Non-Cochrane · aetiology · PM36050830

Meta-analysis of caries microbiome studies can improve upon disease prediction outcomes.

Butcher Mark C, Short Bryn, Veena Chandra Lekha Ramalingam, et al. · APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2022 · PubMed · doi:10.1111/apm.13272

Oral HealthDental cariesAMSTAR 2: not applicable
Full textEvery question was extracted from the full text, figures and supplements by two independent LLM extractors, disagreements adjudicated. Rows cite where in the review the value comes from.
Questions
10
current version
GRADE rated
0
No studies
0
Included studies
16
linked below
No studies 0 · 0%Ungraded 10 · 100%Very low 0 · 0%Low 0 · 0%Moderate 0 · 0%High 0 · 0%

Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.

Review question

ElementPlanned (methods)Found (results)
PopulationIndividuals sampled for oral (saliva/supragingival plaque) 16S rRNA microbiome in relation to dental caries2016 processable oral samples from 19 studies (n=19 studies; 2016 samples)
InterventionDental caries (carious oral microbiome)Dental caries samples
ComparisonCaries-free / healthy oral microbiomeCaries-free / health samples
OutcomesAlpha and beta diversity; microbial composition/differential abundance; predictive/diagnostic capability (random forest ROC-AUC); functional (KEGG) metabolic pathwaysAlpha diversity higher in caries across all indices (p<0.001); beta diversity ADONIS significant (p<0.001) but clustering mainly by study/sequencing region; random forest could not reliably discriminate caries vs health on combined cohort (best AUC approximately 0.75, disease-only KO); predictive taxa incl. Selenomonas sp. HMT-146, Aggregatibacter actinomycetemcomitans, Actinomyces sp. HMT-896, Treponema sp. HMT-257; enriched KEGG pathways phosphonate/phosphinate and glyoxylate/dicarboxylate metabolism (p.adj=0.04)
Study designsPublicly available 16S rRNA microbiome sequencing studies deposited in NCBI/ENA, published from 2012, with data score >=3 (data accessible and mappable to health/disease)Cross-sectional (n=13), Longitudinal (n=4), Interventional (n=1), RCT (n=1)
TimingNot specifiedNot specified

Search date: Not specified (studies published from 2012 onward included; no explicit search date reported). Databases: PubMed (sequence data retrieved from NCBI/ENA)

Questions and results

Dental caries (carious oral microbiome) vs Caries-free / healthy oral microbiome

Population: Individuals providing oral (saliva/supragingival plaque) 16S rRNA microbiome samples; 2016 samples from 19 studies (mixed children and adults)
5 questions
OutcomeEffectEvidenceStatus / GRADE
Discrimination of caries vs health (random forest ROC-AUC)
Microbiome-based random forest classifiers could not reliably discriminate caries from health across the combined cohort (best AUC approximately 0.75 in a disease-only KO subset; ungraded).
Source: Results 'Assessment of diagnostic capability' and 'Summarizing individual predictability' paras; Figure 4; Figure 7A · same question in other reviews
AUC 0.7519 studies · 2016 participantsUngraded
KEGG pathway associations
Population: Participants in oral 16S rRNA caries microbiome studies
Phosphonate and phosphinate metabolism and glyoxylate and dicarboxylate metabolism had the lowest reported adjusted P values (0.04); no pooled effect estimate was reported.
Source: Recurrent metabolic pathways in study metadata; Figure 5 · same question in other reviews
no estimate extracted19 studies · 2016 participantsUngraded
Differential microbial abundance / taxa predictive of caries
A group of genera/species (notably Selenomonas, Aggregatibacter, Actinomyces, Treponema) was predictive of caries, whereas Streptococcus was not (ungraded).
Source: Results 'Organisms of interest in caries and health' para; Figure 6 · same question in other reviews
Mean-decrease-accuracy discriminating taxa: Capnocytophaga HMT-338, Lactobacillus panis, Treponema HMT-230, Bifidobacterium longum, Delftia acidovorans, Staphylococcus schleiferi; higher log2FC in caries: Selenomonas HMT-146, Aggregatibacter actinomycetemcomitans, Actinomyces HMT-896, Treponema HMT-257; Streptococcus not predictive19 studies · 2016 participantsUngraded
Alpha diversity (Observed, Chao1, Shannon, and Simpson)
Population: Participants in oral 16S rRNA caries microbiome studies
Across the combined sample set, alpha-diversity metrics were significantly higher in caries than in health, but no pooled effect estimate was reported.
Source: Assessment of alpha and beta diversity; Figure 2 · same question in other reviews
Higher alpha diversity in caries than health; p<0.001 (Wilcoxon; no pooled effect size reported)19 studies · 2016 participantsUngraded
Beta diversity and community composition
Population: Participants in oral 16S rRNA caries microbiome studies
Beta-diversity matrices showed statistically significant ADONIS results, while clustering by study and 16S region was also observed; no pooled effect estimate was reported.
Source: Assessment of alpha and beta diversity; Figure 3; Table S1 · same question in other reviews
no estimate extracted19 studies · 2016 participantsUngraded

Dental caries (carious oral microbiome) vs Caries-free / healthy oral microbiome

Population: Adults providing oral (saliva/supragingival plaque) 16S rRNA microbiome samples
2 questions
OutcomeEffectEvidenceStatus / GRADE
Alpha diversity (Chao1, Observed, Shannon)
Adults
In adults, caries-vs-health alpha diversity differed for the Shannon index but not Chao1/Observed (ungraded).
Source: Results 'Assessment of alpha and beta diversity' para; Figure S1 · same question in other reviews
In adults, there was no significant caries-vs-health difference in Chao1 or Observed diversity, whereas the Shannon index differed significantly (p < 0.001).NRUngraded
External disease-state discrimination
Population: Oral microbiome samples from four selected case-control studies
The KEGG Orthology classifier had an approximate AUC of 0.75 in the disease-only study test set.
Source: Assessment of diagnostic capability of study metadata; Figure 4 · same question in other reviews
AUC 0.754 studiesUngraded

Dental caries (carious oral microbiome) vs Caries-free / healthy oral microbiome

Population: Children providing oral (saliva/supragingival plaque) 16S rRNA microbiome samples
2 questions
OutcomeEffectEvidenceStatus / GRADE
Alpha diversity (Shannon)
Children
In children, caries-vs-health Shannon alpha diversity differed significantly (ungraded).
Source: Results 'Assessment of alpha and beta diversity' para; Figure S1 · same question in other reviews
In children, the Shannon alpha-diversity index differed significantly between caries and health (p < 0.001).NRUngraded
Study-specific disease-state discrimination
Population: Oral microbiome samples in 15 case-controlled studies
Bong-Soo 2017, Zhu 2018, and Jiang 2019 had mean AUC scores over 0.75; exact study-specific AUCs were not reported in text or readable figure labels.
Source: Summarizing the individual predictability of cohort studies; Figure 7 · same question in other reviews
no estimate extracted15 studiesUngraded

Comparison

1 question
OutcomeEffectEvidenceStatus / GRADE
Alpha diversity (study-level, caries vs health)
Per-study across 15 studies (log2 fold change; Figure 7B)
Chao1 and Observed significantly increased in caries in only 3 of 15 studies (and pooled); overall little significance across studies15 studiesUngraded

Included primary studies 16

Open as a trial list
StudyAlso included byOutcomes it informs hereTrial PICOResults
Bong-Soo, 2017
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Cherkasov, 2018
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
De Jesus, 2020
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
deJesus, 2021
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Ferrer, 2020
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Gomez, 2017
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Havsed, 2021
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Jiang, 2019
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Kalpana, 2020
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Kashimoglu, 2020
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Onyango, 2020
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Premaraj, 2020
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Schulz-Weidner, 2021
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Simon-Soro, 2018
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Xiao, 2016
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet
Zheng, 2017
matched by author and year (probable)
this review onlynot statednot extracted yetnot extracted yet