Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy

Study information

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-4-5

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

35863004

DOI Digital object identifier for electronic documents.

10.1128/spectrum.00324-22

URI

Authors

Zhang L, Wang Z, Zhang X, Zhao L, Chu J, Li H, Sun W, Yang C, Wang H, Dai W, Yan S, Chen X, Xu D

Journal

Microbiology spectrum

Year

2022

Keywords:

composition, diabetic nephropathy, function, gut microbiota, metagenomics

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.

Experiment 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-4-5

Curated date: 2024/03/12

Curator: Rahila

Revision editor(s): Rahila

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Diabetic nephropathy Diabetes with renal manifestations,Diabetes with renal manifestations (disorder),Diabetes-nephrosis syndrome,Diabetes-nephrosis syndrome (disorder),Diabetic Glomerulosclerosis,Diabetic Kidney Disease,diabetic kidney disease,Diabetic Kidney Diseases,Diabetic Nephropathies,diabetic nephropathy,Diabetic renal disease,Diabetic renal disease (disorder),DKD,DMII RENAL UNCNTRLD,DMII RENL NT ST UNCNTRLD,Glomerulosclerosis, Diabetic,Glomerulosclerosis, Nodular,Intracapillary Glomerulosclerosis,Kidney Disease, Diabetic,Kidney Diseases, Diabetic,Kimmelstiel - Wilson disease,Kimmelstiel Wilson Disease,Kimmelstiel Wilson Syndrome,Kimmelstiel-Wilson Disease,Kimmelstiel-Wilson Syndrome,Nephropathies, Diabetic,Nephropathy, Diabetic,Nephrotic syndrome due to diabetes mellitus,Nephrotic syndrome in diabetes mellitus,Nephrotic syndrome in diabetes mellitus (disorder),Nodular Glomerulosclerosis,Renal disorder associated with diabetes mellitus,Syndrome, Kimmelstiel-Wilson,type 1 diabetes nephropathy,type 2 diabetes nephropathy,Diabetic nephropathy

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy controls (CON)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Diabetic nephropathy (DN)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with diabetic nephropathy (DN). DN is a chronic kidney disease (CKD), which is one of the most common complications of diabetic microangiopathy and the primary cause of end-stage renal disease (ESRD).

Group 0 sample size Number of subjects in the control (unexposed) group: 14

Group 1 sample size Number of subjects in the case (exposed) group: 12

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Past 1 month

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2.0

Matched on Factors on which subjects have been matched on in a case-control study: age, body mass index, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Chao1 Abundance-based estimator of species richness: unchanged

Richness Number of species: unchanged

Signature 1

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Curated date: 2024/03/12

Curator: Rahila

Revision editor(s): Rahila, ChiomaBlessing

Source: FIG 3 (B)

Description: Differentially abundant taxa identified in the diabetic nephropathy (DN) group compared to the healthy control (CON) group

Abundance in Group 1: increased abundance in Diabetic nephropathy (DN)

NCBI	Quality Control	Links
Alistipes ihumii
Bacteroides stercoris
Bacteroides stercoris CAG:120
Barnesiella sp.
Parabacteroides sp. 20_3
Prevotella sp. MSX73
Tannerella sp. CAG:51

Revision editor(s): Rahila, ChiomaBlessing

Experiment 2

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Curated date: 2024/03/12

Curator: Rahila

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Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Diabetes mellitus Diabetes,diabetes,diabetes mellitus,diabetes mellitus (disease),Diabetes mellitus (disorder),Diabetes mellitus, NOS,Diabetes NOS,DM,DM - Diabetes mellitus,Diabetes mellitus

Group 1 name Corresponds to the case (exposed) group for case-control studies: type 2 diabetes mellitus (T2DM)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with type 2 diabetes mellitus (T2DM) without DN

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Chao1 Abundance-based estimator of species richness: unchanged

Richness Number of species: unchanged

Signature 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-4-5

Curated date: 2024/03/12

Curator: Rahila

Revision editor(s): Rahila, ChiomaBlessing

Source: FIG 3 (B)

Description: Differentially abundant taxa identified in the Type 2 diabetes mellitus (T2DM) group compared to the healthy control (CON) group

Abundance in Group 1: increased abundance in type 2 diabetes mellitus (T2DM)

NCBI	Quality Control	Links
Bacteroides hominis
Bacteroides sp. PHL 2737
Clostridium sp. CAG:715
Limosilactobacillus mucosae
Parabacteroides sp. AF19-14
Prevotella sp. CAG:873
Veillonella dispar

Revision editor(s): Rahila, ChiomaBlessing

Experiment 3

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-4-5

Curated date: 2024/03/13

Curator: Rahila

Revision editor(s): Rahila, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Gut microbiome measurement Gut microbiome measurement,gut microbiome measurement

Group 0 name Corresponds to the control (unexposed) group for case-control studies: type 2 diabetes mellitus (T2DM)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Diabetic nephropathy (DN)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with diabetic nephropathy (DN).