cystitis frequently harbor diverse coexisting bacterial taxa. How such polymicrobial urobiota can functionally modulate bladder susceptibility to UPEC infection remains unclear.</p> Results <p>We integrated 16S rRNA-based microbiota profiling of a recurrent cystitis cohort with mechanistic in vitro and in vivo models to assess host–microbe interactions within the urinary tract. We identified <i>Gardnerella piotii</i> as a microbial modifier that enhances the infectivity of UPEC without inducing overt epithelial damage or inflammation. Exposure to <i>G. piotii</i> increased UPEC burden in the bladder and in bladder epithelial cells by promoting early bacterial adhesion. Mechanistically, <i>G. piotii</i> actively produced succinate, which acted as a host-active metabolite to selectively upregulate uroplakin expression through signaling via the succinate receptor GPR91. Genetic ablation of GPR91 abolished succinate- and <i>G. piotii</i>-induced uroplakin upregulation and UPEC adhesion, establishing that this epithelial signaling axis is necessary for infection sensitization. Importantly, the heightened UPEC susceptibility induced by <i>G. piotii</i> could be partially mitigated; introduction of the beneficial commensal <i>Lactobacillus crispatus</i> or exposure to lactate partially reduced UPEC burden in vivo, highlighting the functional plasticity of the bladder microenvironment.</p> Conclusions <p>These findings unravel a metabolite-driven mechanism by which members of the urinary microbiota modulate host epithelial programs to influence UPEC infection. By identifying a succinate–GPR91–uroplakin signaling axis that links polymicrobial community structure to epithelial susceptibility, our study reframes recurrent cystitis as a dynamic ecological process shaped by microbial existence and metabolic signaling rather than by an individual pathogen.</p> <p><MediaObject ID="MOESM2"><VideoObject FileRef="MediaObjects/40168_2026_2499_MOESM2_ESM.mp4" VideoID="ChGKhBzCW4H5PHuKpnkAaR"><Caption Language="En" xml:lang="en"><CaptionContent><p>Video Abstract</p></CaptionContent></Caption></VideoObject></MediaObject></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Gardnerella piotii enhances uropathogenic Escherichia coli infection through a succinate–GPR91–uroplakin axis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月5日

查看全文
  • Ho Young Lee,
  • Min Jung Kim,
  • Manisha Naskar,
  • Karen Serrano-Arevalo,
  • Yong-Joon Cho,
  • Hee Bong Shin,
  • Hae Woong Choi,
  • Young Ho Kim

摘要

Background

Uropathogenic Escherichia coli (UPEC) is the principal causative agent of urinary tract infections (UTIs); however, urine samples from patients with recurrent cystitis frequently harbor diverse coexisting bacterial taxa. How such polymicrobial urobiota can functionally modulate bladder susceptibility to UPEC infection remains unclear.

Results

We integrated 16S rRNA-based microbiota profiling of a recurrent cystitis cohort with mechanistic in vitro and in vivo models to assess host–microbe interactions within the urinary tract. We identified Gardnerella piotii as a microbial modifier that enhances the infectivity of UPEC without inducing overt epithelial damage or inflammation. Exposure to G. piotii increased UPEC burden in the bladder and in bladder epithelial cells by promoting early bacterial adhesion. Mechanistically, G. piotii actively produced succinate, which acted as a host-active metabolite to selectively upregulate uroplakin expression through signaling via the succinate receptor GPR91. Genetic ablation of GPR91 abolished succinate- and G. piotii-induced uroplakin upregulation and UPEC adhesion, establishing that this epithelial signaling axis is necessary for infection sensitization. Importantly, the heightened UPEC susceptibility induced by G. piotii could be partially mitigated; introduction of the beneficial commensal Lactobacillus crispatus or exposure to lactate partially reduced UPEC burden in vivo, highlighting the functional plasticity of the bladder microenvironment.

Conclusions

These findings unravel a metabolite-driven mechanism by which members of the urinary microbiota modulate host epithelial programs to influence UPEC infection. By identifying a succinate–GPR91–uroplakin signaling axis that links polymicrobial community structure to epithelial susceptibility, our study reframes recurrent cystitis as a dynamic ecological process shaped by microbial existence and metabolic signaling rather than by an individual pathogen.

Video Abstract