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Gut microbiome composition and oxalate-related metabolic functions in staghorn calcium oxalate stone formers: a shotgun metagenomic analysis

Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction: To characterize gut microbiome composition and oxalate-related metabolic functions in patients with staghorn calcium oxalate (CaOx) stones using shotgun metagenomic sequencing, and to determine whether specific bacterial taxa and pathways differ from stone-free controls. Methods: We conducted a prospective study of adults aged 21–75 years with partial or complete staghorn stones composed of >80% CaOx who underwent percutaneous nephrolithotomy between January 2023 and April 2024. Age-matched stone-free individuals served as controls. Stool samples were collected before intervention, preserved in stabilizing buffer, and analyzed using metagenomic shotgun sequencing. Microbial diversity, taxonomic composition, and metabolic pathway abundances were assessed using standard bioinformatic pipelines. Dietary intake and clinical covariates were incorporated into multivariable models. Oxalobacter formigenes prevalence was determined from metagenomic reads. Results: Fifty-six participants were included (28 stone formers, 28 controls). Stone formers demonstrated significantly reduced alpha diversity (Shannon and Chao1 indices, p<0.05) and distinct beta diversity profiles (PERMANOVA R²=0.030, p=0.009), independent of diabetes, hypertension, urolithiasis history, and respiratory conditions. Differential abundance analysis showed increased Erysipelatoclostridium ramosum SGB6744 and reduced levels of several commensals, including Bifidobacterium adolescentis , Faecalibacterium spp ., and Eubacterium rectale . Functional profiling revealed reduced abundance of bacterial pathways related to glycine, serine, and tryptophan metabolism. Oxalobacter formigenes was detected less frequently in stone formers than controls (3.6% vs 21.4%). Conclusions: Staghorn CaOx stone formers exhibit gut microbiome dysbiosis and reduced representation of metabolic pathways linked to endogenous oxalate handling. These findings support a potential mechanistic role of the gut microbiome in CaOx stone biology and justify future interventional studies targeting microbial metabolic functions.
Language: English
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7215826841
FWCI:
Cites: 26
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