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Mechanisms of the intestinal and urinary microbiome in kidney stone disease

Abstract

Kidney stone disease affects ~10% of the global population and the incidence continues to rise owing to the associated global increase in the incidence of medical conditions associated with kidney stone disease including, for example, those comprising the metabolic syndrome. Considering that the intestinal microbiome has a substantial influence on host metabolism, that evidence has suggested that the intestinal microbiome might have a role in maintaining oxalate homeostasis and kidney stone disease is unsurprising. In addition, the discovery that urine is not sterile but, like other sites of the human body, harbours commensal bacterial species that collectively form a urinary microbiome, is an additional factor that might influence the induction of crystal formation and stone growth directly in the kidney. Collectively, the microbiomes of the host could influence kidney stone disease at multiple levels, including intestinal oxalate absorption and direct crystal formation in the kidneys.

Key points

  • Composition of the intestinal microbiome influences host metabolism and overall health.

  • Patients with recurrent kidney stone disease have a disrupted intestinal microbiome composition, including reduced overall abundance of butyrate-producing species.

  • Butyrate is a key short-chain fatty acid responsible for overall intestinal epithelial integrity and health, a major determinant affecting the absorption of oxalate and other ions relevant to kidney stone disease.

  • Long-term history of antibiotic use is associated with an antibiotics-driven shift in intestinal microbiome composition and increased risk of kidney stone disease.

  • Members of the microbiome have a role in different processes of stone formation, including intestinal oxalate absorption and crystal formation.

  • Urine also has a native urinary microbiome, the composition of which is better able to differentiate between stone and non-stone formers than that of the intestine.

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Fig. 1: The effect of short-chain fatty acids on mechanisms that might affect oxalate absorption and mechanisms of stone formation.
Fig. 2: The role of butyrate in regulating intestinal epithelial cell tight junctions.
Fig. 3: Oxalate transport across intestinal epithelium.

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Miller, A.W., Penniston, K.L., Fitzpatrick, K. et al. Mechanisms of the intestinal and urinary microbiome in kidney stone disease. Nat Rev Urol (2022). https://doi.org/10.1038/s41585-022-00647-5

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