Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation 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 Uniform resource identifier for web resources.
Authors
Laheij AMGA, Raber-Durlacher JE, Koppelmans RGA, Huysmans MDNJM, Potting C, van Leeuwen SJM, Hazenberg MD, Brennan MT, von Bültzingslöwen I, Johansson JE, de Soet JJ, Haverman TM, Buijs MJ, Brandt BW, Rozema FR, Blijlevens NMA, Zaura E
Journal
Scientific reports
Year
2019
The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.
Experiment 1
Subjects
- Location of subjects
- Netherlands
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Mouth Adult mouth,Cavital oralis,Cavitas oris,Cavum oris,Mouth cavity,Oral region,Oral vestibule,Regio oralis,Rima oris,Stoma,Stomatodaeum,Trophic apparatus,Vestibule of mouth,Vestibulum oris,Mouth
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- oral mucositis inflammation of the mouth,oral cavity mucosal damage,oral mucosa irritation,oral mucosal damage,oral mucosal injury,oral mucosal lesions,stomatitis,oral mucositis
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- no ulcerative oral mucositis
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- ulcerative oral mucositis
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patient developed uclerative oral mucositis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 31
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
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
- RT-qPCR
Statistical Analysis
- 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
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Signature 1
Needs review
Source: Figure 3
Description: Minimum entropy decomposition nodes (MEDs) that significantly discriminate multiple myeloma patients that did not develop uclerative oral mucositis and patients that did develop uclerative oral mucositis before auto stem cell transplant identified by LEfSe
Abundance in Group 1: increased abundance in ulcerative oral mucositis
| NCBI | Links |
|---|---|
| Veillonella | |
| Enterococcus | |
| Streptococcus | |
| Staphylococcus | |
| Fusobacterium | |
| Prevotella |
Revision editor(s): WikiWorks
Signature 2
Needs review
Source: Figure 3
Description: Minimum entropy decomposition nodes (MEDs) that significantly discriminate multiple myeloma patients that did not develop uclerative oral mucositis and patients that did develop uclerative oral mucositis before auto stem cell transplant identified by LEfSe
Abundance in Group 1: decreased abundance in ulcerative oral mucositis
| NCBI | Links |
|---|---|
| Streptococcus | |
| Actinomyces |
Revision editor(s): WikiWorks
Experiment 2
Subjects
- Location of subjects
- Netherlands
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Mouth Adult mouth,Cavital oralis,Cavitas oris,Cavum oris,Mouth cavity,Oral region,Oral vestibule,Regio oralis,Rima oris,Stoma,Stomatodaeum,Trophic apparatus,Vestibule of mouth,Vestibulum oris,Mouth
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- oral mucositis inflammation of the mouth,oral cavity mucosal damage,oral mucosa irritation,oral mucosal damage,oral mucosal injury,oral mucosal lesions,stomatitis,oral mucositis
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- one and two weeks after stem cell transplant
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- pre- and three month after auto stem cell transplant
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patient developed uclerative oral mucositis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 31
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
Lab analysis
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- RT-qPCR
Statistical Analysis
- Statistical test
- PERMANOVA
- 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
- increased
Signature 1
Needs review
Source: Figure 1, Figure 2a and text
Description: Based on principle component analysis asses taxa were responsible for the observed microbial shifts over time in non-uclerative oral mucositis group
Abundance in Group 1: increased abundance in pre- and three month after auto stem cell transplant
| NCBI | Links |
|---|---|
| Veillonella atypica | |
| Veillonella dispar | |
| Actinomyces sp. | |
| Actinomyces graevenitzii | |
| Prevotella | |
| Leptotrichia | |
| Megasphaera micronuciformis | |
| Veillonella sp. |
Revision editor(s): WikiWorks
Signature 2
Needs review
Source: Figure 1, Figure 2a and text
Description: Based on principle component analysis asses taxa were responsible for the observed microbial shifts over time in non-uclerative oral mucositis group
Abundance in Group 1: decreased abundance in pre- and three month after auto stem cell transplant
| NCBI | Links |
|---|---|
| Lactobacillus | |
| Limosilactobacillus fermentum | |
| Scardovia wiggsiae |
Revision editor(s): WikiWorks
Experiment 3
Subjects
- Location of subjects
- Netherlands
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Mouth Adult mouth,Cavital oralis,Cavitas oris,Cavum oris,Mouth cavity,Oral region,Oral vestibule,Regio oralis,Rima oris,Stoma,Stomatodaeum,Trophic apparatus,Vestibule of mouth,Vestibulum oris,Mouth
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- oral mucositis inflammation of the mouth,oral cavity mucosal damage,oral mucosa irritation,oral mucosal damage,oral mucosal injury,oral mucosal lesions,stomatitis,oral mucositis
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- one and two weeks after stem cell transplant
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- pre- and three month after auto stem cell transplant
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patient developed uclerative oral mucositis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 31
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
Lab analysis
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- RT-qPCR
Statistical Analysis
- Statistical test
- PERMANOVA
- 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
- unchanged
Signature 1
Needs review
Source: Figure 2a and text
Description: Based on principle component analysis asses taxa were responsible for the observed microbial shifts over time in uclerative oral mucositis group
Abundance in Group 1: increased abundance in pre- and three month after auto stem cell transplant
| NCBI | Links |
|---|---|
| Streptococcus australis | |
| Streptococcus parasanguinis | |
| Veillonella atypica | |
| Veillonella dispar | |
| Actinomyces | |
| Actinomyces graevenitzii | |
| Gemella haemolysans | |
| Gemella morbillorum | |
| Gemella sanguinis |
Revision editor(s): WikiWorks
Signature 2
Needs review
Source: Figure 2a and text
Description: Based on principle component analysis asses taxa were responsible for the observed microbial shifts over time in uclerative oral mucositis group
Abundance in Group 1: decreased abundance in pre- and three month after auto stem cell transplant
| NCBI | Links |
|---|---|
| Staphylococcus aureus | |
| Staphylococcus caprae | |
| Staphylococcus epidermidis | |
| Staphylococcus warneri | |
| Scardovia wiggsiae | |
| Enterococcus faecalis |
Revision editor(s): WikiWorks
Experiment 4
Subjects
- Location of subjects
- Netherlands
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Mouth Adult mouth,Cavital oralis,Cavitas oris,Cavum oris,Mouth cavity,Oral region,Oral vestibule,Regio oralis,Rima oris,Stoma,Stomatodaeum,Trophic apparatus,Vestibule of mouth,Vestibulum oris,Mouth
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- oral mucositis inflammation of the mouth,oral cavity mucosal damage,oral mucosa irritation,oral mucosal damage,oral mucosal injury,oral mucosal lesions,stomatitis,oral mucositis
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- low or no fungi load
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- 0.1% or higher fungi load
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patient developed uclerative oral mucositis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 31
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
Lab analysis
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- RT-qPCR
Statistical Analysis
- 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
Needs review
Source: Figure 5 and text
Description: Principle component analysis of salivary microbial profiles based on fungal load relative to bacterial 16s rDNA
Abundance in Group 1: increased abundance in 0.1% or higher fungi load
| NCBI | Links |
|---|---|
| Scardovia | |
| Staphylococcus | |
| Lactobacillus |
Revision editor(s): WikiWorks
Signature 2
Needs review
Source: Figure 5 and text
Description: Principle component analysis of salivary microbial profiles based on fungal load relative to bacterial 16s rDNA
Abundance in Group 1: decreased abundance in 0.1% or higher fungi load
| NCBI | Links |
|---|---|
| Veillonella | |
| Actinomyces | |
| Prevotella | |
| Leptotrichia | |
| Megasphaera | |
| Streptococcus |
Revision editor(s): WikiWorks
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