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Deficient butyrate metabolism in the intestinal microbiome is a potential risk factor for recurrent kidney stone disease

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Abstract

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.

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Data availability

Raw shotgun metagenomic data were deposited to the sequence read archive under accession # SRR15021121- SRR15021153.

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Funding

Canadian Urologic Association—Astellas Research Grant Awarded to Dirk Lange. The funding body had no role in the design of the study and collection, analysis and interpretation of data or the writing of the manuscript.

Author information

Authors and Affiliations

  1. 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

    Wai Ho Choy, Ben H. Chew & Dirk Lange

  2. Graduate Program in Bioinformatics, University of British Columbia, Vancouver, BC, Canada

    Connor Morgan-Lang & Steven J. Hallam

  3. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada

    Amee R. Manges

  4. BC Centre for Disease Control, Vancouver, BC, Canada

    Amee R. Manges

  5. Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada

    Steven J. Hallam

  6. Genome Science and Technology Program, University of British Columbia, Vancouver, BC, Canada

    Steven J. Hallam

  7. ECOSCOPE Training Program, University of British Columbia, Vancouver, BC, Canada

    Steven J. Hallam

  8. Department of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA

    Kristina Penniston

  9. Departments of Urology and Immunology, Cleveland Clinic, Cleveland, OH, USA

    Ava Adler & Aaron Miller

  10. Johns Hopkins Bloomberg School of Public Health US, Baltimore, USA

    Ethan K. Gough

Authors
  1. Wai Ho Choy
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  2. Ava Adler
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  3. Connor Morgan-Lang
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  4. Ethan K. Gough
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  5. Steven J. Hallam
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  6. Amee R. Manges
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  7. Ben H. Chew
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  8. Kristina Penniston
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  9. Aaron Miller
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  10. Dirk Lange
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Contributions

Conception/design of the work: BC, DL. Acquisition, analysis, interpretation of data: BC, DL, WHC, AA, CML, EKG, SH, ARM, AM, KP. Software used in the work: WHC, SH, CML, AKG, ARM, AM, AA. Drafting/revision of manuscript: all authors.

Corresponding author

Correspondence to Dirk Lange.

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Conflict of interest

The authors declare that they have no competing interests associated with this work.

Ethical approval and consent to participate

The study was approved by the University of British Columbia Clinical Research Ethics Board with informed consent obtained from all participants.

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Choy, W.H., Adler, A., Morgan-Lang, C. et al. Deficient butyrate metabolism in the intestinal microbiome is a potential risk factor for recurrent kidney stone disease. Urolithiasis 52, 38 (2024). https://doi.org/10.1007/s00240-024-01534-x

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