Development of the oral resistome during the first decade of life

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Sukumar S, Wang F, Simpson CA, Willet CE, Chew T, Hughes TE, Bockmann MR, Sadsad R, Martin FE, Lydecker HW, Browne GV, Davis KM, Bui M, Martinez E, Adler CJ
Journal
Nature communications
Year
2023
Antibiotic overuse has promoted the spread of antimicrobial resistance (AMR) with significant health and economic consequences. Genome sequencing reveals the widespread presence of antimicrobial resistance genes (ARGs) in diverse microbial environments. Hence, surveillance of resistance reservoirs, like the rarely explored oral microbiome, is necessary to combat AMR. Here, we characterise the development of the paediatric oral resistome and investigate its role in dental caries in 221 twin children (124 females and 97 males) sampled at three time points over the first decade of life. From 530 oral metagenomes, we identify 309 ARGs, which significantly cluster by age, with host genetic effects detected from infancy onwards. Our results suggest potential mobilisation of ARGs increases with age as the AMR associated mobile genetic element, Tn916 transposase was co-located with more species and ARGs in older children. We find a depletion of ARGs and species in dental caries compared to health. This trend reverses in restored teeth. Here we show the paediatric oral resistome is an inherent and dynamic component of the oral microbiome, with a potential role in transmission of AMR and dysbiosis.

Experiment 1


Reviewed Marked as Reviewed by Peace Sandy on 2024-2-23

Curated date: 2023/10/18

Curator: Ojotuleonalo

Revision editor(s): Ojotuleonalo, Peace Sandy

Subjects

Location of subjects
Australia
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
Mouth Adult mouth,Cavital oralis,Cavitas oris,Cavum oris,Mouth cavity,Oral region,Oral vestibule,Regio oralis,Rima oris,Stoma,Stomatodaeum,Trophic apparatus,Vestibule of mouth,Vestibulum oris,Mouth,mouth
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
T1 - Timepoint 1 - (T1. edentulous (no teeth))
Group 1 name Corresponds to the case (exposed) group for case-control studies
T2 - Timepoint 2
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Samples (1.6 ± 0.4 years) at T2 (primary/deciduous/baby teeth only)
Group 0 sample size Number of subjects in the control (unexposed) group
139
Group 1 sample size Number of subjects in the case (exposed) group
180
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
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
arcsine square-root
Statistical test
MaAsLin2
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


Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-23

Curated date: 2024/02/23

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure S4 C

Description: Vector loadings for ARGs, functional pathways and species that contribute to discrimination of individuals by time point/stage of dental development from DIABLO analysis. For each data type, DIABLO was performed on features above 0.01% abundance that had been TSS and CLR transformed. For each data block, displayed are the top ten features (ARG, function and species) with the largest vector loadings.

Abundance in Group 1: decreased abundance in T2 - Timepoint 2

NCBI Quality ControlLinks
Enterococcus wangshanyuanii
Streptococcus himalayensis
Streptococcus marmotae
Streptococcus parauberis
Streptococcus pluranimalium
Streptococcus urinalis

Revision editor(s): Peace Sandy

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-2-23

Curated date: 2024/02/23

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
T3 - Timepoint 3
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Samples at T3 (mixed dentition, 8.5 ± 1.2 years old)
Group 1 sample size Number of subjects in the case (exposed) group
211

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-23

Curated date: 2024/02/23

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure S4 C

Description: Vector loadings for ARGs, functional pathways and species that contribute to discrimination of individuals by time point/stage of dental development from DIABLO analysis. For each data type, DIABLO was performed on features above 0.01% abundance that had been TSS and CLR transformed. For each data block, displayed are the top ten features (ARG, function and species) with the largest vector loadings.

Abundance in Group 1: increased abundance in T3 - Timepoint 3

NCBI Quality ControlLinks
Actinomyces sp.
Actinomyces viscosus

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-23

Curated date: 2024/02/23

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure S4 C

Description: Vector loadings for ARGs, functional pathways and species that contribute to discrimination of individuals by time point/stage of dental development from DIABLO analysis. For each data type, DIABLO was performed on features above 0.01% abundance that had been TSS and CLR transformed. For each data block, displayed are the top ten features (ARG, function and species) with the largest vector loadings.

Abundance in Group 1: decreased abundance in T3 - Timepoint 3

NCBI Quality ControlLinks
Enterococcus wangshanyuanii
Streptococcus himalayensis
Streptococcus marmotae
Streptococcus parauberis
Streptococcus pluranimalium
Streptococcus urinalis

Revision editor(s): Peace Sandy

Experiment 3


Reviewed Marked as Reviewed by Peace Sandy on 2024-2-23

Curated date: 2024/02/23

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
T2 - Timepoint 2
Group 0 sample size Number of subjects in the control (unexposed) group
180

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-23

Curated date: 2024/02/23

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure S4 C

Description: Vector loadings for ARGs, functional pathways and species that contribute to discrimination of individuals by time point/stage of dental development from DIABLO analysis. For each data type, DIABLO was performed on features above 0.01% abundance that had been TSS and CLR transformed.For each data block, displayed are the top ten features (ARG, function and species) with the largest vector loadings.

Abundance in Group 1: increased abundance in T3 - Timepoint 3

NCBI Quality ControlLinks
Actinomyces sp.
Actinomyces viscosus

Revision editor(s): Peace Sandy