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
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
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
- Treatment Treatment,treatment
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pre-treatment (baseline)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Post-treatment (6 months later)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Saliva samples collected from patients with oral squamous cell carcinoma (SCC) at 6 months after treatment
- 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
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None
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
- 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
- decreased
- Richness Number of species
- decreased
Signature 3
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Source: Supplementary Fig. 1B
Description: Differentially abundant taxa at pre-treatment (0 month) compared to post-treatment (6 months later) by Linear discriminant analysis Effect Size (LEfSe) analysis
Abundance in Group 1: increased abundance in Post-treatment (6 months later)
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus | ||
| Streptococcus | ||
| Prevotella | ||
| Rothia | ||
| Pseudomonas | ||
| Scardovia | ||
| unclassified Veillonellaceae |
Revision editor(s): Nityasinghal 14, Scholastica
Signature 4
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Source: Supplementary Fig. 1B
Description: Differentially abundant taxa at pre-treatment (0 month) compared to post-treatment (6 months later) by Linear discriminant analysis Effect Size (LEfSe) analysis
Abundance in Group 1: decreased abundance in Post-treatment (6 months later)
Revision editor(s): Nityasinghal 14, Scholastica
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to surgery post operative response,post-operative response,response to operation,response to surgical intervention,Response to surgery,response to surgery
- 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
- Saliva samples collected from patients with oral squamous cell carcinoma (SCC) at 6 months after treatment with surgery alone
- 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
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
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
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Source: Figure 3E
Description: Most differentially abundant OTUs between pre‑ and post‑surgery salivary microbiomes based on LEfSe analysis
Abundance in Group 1: increased abundance in Post-surgery
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonas |
Revision editor(s): Nityasinghal 14, Scholastica
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Source: Figure 3E
Description: Most differentially abundant OTUs between pre‑ and post‑surgery salivary microbiomes based on LEfSe analysis
Abundance in Group 1: decreased abundance in Post-surgery
| NCBI | Quality Control | Links |
|---|---|---|
| Leptotrichia | ||
| Veillonella | ||
| unclassified Flavobacteriaceae | ||
| unclassified Lactobacillaceae |
Revision editor(s): Nityasinghal 14, Scholastica
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Microbiome measurement Microbiome measurement,microbiome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pre-chemoradiotherapy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- 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 with oral squamous cell carcinoma (SCC) at 6 months who had undergone chemoradiotherapy
- Group 0 sample size Number of subjects in the control (unexposed) group
- 33
- Group 1 sample size Number of subjects in the case (exposed) group
- 33
Lab analysis
Statistical Analysis
- 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
- unchanged
- Richness Number of species
- decreased
Signature 3
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Source: Supplementary Fig. 2
Description: Differentially abundant taxa before and after chemoradiotherapy (6 months later) by Linear discriminant analysis Effect Size (LEfSe) analysis
Abundance in Group 1: increased abundance in Post-chemoradiotherapy
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus | ||
| Scardovia | ||
| Pseudomonas | ||
| Rothia | ||
| Streptococcus | ||
| Prevotella |
Revision editor(s): Nityasinghal 14, Scholastica
Signature 4
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Source: Supplementary Fig. 2
Description: Differentially abundant taxa before and after chemoradiotherapy (6 months later) by Linear discriminant analysis Effect Size (LEfSe) analysis
Abundance in Group 1: decreased abundance in Post-chemoradiotherapy
Revision editor(s): Nityasinghal 14, Scholastica
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to combination chemotherapy Response to combination chemotherapy,response to combination chemotherapy
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Responders at baseline
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Non-Responders at baseline
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with oral squamous cell carcinoma (SCC) at baseline deemed non-responders if any recurrence (local or metastatic) occurred within the follow-up period
- Group 0 sample size Number of subjects in the control (unexposed) group
- 39
- Group 1 sample size Number of subjects in the case (exposed) group
- 11
Lab analysis
Statistical Analysis
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
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
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Source: Figure 4F
Description: LEfSe analysis showing the most differentially abundant OTUs in responders versus non‑responders before chemoradiotherapy
Abundance in Group 1: increased abundance in Non-Responders at baseline
| NCBI | Quality Control | Links |
|---|---|---|
| Anaeroglobus | ||
| Prevotella | ||
| Streptococcus |
Revision editor(s): Nityasinghal 14, Scholastica
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Source: Figure 4F
Description: LEfSe analysis showing the most differentially abundant OTUs in responders versus non‑responders before chemoradiotherapy
Abundance in Group 1: decreased abundance in Non-Responders at baseline
| NCBI | Quality Control | Links |
|---|---|---|
| Abiotrophia | ||
| Actinomyces | ||
| Corynebacterium | ||
| Lautropia | ||
| Leptotrichia | ||
| Neisseria | ||
| Prevotella | ||
| Veillonella | ||
| unclassified Pasteurellaceae |
Revision editor(s): Nityasinghal 14, Scholastica
Experiment 5
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Responders at 6 months
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Non-Responders at 6 months
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with oral squamous cell carcinoma (SCC) at 6 months deemed non-responders if any recurrence (local or metastatic) occurred within the follow-up period
- 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
- 8
Lab analysis
Statistical Analysis
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 3.5
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-25
Source: Figure 5F
Description: LEfSe analysis identifying the most differentially abundant OTUs in responders versus non‑responders after chemoradiotherapy.
Abundance in Group 1: decreased abundance in Non-Responders at 6 months
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces | ||
| Atopobium | ||
| Gemella | ||
| Rothia | ||
| Streptococcus | ||
| Veillonella |
Revision editor(s): Nityasinghal 14, Scholastica
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