Intestinal microbiome dysbiosis is a known risk factor for recurrent kidney stone disease (KSD) with prior data suggesting a role for dysfunctional metabolic pathways other than those directly utilizing oxalate. To identify alternative mechanisms, the current study analyzed differences in the metabolic potential of intestinal microbiomes of patients (n = 17) and live-in controls (n = 17) and determined their relevance to increased risk for KSD using shotgun metagenomic sequencing. We found no differences in the abundance of genes associated with known oxalate degradation pathways, supporting the notion that dysfunction in other metabolic pathways plays a role in KSD. Further analysis showed decreased abundance of key enzymes involved in butyrate biosynthesis in patient intestinal microbiomes. Furthermore, de novo construction of microbial genomes showed that the majority of genes significantly enriched in non-stone formers are affiliated with Faecalibacterium prausnitzii, a major butyrate producer. Specifically pertaining to butyrate metabolism, the majority of abundant genes mapped back to F. prausnitzii, Alistipes spp., and Akkermansia muciniphila. No differences were observed in ascorbate or glyoxylate metabolic pathways. Collectively, these data suggest that impaired bacterial-associated butyrate metabolism may be an oxalate-independent mechanism that contributes to an increased risk for recurrent KSD. This indicates that the role of the intestinal microbiome in recurrent KSD is multi-factorial, which is representative of the highly intertwined metabolic nature of this complex environment. Future bacteria-based treatments must not be restricted to targeting only oxalate metabolism.
Urolithiasis. 2024 Feb 28*** epublish ***
Wai Ho Choy, Ava Adler, Connor Morgan-Lang, Ethan K Gough, Steven J Hallam, Amee R Manges, Ben H Chew, Kristina Penniston, Aaron Miller, Dirk Lange
Department of Urologic Sciences, The Stone Centre at VGH, University of British Columbia, Jack Bell Research Centre, Rm. 550-3, 2660 Oak Street, Vancouver, BC, V6J 1G7, Canada., Departments of Urology and Immunology, Cleveland Clinic, Cleveland, OH, USA., Graduate Program in Bioinformatics, University of British Columbia, Vancouver, BC, Canada., Johns Hopkins Bloomberg School of Public Health US, Baltimore, USA., School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada., Department of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA., Department of Urologic Sciences, The Stone Centre at VGH, University of British Columbia, Jack Bell Research Centre, Rm. 550-3, 2660 Oak Street, Vancouver, BC, V6J 1G7, Canada. .