Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients

Study information

Needs review

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

32024079

DOI Digital object identifier for electronic documents.

https://doi.org/10.3390/jcm9020386

URI Uniform resource identifier for web resources.

Authors

Swarte JC, Douwes RM, Hu S, Vich Vila A, Eisenga MF, van Londen M, Gomes-Neto AW, Weersma RK, Harmsen HJM, Bakker SJL

Journal

Journal of clinical medicine

Year

2020

Keywords:

16S rRNA sequencing, Proteobacteria, butyrate-producing bacteria, diarrhea, gut microbiome, gut microbiota, immunosuppressive medication, kidney transplantation, renal transplant recipient

Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5-12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome.

Experiment 1

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Curated date: 2025/04/15

Curator: Agatha

Revision editor(s): Agatha, Montana-D

Subjects

Location of subjects: Netherlands

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: Renal transplant outcome measurement Renal transplant outcome measurement,renal transplant outcome measurement

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: RTR (Renal Transplant Recipients)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: These are renal transplant recipients that were at least one year post transplantation

Group 0 sample size Number of subjects in the control (unexposed) group: 105

Group 1 sample size Number of subjects in the case (exposed) group: 139

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4-V5

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: MaAsLin2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.1

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, smoking behavior, sex, Confounders controlled for: "medication use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.medication use

Alpha Diversity

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

Richness Number of species: unchanged

Signature 1

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Curated date: 2025/04/19

Curator: Agatha

Revision editor(s): Agatha, Montana-D

Source: Figure 4

Description: Significantly differential abundant taxa between RTRs and healthy controls.

Abundance in Group 1: increased abundance in RTR (Renal Transplant Recipients)

NCBI	Quality Control	Links
Blautia glucerasea
Blautia wexlerae
Eggerthella lenta
Escherichia coli
Rothia mucilaginosa
Schaalia odontolytica
Streptococcus mitis
Streptococcus parasanguinis
Streptococcus thermophilus

Revision editor(s): Agatha, Montana-D

Signature 2

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Curated date: 2025/04/22

Curator: Agatha

Revision editor(s): Agatha, Montana-D

Source: Figure 4

Description: Significantly differential abundant taxa between RTRS and healthy controls.

Abundance in Group 1: decreased abundance in RTR (Renal Transplant Recipients)

NCBI	Quality Control	Links
Bifidobacterium ruminantium
Collinsella aerofaciens
Coprococcus eutactus
Dorea longicatena
Faecalibacterium prausnitzii
Holdemanella biformis
Ruminococcus bromii
Slackia isoflavoniconvertens
[Eubacterium] siraeum
Bifidobacterium adolescentis
Bifidobacterium catenulatum subsp. kashiwanohense

Revision editor(s): Agatha, Montana-D