Microbiota and kidney disease: the road ahead

Patricia P Bloom¹, Wendy S Garrett^{2

3}, Kristina L Penniston⁴, Mari-Karoliina H Winkler⁵, Stanley L Hazen^{6

7}, Jose Agudelo⁶, Mangesh Suryavanshi⁶, Ahmed Babiker⁸, Dylan Dodd^{9

10}, Michael A Fischbach^{11

12}, Kerwyn Casey Huang^{10

12

13}, Curtis Huttenhower^{2

3}, Bina Joe¹⁴, Kamyar Kalantar-Zadeh^{15

16

17}, Rob Knight^{18

19

20

21

22}, Aaron W Miller^{6

23}, Hamid Rabb²⁴, Anvesha Srivastava²⁵, W H Wilson Tang⁶, Peter J Turnbaugh^{12

26}, Alan W Walker²⁷, Nicola Wilck^{28

29}, Jiaojiao Xu³⁰, Tao Yang¹⁴, Jonathan Himmelfarb³¹, Matthew R Redinbo³², Gary D Wu³³, Michael H Woodworth³⁴, A Lenore Ackerman³⁵, Sebastian Winter³⁶, Markus M Rinschen^{37

38}, Hatim A Hassan^{39

40}, Annabel Biruete⁴¹, Amanda H Anderson⁴², Jennifer L Pluznick⁴³

Affiliations

¹ Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA. ppbloom@med.umich.edu.
² Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ University of Wisconsin School of Medicine and Public Health, Department of Urology, Madison, WI, USA.
⁵ School of Engineering, Civil and Environmental Engineering, University of Washington, Seattle, WA, USA.
⁶ Center for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
⁷ Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.
⁸ Division of Infectious Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
⁹ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA.
¹² Chan Zuckerberg Biohub-San Francisco, San Francisco, CA, USA.
¹³ Department of Bioengineering, Stanford University, Stanford, CA, USA.
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.
¹⁵ Division of Nephrology, Hypertension and Transplantation, The Lundquist Institute for Biomedical Innovation at Harbour UCLA Medical Center, Torrance, CA, USA.
¹⁶ Division of Nephrology, Hypertension and Transplantation, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA, USA.
¹⁷ Tibor Rubin Veterans Affairs Healthcare System, Long Beach, CA, USA.
¹⁸ Center for Microbiome innovation, University of California San Diego, La Jolla, CA, USA.
¹⁹ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
²⁰ Department of Computer Science & Engineering, University of California San Diego, La Jolla, CA, USA.
²¹ Shu Chien-Gene Lay Department of Engineering, University of California San Diego, La Jolla, CA, USA.
²² Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, CA, USA.
²³ Department of Urology, Cleveland Clinic, Cleveland, OH, USA.
²⁴ Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
²⁵ Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University School of Medicine, Washington, DC, USA.
²⁶ Department of Microbiology & Immunology, University of California, San Francisco, CA, USA.
²⁷ Microbiome, Food Innovation and Food Security Theme, Rowett Institute, University of Aberdeen, Aberdeen, UK.
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.
²⁹ Experimental and Clinical Research Center, A cooperation of Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
³⁰ Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
³¹ Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³² Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³³ Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³⁴ Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
³⁵ Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
³⁶ Department of Internal Medicine, Division of Infectious Diseases, UC Davis, Davis, CA, USA.
³⁷ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
³⁸ Department of Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
³⁹ Division of Nephrology & Hypertension, Mayo Clinic, Rochester, MN, USA.
⁴⁰ Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
⁴¹ Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
⁴² Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁴³ Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD, USA. jpluznick@jhmi.edu.

PMID: 40721656
PMCID: PMC12434838
DOI: 10.1038/s41581-025-00988-5

Review

Microbiota and kidney disease: the road ahead

Patricia P Bloom et al. Nat Rev Nephrol. 2025 Oct.

. 2025 Oct;21(10):702-716.

doi: 10.1038/s41581-025-00988-5. Epub 2025 Jul 28.

Authors

Affiliations

¹ Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA. ppbloom@med.umich.edu.
² Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ University of Wisconsin School of Medicine and Public Health, Department of Urology, Madison, WI, USA.
⁵ School of Engineering, Civil and Environmental Engineering, University of Washington, Seattle, WA, USA.
⁶ Center for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
⁷ Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.
⁸ Division of Infectious Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
⁹ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA.
¹² Chan Zuckerberg Biohub-San Francisco, San Francisco, CA, USA.
¹³ Department of Bioengineering, Stanford University, Stanford, CA, USA.
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.
¹⁵ Division of Nephrology, Hypertension and Transplantation, The Lundquist Institute for Biomedical Innovation at Harbour UCLA Medical Center, Torrance, CA, USA.
¹⁶ Division of Nephrology, Hypertension and Transplantation, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA, USA.
¹⁷ Tibor Rubin Veterans Affairs Healthcare System, Long Beach, CA, USA.
¹⁸ Center for Microbiome innovation, University of California San Diego, La Jolla, CA, USA.
¹⁹ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
²⁰ Department of Computer Science & Engineering, University of California San Diego, La Jolla, CA, USA.
²¹ Shu Chien-Gene Lay Department of Engineering, University of California San Diego, La Jolla, CA, USA.
²² Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, CA, USA.
²³ Department of Urology, Cleveland Clinic, Cleveland, OH, USA.
²⁴ Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
²⁵ Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University School of Medicine, Washington, DC, USA.
²⁶ Department of Microbiology & Immunology, University of California, San Francisco, CA, USA.
²⁷ Microbiome, Food Innovation and Food Security Theme, Rowett Institute, University of Aberdeen, Aberdeen, UK.
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.
²⁹ Experimental and Clinical Research Center, A cooperation of Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
³⁰ Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
³¹ Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³² Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³³ Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³⁴ Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
³⁵ Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
³⁶ Department of Internal Medicine, Division of Infectious Diseases, UC Davis, Davis, CA, USA.
³⁷ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
³⁸ Department of Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
³⁹ Division of Nephrology & Hypertension, Mayo Clinic, Rochester, MN, USA.
⁴⁰ Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
⁴¹ Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
⁴² Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁴³ Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD, USA. jpluznick@jhmi.edu.

PMID: 40721656
PMCID: PMC12434838
DOI: 10.1038/s41581-025-00988-5

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.

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Conflict of interest statement

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.

Figures

**Fig. 1 ∣. Interactions between the kidney and gut microbiota.**
Changes in kidney function can induce changes in gut microbial composition and conversely, gut microbial changes can influence kidney function. Of note, the microbiome changes that occur in the context of chronic kidney disease are complex and are also probably influenced by environmental factors, such as diet and age, and intrinsic host factors that are not yet fully understood. Altered microbial metabolites in chronic kidney disease include those produced by saccharolytic fermentation, such as short-chain fatty acids (SCFAs), and protein fermentation, such as aromatic amino-acid-derived uraemic toxins including oxalate, trimethylamine (TMA) and trimethylamine oxide (TMAO). In turn, alterations in microbial composition and function have been linked to several downstream effects, including alterations in immune cell function and impaired barrier function. TMAO has been linked to adverse cardiovascular outcomes and oxalate is a risk factor for renal stone disease.

See this image and copyright information in PMC

References

1. Hill NR et al. Global prevalence of chronic kidney disease - a systematic review and meta-analysis. PLoS ONE 11, e0158765 (2016). - PMC - PubMed
1. Snelson M et al. A renal clinician’s guide to the gut microbiota. J. Ren. Nutr. 30, 384–395 (2020). - PMC - PubMed
1. Lambert K et al. Targeting the gut microbiota in kidney disease: the future in renal nutrition and metabolism. J. Ren. Nutr. 33, S30–S39 (2023). - PMC - PubMed
1. Stanford J et al. The gut microbiota profile of adults with kidney disease and kidney stones: a systematic review of the literature. BMC Nephrol. 21, 215 (2020). - PMC - PubMed
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Microbiota and kidney disease: the road ahead

Affiliations

Microbiota and kidney disease: the road ahead

Authors

Affiliations

Abstract

Conflict of interest statement

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