The stone-degrading metabolic potential of the urinary microbiome: Sexual dimorphism and dysbiosis in urolithiasis

Ying Li; Chengqiang Mo; Yun Xie; Zhixin Huang; Lingwu Chen; Xinqiang Xie; Junhang Luo; Shixuan Huang; Shuangjian Jiang; Tianhao Zhang; Jumei Zhang; Rongpei Wu; Qingping Wu; Ying Li; Chengqiang Mo; Yun Xie; Zhixin Huang; Lingwu Chen; Xinqiang Xie; Junhang Luo; Shixuan Huang; Shuangjian Jiang; Tianhao Zhang; Jumei Zhang; Rongpei Wu; Qingping Wu

doi:10.3934/microbiol.2026026

AIMS Microbiology

2026, Volume 12, Issue 3: 595-609. doi: 10.3934/microbiol.2026026

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Research article

The stone-degrading metabolic potential of the urinary microbiome: Sexual dimorphism and dysbiosis in urolithiasis

1.
State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Safety and Health, National Health Commission Science and Technology Innovation Platform for Nutrition and Safety of Microbial Food, Key Laboratory of Big Data Technologies for Food Microbiological Safety, State Administration for Market Regulation, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China
2.
Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
3.
Division of Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
4.
Food and Drug Laboratory, Guangdong Detection Center of Microbiology, Guangzhou, 510070, China
These three authors contributed equally.

Received: 27 February 2026 Revised: 04 August 2026 Accepted: 24 August 2026 Published: 03 September 2026

Urolithiasis is a prevalent global health burden characterized by high recurrence rates and marked sexual dimorphism. While the gut microbiome's role in oxalate degradation is established, the functional capacity of the local urinary microbiome remains largely unexplored. This study investigated the composition and function of the urinary microbiome in 40 healthy volunteers and 61 urolithiasis patients using 16S rRNA amplicon sequencing, alongside a retrospective analysis of stone composition in 2027 patients. We identified a diverse, ecologically structured microbiome in healthy urine dominated by genera such as Lactobacillus, Streptococcus, and Gardnerella. Significant sex-dependent differences were observed: While males exhibited higher microbial α-diversity, females demonstrated a distinct compositional structure with superior predicted functional capacity for stone degradation. Specifically, the female microbiome was enriched with enzymes including oxalyl-CoA decarboxylase, formyl-CoA transferase, urate oxidase, and purine nucleosidase. Correlation analysis identified Lactobacillus, Enterococcus, and Gardnerella as key contributors to this litholytic potential. Conversely, urolithiasis patients displayed significant dysbiosis, characterized by disrupted microbial networks and a marked reduction in these stone-degrading enzymes. Clinical data supported these findings, revealing a significantly higher prevalence of uric acid stones in males, consistent with their lower microbial degradation capacity. These findings suggest that the healthy urinary microbiome functions as a metabolically active defense system against stone formation. The observed sex-specific variations in microbial composition and enzymatic function provide a novel mechanistic explanation for the epidemiological sex disparities in urolithiasis, highlighting the urinary–kidney axis as a potential therapeutic target.
- urinary microbiome,
- sex discrepancy,
- Lactobacillus,
- urolithiasis,
- urolith degradation
Citation: Ying Li, Chengqiang Mo, Yun Xie, Zhixin Huang, Lingwu Chen, Xinqiang Xie, Junhang Luo, Shixuan Huang, Shuangjian Jiang, Tianhao Zhang, Jumei Zhang, Rongpei Wu, Qingping Wu. The stone-degrading metabolic potential of the urinary microbiome: Sexual dimorphism and dysbiosis in urolithiasis[J]. AIMS Microbiology, 2026, 12(3): 595-609. doi: 10.3934/microbiol.2026026

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Abstract

Urolithiasis is a prevalent global health burden characterized by high recurrence rates and marked sexual dimorphism. While the gut microbiome's role in oxalate degradation is established, the functional capacity of the local urinary microbiome remains largely unexplored. This study investigated the composition and function of the urinary microbiome in 40 healthy volunteers and 61 urolithiasis patients using 16S rRNA amplicon sequencing, alongside a retrospective analysis of stone composition in 2027 patients. We identified a diverse, ecologically structured microbiome in healthy urine dominated by genera such as Lactobacillus, Streptococcus, and Gardnerella. Significant sex-dependent differences were observed: While males exhibited higher microbial α-diversity, females demonstrated a distinct compositional structure with superior predicted functional capacity for stone degradation. Specifically, the female microbiome was enriched with enzymes including oxalyl-CoA decarboxylase, formyl-CoA transferase, urate oxidase, and purine nucleosidase. Correlation analysis identified Lactobacillus, Enterococcus, and Gardnerella as key contributors to this litholytic potential. Conversely, urolithiasis patients displayed significant dysbiosis, characterized by disrupted microbial networks and a marked reduction in these stone-degrading enzymes. Clinical data supported these findings, revealing a significantly higher prevalence of uric acid stones in males, consistent with their lower microbial degradation capacity. These findings suggest that the healthy urinary microbiome functions as a metabolically active defense system against stone formation. The observed sex-specific variations in microbial composition and enzymatic function provide a novel mechanistic explanation for the epidemiological sex disparities in urolithiasis, highlighting the urinary–kidney axis as a potential therapeutic target.

Acknowledgments

This study was supported by the National Key R&D Program of China (2023YFF1104100), Key Laboratory of Guangdong Province (2020B121201009), Natural Science Foundation of Guangdong Province (2025A1515012225), and Guangdong Academy of Sciences (2022GDASZH-2022010101).

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