Salivary microbiome changes distinguish response to chemoradiotherapy in patients with oral cancer
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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
Medeiros MC, The S, Bellile E, Russo N, Schmitd L, Danella E, Singh P, Banerjee R, Bassis C, Murphy GR, Sartor MA, Lombaert I, Schmidt TM, Eisbruch A, Murdoch-Kinch CA, Rozek L, Wolf GT, Li G, Chen GY, D'Silva NJ
Journal
Microbiome
Year
2023
BACKGROUND: Oral squamous cell carcinoma (SCC) is associated with oral microbial dysbiosis. In this unique study, we compared pre- to post-treatment salivary microbiome in patients with SCC by 16S rRNA gene sequencing and examined how microbiome changes correlated with the expression of an anti-microbial protein. RESULTS: Treatment of SCC was associated with a reduction in overall bacterial richness and diversity. There were significant changes in the microbial community structure, including a decrease in the abundance of Porphyromonaceae and Prevotellaceae and an increase in Lactobacillaceae. There were also significant changes in the microbial community structure before and after treatment with chemoradiotherapy, but not with surgery alone. In patients treated with chemoradiotherapy alone, several bacterial populations were differentially abundant between responders and non-responders before and after therapy. Microbiome changes were associated with a change in the expression of DMBT1, an anti-microbial protein in human saliva. Additionally, we found that salivary DMBT1, which increases after treatment, could serve as a post-treatment salivary biomarker that links to microbial changes. Specifically, post-treatment increases in human salivary DMBT1 correlated with increased abundance of Gemella spp., Pasteurellaceae spp., Lactobacillus spp., and Oribacterium spp. This is the first longitudinal study to investigate treatment-associated changes (chemoradiotherapy and surgery) in the oral microbiome in patients with SCC along with changes in expression of an anti-microbial protein in saliva. CONCLUSIONS: The composition of the oral microbiota may predict treatment responses; salivary DMBT1 may have a role in modulating the oral microbiome in patients with SCC. After completion of treatment, 6 months after diagnosis, patients had a less diverse and less rich oral microbiome. Leptotrichia was a highly prevalent bacteria genus associated with disease. Expression of DMBT1 was higher after treatment and associated with microbiome changes, the most prominent genus being Gemella Video Abstract.
Experiment 1
Needs review
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
- Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Oral squamous cell carcinoma mouth scc,mouth squamous cell carcinoma,OCSC,oral cavity scc,oral cavity squamous cell cancer,oral cavity squamous cell carcinoma,oral squamous cell carcinoma,scc of mouth,scc of oral cavity,scc of the mouth,scc of the oral cavity,squamous cell carcinoma of mouth,squamous cell carcinoma of oral cavity,squamous cell carcinoma of the mouth,squamous cell carcinoma of the oral cavity,Oral squamous cell carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Salivary Microbiome pre treatment
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Salivary Microbiome post treatment
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Changes in the oral microbiome from pre- to post-treatment saliva collected from patients with SCC at diagnosis and 6 months later (0 and 6 months), to identify changes that occurred soon after completion of therapy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 106
- Group 1 sample size Number of subjects in the case (exposed) group
- 72
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
- 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
- 2.5
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
- Richness Number of species
- decreased
Signature 3
Needs review
Source: Figure 1F
Description: Significance of bacterial families that were at least 0.1% in differential abundance.
Abundance in Group 1: increased abundance in Salivary Microbiome post treatment
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacteriaceae | ||
| Burkholderiaceae | ||
| Lachnospiraceae | ||
| Lactobacillaceae | ||
| Prevotellaceae | ||
| Pseudomonadaceae | ||
| Staphylococcaceae | ||
| unclassified Lactobacillales | ||
| Leptotrichiaceae |
Revision editor(s): Nityasinghal 14
Signature 4
Needs review
Source: Figure 1F
Description: Significance of bacterial families that were at least 0.1% in differential abundance.
Abundance in Group 1: decreased abundance in Salivary Microbiome post treatment
| NCBI | Quality Control | Links |
|---|---|---|
| Erysipelotrichaceae | ||
| Flavobacteriaceae | ||
| Neisseriaceae | ||
| Pasteurellaceae | ||
| Peptostreptococcaceae | ||
| Porphyromonadaceae | ||
| unclassified Bacteroidales |
Revision editor(s): Nityasinghal 14
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pre-surgery
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Post-surgery
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients who underwent surgery alone for six months were analyzed post-treatment.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 15
- Group 1 sample size Number of subjects in the case (exposed) group
- 15
Lab analysis
Statistical Analysis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
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
- Richness Number of species
- decreased
Signature 1
Needs review
Source: Figure 3E
Description: Post-treatment dominance shown using LEfSe analysis.
Abundance in Group 1: increased abundance in Post-surgery
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonas |
Revision editor(s): Nityasinghal 14
Signature 2
Needs review
Source: Figure 3E
Description: The pre-treatment predominance of OTUs is shown by LEfSe analysis.
Abundance in Group 1: decreased abundance in Post-surgery
| NCBI | Quality Control | Links |
|---|---|---|
| Veillonella | ||
| unclassified Flavobacteriaceae | ||
| Leptotrichia | ||
| unclassified Lactobacillaceae |
Revision editor(s): Nityasinghal 14
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- salivary microbiota pre-chemoradiotherapy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- salivary microbiota post-chemoradiotherapy
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Saliva samples collected from patients post-chemoradiotherapy were used to identify potential microbial biomarkers associated with response to chemoradiotherapy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 50
- Group 1 sample size Number of subjects in the case (exposed) group
- 33
Lab analysis
Statistical Analysis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.001
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 3
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
- Richness Number of species
- decreased
Signature 3
Needs review
Source: Figure 2E
Description: Differential abundance of the families that were > 0.1% in abundance after chemoradiation.
Abundance in Group 1: increased abundance in salivary microbiota post-chemoradiotherapy
| NCBI | Quality Control | Links |
|---|---|---|
| Erysipelotrichaceae | ||
| Neisseriaceae | ||
| Pseudomonadaceae | ||
| Staphylococcaceae | ||
| unclassified Bacteroidales | ||
| unclassified Lactobacillales | ||
| Lactobacillaceae |
Revision editor(s): Nityasinghal 14
Signature 4
Needs review
Source: Figure 2E
Description: Differential abundance of the families that were > 0.1% in abundance after chemoradiation.
Abundance in Group 1: decreased abundance in salivary microbiota post-chemoradiotherapy
| NCBI | Quality Control | Links |
|---|---|---|
| Flavobacteriaceae | ||
| Leptotrichiaceae | ||
| Pasteurellaceae | ||
| Prevotellaceae |
Revision editor(s): Nityasinghal 14
Experiment 4
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-Responders (0 months)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders (0 months)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients who didn't face recurrence (local or metastatic) within the follow-up period of chemoradiotherapy and were disease-free at the baseline (0 months).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 11
- Group 1 sample size Number of subjects in the case (exposed) group
- 39
Lab analysis
Statistical Analysis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.026
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 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
- unchanged
- Richness Number of species
- unchanged
Signature 1
Needs review
Source: Figure 4F
Description: LEfSe analysis of baseline salivary samples showed a significant association of responders.
Abundance in Group 1: increased abundance in Responders (0 months)
| NCBI | Quality Control | Links |
|---|---|---|
| Corynebacterium | ||
| Lautropia | ||
| Leptotrichia | ||
| Veillonella | ||
| unclassified Pasteurellaceae | ||
| Prevotella | ||
| Abiotrophia | ||
| Neisseria | ||
| Actinomyces |
Revision editor(s): Nityasinghal 14
Signature 2
Needs review
Source: Figure 4F
Description: LEfSe analysis of baseline salivary samples showed a significant association of responders.
Abundance in Group 1: decreased abundance in Responders (0 months)
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella | ||
| Streptococcus | ||
| Anaeroglobus |
Revision editor(s): Nityasinghal 14
Experiment 5
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-Responders (6 months)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders (6 months)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients who didn't face recurrence (local or metastatic) within the follow-up period after completion of chemoradiotherapy at six months from baseline and were disease-free.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 8
- Group 1 sample size Number of subjects in the case (exposed) group
- 25
Lab analysis
Statistical Analysis
- 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
- 3.5
Alpha Diversity
- Richness Number of species
- unchanged
Signature 1
Needs review
Source: Figure 5F
Description: Relative Abundance of taxon
Abundance in Group 1: increased abundance in Responders (6 months)
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces | ||
| Atopobium | ||
| Gemella | ||
| Rothia | ||
| Streptococcus | ||
| Veillonella |
Revision editor(s): Nityasinghal 14
Signature 2
Needs review
Source: Figure 5E
Description: Relative abundance of taxon after chemoradiotherapy showing abundance in non-responders.
Abundance in Group 1: decreased abundance in Responders (6 months)
| NCBI | Quality Control | Links |
|---|---|---|
| Porphyromonadaceae | ||
| Fusobacteriaceae |
Revision editor(s): Nityasinghal 14
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