Enterobacter cloacae: a villain in CaOx stone disease?

Area of Science:

• Urology
• Microbiology
• Nephrology

Background:

• Calcium oxalate (CaOx) stones are a common kidney stone type.
• The role of the urinary tract microbiome in CaOx stone pathogenesis remains unclear.
• Understanding microbial contributions is crucial for developing novel prevention and treatment strategies.

Purpose of the Study:

• To investigate the association between urinary tract microbiome composition and CaOx stone formation.
• To identify specific bacterial species and their mechanisms involved in CaOx stone development.
• To explore the synergistic effects of bacteria and metabolites in promoting stone formation.

Main Methods:

• Recruitment of patients with unilateral CaOx stones for self-controlled urine sample collection.
• 16S rRNA gene sequencing for urinary microbiome analysis.
• Whole-genome sequencing of Enterobacter cloacae and bioinformatic pathway analysis.
• In vivo studies using SD rats involving glyoxylic acid administration and Enterobacter cloacae inoculation, with histological and molecular analyses (Von Kossa, TUNEL, Western Blot).

Main Results:

• Significant differences in urinary microbiome composition were observed between stone-affected and unaffected kidneys.
• Enterobacter cloacae was identified as a key differentiating bacterium, possessing virulence factors like Flagellin and LPS.
• Bioinformatic analysis suggested Enterobacter cloacae induces CaOx stones via ion binding and signaling pathways.
• In vivo experiments showed Enterobacter cloacae exacerbates glyoxylic acid-induced kidney apoptosis, crystal deposition, and inflammatory responses (IL-6, Mcp-1, BMP2, OPN).

Conclusions:

• The urinary tract microbiome, particularly Enterobacter cloacae, may play a significant role in the pathogenesis of calcium oxalate stones.
• Enterobacter cloacae appears to promote CaOx stone formation through specific virulence factors and by interacting with host inflammatory pathways.
• These findings represent a preliminary exploration, highlighting the need for further investigation into the complex interplay between the microbiome, metabolites, and kidney stone disease.