Salivary microbiome profiles of oral cancer patients analyzed before and after treatment
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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.
Authors
Mäkinen AI, Pappalardo VY, Buijs MJ, Brandt BW, Mäkitie AA, Meurman JH, Zaura E
Journal
Microbiome
Year
2023
Keywords:
Cancer treatment, Oral cancer, Oral microbiome
BACKGROUND: Treating oral squamous cell carcinoma (OSCC) introduces new ecological environments in the oral cavity. This is expected to cause changes in the oral microbiome. The purpose of this study was to gain new information on the salivary microbiome of OSCC patients in order to improve the aftercare of OSCC patients. The aims of this study were to investigate possible changes in the salivary microbiome profiles of OSCC patients before and after cancer treatment and to compare these changes with the profiles of healthy controls. PATIENTS AND METHODS: Paraffin-stimulated whole saliva samples were collected, and the salivary flow rate was measured from 99 OSCC patients prior to surgical resection of the tumor and other adjuvant therapy. After treatment, 28 OSCC patients were re-examined with a mean follow-up time of 48 months. In addition, 101 healthy controls were examined and sampled. After DNA extraction and purification, the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced using Illumina MiSeq. The merged read pairs were denoised using UNOISE3, mapped to zero-radius operational taxonomic units (zOTUs), and the representative zOTU sequences were assigned a taxonomy using HOMD. Descriptive statistics were used to study the differences in the microbial profiles of OSCC patients before and after treatment and in comparison to healthy controls. RESULTS: At baseline, the OSCC patients showed a higher relative abundance of zOTUs classified as Streptococcus anginosus, Abiotrophia defectiva, and Fusobacterium nucleatum. The microbial profiles differed significantly between OSCC patients and healthy controls (F = 5.9, p < 0.001). Alpha diversity of the salivary microbiome of OSCC patients was decreased at the follow-up, and the microbial profiles differed significantly from the pre-treatment (p < 0.001) and from that of healthy controls (p < 0.001). CONCLUSIONS: OSCC patients' salivary microbiome profile had a higher abundance of potentially pathogenic bacteria compared to healthy controls. Treatment of the OSCC caused a significant decrease in alpha diversity and increase in variability of the salivary microbiome, which was still evident after several years of follow-up. OSCC patients may benefit from preventive measures, such as the use of pre- or probiotics, salivary substitutes, or dietary counseling. Video Abstract.
Experiment 1
Subjects
- Location of subjects
- Finland
- 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
- Oral cavity Bucca,Buccal cavity,Cavity of mouth,Oral cavity
- 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
- 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
- pre-treatment oral squamous cell carcinoma patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients diagnosed with Oral Squamous Cell Carcinoma (OSCC), prior to receiving cancer treatment
- Group 0 sample size Number of subjects in the control (unexposed) group
- 101
- Group 1 sample size Number of subjects in the case (exposed) group
- 99
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Not mentioned
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
- 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
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Figure 2 A
Description: Discriminatory zero-radius operational taxonomic units (zOTUs) between oral squamous cell carcinoma (OSCC) patients and healthy controls
Abundance in Group 1: increased abundance in pre-treatment oral squamous cell carcinoma patients
| NCBI | Quality Control | Links |
|---|---|---|
| Streptococcus constellatus | ||
| Abiotrophia defectiva | ||
| Capnocytophaga leadbetteri | ||
| Streptococcus anginosus | ||
| Fusobacterium animalis | ||
| Rothia mucilaginosa | ||
| Streptococcus oralis |
Revision editor(s): Andre
Signature 2
Source: Figure 2 A
Description: Discriminatory zero-radius operational taxonomic units (zOTUs) between oral squamous cell carcinoma (OSCC) patients and healthy controls
Abundance in Group 1: decreased abundance in pre-treatment oral squamous cell carcinoma patients
Revision editor(s): Andre
Experiment 2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Nonsmoking, nondrinking, and dentate healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Nonsmoking, nondrinking, and dentate pre-treatment OSCC patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- OSCC patients who have not received any cancer treatment yet and who do not smoke tobacco or drink alcohol, and have at least one remaining tooth in their mouth.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 34
- Group 1 sample size Number of subjects in the case (exposed) group
- 24
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Source: Figure 2 B
Description: Discriminatory zOTUs between OSCC patients and healthy controls
Abundance in Group 1: increased abundance in Nonsmoking, nondrinking, and dentate pre-treatment OSCC patients
Revision editor(s): Andre
Signature 2
Source: Figure 2 B
Description: Discriminatory zOTUs between OSCC patients and healthy controls
Abundance in Group 1: decreased abundance in Nonsmoking, nondrinking, and dentate pre-treatment OSCC patients
| NCBI | Quality Control | Links |
|---|---|---|
| Veillonella dispar | ||
| Streptococcus australis | ||
| Prevotella histicola | ||
| Prevotella veroralis | ||
| Actinomyces sp. oral taxon 172 | ||
| Prevotella oulorum | ||
| Leptotrichia sp. oral taxon 221 |
Revision editor(s): Andre
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- pre-treatment OSCC patients
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- post-treatment OSCC patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- OSCC patients who received cancer treatment, and seen after a mean follow-up of 47.8 months.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 28
- Group 1 sample size Number of subjects in the case (exposed) group
- 28
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Source: Fig 4
Description: Discriminatory zOTUs between baseline and post-therapy samples in 28 OSCC patients (output of LEfSe analysis).
Abundance in Group 1: increased abundance in post-treatment OSCC patients
Revision editor(s): Andre
Signature 2
Source: 4
Description: Discriminatory zOTUs between baseline and post-therapy samples in 28 OSCC patients (output of LEfSe analysis)
Abundance in Group 1: decreased abundance in post-treatment OSCC patients
| NCBI | Quality Control | Links |
|---|---|---|
| Rothia dentocariosa | ||
| Lacticaseibacillus paracasei | ||
| Lacticaseibacillus rhamnosus | ||
| Actinomyces gerencseriae |
Revision editor(s): Andre
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