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Microbiota and kidney disease: the road ahead

Nature Reviews Nephrology volume 21, pages 702–716 (2025)Cite this article

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Abstract

More than 850 million individuals worldwide, accounting for 10–15% of the adult population, are estimated to have chronic kidney disease. Each of these individuals is host to tens of trillions of microorganisms that are collectively referred to as microbiota — a dynamic ecosystem that both influences host health and is itself influenced by changes in the host. Available evidence supports the existence of functional connections between resident microorganisms and kidney health that are altered in the context of specific kidney diseases, including acute kidney injury, chronic kidney disease and renal stone disease. Moreover, promising data from preclinical studies suggest that targeting of gut microbial pathways may provide new therapeutic opportunities for the treatment of kidney disease. This Roadmap describes current understanding of the mechanisms by which microorganisms regulate host organ function, the effects of kidney disease on the gut microbiome, and how these insights may contribute to the development of microbe-targeted therapeutics. We highlight key knowledge gaps that remain to be addressed and strategies for addressing these, outlining both the promise and the potential pitfalls of leveraging our understanding of the gut microbiota to better understand and treat kidney disease.

Key points

  • A bidirectional relationship exists between microorganisms and kidney disease: microorganisms can influence host health, and are themselves influenced by changes in host health.

  • The relationship between microorganisms and renal disease is likely to be at least somewhat specific to each disease type.

  • Further studies are needed to determine the prognostic value of gut microorganisms in kidney disease.

  • Available evidence suggests that interactions occur between microorganisms and drugs used to treat kidney disease; further studies are needed to determine the nature and consequences of these interactions.

  • There is also promise in the possibility of targeting gut microorganisms as a therapeutic strategy.

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Fig. 1: Interactions between the kidney and gut microbiota.

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Acknowledgements

The authors would like to acknowledge the workshop sponsored by the National Institutes of Health (NIH) on 28 and 29 May 2024 entitled “Gut Microbiota and Kidney Disease” and hosted by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The authors would specifically like to acknowledge D. Nihalani for helping to develop the workshop and bringing this expert panel together. They would also like to acknowledge other members of the NIDDK — P. Perrin, R. Lunsford, C. Maric-Bilkan, C. Mullins, C. J. Ketchum, and D. Gossett — who also helped to develop the workshop. The authors are grateful for funding that has supported their work: P.P.B. was supported by NIDDK grant K23 DK138239, and a research grant from Vedanta Biosciences, Inc.; K.L.P. was supported by NIH grant U24 DK127726; M.-K.H.W. was supported by NIH Katz Early Investigator Award R01 DK130815; S.L.H. was supported by NIH grants R01 HL172805, R01 HL103866 and P01 HL147823; J.A. was supported by the Urology Care Foundation grant UCF202-JA and ISAC award 22AU4279; A. Babiker was supported by an Antibacterial Resistance Leadership Group Early Faculty Seedling Award (NIAID) UM1 AI104681; D.D. was supported by NIH grants R35 GM142873 and R01 AT011396, the Stanford Microbiome Therapies Initiative and an OHF-ASN Foundation for Kidney Research Career Development Award; K.C.H. was supported by NIH grant RM1 GM135102; B.J. was supported by NHLBI grant R01 HL171401; A.W.M. was supported by NIDDK grant R01 DK121689; A.S. was supported by NIH grants R01 DK125256, U01 DK099914, and U01 DK099924; P.J.T. was supported by NIH grants R01 DK114034, R01 HL122593 and R01 CA255116; A.W.W. and the Rowett Institute were supported by core funding from the Scottish Government’s Rural and Environment Science and Analytical Services Division; N.W. was supported by the European Research Council grant 852796 under the European Union’s Horizon 2020 research and innovation programme, Corona-Stiftung grant S199/10080/2019, German Federal Ministry of Education and Research TAhRget grant 01EJ2202A and German Research Foundation (DFG) grant CRC 1470, 437531118; J.X. was supported by American Heart Association Career Development Award 23CDA1050485; T.Y. was supported by American Heart Association Career Development Award 852969, NIH grant R21 AG079357 and the University of Toledo Startup Fund; J.H. was supported by NIH grants UH3 TR003288, U2CTR004867, U01 DK133090, U24 DK114886, R01 DK133177 and R01 DK130815; M.R.R. is supported by NIH R35 GM152079; G.D.W. was supported by NIH grant R01 DK107566, the Center for Molecular Studies in Digestive and Liver Diseases under NIH grant P30 DK 050306, the PennCHOP MIcrobiome Program and the Penn Center for Nutritional Science and Medicine; H.R. was supported by NIDDK grants R01 DK123342 and R01 DK132278; M.H.W. was supported by NIAID grant K23 AI144036 and the US Centers for Disease Control and Prevention grant U54 CK000601; A.L.A. was supported by NIDDK grants K08 DK118176 and R01 DK138121, NCCIH grant R61 AT013008, DOD grant W81XWH2110644, the ISAC Award program, SUFU Foundation, Bristol Meyers Squibb Foundation, Cures Within Reach and the Urology Care Foundation; S.W. was supported by NIH grants R01 AI118807, R01 DK138912, R21 AI166263 and R21 AI171537 and Burroughs Wellcome Fund grant 1017880; M.M.R. was supported by DFG grants RI 2811/2-2 and SFB1192-project B10, Young Investigator Award NNF19OC0056043 from the Novo Nordisk Foundation, the Carlsberg Young Investigator fellowship and a grant by the Augustinusfonden, Denmark; A. Biruete was supported by NIH grant K12 TR004415 and the Showalter Trust Fund; A.H.A. was supported by NIH grants R01 DK107566, U24 DK060990, U24 DK137318 and UM1 TR004771; J.L.P. was supported by an American Heart Association Established Investigator Award and NIH grants R21 AG081683, R01 DK137762, R01 DK139021 and U54 DK137331.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA

    Patricia P. Bloom

  2. Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Wendy S. Garrett & Curtis Huttenhower

  3. Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Wendy S. Garrett & Curtis Huttenhower

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

    Kristina L. Penniston

  5. School of Engineering, Civil and Environmental Engineering, University of Washington, Seattle, WA, USA

    Mari-Karoliina H. Winkler

  6. Center for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Stanley L. Hazen, Jose Agudelo, Mangesh Suryavanshi, Aaron W. Miller & W. H. Wilson Tang

  7. Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA

    Stanley L. Hazen

  8. Division of Infectious Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA

    Ahmed Babiker

  9. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

    Dylan Dodd

  10. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA

    Dylan Dodd & Kerwyn Casey Huang

  11. Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA

    Michael A. Fischbach

  12. Chan Zuckerberg Biohub-San Francisco, San Francisco, CA, USA

    Michael A. Fischbach, Kerwyn Casey Huang & Peter J. Turnbaugh

  13. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Kerwyn Casey Huang

  14. Department of Physiology and Pharmacology, Center for Hypertension and Precision Medicine, Microbiome Consortium, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Bina Joe & Tao Yang  (杨涛)

  15. Division of Nephrology, Hypertension and Transplantation, The Lundquist Institute for Biomedical Innovation at Harbour UCLA Medical Center, Torrance, CA, USA

    Kamyar Kalantar-Zadeh

  16. Division of Nephrology, Hypertension and Transplantation, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA, USA

    Kamyar Kalantar-Zadeh

  17. Tibor Rubin Veterans Affairs Healthcare System, Long Beach, CA, USA

    Kamyar Kalantar-Zadeh

  18. Center for Microbiome innovation, University of California San Diego, La Jolla, CA, USA

    Rob Knight

  19. Department of Pediatrics, University of California San Diego, La Jolla, CA, USA

    Rob Knight

  20. Department of Computer Science & Engineering, University of California San Diego, La Jolla, CA, USA

    Rob Knight

  21. Shu Chien-Gene Lay Department of Engineering, University of California San Diego, La Jolla, CA, USA

    Rob Knight

  22. Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, CA, USA

    Rob Knight

  23. Department of Urology, Cleveland Clinic, Cleveland, OH, USA

    Aaron W. Miller

  24. Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Hamid Rabb

  25. Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University School of Medicine, Washington, DC, USA

    Anvesha Srivastava

  26. Department of Microbiology & Immunology, University of California, San Francisco, CA, USA

    Peter J. Turnbaugh

  27. Microbiome, Food Innovation and Food Security Theme, Rowett Institute, University of Aberdeen, Aberdeen, UK

    Alan W. Walker

  28. Department of Nephrology and Internal Intensive Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Nicola Wilck

  29. Experimental and Clinical Research Center, A cooperation of Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Nicola Wilck

  30. Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Jiaojiao Xu & Jennifer L. Pluznick

  31. Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jonathan Himmelfarb

  32. Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Matthew R. Redinbo

  33. Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Gary D. Wu

  34. Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA

    Michael H. Woodworth

  35. Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    A. Lenore Ackerman

  36. Department of Internal Medicine, Division of Infectious Diseases, UC Davis, Davis, CA, USA

    Sebastian Winter

  37. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Markus M. Rinschen

  38. Department of Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany

    Markus M. Rinschen

  39. Division of Nephrology & Hypertension, Mayo Clinic, Rochester, MN, USA

    Hatim A. Hassan

  40. Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN, USA

    Hatim A. Hassan

  41. Department of Nutrition Science, Purdue University, West Lafayette, IN, USA

    Annabel Biruete

  42. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Amanda H. Anderson

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Contributions

The authors contributed equally to all aspects of the article.

Corresponding authors

Correspondence to Patricia P. Bloom or Jennifer L. Pluznick.

Ethics declarations

Competing interests

P.P.B. has received research funding from Vedanta Biosciences and consults for Nexilico and Boehringer Ingelheim. W.S.G. has received research funding from Merck, Sharpe & Dohme, and Astellas Pharmaceuticals. and serves on the scientific advisory boards of Empress Therapeutics, Freya Biosciences, Sail Biosciences and Seres Therapeutics. S.L.H. is a co-inventor on patents relating to diagnostics and therapeutics with a right to receive royalty payments for inventions or discoveries related to diagnostics or therapeutics from Cleveland Heart Lab, a fully owned subsidiary of Quest Diagnostics, and is a consultant for and receives research funds from Zehna Therapeutics. A. Babiker has served on a clinical advisory board for Beckman Coulter. M.A.F. is a co-founder of Kelonia and Revolution Medicines, a co-founder and director of Azalea Therapeutics, a member of the scientific advisory boards of the Chan Zuckerberg Initiative, NGM Biopharmaceuticals and TCG Labs/Soleil Labs, and an innovation partner at The Column Group. C.H. serves on the scientific advisory committee for Seres Therapeutics and Empress Therapeutics. K.K.-Z. has received honoraria from Fresenius Kabi. R.K. is a scientific advisory board member and consultant for BiomeSense, Inc., through which he has equity and receives income, is a scientific advisory board member and has equity in GenCirq, is a consultant for and receives income from DayTwo, has equity in and acts as a consultant for Cybele, is a co-founder of and has equity in Biota, Inc., and is a cofounder and scientific advisory board member of and has equity in Micronoma; the terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. A.W.M. has received funding from Coloplast and is a scientific advisory board member for the Oxalosis and Hyperoxaluria Foundation. H.R. is a scientific advisory board member for Renibus Therapeutics and Rapafusyn Pharmaceuticals. W.H.W.T. serves as consultant for Sequana Medical, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics, WhiteSwell, Boston Scientific, CardiaTec Biosciences, Bristol Myers Squibb, Alleviant Medical, Alexion Pharmaceuticals, Salubris Biotherapeutics and BioCardia, and has received honoraria from Springer, Belvoir Media Group and the American Board of Internal Medicine. A.W.W. has a research grant from ZOE, Ltd. and consults for EnteroBiotix, Ltd. M.R.R. has received research funding from Merck and Lilly, and is a founder of Symberix, Inc. N.W. received speaker honoraria from Novartis and Bayer. G.D.W. is an advisory board member for Danone and BioCodex and receives research support from Intercept Pharmaceuticals. A.L.A. has received consulting fees from AbbVie, Inc., holds stock options in Watershed Medical and serves on advisory boards for GlaxoSmithKline and Desert Harvest. M.M.R. has received research funding from Novo Nordisk A/S, Copenhagen. H.A.H. is the co-founder, president and Chief Scientific Officer of Oxalo Therapeutics, and is a scientific advisory council member of Oxalosis and the Hyperoxaluria Foundation. A. Biruete has received honoraria from Ardelyx, FMC North America, Dialysis Clinic Inc. and the National Kidney Foundation, and is part of the NextGen Scientist Cohort of the National Dairy Council. All other authors declare that they have no competing interests.

Peer review

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Nature Reviews Nephrology thanks Sang-Kyung Jo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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This report does not represent the official view of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institutes of Health (NIH), the Department of Health and Human Services (HHS) or any part of the US Federal Government. No official support or endorsement of this article by the NIDDK, NIAID or NIH is intended or should be inferred. This content is solely the responsibility of the authors and does not necessarily represent the official views of the Centers for Disease Control and Prevention (CDC).

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Bloom, P.P., Garrett, W.S., Penniston, K.L. et al. Microbiota and kidney disease: the road ahead. Nat Rev Nephrol 21, 702–716 (2025). https://doi.org/10.1038/s41581-025-00988-5

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