Salivary microbiome profiles of oral cancer patients analyzed before and after treatment

From BugSigDB
Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20
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


Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20

Curated date: 2023/08/08

Curator: Andre

Revision editor(s): Andre, Peace Sandy

Subjects

Location of subjects
Finland
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
Oral cavity Bucca,Buccal cavity,Cavity of mouth,Oral cavity,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,Oral squamous cell carcinoma
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

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
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

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20

Curated date: 2023/08/08

Curator: Andre

Revision editor(s): Andre

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 ControlLinks
Streptococcus constellatus
Abiotrophia defectiva
Capnocytophaga leadbetteri
Streptococcus anginosus
Fusobacterium animalis
Rothia mucilaginosa
Streptococcus oralis

Revision editor(s): Andre

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20

Curated date: 2023/08/08

Curator: Andre

Revision editor(s): Andre

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

NCBI Quality ControlLinks
Prevotella melaninogenica
Streptococcus salivarius
Neisseria flavescens
Haemophilus parainfluenzae
Veillonella dispar
Streptococcus australis
Veillonella parvula
Rothia mucilaginosa
Actinomyces sp. oral taxon 172
Fusobacterium periodonticum
Actinomyces graevenitzii
Prevotella pallens

Revision editor(s): Andre

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20

Curated date: 2023/08/08

Curator: Andre

Revision editor(s): Andre, Peace Sandy

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

Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20

Curated date: 2023/08/08

Curator: Andre

Revision editor(s): Andre

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

NCBI Quality ControlLinks
Selenomonas sp. oral taxon 134
TM7 phylum sp. oral taxon 351
Leptotrichia sp. oral taxon 392
Lactococcus lactis
Streptococcus anginosus
Granulicatella elegans
Abiotrophia defectiva
Aggregatibacter aphrophilus
Fusobacterium sp. oral taxon 203
Leptotrichia shahii
Neisseria flava
Gemella sanguinis
Streptococcus oralis

Revision editor(s): Andre

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20

Curated date: 2023/08/09

Curator: Andre

Revision editor(s): Andre

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 ControlLinks
Veillonella dispar
Streptococcus australis
Prevotella histicola
Prevotella veroralis
Actinomyces sp. oral taxon 172
Segatella oulorum
Leptotrichia sp. oral taxon 221

Revision editor(s): Andre

Experiment 3


Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20

Curated date: 2023/08/09

Curator: Andre

Revision editor(s): Andre, Peace Sandy

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
unchanged

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20

Curated date: 2023/08/09

Curator: Andre

Revision editor(s): Andre

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

NCBI Quality ControlLinks
Solobacterium moorei
Mogibacterium diversum
Streptococcus sp.
Leptotrichia sp.
Treponema sp.
Bergeyella sp. oral taxon 322
Bacteroidetes bacterium oral taxon 511
Porphyromonas endodontalis
Lancefieldella parvula
Lautropia mirabilis
Leptotrichia sp. oral taxon 417
Peptostreptococcus stomatis
Parvimonas micra
Prevotella sp. oral taxon 313
Leptotrichia hongkongensis
Capnocytophaga leadbetteri
Fusobacterium vincentii
Veillonella rogosae
Prevotella veroralis
Abiotrophia defectiva
Actinomyces sp. oral taxon 180
Streptococcus sanguinis
Streptococcus oralis subsp. dentisani

Revision editor(s): Andre

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2023-12-20

Curated date: 2023/08/09

Curator: Andre

Revision editor(s): Andre

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 ControlLinks
Rothia dentocariosa
Lacticaseibacillus paracasei
Lacticaseibacillus rhamnosus
Actinomyces gerencseriae

Revision editor(s): Andre