Intestinal Microbiota at Engraftment Influence Acute Graft-Versus-Host Disease via the Treg/Th17 Balance in Allo-HSCT Recipients
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Han L, Jin H, Zhou L, Zhang X, Fan Z, Dai M, Lin Q, Huang F, Xuan L, Zhang H, Liu Q
Journal
Frontiers in immunology
Year
2018
Keywords:
acute graft-versus-host disease, allogeneic hematopoietic stem cell transplantation, histone acetylation, immune homeostasis, intestinal microbiota
Animal models have indicated that intestinal microbiota influence acute graft-versus-host disease (aGVHD) by modulating immune homeostasis. But, in humans, the mechanism by which the microbiota induces aGVHD remains unclear. In this study, we investigated the relationship between the intestinal microbiota and T cell subsets in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) to explore the mechanism by which microbiota induced aGVHD. Based on aGVHD, this study was categorized into two groups: grades II-IV aGVHD (aGVHD group, n = 32) and grade 0-I aGVHD (non-aGVHD group, n = 49). The intestinal microbiota was detected by 16S rRNA gene sequencing, and the T cell subsets and histone 3 (H3) acetylation in CD4+ T cells in the peripheral blood was assayed by flow cytometry at the time of engraftment. The aGVHD group had greater low microbial diversity than the non-aGVHD group (56.3 versus 24.5%, p = 0.004). The bacterial community was depleted of Clostridia (e.g., the Lachnospiraceae and Ruminococcaceae families) and enriched for Gammaproteobacteria (e.g., the Enterobacteriaceae family) in the aGVHD group compared with the non-aGVHD group. The relative abundance of Lachnospiraceae and Ruminococcaceae was positively correlated with the Treg/Th17 ratio counts (r = 0.469 and 0.419; p < 0.001 and <0.001, respectively), whereas Enterobacteriaceae was negatively correlated with the Treg/Th17 ratio (r = -0.277; p = 0.012). The level of acetylated H3 in CD4+ T cells was not only correlated with Lachnospiraceae/Ruminococcaceae, but also with the Treg/Th17 ratio (r = 0.354; p = 0.001). In conclusions, our results suggest that decreased Lachnospiraceae and Ruminococcaceae and increased Enterobacteriaceae, correlate with a Treg/Th17 imbalance, which might be through acetylated H3 in CD4+ T cells. These findings suggest that intestinal microbiota might induce aGVHD by influencing the Treg/Th17 balance.
Experiment 1
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
- Graft versus host disease disease, graft-versus-host,disease, graft-VS-host,disease, homologous wasting,disease, runt,diseases, graft-versus-host,diseases, graft-VS-host,graft versus host disease,graft VS host disease,graft VS. host disease,graft-versus-host disease,graft-versus-host disease, resistance to,graft-versus-host disease, susceptibility to,graft-versus-host diseases,graft-versus-host-disease,graft-VS-host disease,graft-VS-host diseases,GVH,GVHD,GVHDS,homologous wasting disease,runt disease,Graft versus host disease
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Grades 0-I (non-acute graft-host disease)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Grades II-IV (acute graft-host-disease)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients diagnoised with acute graft-versus-host disease (aGVHD)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 49
- Group 1 sample size Number of subjects in the case (exposed) group
- 32
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V4
- 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
- LEfSe
- 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
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Atrayees on 2023-7-11
Source: Figure 3a, b and text
Description: Differences of intestinal microbiota at engraftment between acute graft-verse-house disease (aGVHD) and non-acute graft-versus host disease (non-aGVHD) patients
Abundance in Group 1: increased abundance in Grades II-IV (acute graft-host-disease)
| NCBI | Quality Control | Links |
|---|---|---|
| Porphyromonadaceae | ||
| Enterobacteriaceae | ||
| Enterobacterales | ||
| Gammaproteobacteria | ||
| Pseudomonadota |
Revision editor(s): WikiWorks
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-7-11
Source: Figure 3a, b and text
Description: Differences of intestinal microbiota at engraftment between acute graft-verse-house disease (aGVHD) and non-acute graft-versus host disease (non-aGVHD) patients
Abundance in Group 1: decreased abundance in Grades II-IV (acute graft-host-disease)
| NCBI | Quality Control | Links |
|---|---|---|
| Eubacteriaceae | ||
| Lachnospiraceae | ||
| Peptostreptococcaceae | ||
| Oscillospiraceae | ||
| Eubacteriales | ||
| Clostridia | ||
| Erysipelotrichaceae | ||
| Lachnoclostridium | ||
| Blautia |
Revision editor(s): WikiWorks
Experiment 2
Reviewed Marked as Reviewed by Atrayees on 2023-7-11
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- standard conditioning
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- intensified conditioning
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients diagnoised with grade II to IV acute graft-versus-host disease (aGVHD) undergoing intense conditioning
- Group 0 sample size Number of subjects in the control (unexposed) group
- 19
- Group 1 sample size Number of subjects in the case (exposed) group
- 13
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
- Statistical test
- Not specified
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- increased
Signature 1
Reviewed Marked as Reviewed by Atrayees on 2023-7-11
Source: Figure 5a, b, c, d
Description: Differences in the intestinal microbiota (diversity and composition) are associated with conditioning intensity in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients
Abundance in Group 1: decreased abundance in intensified conditioning
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospiraceae | ||
| Oscillospiraceae |
Revision editor(s): WikiWorks
Experiment 3
Reviewed Marked as Reviewed by Atrayees on 2023-7-11
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- no b-lactum antibiotics
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- b-lactum antibiotics
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients diagnoised with grade II to IV acute graft-versus-host disease (aGVHD) undergoing intense conditioning treated with b-lactum (include carbapenem, cephalosporin, and b-lactam-b-lactamase combinations.)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 48
- Group 1 sample size Number of subjects in the case (exposed) group
- 31
Lab analysis
Statistical Analysis
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
Signature 1
Reviewed Marked as Reviewed by Atrayees on 2023-7-11
Source: Figure 4 a, b, d
Description: Differences in the intestinal microbiota (diversity and composition) are associated with Beta-Lactum antibiotic in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients
Abundance in Group 1: decreased abundance in b-lactum antibiotics
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospiraceae |
Revision editor(s): WikiWorks
Experiment 4
Reviewed Marked as Reviewed by Atrayees on 2023-7-11
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- no vancomycin antibiotics
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- vancomycin antibiotics
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients diagnoised with grade II to IV acute graft-versus-host disease (aGVHD) undergoing intense conditioning treated with vancomycin
- Group 0 sample size Number of subjects in the control (unexposed) group
- 59
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
Lab analysis
Statistical Analysis
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
Signature 1
Reviewed Marked as Reviewed by Atrayees on 2023-7-11
Source: Figure 4 a, b, d
Description: Differences in the intestinal microbiota (diversity and composition) are associated with Vancomycin antibiotic in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients
Abundance in Group 1: increased abundance in vancomycin antibiotics
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae |
Revision editor(s): WikiWorks
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