Fecal microbiota transplantation restores normal fecal composition and delays malignant development of mild chronic kidney disease in rats

Study information

Needs review

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

36532422

DOI Digital object identifier for electronic documents.

10.3389/fmicb.2022.1037257

URI

Authors

Liu X, Zhang M, Wang X, Liu P, Wang L, Li Y, Wang X, Ren F

Journal

Frontiers in microbiology

Year

2022

Keywords:

chronic kidney disease, fecal microbiota transplantation, lysine production, metagenomics, protein-bound uremic toxins

Chronic kidney disease (CKD) is associated with gut microbiome dysbiosis, but the role of intestinal flora in CKD treatment remains to be elucidated. Fecal microbiota transplantation (FMT) can be utilized to re-establish healthy gut microbiota for a variety of diseases, which offers new insight for treating CKD. First, 5/6 nephrectomy rats (Donor CKD) and sham rats (Donor Sham) were used as donors for FMT, and fecal metagenome were analyzed to explore potential therapeutic targets. Then, to assess the effect of FMT on CKD, sterilized 1/2 nephrectomy rats were transplanted with fecal microbiota from Donor sham (CKD/Sham) or Donor CKD (CKD/CKD) rats, and 1/2 nephrectomy rats without FMT (CKD) or no nephrectomy (Sham) were used as model control or normal control. Results showed that Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 were enriched in Donor CKD, while Lactobacillus johnsonii and Lactobacillus intestinalis were reduced. In addition, the increased abundance of microbial functions included tryptophan metabolism and lysine degradation contributing to the accumulation of protein-bound uremic toxins (PBUTs) in Donor CKD. Genome analysis indicated that FMT successfully differentiated groups of gut microbes and altered specific gut microbiota after 1 week of treatment, with Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 increasing in CKD/CKD group as well as Lactobacillus johnsonii and Lactobacillus intestinalis being improved in CKD/Sham group. In comparison to CKD group, substantial PBUT buildup and renal damage were observed in CKD/CKD. Interestingly, compared to CKD or CKD/CKD group, tryptophan metabolism and lysine degradation were efficiently suppressed in CKD/Sham group, while lysine biosynthesis was promoted. Therefore, FMT considerably reduced PBUTs accumulation. After FMT, PBUTs and renal function in CKD/Sham rats remained the same as in Sham group throughout the experimental period. In summary, FMT could delay the malignant development of CKD by modifying microbial amino acid metabolism through altering the microenvironment of intestinal flora, thereby providing a novel potential approach for treating CKD.

Experiment 1

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Curated date: 2025/05/07

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Subjects

Location of subjects: China

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

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: Response to transplant Response to transplant,response to transplant

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Donor Sham rats

Group 1 name Corresponds to the case (exposed) group for case-control studies: CKD/CKD (Donor chronic kidney disease) rats

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: The 5/6 nephrectomy rats which developed severe chronic kidney disease (CKD) after 10 months used as fecal donors for Fecal microbiota transplantation (FMT)

Group 0 sample size Number of subjects in the control (unexposed) group: 5

Group 1 sample size Number of subjects in the case (exposed) group: 5

Lab analysis

Sequencing type: WMS

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

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)?: No

Signature 1

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Source: Figure 3C

Description: Differential microbial species (Wilcoxon rank sum test). The vertical coordinates indicate the species names at different taxonomic levels, and the horizontal coordinates indicate the percentage value of the abundance of a species for that sample, with different colors indicating different groupings.

Abundance in Group 1: increased abundance in CKD/CKD (Donor chronic kidney disease) rats

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Bacteroides uniformis
Escherichia coli
Parabacteroides distasonis
Phocaeicola vulgatus
Anaerotruncus sp. 1XD22-93
Bacteroides caccae
Bacteroides thetaiotaomicron

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Signature 2

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Source: Figure 3C

Description: Differential microbial species (Wilcoxon rank sum test). The vertical coordinates indicate the species names at different taxonomic levels, and the horizontal coordinates indicate the percentage value of the abundance of a species for that sample, with different colors indicating different groupings.

Abundance in Group 1: decreased abundance in CKD/CKD (Donor chronic kidney disease) rats

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Lactobacillus intestinalis
Lactobacillus johnsonii
bacterium 1xD42-87

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Experiment 2

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: CKD/Sham (Donor sham) rats

Group 1 name Corresponds to the case (exposed) group for case-control studies: CKD/CKD (Donor Chronic kidney disease) rats

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: The 1/2 nephrectomy rats treated with a 3 week course of mixed antibiotics treatment (ampicillin, metronidazole, neomycin, and vancomycin according to the ratio 2:2:2:1) randomly assigned into the fecal microbiota transplantation (FMT) recipient group which received intestinal flora from Donor Chronic Kidney disease (CKD).

Lab analysis

Statistical Analysis

Experiment 3

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: CKD (Chronic kidney disease- 1/2 nephrectomy rats)

Lab analysis

Statistical Analysis

Experiment 4

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Sham (no nephrectomy) rats

Lab analysis

Statistical Analysis

Experiment 5

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: CKD (Chronic kidney disease- 1/2 nephrectomy rats)

Group 1 name Corresponds to the case (exposed) group for case-control studies: CKD/Sham (Donor Sham) rats

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: The 1/2 nephrectomy rats treated with a 3 week course of mixed antibiotics treatment (ampicillin, metronidazole, neomycin, and vancomycin according to the ratio 2:2:2:1) randomly assigned into the fecal microbiota transplantation (FMT) recipient group which received intestinal flora from Donor Sham.

Lab analysis

Statistical Analysis