Abstract / Summary
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 controls without known urolithiasis. 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. Community controls without a self-reported lifetime history of urolithiasis were matched to stone-forming participants by sex and nearest available age. 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. Exploratory functional profiling revealed reduced abundance of bacterial pathways related to glycine, serine, and tryptophan metabolism, although these associations did not remain significant after FDR correction in fully adjusted models. 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 distinct gut microbiome profile in CaOx stone formers, while the functional pathway signals remain exploratory and require validation in larger mechanistic studies.