Metagenomic research on the structural difference of plaque microbiome from different caries stages and the construction of a caries diagnostic model

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Dong L., Yang J., Wu H., Sun Y., Liu J., Yuan H., Wang M., Dai Y., Teng F., Jing G., Yang F.
Journal
mSystems
Year
2025
Keywords:
2bRAD sequencing for microbiome, dentin caries, diagnostic model, different caries stages, microbiome
Development of dental caries is a dynamic process; yet, there is limited knowledge on microbial differences at various stages of caries at higher resolution. To investigate the shifting microbiome profiles across different caries stages, 30 children were enrolled in this study, including 15 caries-active patients and 15 caries-free individuals. Plaque samples were collected from the buccal surface of caries-free subjects, defined as confident health (CH; n = 15). For caries-active individuals, plaque samples were collected from non-cavitated surfaces (defined as relative health [RH], n = 15), enamel caries (EC; n = 15), and dentin caries samples (DC; n = 15). All the above samples were sequenced through the 2bRAD sequencing platform to reveal the microbial community structures in each group. We identified significant differences in microbial community structures from different caries stages. First, the CH group showed the highest species richness (P < 0.05), and then followed by the RH and EC groups with lower richness, and the lowest richness was found in the DC group, yet no significant difference was found among the last three groups (P > 0.05). Second, the microbial structure exhibited the greatest difference between CH and DC groups, followed by the distance between RH/EC and DC groups, and the smallest difference was found between RH and EC groups. Third, specific species were found with a significant difference during the different caries stages. Therefore, we developed a diagnostic model using deep learning methods based on neural networks to diagnose different caries stages with an AUC of over 98%. This may provide methodological support for the understanding of the etiological factor in the pathological progression of dental caries.IMPORTANCEThe diagnosis and treatment of dental caries are crucial for human oral health. Previous studies have focused on the microbial differences between caries and healthy teeth, but there was not enough knowledge on the microbial differences at different stages of dental caries. Our findings could provide a high-resolution understanding of the microbial divergencies among different stages of dental caries and thus build microbial-based diagnostic models for differentiating dental caries status using deep learning methods with an accuracy of over 98%. This may provide methodological support for the understanding of the etiological factor in the pathological progression of dental caries.

Experiment 1


Needs review

Curated date: 2025/10/10

Curator: Chyono2

Revision editor(s): Chyono2

Subjects

Location of subjects
China
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
Dental plaque Bacterial plaque,Plaque,Dental plaque,dental plaque
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Dental caries caries,CARIES DENT,Caries, Dental,DECAY DENT,Decay, Dental,DENT CARIES,DENT DECAY,DENT WHITE SPOT,DENT WHITE SPOTS,dental caries,dental caries extending into pulp,dental caries of smooth surface,dental caries pit and fissure,Dental Decay,Dental White Spot,Dental White Spots,Spot, White,Spots, White,White Spot,WHITE SPOT DENT,White Spot, Dental,White Spots,WHITE SPOTS DENT,White Spots, Dental,Dental caries
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Relative health(RH)+Enamel caries(EC)+Dentin caries(DC)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Confident health
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Plaque samples were collected from the buccal surface of caries-free subjects, defined as confident health(CH).
Group 0 sample size Number of subjects in the control (unexposed) group
45
Group 1 sample size Number of subjects in the case (exposed) group
15
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
2b-RAD

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
4


Signature 1

Needs review

Curated date: 2025/10/10

Curator: Chyono2

Revision editor(s): Chyono2

Source: Fig 3B & S1b

Description: Dominant species and genus with significant differences in different groups were detected by LDA effect size (LEfSe) analysis(LDA>4.0,P<0.05).

Abundance in Group 1: increased abundance in Confident health

NCBI Quality ControlLinks
Arachnia
Arachnia propionica
Corynebacterium
Corynebacterium durum
Corynebacterium matruchotii
Lautropia
Neisseria
Neisseria oralis
Rothia aeria
Rothia 508215Rothia 508215

Revision editor(s): Chyono2

Experiment 2


Needs review

Curated date: 2025/10/10

Curator: Chyono2

Revision editor(s): Chyono2

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Enamel caries(EC) +Dentin caries(DC)+Confident Health(CH)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Relative health(RH) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The RH group samples were collected from spatially paired “healthy” sites specifically, the non-cavitated buccal surfaces of caries-active deciduous molars.

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/10/11

Curator: Chyono2

Revision editor(s): Chyono2

Source: Fig 3B & S1b

Description: Dominant species and genus with significant differences in different groups were detected by LDA effect size (LEfSe) analysis (LDA > 4.0, P < 0.05).

Abundance in Group 1: increased abundance in Relative health(RH) group

NCBI Quality ControlLinks
Actinomyces naeslundii
Actinomyces oris
Capnocytophaga

Revision editor(s): Chyono2

Experiment 3


Needs review

Curated date: 2025/10/10

Curator: Chyono2

Revision editor(s): Chyono2

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Relative Health(RH) +Dentin Caries(EC) +Confident Health(CH)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Enamel Caries group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
15 enamel caries (EC) samples were collected from the enamel layers of caries-active teeth.

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/10/11

Curator: Chyono2

Revision editor(s): Chyono2

Source: fig3b & figS1b

Description: Dominant species and genus with significant differences in different groups were detected by LDA effect size (LEfSe) analysis (LDA > 4.0, P < 0.05)

Abundance in Group 1: increased abundance in Enamel Caries group

NCBI Quality ControlLinks
Fusobacterium
Lautropia mirabilis
Porphyromonas pasteri
Streptococcus oralis
Veillonella parvula AVeillonella parvula A
Haemophilus D parainfluenzaeHaemophilus D parainfluenzae
Veillonella
Haemophillus DHaemophillus D
SreptococcusSreptococcus

Revision editor(s): Chyono2

Experiment 4


Needs review

Curated date: 2025/10/10

Curator: Chyono2

Revision editor(s): Chyono2

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Enamel caries(EC) +Relative health(RH) + Confident Health(CH)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Dentin Caries(DC group)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
15 dentin caries (DC) samples were collected from the dentin layers of caries-active teeth.

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/10/11

Curator: Chyono2

Revision editor(s): Chyono2

Source: fig3b & figS1b

Description: Dominant species and genus with significant differences in different groups were detected by LDA effect size(LEfSe)analysis (LDA>4.0,P<0.05)

Abundance in Group 1: increased abundance in Dentin Caries(DC group)

NCBI Quality ControlLinks
Propionibacterium acidifaciens
Lactobacillus paragasseriLactobacillus paragasseri
Streptococcus mutansStreptococcus mutans
Scardovia wiggsiae
Prevotella

Revision editor(s): Chyono2