Pronounced gut microbiota signatures in patients with JAK2V617F-positive essential thrombocythemia
From BugSigDB
Jump to:navigation, search
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
Eickhardt-Dalbøge CS, Ingham AC, Nielsen HV, Fuursted K, Stensvold CR, Andersen LO, Larsen MK, Kjær L, Christensen SF, Knudsen TA, Skov V, Ellervik C, Olsen LR, Hasselbalch HC, Elmer Christensen JJ, Nielsen XC
Journal
Microbiology spectrum
Year
2023
Keywords:
ET, JAK2V617F, essential thrombocythemia, gut microbiome, gut microbiota, inflammation, myelofibrosis, myeloproliferative neoplasms, polycythemia vera
Essential thrombocythemia (ET) is part of the Philadelphia chromosome-negative myeloproliferative neoplasms. It is characterized by an increased risk of thromboembolic events and also to a certain degree hypermetabolic symptoms. The gut microbiota is an important initiator of hematopoiesis and regulation of the immune system, but in patients with ET, where inflammation is a hallmark of the disease, it is vastly unexplored. In this study, we compared the gut microbiota via amplicon-based 16S rRNA gene sequencing of the V3-V4 region in 54 patients with ET according to mutation status Janus-kinase 2 (JAK2V617F)-positive vs JAK2V617F-negative patients with ET, and in 42 healthy controls (HCs). Gut microbiota richness was higher in patients with ET (median-observed richness, 283.5; range, 75-535) compared with HCs (median-observed richness, 191.5; range, 111-300; P < 0.001). Patients with ET had a different overall bacterial composition (beta diversity) than HCs (analysis of similarities [ANOSIM]; R = 0.063, P = 0.004). Patients with ET had a significantly lower relative abundance of taxa within the Firmicutes phylum compared with HCs (51% vs 59%, P = 0.03), and within that phylum, patients with ET also had a lower relative abundance of the genus Faecalibacterium (8% vs 15%, P < 0.001), an important immunoregulative bacterium. The microbiota signatures were more pronounced in patients harboring the JAK2V617F mutation, and highly similar to patients with polycythemia vera as previously described. These findings suggest that patients with ET may have an altered immune regulation; however, whether this dysregulation is induced in part by, or is itself inducing, an altered gut microbiota remains to be investigated. IMPORTANCE Essential thrombocythemia (ET) is a cancer characterized by thrombocyte overproduction. Inflammation has been shown to be vital in both the initiation and progression of other myeloproliferative neoplasms, and it is well known that the gut microbiota is important in the regulation of our immune system. However, the gut microbiota of patients with ET remains uninvestigated. In this study, we characterized the gut microbiota of patients with ET compared with healthy controls and thereby provide new insights into the field. We show that the gut microbiota of patients with ET differs significantly from that of healthy controls and the patients with ET have a lower relative abundance of important immunoregulative bacteria. Furthermore, we demonstrate that patients with JAK2V617F-positive ET have pronounced gut microbiota signatures compared with JAK2V617F-negative patients. Thereby confirming the importance of the underlying mutation, the immune response as well as the composition of the microbiota.
Experiment 1
Subjects
- Location of subjects
- Denmark
- 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
- Essential thrombocythemia essential thrombocytemia,essential thrombocythaemia,essential thrombocythemia,essential thrombocytosis,ET,hemorrhagic thrombocythemia,idiopathic thrombocythemia,primary thrombocythemia,primary thrombocytosis,Essential thrombocythemia
- 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
- ET Patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants with cancer characterised by thrombocyte overproduction
- Group 0 sample size Number of subjects in the control (unexposed) group
- 42
- Group 1 sample size Number of subjects in the case (exposed) group
- 54
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 2 months
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-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)?
- Yes
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 0.005
- Matched on Factors on which subjects have been matched on in a case-control study
- sex
Alpha Diversity
- Richness Number of species
- increased
Signature 1
Source: Fig 6a
Description: Differential abundance analysis identified using LEfSe between healthy controls and patients with Essential Thrombocythemia
Abundance in Group 1: increased abundance in ET Patients
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Coriobacteriales | ||
| Coriobacteriia | ||
| Erysipelotrichaceae | ||
| Veillonella |
Revision editor(s): Deacme
Signature 2
Source: Fig 6a
Description: Differential abundance analysis identified using LEfSe between healthy controls and patients with Essential Thrombocythemia
Abundance in Group 1: decreased abundance in ET Patients
| NCBI | Quality Control | Links |
|---|---|---|
| Agathobacter | ||
| Clostridia | ||
| Eubacteriales | ||
| Faecalibacterium | ||
| Lachnospiraceae | ||
| Lachnospirales | ||
| Oscillospiraceae |
Revision editor(s): Deacme
Experiment 2
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- JAK2V617F-positive
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Essential thrombocythemia patients positive for the JAK2V617F mutation
- Group 1 sample size Number of subjects in the case (exposed) group
- 36
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
- unchanged
- Richness Number of species
- increased
Signature 1
Source: Fig 6b
Description: Differential abundance analysis identified using LEfSe between healthy controls and Essential thrombocythemia patients positive for the JAK2V617F mutation
Abundance in Group 1: increased abundance in JAK2V617F-positive
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Coriobacteriales | ||
| Coriobacteriia | ||
| Erysipelotrichaceae | ||
| Erysipelotrichales | ||
| Turicibacter | ||
| Veillonella |
Revision editor(s): Deacme
Signature 2
Source: Fig 6b
Description: Differential abundance analysis identified using LEfSe between healthy controls and Essential thrombocythemia patients positive for the JAK2V617F mutation
Abundance in Group 1: decreased abundance in JAK2V617F-positive
| NCBI | Quality Control | Links |
|---|---|---|
| Agathobacter | ||
| Clostridia | ||
| Faecalibacterium | ||
| Lachnospiraceae | ||
| Lachnospirales | ||
| Oscillospiraceae |
Revision editor(s): Deacme
Experiment 3
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- JAK2V617F-negaive
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Essential thrombocythemia patients negative for the JAK2V617F mutation
- Group 1 sample size Number of subjects in the case (exposed) group
- 16
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
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Fig 6c
Description: Differential abundance analysis identified using LEfSe between healthy controls and Essential thrombocythemia patients negative for the JAK2V617F mutation
Abundance in Group 1: increased abundance in JAK2V617F-negaive
| NCBI | Quality Control | Links |
|---|---|---|
| Coriobacteriales | ||
| Coriobacteriia | ||
| Oscillospiraceae | ||
| Subdoligranulum | ||
| UCG-002UCG-002 |
Revision editor(s): Deacme
Signature 2
Source: Fig 6c
Description: Differential abundance analysis identified using LEfSe between healthy controls and Essential thrombocythemia patients negative for the JAK2V617F mutation
Abundance in Group 1: decreased abundance in JAK2V617F-negaive
| NCBI | Quality Control | Links |
|---|---|---|
| Agathobacter | ||
| Faecalibacterium | ||
| Lachnospiraceae | ||
| Lachnospirales |
Revision editor(s): Deacme
Experiment 4
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- JAK2V617F-negative
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- JAK2V617F-positive
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Essential thrombocythemia patients positive for the JAK2V617F mutation
- Group 0 sample size Number of subjects in the control (unexposed) group
- 16
- Group 1 sample size Number of subjects in the case (exposed) group
- 36
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
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Fig 6d
Description: Differential abundance analysis identified using LEfSe between Essential thrombocythemia patients negative for the JAK2V617F mutation and patients positive for the JAK2V617F mutation
Abundance in Group 1: increased abundance in JAK2V617F-positive
| NCBI | Quality Control | Links |
|---|---|---|
| Bacilli | ||
| Bifidobacteriaceae | ||
| Bifidobacteriales | ||
| Bifidobacterium | ||
| Erysipelotrichales |
Revision editor(s): Deacme
Signature 2
Source: Fig 6d
Description: Differential abundance analysis identified using LEfSe between Essential thrombocythemia patients negative for the JAK2V617F mutation and patients positive for the JAK2V617F mutation
Abundance in Group 1: decreased abundance in JAK2V617F-positive
| NCBI | Quality Control | Links |
|---|---|---|
| UCG-002UCG-002 |
Revision editor(s): Deacme
Retrieved from "https://bugsigdb.org/w/index.php?title=Study_959&oldid=124192"
Hidden category:
