The alternations of gut microbiota in diabetic kidney disease: insights from a triple comparative cohort

BackgroundDiabetic kidney disease (DKD) exhibits heterogeneous progression, implicating factors beyond hyperglycemia, such as gut microbiota dysbiosis. However, microbial distinctions among biopsy-confirmed pure DKD, DKD with non-diabetic renal disease (DKD+NDRD), and long-term diabetes without neph...

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Main Authors: Mengqi Wu, Xin Zhou, Saiping Chen, Yuqing Wang, Bin Lu, Aiping Zhang, Yanqin Zhu, Min Huang, Jiarui Wang, Junyi Liu, Fenggui Zhu, Hong Liu, Riyang Lin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1606700/full
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author Mengqi Wu
Xin Zhou
Saiping Chen
Yuqing Wang
Bin Lu
Aiping Zhang
Yanqin Zhu
Min Huang
Jiarui Wang
Junyi Liu
Fenggui Zhu
Hong Liu
Riyang Lin
Riyang Lin
author_facet Mengqi Wu
Xin Zhou
Saiping Chen
Yuqing Wang
Bin Lu
Aiping Zhang
Yanqin Zhu
Min Huang
Jiarui Wang
Junyi Liu
Fenggui Zhu
Hong Liu
Riyang Lin
Riyang Lin
author_sort Mengqi Wu
collection DOAJ
description BackgroundDiabetic kidney disease (DKD) exhibits heterogeneous progression, implicating factors beyond hyperglycemia, such as gut microbiota dysbiosis. However, microbial distinctions among biopsy-confirmed pure DKD, DKD with non-diabetic renal disease (DKD+NDRD), and long-term diabetes without nephropathy (DM) remain unclear. This study aimed to identify gut microbial and functional biomarkers differentiating these groups.MethodsWe enrolled 40 biopsy-confirmed participants classified into DKD (n=26), DM (n=8), and DKD+NDRD (n=6) groups. Gut microbiota was profiled using 16S rRNA sequencing. Microbial diversity, composition, and functional prediction (PICRUSt2 analysis) were compared among groups. Biomarkers were identified using LEfSe analysis.ResultsNo significant differences in alpha-diversity (Chao1, Shannon indices) or beta-diversity (PCoA/PCA) were observed among groups. Taxonomic analysis revealed distinct microbial signatures: DKD patients showed enrichment of Olsenella and reduced Faecalibacterium prausnitzii (a short-chain fatty acid producer), while DM patients exhibited higher Roseburia and Flavonifractor. The DKD+NDRD group was uniquely enriched in Prevotella_9. Functional prediction highlighted elevated pyruvate metabolism and bacterial toxin pathways in DKD, contrasting with enhanced linoleic acid metabolism in DM and attenuated endotoxin-related pathways in DKD+NDRD.ConclusionsThis study delineates gut microbiota profiles and functional shifts across DKD, DM, and DKD+NDRD. Key taxa (Olsenella, Prevotella_9) and metabolic pathways (pyruvate, toxin production) may serve as biomarkers for DKD progression and differential diagnosis. The findings underscore the gut-kidney axis’s role in DKD pathogenesis and suggest microbiota-targeted interventions for precision management. Further validation in larger cohorts is warranted.
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spelling doaj-art-63a264634b3844ae85e9f135e151ba2c2025-08-20T03:24:44ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-06-011510.3389/fcimb.2025.16067001606700The alternations of gut microbiota in diabetic kidney disease: insights from a triple comparative cohortMengqi Wu0Xin Zhou1Saiping Chen2Yuqing Wang3Bin Lu4Aiping Zhang5Yanqin Zhu6Min Huang7Jiarui Wang8Junyi Liu9Fenggui Zhu10Hong Liu11Riyang Lin12Riyang Lin13Department of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of General Medicine, Tianshui Wulin Street Community Heal Care Centre, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaKey Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, ChinaBackgroundDiabetic kidney disease (DKD) exhibits heterogeneous progression, implicating factors beyond hyperglycemia, such as gut microbiota dysbiosis. However, microbial distinctions among biopsy-confirmed pure DKD, DKD with non-diabetic renal disease (DKD+NDRD), and long-term diabetes without nephropathy (DM) remain unclear. This study aimed to identify gut microbial and functional biomarkers differentiating these groups.MethodsWe enrolled 40 biopsy-confirmed participants classified into DKD (n=26), DM (n=8), and DKD+NDRD (n=6) groups. Gut microbiota was profiled using 16S rRNA sequencing. Microbial diversity, composition, and functional prediction (PICRUSt2 analysis) were compared among groups. Biomarkers were identified using LEfSe analysis.ResultsNo significant differences in alpha-diversity (Chao1, Shannon indices) or beta-diversity (PCoA/PCA) were observed among groups. Taxonomic analysis revealed distinct microbial signatures: DKD patients showed enrichment of Olsenella and reduced Faecalibacterium prausnitzii (a short-chain fatty acid producer), while DM patients exhibited higher Roseburia and Flavonifractor. The DKD+NDRD group was uniquely enriched in Prevotella_9. Functional prediction highlighted elevated pyruvate metabolism and bacterial toxin pathways in DKD, contrasting with enhanced linoleic acid metabolism in DM and attenuated endotoxin-related pathways in DKD+NDRD.ConclusionsThis study delineates gut microbiota profiles and functional shifts across DKD, DM, and DKD+NDRD. Key taxa (Olsenella, Prevotella_9) and metabolic pathways (pyruvate, toxin production) may serve as biomarkers for DKD progression and differential diagnosis. The findings underscore the gut-kidney axis’s role in DKD pathogenesis and suggest microbiota-targeted interventions for precision management. Further validation in larger cohorts is warranted.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1606700/fulldiabetic kidney disease (DKD)gut microbiota16S rRNAintestinal biomarkerdisease progression
spellingShingle Mengqi Wu
Xin Zhou
Saiping Chen
Yuqing Wang
Bin Lu
Aiping Zhang
Yanqin Zhu
Min Huang
Jiarui Wang
Junyi Liu
Fenggui Zhu
Hong Liu
Riyang Lin
Riyang Lin
The alternations of gut microbiota in diabetic kidney disease: insights from a triple comparative cohort
Frontiers in Cellular and Infection Microbiology
diabetic kidney disease (DKD)
gut microbiota
16S rRNA
intestinal biomarker
disease progression
title The alternations of gut microbiota in diabetic kidney disease: insights from a triple comparative cohort
title_full The alternations of gut microbiota in diabetic kidney disease: insights from a triple comparative cohort
title_fullStr The alternations of gut microbiota in diabetic kidney disease: insights from a triple comparative cohort
title_full_unstemmed The alternations of gut microbiota in diabetic kidney disease: insights from a triple comparative cohort
title_short The alternations of gut microbiota in diabetic kidney disease: insights from a triple comparative cohort
title_sort alternations of gut microbiota in diabetic kidney disease insights from a triple comparative cohort
topic diabetic kidney disease (DKD)
gut microbiota
16S rRNA
intestinal biomarker
disease progression
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1606700/full
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