Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study

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Reviewed Marked as Reviewed by Atrayees on 2023-7-25
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Frid P, Baraniya D, Halbig J, Rypdal V, Songstad NT, Rosèn A, Berstad JR, Flatø B, Alakwaa F, Gil EG, Cetrelli L, Chen T, Al-Hebshi NN, Nordal E, Al-Haroni M
Journal
Frontiers in cellular and infection microbiology
Year
2020
Keywords:
16S rRNA, juvenile idiopathic arthritis, next generation sequencing (NGS), oral health, salivary microbiome
Background: The oral microbiota has been connected to the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. The objective of this study was to characterize the salivary oral microbiome associated with juvenile idiopathic arthritis (JIA), and correlate it with the disease activity including gingival inflammation. Methods: Fifty-nine patients with JIA (mean age, 12.6 ± 2.7 years) and 34 healthy controls (HC; mean age 12.3 ± 3.0 years) were consecutively recruited in this Norwegian cross-sectional study. Information about demographics, disease activity, medication history, frequency of tooth brushing and a modified version of the gingival bleeding index (GBI) and the simplified oral hygiene index (OHI-S) was obtained. Microbiome profiling of saliva samples was performed by sequencing of the V1-V3 region of the 16S rRNA gene, coupled with a species-level taxonomy assignment algorithm; QIIME, LEfSe and R-package for Spearman correlation matrix were used for downstream analysis. Results: There were no significant differences between JIA and HC in alpha- and beta-diversity. However, differential abundance analysis revealed several taxa to be associated with JIA: TM7-G1, Solobacterium and Mogibacterium at the genus level; and Leptotrichia oral taxon 417, TM7-G1 oral taxon 352 and Capnocytophaga oral taxon 864 among others, at the species level. Haemophilus species, Leptotrichia oral taxon 223, and Bacillus subtilis, were associated with healthy controls. Gemella morbillorum, Leptotrichia sp. oral taxon 498 and Alloprevotella oral taxon 914 correlated positively with the composite juvenile arthritis 10-joint disease activity score (JADAS10), while Campylobacter oral taxon 44 among others, correlated with the number of active joints. Of all microbial markers identified, only Bacillus subtilis and Campylobacter oral taxon 44 maintained false discovery rate (FDR) < 0.1. Conclusions: In this exploratory study of salivary oral microbiome we found similar alpha- and beta-diversity among children with JIA and healthy. Several taxa associated with chronic inflammation were found to be associated with JIA and disease activity, which warrants further investigation.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-7-25

Curated date: 2021/09/28

Curator: Tislam

Revision editor(s): Tislam, WikiWorks, Victoria

Subjects

Location of subjects
Norway
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
Juvenile idiopathic arthritis acute juvenile rheumatoid arthritis,Arthritis (juvenile idiopathic),arthritis, juvenile rheumatoid,breast myoepithelial carcinoma,chronic childhood arthritis,JIA,juvenile arthritis,juvenile chronic arthritis,Juvenile chronic arthritis (disorder),juvenile chronic polyarthritis,Juvenile idiopathic arthritis,juvenile idiopathic arthritis,Juvenile idiopathic arthritis (disorder),Juvenile rheumatoid a.,Juvenile Rheumatoid Arthritis,juvenile rheumatoid arthritis,Juvenile rheumatoid arthritis (disorder),Juvenile rheumatoid arthritis NOS (disorder),Juvenile rheumatoid arthritis, NOS,Juvenile seropositive polyarthritis,monarticular juvenile rheumatoid arthritis,pauciarticular juvenile arthritis,pauciarticular onset juvenile chronic arthritis,rheumatoid arthritis, systemic juvenile,systemic juvenile rheumatoid arthritis
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
JIA patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
children with juvenile idiopathic arthritis
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
59
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Patients on antibiotics prior to sampling were excluded.

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V1-V3
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)
.1
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
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
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-25

Curated date: 2021/09/28

Curator: Tislam

Revision editor(s): Tislam, Atrayees

Source: Figure 3

Description: Differentially abundant taxa

Abundance in Group 1: increased abundance in JIA patients

NCBI Quality ControlLinks
Alloprevotella sp.
Lachnoanaerobaculum orale
Rothia aeria
Solobacterium moorei
Stomatobaculum longum
Hoylesella nanceiensis
Mogibacterium diversum
Veillonella atypica
Capnocytophaga sp.
TM7 phylum sp. oral taxon 352
Leptotrichia sp. oral taxon 417
Candidatus Saccharibacteria
Solobacterium
Mogibacterium

Revision editor(s): Tislam, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-25

Curated date: 2021/09/28

Curator: Tislam

Revision editor(s): Tislam, Atrayees

Source: Figure 3C

Description: Differentially abundant taxa.

Abundance in Group 1: decreased abundance in JIA patients

NCBI Quality ControlLinks
Haemophilus parainfluenzae
Leptotrichia sp. oral taxon 223
Prevotella denticola
Haemophilus pittmaniae
Bacillus subtilis
Olsenella sp. oral taxon 807
Haemophilus parahaemolyticus
Rothia dentocariosa
Prevotella sp. oral taxon 314
Bergeyella sp. oral taxon 322
Pseudomonadota
Haemophilus
Bacillus
Olsenella

Revision editor(s): Tislam, Atrayees

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-7-25

Curated date: 2021/09/28

Curator: Tislam

Revision editor(s): Tislam, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Temporomandibular joint disorder temporomandibular joint disorder,TMD,Temporomandibular joint disorder
Group 0 name Corresponds to the control (unexposed) group for case-control studies
JIA patients without TMJ
Group 1 name Corresponds to the case (exposed) group for case-control studies
JIA patients with TMJ
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
44
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Patients on antibiotics on the day of sampling were excluded, but previous antibiotic use were not recorded.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-25

Curated date: 2021/09/28

Curator: Tislam

Revision editor(s): Tislam, Atrayees

Source: Figure 6C,

Description: species that showed significant differences in relative abundance between the JIA subjects with and without TMJ involvement, as identified by linear discriminant analysis (LDA) effect size analysis (LEfSe). 2.5 LDA score cutoff. OT, oral taxon. **FDR ≤ 0.1 (Benjamini-Hochberg method).

Abundance in Group 1: decreased abundance in JIA patients with TMJ

NCBI Quality ControlLinks
Rothia mucilaginosa
Lancefieldella parvula
Oribacterium sinus
Pseudoleptotrichia goodfellowii
Streptococcus sp. oral taxon 070
Bacillus subtilis
Haemophilus
Oribacterium
Atopobium
Bacillus
Actinomycetota
Rothia

Revision editor(s): Tislam, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-25

Curated date: 2021/09/28

Curator: Tislam

Revision editor(s): Tislam, Atrayees

Source: Figure 6C, text

Description: species that showed significant differences in relative abundance between the JIA subjects with and without TMJ involvement, as identified by linear discriminant analysis (LDA) effect size analysis (LEfSe). 2.5 LDA score cutoff. OT, oral taxon. **FDR ≤ 0.1 (Benjamini-Hochberg method).

Abundance in Group 1: increased abundance in JIA patients with TMJ

NCBI Quality ControlLinks
Porphyromonas sp.
Prevotella sp. oral taxon 313
SR1 bacterium oral taxon 875
Oribacterium parvum
Eikenella corrodens
Hoylesella shahii
SR1 bacterium oral taxon 874
Alloprevotella sp.
Campylobacter sp. oral taxon 044
Kingella oralis
Hoylesella nanceiensis
Porphyromonas pasteri
Neisseria elongata
Prevotella pallens
Bergeyella sp.
Haemophilus parainfluenzae
Pseudomonadota
Eikenella
Haemophilus
Alloprevotella

Revision editor(s): Tislam, Atrayees