Beyond Infection: How Antimicrobial Therapies Influence the Urinary Microbiome and Stone Disease

The discovery of a resident urinary microbiome has significantly altered the understanding of urolithiasis, expanding its etiology beyond metabolic and dietary factors to include microbial contributions. This review highlights how specific uropathogens-particularly Proteus mirabilis, Klebsiella pneumoniae, and Escherichia coli-facilitate stone formation through mechanisms such as urease activity, citrate degradation, urine alkalinization, biofilm development, and inflammatory signaling. We critically examine how antibiotic therapies, while essential for treating urinary tract infections (UTIs), disrupt microbial homeostasis by depleting beneficial taxa like Lactobacillus and enabling colonization by lithogenic and resistant strains. Recurrent or broad-spectrum antibiotic use is linked to persistent dysbiosis and increased risk of stone recurrence. Additionally, this paper explores emerging microbiome-targeted strategies-such as probiotics, prebiotics, bacteriotherapy, and precision antimicrobials-as potential interventions to restore microbial balance and mitigate stone risk. Recognizing the urinary microbiome as a therapeutic target opens new avenues for personalized, microbiota-conscious strategies in the prevention and management of kidney stone disease.