Gut microbiota dysbiosis and diarrhea in kidney transplant recipients

From BugSigDB
Reviewed Marked as Reviewed by Atrayees on 2023-6-6
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Lee JR, Magruder M, Zhang L, Westblade LF, Satlin MJ, Robertson A, Edusei E, Crawford C, Ling L, Taur Y, Schluter J, Lubetzky M, Dadhania D, Pamer E, Suthanthiran M
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Year
2019
Keywords:
complication: medical/metabolic, diarrhea, gut microbiota, kidney disease, kidney transplantation/nephrology, microbiomics, translational research/science
Posttransplant diarrhea is associated with kidney allograft failure and death, but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether posttransplant diarrhea is associated with gut dysbiosis. We enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S ribosomal RNA (rRNA) gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with posttransplant diarrhea than in 112 fecal specimens from 46 recipients without posttransplant diarrhea. We found a lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted P ≤ .15) in the diarrheal fecal specimens including the same 4 genera identified in our prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed polymerase chain reaction (PCR) assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies. Using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to predict metagenomic functions, we found that diarrheal fecal specimens had a lower abundance of metabolic genes. Our findings suggest that posttransplant diarrhea is not associated with common infectious diarrheal pathogens but with a gut dysbiosis.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-6-6

Curated date: 2023/03/29

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite

Subjects

Location of subjects
United States of America
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
Diarrhea Diarrhea,Diarrhoea,Watery stool,diarrhea
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Controls (No Diarrhea Group)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Diarrhea Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Kidney transplant recipients that developed post-transplant diarrhea within the first 3 months after transplantation
Group 0 sample size Number of subjects in the control (unexposed) group
46
Group 1 sample size Number of subjects in the case (exposed) group
18
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Applicable, but exact duration not specified

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
Mann-Whitney (Wilcoxon)

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-6

Curated date: 2023/03/29

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Atrayees

Source: Figure 2, Table 2

Description: Differential microbial abundance between Controls and Diarrhea group

Abundance in Group 1: decreased abundance in Diarrhea Group

NCBI Quality ControlLinks
Anaerostipes
Bacteroides
Bifidobacterium
Blautia
Coprobacillus
Dorea
Eubacterium
Faecalibacterium
Fusicatenibacter
Oscillibacter
Romboutsia
Ruminiclostridium
Ruminococcus
Coprococcus

Revision editor(s): Ufuoma Ejite, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-6

Curated date: 2023/03/29

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite

Source: Figure 2

Description: Differential microbial abundance between Controls and Diarrhea group

Abundance in Group 1: increased abundance in Diarrhea Group

NCBI Quality ControlLinks
Enterococcus
Escherichia
Lachnoclostridium

Revision editor(s): Ufuoma Ejite

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-6-6

Curated date: 2023/04/17

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Antibiotic-excluded Controls (No Diarrhea Group)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Antibiotic-excluded Diarrhea Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Antibiotic-excluded diarrheal group; Kidney transplant recipients that developed post-transplant diarrhea within the first 3 months after transplantation
Group 1 sample size Number of subjects in the case (exposed) group
13
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Applicable; but exact duration not specified

Lab analysis

Statistical Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.15
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
antibiotic exposure


Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-6

Curated date: 2023/04/18

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Atrayees

Source: Table S2

Description: Differential microbial abundance between Antibiotic-excluded Controls and Antibiotic-excluded Diarrhea group

Abundance in Group 1: decreased abundance in Antibiotic-excluded Diarrhea Group

NCBI Quality ControlLinks
Eubacterium
Coprococcus
Anaerostipes
Romboutsia
Dorea
Faecalibacterium
Ruminococcus
Fusicatenibacter
Bifidobacterium
Oscillibacter
Ruminiclostridium
Bacteroides
Gemmiger
Coprobacillus

Revision editor(s): Ufuoma Ejite, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-6

Curated date: 2023/04/18

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Atrayees

Source: Table S2

Description: Differential microbial abundance between Antibiotic-excluded Controls and Antibiotic-excluded Diarrhea group

Abundance in Group 1: increased abundance in Antibiotic-excluded Diarrhea Group

NCBI Quality ControlLinks
Lachnoclostridium
Escherichia
Thomasclavelia
Blautia
Streptococcus

Revision editor(s): Ufuoma Ejite, Atrayees

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-6-6

Curated date: 2023/04/19

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
1000 mg/day MMF Dosage No Diarrhea Group
Group 1 name Corresponds to the case (exposed) group for case-control studies
2000 mg/day MMF Dosage No Diarrhea Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
2000 mg/day MMF Dosage administered to the No Diarrhea Group
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
25
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not specified

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
intake of diabetes medication


Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-6

Curated date: 2023/04/19

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Atrayees

Source: Table S4

Description: Differential microbial abundance between 1000 mg/day MMF Dosage No Diarrhea Group and 2000 mg/day MMF Dosage No Diarrhea Group

Abundance in Group 1: decreased abundance in 2000 mg/day MMF Dosage No Diarrhea Group

NCBI Quality ControlLinks
Erysipelotrichaceae
Romboutsia
Coprococcus
Fusicatenibacter
Dorea
Intestinibacter
Eubacterium
Streptococcus
Anaerostipes

Revision editor(s): Ufuoma Ejite, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-6

Curated date: 2023/06/06

Curator: Atrayees

Revision editor(s): Atrayees

Source: Table S4

Description: Differential microbial abundance between 1000 mg/day MMF Dosage No Diarrhea Group and 2000 mg/day MMF Dosage No Diarrhea Group

Abundance in Group 1: increased abundance in 2000 mg/day MMF Dosage No Diarrhea Group

NCBI Quality ControlLinks
Ruminococcus
Ruminiclostridium
Blautia
Bacteroides
Bifidobacterium
Faecalibacterium
Lachnoclostridium
Gemmiger

Revision editor(s): Atrayees

Experiment 4


Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/04/19

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
1000 mg/day MMF Dosage Diarrhea Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
1000 mg/day MMF Dosage administered to the Diarrhea Group
Group 1 sample size Number of subjects in the case (exposed) group
4

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
Not specified


Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/04/19

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Atrayees

Source: Table S5

Description: Differential microbial abundance between 1000 mg/day MMF Dosage No Diarrhea Group and 1000 mg/day MMF Dosage Diarrhea Group

Abundance in Group 1: decreased abundance in 1000 mg/day MMF Dosage Diarrhea Group

NCBI Quality ControlLinks
Bacteroides
Eubacterium
Oscillibacter
Dorea
Ruminococcus
Anaerostipes
Faecalibacterium
Romboutsia
Fusicatenibacter
Ruminiclostridium
Gemmiger
Coprococcus
Thomasclavelia
Blautia
Intestinibacter

Revision editor(s): Ufuoma Ejite, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/04/19

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Atrayees

Source: Table S5

Description: Differential microbial abundance between 1000 mg/day MMF Dosage No Diarrhea Group and 1000 mg/day MMF Dosage Diarrhea Group

Abundance in Group 1: increased abundance in 1000 mg/day MMF Dosage Diarrhea Group

NCBI Quality ControlLinks
Enterococcus
Escherichia
Streptococcus
Lachnoclostridium
Coprobacillus

Revision editor(s): Ufuoma Ejite, Atrayees

Experiment 5


Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/04/19

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
2000 mg/day MMF Dosage No Diarrhea Group
Group 1 name Corresponds to the case (exposed) group for case-control studies
2000 mg/day MMF Dosage Diarrhea Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
2000 mg/day MMF Dosage administered to the Diarrhea Group
Group 0 sample size Number of subjects in the control (unexposed) group
25
Group 1 sample size Number of subjects in the case (exposed) group
13

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/04/19

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Atrayees

Source: Table S6

Description: Differential microbial abundance between 2000 mg/day MMF Dosage No Diarrhea Group and 2000 mg/day MMF Dosage Diarrhea Group

Abundance in Group 1: decreased abundance in 2000 mg/day MMF Dosage Diarrhea Group

NCBI Quality ControlLinks
Eubacterium
Coprococcus
Anaerostipes
Ruminococcus
Faecalibacterium
Romboutsia
Ruminiclostridium
Dorea
Oscillibacter
Bifidobacterium
Fusicatenibacter
Blautia
Bacteroides
Gemmiger
Coprobacillus
Thomasclavelia

Revision editor(s): Ufuoma Ejite, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/04/19

Curator: Ufuoma Ejite

Revision editor(s): Ufuoma Ejite, Atrayees

Source: Table S6

Description: Differential microbial abundance between 2000 mg/day MMF Dosage No Diarrhea Group and 2000 mg/day MMF Dosage Diarrhea Group

Abundance in Group 1: increased abundance in 2000 mg/day MMF Dosage Diarrhea Group

NCBI Quality ControlLinks
Enterococcus
Lachnoclostridium
Streptococcus
Intestinibacter

Revision editor(s): Ufuoma Ejite, Atrayees

Experiment 6


Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/06/07

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Pre-Diarrheal specimens
Group 1 name Corresponds to the case (exposed) group for case-control studies
Diarrheal specimens
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Diarrheal specimens
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
14

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified


Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/06/07

Curator: Atrayees

Revision editor(s): Atrayees

Source: Table S7

Description: Relative abundance of taxa in Diarrheal specimens

Abundance in Group 1: decreased abundance in Diarrheal specimens

NCBI Quality ControlLinks
Gemmiger
Ruminococcus
Eubacterium
Anaerostipes
Thomasclavelia
Coprobacillus
Oscillibacter
Ruminiclostridium
Bifidobacterium
Coprococcus
Escherichia
Bacteroides
Dorea

Revision editor(s): Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/06/07

Curator: Atrayees

Revision editor(s): Atrayees

Source: Table S7

Description: Relative abundance of taxa in Diarrheal specimens

Abundance in Group 1: increased abundance in Diarrheal specimens

NCBI Quality ControlLinks
Streptococcus
Lachnoclostridium

Revision editor(s): Atrayees

Experiment 7


Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/06/07

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
First Diarrheal Specimens Time-Matched Fecal Specimens from the No Diarrhea Group
Group 1 name Corresponds to the case (exposed) group for case-control studies
First Diarrheal Specimens in the Diarrhea group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
First Diarrheal Specimens in the Diarrhea group
Group 0 sample size Number of subjects in the control (unexposed) group
46
Group 1 sample size Number of subjects in the case (exposed) group
18

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Not specified

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/06/07

Curator: Atrayees

Revision editor(s): Atrayees

Source: Table S1

Description: Relative abundance of taxa in the Diarrhea Group

Abundance in Group 1: decreased abundance in First Diarrheal Specimens in the Diarrhea group

NCBI Quality ControlLinks
Eubacterium
Coprococcus
Anaerostipes
Romboutsia
Faecalibacterium
Fusicatenibacter
Dorea
Ruminococcus
Blautia
Oscillibacter
Ruminiclostridium
Bifidobacterium
Bacteroides
Coprobacillus
Gemmiger
Thomasclavelia
Streptococcus

Revision editor(s): Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-7

Curated date: 2023/06/07

Curator: Atrayees

Revision editor(s): Atrayees

Source: Table S1

Description: Relative abundance of taxa in the Diarrhea Group

Abundance in Group 1: increased abundance in First Diarrheal Specimens in the Diarrhea group

NCBI Quality ControlLinks
Enterococcus
Escherichia
Lachnoclostridium
Intestinibacter

Revision editor(s): Atrayees