Gut Microbiome as a Risk Factor for Future CKD

Introduction: Gut microbiome has been linked with chronic kidney disease (CKD) in several small cross-sectional studies. However, the relationship between baseline gut microbiome and long-term incident CKD remains unknown. Methods: We performed fecal sampling and measured serum creatinine (SCR) (N =...

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Main Authors: Tapio Hellman, Li-Fang Yeo, Joonatan Palmu, Aki Havulinna, Pekka Jousilahti, Ville Laitinen, Katariina Pärnänen, Veikko Salomaa, Leo Lahti, Rob Knight, Teemu Niiranen
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024925002086
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author Tapio Hellman
Li-Fang Yeo
Joonatan Palmu
Aki Havulinna
Pekka Jousilahti
Ville Laitinen
Katariina Pärnänen
Veikko Salomaa
Leo Lahti
Rob Knight
Teemu Niiranen
author_facet Tapio Hellman
Li-Fang Yeo
Joonatan Palmu
Aki Havulinna
Pekka Jousilahti
Ville Laitinen
Katariina Pärnänen
Veikko Salomaa
Leo Lahti
Rob Knight
Teemu Niiranen
author_sort Tapio Hellman
collection DOAJ
description Introduction: Gut microbiome has been linked with chronic kidney disease (CKD) in several small cross-sectional studies. However, the relationship between baseline gut microbiome and long-term incident CKD remains unknown. Methods: We performed fecal sampling and measured serum creatinine (SCR) (N = 6699) and urine albumin-to-creatinine ratio (UACR) (N = 797) in a population-based cohort examined in the year 2002. We assessed the multivariable-adjusted associations of gut metagenome with baseline SCR, baseline UACR, and register-based incident CKD. Results: The mean age of the participants was 49.5 ± 12.9 years and 45.8% were men. During a median follow-up of 18.6 years, 108 participants developed incident CKD. In prospective analyses, increased baseline gut microbiome alpha diversity was associated with lower risk of incident CKD (hazard ratio per 1 SD: 0.84; 95% confidence interval [CI]: 0.71–0.99; P = 0.04). Gut microbial beta diversity and taxa were not related to incident CKD (P ≥ 0.09 for all). In cross-sectional analyses, alpha diversity (beta per 1 SD: 1.28; 95% CI: 0.64–1.98; P < 0.001) and beta diversity (P = 0.002; R2 = 0.12%) were associated with SCR, whereas no associations were observed for UACR. In total, 43 significant species-level associations with SCR were observed and 16 negative associations (37.2%) for species belonging to the Lachnospiraceae family. Conclusion: Our results suggest that decreased gut microbial diversity may be related to risk of future CKD and that a potential link between the Lachnospiraceae family and desirable kidney health exists. Our results extend previous cross-sectional studies and help to establish the basis for examining gut microbiome as a CKD risk factor.
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spelling doaj-art-e9a717ad49684aa6905190849dfe753b2025-08-20T03:46:58ZengElsevierKidney International Reports2468-02492025-06-011061673168210.1016/j.ekir.2025.04.007Gut Microbiome as a Risk Factor for Future CKDTapio Hellman0Li-Fang Yeo1Joonatan Palmu2Aki Havulinna3Pekka Jousilahti4Ville Laitinen5Katariina Pärnänen6Veikko Salomaa7Leo Lahti8Rob Knight9Teemu Niiranen10Kidney Center, Turku University Hospital and University of Turku, Turku, Finland; Correspondence: Tapio Hellman, Kidney Center, Turku University Hospital, Kiinamyllynkatu 4-8, PO Box 52, 20521 Turku, Finland.Division of Medicine, University of Turku, Turku, Finland; Department of Internal Medicine, Turku University Hospital and University of Turku, Turku, FinlandDivision of Medicine, University of Turku, Turku, Finland; Department of Internal Medicine, Turku University Hospital and University of Turku, Turku, Finland; Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, FinlandDepartment of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland; Department of Computing, University of Turku, Turku, FinlandDepartment of Public Health, Finnish Institute for Health and Welfare, Helsinki, FinlandDepartment of Computing, University of Turku, Turku, FinlandDepartment of Computing, University of Turku, Turku, FinlandDepartment of Public Health, Finnish Institute for Health and Welfare, Helsinki, FinlandDepartment of Computing, University of Turku, Turku, FinlandDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA; Center for Microbiome Innovation, Joan and Irwin Jacobs School of Engineering, University of California San Diego, La Jolla, California, USA; Department of Bioengineering, University of California San Diego, La Jolla, California, USA; Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA; Halıcıoğlu Data Science Institute, University of California, San Diego, La Jolla, California, USADivision of Medicine, University of Turku, Turku, Finland; Department of Internal Medicine, Turku University Hospital and University of Turku, Turku, Finland; Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, FinlandIntroduction: Gut microbiome has been linked with chronic kidney disease (CKD) in several small cross-sectional studies. However, the relationship between baseline gut microbiome and long-term incident CKD remains unknown. Methods: We performed fecal sampling and measured serum creatinine (SCR) (N = 6699) and urine albumin-to-creatinine ratio (UACR) (N = 797) in a population-based cohort examined in the year 2002. We assessed the multivariable-adjusted associations of gut metagenome with baseline SCR, baseline UACR, and register-based incident CKD. Results: The mean age of the participants was 49.5 ± 12.9 years and 45.8% were men. During a median follow-up of 18.6 years, 108 participants developed incident CKD. In prospective analyses, increased baseline gut microbiome alpha diversity was associated with lower risk of incident CKD (hazard ratio per 1 SD: 0.84; 95% confidence interval [CI]: 0.71–0.99; P = 0.04). Gut microbial beta diversity and taxa were not related to incident CKD (P ≥ 0.09 for all). In cross-sectional analyses, alpha diversity (beta per 1 SD: 1.28; 95% CI: 0.64–1.98; P < 0.001) and beta diversity (P = 0.002; R2 = 0.12%) were associated with SCR, whereas no associations were observed for UACR. In total, 43 significant species-level associations with SCR were observed and 16 negative associations (37.2%) for species belonging to the Lachnospiraceae family. Conclusion: Our results suggest that decreased gut microbial diversity may be related to risk of future CKD and that a potential link between the Lachnospiraceae family and desirable kidney health exists. Our results extend previous cross-sectional studies and help to establish the basis for examining gut microbiome as a CKD risk factor.http://www.sciencedirect.com/science/article/pii/S2468024925002086clinical studychronic kidney diseasemicrobiologyproteinuria
spellingShingle Tapio Hellman
Li-Fang Yeo
Joonatan Palmu
Aki Havulinna
Pekka Jousilahti
Ville Laitinen
Katariina Pärnänen
Veikko Salomaa
Leo Lahti
Rob Knight
Teemu Niiranen
Gut Microbiome as a Risk Factor for Future CKD
Kidney International Reports
clinical study
chronic kidney disease
microbiology
proteinuria
title Gut Microbiome as a Risk Factor for Future CKD
title_full Gut Microbiome as a Risk Factor for Future CKD
title_fullStr Gut Microbiome as a Risk Factor for Future CKD
title_full_unstemmed Gut Microbiome as a Risk Factor for Future CKD
title_short Gut Microbiome as a Risk Factor for Future CKD
title_sort gut microbiome as a risk factor for future ckd
topic clinical study
chronic kidney disease
microbiology
proteinuria
url http://www.sciencedirect.com/science/article/pii/S2468024925002086
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