Oral microbiomes vary in cariogenic potential; these differences may be established early in life. A major concern is whether mothers transmit cariogenic bacteria to their children. Here we characterize early salivary microbiome development and the potential associations of that development with route of delivery, breastfeeding, and mother’s oral health, and we evaluate transmission of microbes between mother and child. We analyzed saliva and metadata from the Center for Oral Health Research in Appalachia. For this cohort study, we sequenced the V6 region of the 16S rRNA gene and used quantitative polymerase chain reaction to detect Streptococcus mitis, Streptococcus sobrinus, Streptococcus mutans, Streptococcus oralis, and Candida albicans in the saliva from mothers and their infants, collected at 2, 9, and 12 mo (Pennsylvania site) and 2, 12, and 24 mo (West Virginia site). Breastfed children had lower relative abundances of Prevotella and Veillonella. If mothers had decayed, missing, or filled teeth, children had greater abundances of Veillonella and Actinomyces. There was little evidence of maternal transmission of selected microbes. At 12 mo, children’s microbiomes were more similar to other children’s than to their mothers’. Infants’ salivary microbiomes became more adult-like with age but still differed with mothers’ microbiomes at 12 mo. There was little evidence supporting transmission of selected microbes from mothers to children, but risk of colonization was associated with tooth emergence. Children are likely to acquire cariogenic bacteria from a variety of sources, including foods and contact with other children and adults.

Background Early childhood caries (ECC)—dental caries (cavities) occurring in primary teeth up to age 6 years—is a prevalent childhood oral disease with a microbial etiology. Streptococcus mutans was previously considered a primary cause, but recent research promotes the ecologic hypothesis, in which a dysbiosis in the oral microbial community leads to caries. In this incident, density sampled case-control study of 189 children followed from 2 months to 5 years, we use the salivary bacteriome to (1) prospectively test the ecological hypothesis of ECC in salivary bacteriome communities and (2) identify co-occurring salivary bacterial communities predicting future ECC. Results Supervised classification of future ECC case status using salivary samples from age 12 months using bacteriome-wide data (AUC-ROC 0.78 95% CI (0.71–0.85)) predicts future ECC status before S. mutans can be detected. Dirichlet multinomial community state typing and co-occurrence network analysis identified similar robust and replicable groups of co-occurring taxa. Mean relative abundance of a Haemophilus parainfluenzae/Neisseria/Fusobacterium periodonticum group was lower in future ECC cases (0.14) than controls (0.23, P value < 0.001) in pre-incident visits, positively correlated with saliva pH (Pearson rho = 0.33, P value < 0.001) and reduced in individuals who had acquired S. mutans by the next study visit (0.13) versus those who did not (0.20, P value < 0.01). In a subset of whole genome shotgun sequenced samples (n = 30), case plaque had higher abundances of antibiotic production and resistance gene orthologs, including a major facilitator superfamily multidrug resistance transporter (MFS DHA2 family PBH value = 1.9 × 10−28), lantibiotic transport system permease protein (PBH value = 6.0 × 10−6) and bacitracin synthase I (PBH value = 5.6 × 10−6). The oxidative phosphorylation KEGG pathway was enriched in case plaque (PBH value = 1.2 × 10−8), while the ABC transporter pathway was depleted (PBH value = 3.6 × 10−3). Conclusions Early-life bacterial interactions predisposed children to ECC, supporting a time-dependent interpretation of the ecological hypothesis. Bacterial communities which assemble before 12 months of age can promote or inhibit an ecological succession to S. mutans dominance and cariogenesis. Intragenera competitions and intergenera cooperation between oral taxa may shape the emergence of these communities, providing points for preventive interventions.

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Objective: The interactions between yeast and streptococci species that lead to dental decay and gingivitis are poorly understood. Our study describes these associations among a cohort of 101 post-partum women enrolled in the Center for Oral Health Research in Appalachia, 2012-2013. Methods: All eligible women without dental caries were included (n = 21) and the remainder were randomly sampled to represent the total number of decayed, missing, and filled teeth (DMFT) at enrollment. We used amplicon sequencing and qPCR of saliva from 2, 6, 12 and 24 visits to determine microbiome composition. Results: Active decay and generalized gingivitis were strongly predictive of each other. Using adjusted marginal models, Candida albicans and Streptococcus mutans combined were associated with active decay (OR = 3.13; 95% CI 1.26, 7.75). However, C. albicans alone (OR = 2.33; 95% CI: 0.81, 6.75) was associated with generalized gingivitis, but S. mutans alone was not (OR = 0.55; 95% CI: 0.21, 1.44). Models including microbiome community state types (CSTs) showed CSTs positively associated with active decay were negatively associated with generalized gingivitis. Discussion: C. albicans is associated with active decay and generalized gingivitis, but whether one or both are present depends on the structure of the co-existing microbial community.

Introduction: Dental caries are not due to a single organism, but to complex interactions among multiple microbes found in the oral cavity. Microbiome studies have identified multiple organisms associated with dental caries in both the saliva and dental plaque, but taxa identified vary largely by study. Our scoping review aims to create a comprehensive list of cariogenic and prohealth taxa found in saliva and dental plaque among healthy children and adults that compare caries-active and caries-free populations. Methods: We searched published studies querying the PUBMED and EMBASE databases using the following keywords: (plaque OR saliva) AND caries AND (next generation sequencing OR checkerboard OR 16s rRNA or qPCR). Studies were limited to human studies published in English between January 1, 2010 and June 24, 2020.Results: Our search strategy identified 298 identified articles. After applying the exclusion criteria, 22 articles were included (Figure 1, Table 1 and 2). Taxa associated with caries or health varied widely among the studies reviewed, with notable differences by age and biologic sample type. While no single taxa was associated with caries in all studies, Streptococcus mutans was significantly associated with caries in 12/24 studies (50%) and Fusobacterium periodonticum was significantly associated with prohealth in 4/24 studies (16.7%). Conclusion: No taxa in plaque and salivary microbiomes were consistently associated with caries or prohealth across all studies. This may be due to the inconsistency of timing of sample collection during the caries process, differing sequencing methods, lack of correction for multiple testing or possibly indicate that there are multiple ways that the oral microbiome can be cariogenic or prohealth.

Background Early childhood caries (ECC) – dental caries (cavities) occurring in primary teeth up to age 6-years - is a prevalent childhood oral disease with a microbial etiology. Streptococcus mutans was previously considered a primary cause, but recent research promotes the ecologic hypothesis, in which a dysbiosis in the oral microbial community leads to caries. In this incident density sampled case control study of 189 children followed from 2-months to 5-years, we use the salivary bacteriome to 1) prospectively test the ecological hypothesis of ECC in salivary bacteriome communities and 2) identify co-occurring salivary bacterial communities predicting future ECC. Results Supervised classification of future ECC case status using salivary samples from age 12-months using bacteriome-wide data (AUC-ROC 0.78 95% CI: (0.71–0.85)) predicts future ECC status before S. mutans can be detected. Dirichlet multinomial community state typing and co-occurrence network analysis identified similar robust and replicable groups of co-occurring taxa. Mean relative abundance of a Haemophilus parainfluenzae/Neisseria/Fusobacterium periodonticum group was lower in future ECC cases (0.14) than controls (0.23, P value < 0.001) in pre-incident visits, positively correlated with saliva pH (Pearson rho = 0.31, P value < 0.01) and reduced in individuals who had acquired S. mutans by the next study visit (0.12) versus those who did not (0.19, P value < 0.01). In a subset of whole genome shotgun sequenced samples, case plaque had higher abundances of antibiotic production and resistance gene orthologs, including a major facilitator superfamily multidrug resistance transporter (MFS DHA2 family PBH value = 1.9*10− 28), lantibiotic transport system permease protein (PBH value = 6.0*10− 6) and bacitracin synthase I (PBH value = 5.6*10− 6). The oxidative phosphorylation KEGG pathway was enriched in case plaque (PBH value = 1.2*10− 8), while the ABC transporter pathway was depleted (PBH value = 3.6*10− 3). Conclusions Early-life bacterial interactions predisposed children to ECC, supporting a time-dependent interpretation of the ecological hypothesis. Bacterial communities which assemble before 12-months of age can promote or inhibit an ecological succession to S. mutans dominance and cariogenesis. Intragenera competitions and intergenera cooperation between oral taxa may shape the emergence of these communities, providing points for preventive interventions.

Objective: Describe associations between dental caries and dental plaque microbiome, by dentition and family membership. Methods: This cross-sectional analysis included 584 participants in the Center for Oral Health Research in Appalachia Cohort 1 (COHRA1). We sequenced the 16S ribosomal RNA gene (V4 region) of frozen supragingival plaque, collected 10 y prior, from 185 caries-active (enamel and dentinal) and 565 caries-free (no lesions) teeth using the Illumina MiSeq platform. Sequences were filtered using the R DADA2 package and assigned taxonomy using the Human Oral Microbiome Database. Results: Microbiomes of caries-active and caries-free teeth were most similar in primary dentition and least similar in permanent dentition, but caries-active teeth were significantly less diverse than caries-free teeth in all dentition types. Streptococcus mutans had greater relative abundance in caries-active than caries-free teeth in all dentition types ( P < 0.01), as did Veillonella dispar in primary and mixed dentition ( P < 0.01). Fusobacterium sp. HMT 203 had significantly higher relative abundance in caries-free than caries-active teeth in all dentition types ( P < 0.01). In a linear mixed model adjusted for confounders, the relative abundance of S. mutans was significantly greater in plaque from caries-active than caries-free teeth ( P < 0.001), and the relative abundance of Fusobacterium sp. HMT 203 was significantly lower in plaque from caries-active than caries-free teeth ( P < 0.001). Adding an effect for family improved model fit for Fusobacterium sp. HMT 203 but not S. mutans. Conclusions: The diversity of supragingival plaque composition from caries-active and caries-free teeth changed with dentition, but S. mutans was positively and Fusobacterium sp. HMT 203 was negatively associated with caries regardless of dentition. There was a strong effect of family on the associations of Fusobacterium sp. HMT 203 with the caries-free state, but this was not true for S. mutans and the caries-active state. Knowledge Transfer Statement: Patients’ and dentists’ concerns about transmission of bacteria within families causing caries should be tempered by the evidence that some shared bacteria may contribute to good oral health.

Background Early childhood caries (ECC) – dental caries (cavities) occurring in primary teeth up to age 6-years - is a prevalent childhood oral disease that includes a microbial etiology. Streptococcus mutans was previously considered a primary cause, but recent research promotes the ecologic hypothesis, in which a dysbiosis in the oral microbial community leads to caries. In this incident density sampled case control study of 189 children followed from 2-months to 5-years, we use the salivary bacteriome to 1) prospectively test the ecological hypothesis in salivary bacteriome communities and 2) identify co-occurring salivary bacterial communities predicting future ECC. Results Supervised classification of future ECC case status using salivary samples from age 12-months using bacteriome-wide data (AUC-ROC 0.78 95% CI: (0.71–0.85)) improves prediction of future ECC status over using S. mutans amplicon abundance alone (AUC-ROC 0.44 (0.35–0.53)). Dirichlet multinomial community state typing and co-occurrence network analysis identified similar robust and replicable groups of co-occurring taxa. Mean relative abundance of a Haemophilus parainfluenzae/Neisseria/Fusobacterium periodonticum group was lower in future ECC cases (0.14) than controls (0.23, P value < 0.001) in pre-incident visits, positively correlated with saliva pH (Pearson rho = 0.31, P value < 0.01) and reduced in individuals who had acquired S. mutans by the next study visit (0.12) versus those who did not (0.19, P value < 0.01). In a subset of whole genome shotgun sequenced samples, case plaque had higher abundances of antibiotic production and resistance gene orthologs, including a major facilitator superfamily multidrug resistance transporter (MFS DHA2 family PBH value = 1.9*10− 28), lantibiotic transport system permease protein (PBH value = 6.0*10− 6) and bacitracin synthase I (PBH value = 5.6*10− 6). The oxidative phosphorylation KEGG pathway was enriched in case plaque (PBH value = 1.2*10− 8), while the ABC transporter pathway was depleted (PBH value = 3.6*10− 3). Conclusions Early-life bacterial interactions predisposed children to ECC, supporting a time-dependent interpretation of the ecological hypothesis. Bacterial communities which assemble before 12-months of age can promote or inhibit an ecological succession to S. mutans dominance and cariogenesis. Intragenera competitions and intergenera cooperation between oral taxa may shape the emergence of these communities, providing points for preventive interventions.