Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents

Study information

Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

32241904

DOI Digital object identifier for electronic documents.

10.1136/gutjnl-2019-319766

URI

Authors

Wang X, Yang S, Li S, Zhao L, Hao Y, Qin J, Zhang L, Zhang C, Bian W, Zuo L, Gao X, Zhu B, Lei XG, Gu Z, Cui W, Xu X, Li Z, Zhu B, Li Y, Chen S, Guo H, Zhang H, Sun J, Zhang M, Hui Y, Zhang X, Liu X, Sun B, Wang L, Qiu Q, Zhang Y, Li X, Liu W, Xue R, Wu H, Shao D, Li J, Zhou Y, Li S, Yang R, Pedersen OB, Yu Z, Ehrlich SD, Ren F

Journal

Gut

Year

2020

Keywords:

bile acid, enteric bacterial microflora

OBJECTIVE: Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD). DESIGN: Characterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity. RESULTS: A group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, Eggerthella lenta and Fusobacterium nucleatum, increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic Bifidobacterium animalis decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats. CONCLUSION: Aberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients. TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov (NCT03010696).

Experiment 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

Curated date: 2025/05/02

Curator: MyleeeA

Revision editor(s): MyleeeA

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: Kidney disease disease of kidney,disease or disorder of kidney,disorder of kidney,kidney disease,kidney disease or disorder,kidney diseases,Kidney Disorder,kidney disorder,nephropathy,renal disease,renal disorder,renal system disease,Kidney disease

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy Controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: End Stage Renal Disease (ESRD)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients diagnosed with End stage Renal Disease (ESRD) according to the Kidney Disease: Improving Global Outcomes Clinical Practice guidelines and were undergoing stable haemodialysis (1–3 times per week).

Group 0 sample size Number of subjects in the control (unexposed) group: 69

Group 1 sample size Number of subjects in the case (exposed) group: 223

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 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: Mann-Whitney (Wilcoxon)

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

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Alpha Diversity

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

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

Curated date: 2025/05/02

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2B

Description: Differentially abundant Species between patients with End stage Renal disease (ESRD) and healthy controls.

Abundance in Group 1: increased abundance in End Stage Renal Disease (ESRD)

NCBI	Quality Control	Links
Alistipes finegoldii
Alistipes shahii
Blautia
Blautia hansenii
Eggerthella lenta
Enterocloster bolteae
Flavonifractor
Fusobacterium
Lachnoclostridium sp. YL32
Mediterraneibacter gnavus
Ruminococcus sp. 5_1_39BFAA

Revision editor(s): MyleeeA

Signature 2

Edit History Delete

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Your review change was submitted

Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

Curated date: 2025/05/02

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2B

Description: Differentially abundant Species between patients with End stage Renal disease (ESRD) and healthy controls.

Abundance in Group 1: decreased abundance in End Stage Renal Disease (ESRD)

NCBI	Quality Control	Links
Agathobacter rectalis
Clostridium
Faecalibacterium prausnitzii
Lachnoclostridium
Prevotella
Roseburia
Roseburia intestinalis
Roseburia inulinivorans
Ruminococcus
Segatella copri
Ruminococcus bicirculans (ex Liu et al. 2021)

Revision editor(s): MyleeeA