Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy

ABSTRACT Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus (DM) and DN. However, the precise roles and regulatory mechanisms of the gut microbiota in the pathogenesis of DN remain l...

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Main Authors: Lili Zhang, Zhisheng Wang, Xiaona Zhang, Lu Zhao, Jinjin Chu, Haibo Li, Wenchang Sun, Chunjuan Yang, Hui Wang, Wenqing Dai, Shushan Yan, Xiaohua Chen, Donghua Xu
Format: Article
Language:English
Published: American Society for Microbiology 2022-08-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.00324-22
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author Lili Zhang
Zhisheng Wang
Xiaona Zhang
Lu Zhao
Jinjin Chu
Haibo Li
Wenchang Sun
Chunjuan Yang
Hui Wang
Wenqing Dai
Shushan Yan
Xiaohua Chen
Donghua Xu
author_facet Lili Zhang
Zhisheng Wang
Xiaona Zhang
Lu Zhao
Jinjin Chu
Haibo Li
Wenchang Sun
Chunjuan Yang
Hui Wang
Wenqing Dai
Shushan Yan
Xiaohua Chen
Donghua Xu
author_sort Lili Zhang
collection DOAJ
description ABSTRACT Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus (DM) and DN. However, the precise roles and regulatory mechanisms of the gut microbiota in the pathogenesis of DN remain largely unclear. In this study, metagenomics sequencing was performed using fecal samples from healthy controls (CON) and type 2 diabetes mellitus (T2DM) patients with or without DN. Fresh fecal samples from 15 T2DM patients without DN, 15 DN patients, and 15 age-, gender-, and body mass index (BMI)-matched healthy controls were collected. The compositions and potential functions of the gut microbiota were estimated. Although no difference of gut microbiota α and β diversity was observed between the CON, T2DM, and DN groups, the relative abundances of butyrate-producing bacteria (Clostridium, Eubacterium, and Roseburia intestinalis) and potential probiotics (Lachnospira and Intestinibacter) were significantly reduced in T2DM and DN patients. Besides, Bacteroides stercoris was significantly enriched in fecal samples from patients with DN. Moreover, Clostridium sp. 26_22 was negatively associated with serum creatinine (P < 0.05). DN patients could be accurately distinguished from CON by Clostridium sp. CAG_768 (area under the curve [AUC] = 0.941), Bacteroides propionicifaciens (AUC = 0.905), and Clostridium sp. CAG_715 (AUC = 0.908). DN patients could be accurately distinguished from T2DM patients by Pseudomonadales, Fusobacterium varium, and Prevotella sp. MSX73 (AUC = 0.889). Regarding the potential bacterial functions of the gut microbiota, the citrate cycle, base excision repair, histidine metabolism, lipoic acid metabolism, and bile acid biosynthesis were enriched in DN patients, while selenium metabolism and branched-chain amino acid biosynthesis were decreased in DN patients. IMPORTANCE Gut microbiota imbalance is found in fecal samples from DN patients, in which Roseburia intestinalis is significantly decreased, while Bacteroides stercoris is increased. There is a significant correlation between gut microbiota imbalance and clinical indexes related to lipid metabolism, glucose metabolism, and renal function. The gut microbiota may be predictive factors for the development and progression of DN, although further studies are warranted to illustrate their regulatory mechanisms.
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spelling doaj.art-e546e0d770b4471a986d32fc588e96c42022-12-22T02:08:51ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-08-0110410.1128/spectrum.00324-22Alterations of the Gut Microbiota in Patients with Diabetic NephropathyLili Zhang0Zhisheng Wang1Xiaona Zhang2Lu Zhao3Jinjin Chu4Haibo Li5Wenchang Sun6Chunjuan Yang7Hui Wang8Wenqing Dai9Shushan Yan10Xiaohua Chen11Donghua Xu12Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Neurosurgery, Sunshine Union Hospital, Weifang, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of General Surgery, The Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, ChinaABSTRACT Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus (DM) and DN. However, the precise roles and regulatory mechanisms of the gut microbiota in the pathogenesis of DN remain largely unclear. In this study, metagenomics sequencing was performed using fecal samples from healthy controls (CON) and type 2 diabetes mellitus (T2DM) patients with or without DN. Fresh fecal samples from 15 T2DM patients without DN, 15 DN patients, and 15 age-, gender-, and body mass index (BMI)-matched healthy controls were collected. The compositions and potential functions of the gut microbiota were estimated. Although no difference of gut microbiota α and β diversity was observed between the CON, T2DM, and DN groups, the relative abundances of butyrate-producing bacteria (Clostridium, Eubacterium, and Roseburia intestinalis) and potential probiotics (Lachnospira and Intestinibacter) were significantly reduced in T2DM and DN patients. Besides, Bacteroides stercoris was significantly enriched in fecal samples from patients with DN. Moreover, Clostridium sp. 26_22 was negatively associated with serum creatinine (P < 0.05). DN patients could be accurately distinguished from CON by Clostridium sp. CAG_768 (area under the curve [AUC] = 0.941), Bacteroides propionicifaciens (AUC = 0.905), and Clostridium sp. CAG_715 (AUC = 0.908). DN patients could be accurately distinguished from T2DM patients by Pseudomonadales, Fusobacterium varium, and Prevotella sp. MSX73 (AUC = 0.889). Regarding the potential bacterial functions of the gut microbiota, the citrate cycle, base excision repair, histidine metabolism, lipoic acid metabolism, and bile acid biosynthesis were enriched in DN patients, while selenium metabolism and branched-chain amino acid biosynthesis were decreased in DN patients. IMPORTANCE Gut microbiota imbalance is found in fecal samples from DN patients, in which Roseburia intestinalis is significantly decreased, while Bacteroides stercoris is increased. There is a significant correlation between gut microbiota imbalance and clinical indexes related to lipid metabolism, glucose metabolism, and renal function. The gut microbiota may be predictive factors for the development and progression of DN, although further studies are warranted to illustrate their regulatory mechanisms.https://journals.asm.org/doi/10.1128/spectrum.00324-22gut microbiotadiabetic nephropathymetagenomicscompositionfunction
spellingShingle Lili Zhang
Zhisheng Wang
Xiaona Zhang
Lu Zhao
Jinjin Chu
Haibo Li
Wenchang Sun
Chunjuan Yang
Hui Wang
Wenqing Dai
Shushan Yan
Xiaohua Chen
Donghua Xu
Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy
Microbiology Spectrum
gut microbiota
diabetic nephropathy
metagenomics
composition
function
title Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy
title_full Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy
title_fullStr Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy
title_full_unstemmed Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy
title_short Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy
title_sort alterations of the gut microbiota in patients with diabetic nephropathy
topic gut microbiota
diabetic nephropathy
metagenomics
composition
function
url https://journals.asm.org/doi/10.1128/spectrum.00324-22
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