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

From BugSigDB
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


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

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 ControlLinks
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

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 ControlLinks
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