skip to main content

This content will become publicly available on May 23, 2023

Title: Multimodal Data Integration Reveals Mode of Delivery and Snack Consumption Outrank Salivary Microbiome in Association With Caries Outcome in Thai Children
Early childhood caries (ECC) is not only the most common chronic childhood disease but also disproportionately affects underserved populations. Of those, children living in Thailand have been found to have high rates of ECC and severe ECC. Frequently, the cause of ECC is blamed on a handful of cariogenic organisms, such as Streptococcus mutans and Streptococcus sobrinus . However, ECC is a multifactorial disease that results from an ecological shift in the oral cavity from a neutral pH (~7.5) to an acidic pH (<5.5) environment influenced by the host individual’s biological, socio-behavioral, and lifestyle factors. Currently, there is a lack of understanding of how risk factors at various levels influence the oral health of children at risk. We applied a statistical machine learning approach for multimodal data integration (parallel and hierarchical) to identify caries-related multiplatform factors in a large cohort of mother-child dyads living in Chiang Mai, Thailand (N=177). Whole saliva (1 mL) was collected from each individual for DNA extraction and 16S rRNA sequencing. A set of maternal and early childhood factors were included in the data analysis. Significantly, vaginal delivery, preterm birth, and frequent sugary snacking were found to increase the risk for ECC. The salivary microbial diversity more » was significantly different in children with ECC or without ECC. Results of linear discriminant analysis effect size (LEfSe) analysis of the microbial community demonstrated that S. mutans , Prevotella histicola , and Leptotrichia hongkongensis were significantly enriched in ECC children. Whereas Fusobacterium periodonticum was less abundant among caries-free children, suggesting its potential to be a candidate biomarker for good oral health. Based on the multimodal data integration and statistical machine learning models, the study revealed that the mode of delivery and snack consumption outrank salivary microbiome in predicting ECC in Thai children. The biological and behavioral factors may play significant roles in the microbial pathobiology of ECC and warrant further investigation. « less
Authors:
; ; ; ; ; ; ; ; ; ;
Award ID(s):
1934962
Publication Date:
NSF-PAR ID:
10352995
Journal Name:
Frontiers in Cellular and Infection Microbiology
Volume:
12
ISSN:
2235-2988
Sponsoring Org:
National Science Foundation
More Like this
  1. Despite the cariogenic role of Candida suggested from recent studies, oral Candida acquisition in children at high risk for early childhood caries (ECC) and its association with cariogenic bacteria Streptococcus mutans remain unclear. Although ECC disproportionately afflicts socioeconomically disadvantaged and racial-minority children, microbiological studies focusing on the underserved group are scarce. Our prospective cohort study examined the oral colonization of Candida and S. mutans among 101 infants exclusively from a low-income and racial-minority background in the first year of life. The Cox hazard proportional model was fitted to assess factors associated with the time to event of the emergence of oral Candida and S. mutans. Oral Candida colonization started as early as 1 wk among 13% of infants, increased to 40% by 2 mo, escalated to 48% by 6 mo, and remained the same level until 12 mo. S. mutans in saliva was detected among 20% infants by 12 mo. The emergence of S. mutans by year 1 was 3.5 times higher (hazard ratio [HR], 3.5; confidence interval [CI], 1.1–11.3) in infants who had early colonization of oral Candida compared to those who were free of oral Candida ( P = 0.04) and 3 times higher (HR, 3.0; CI, 1.3–6.9)more »among infants whose mother had more than 3 decayed teeth ( P = 0.01), even after adjusting demographics, feeding, mother’s education, and employment status. Infants’ salivary S. mutans abundance was positively correlated with infants’ Candida albicans ( P < 0.01) and Candida krusei levels ( P < 0.05). Infants’ oral colonization of C. albicans was positively associated with mother’s oral C. albicans carriage and education ( P < 0.01) but negatively associated with mother’s employment status ( P = 0.01). Future studies are warranted to examine whether oral Candida modulates the oral bacterial community as a whole to become cariogenic during the onset and progression of ECC, which could lead to developing novel ECC predictive and preventive strategies from a fungal perspective.« less
  2. Untreated tooth decays affect nearly one third of the world and is the most prevalent disease burden among children. The disease progression of tooth decay is multifactorial and involves a prolonged decrease in pH, resulting in the demineralization of tooth surfaces. Bacterial species that are capable of fermenting carbohydrates contribute to the demineralization process by the production of organic acids. The combined use of machine learning and 16s rRNA sequencing offers the potential to predict tooth decay by identifying the bacterial community that is present in an individual’s oral cavity. A few recent studies have demonstrated machine learning predictive modeling using 16s rRNA sequencing of oral samples, but they lack consideration of the multifactorial nature of tooth decay, as well as the role of fungal species within their models. Here, the oral microbiome of mother–child dyads (both healthy and caries-active) was used in combination with demographic–environmental factors and relevant fungal information to create a multifactorial machine learning model based on the LASSO-penalized logistic regression. For the children, not only were several bacterial species found to be caries-associated ( Prevotella histicola, Streptococcus mutans , and Rothia muciloginosa ) but also Candida detection and lower toothbrushing frequency were also caries-associated. Mothers enrolledmore »in this study had a higher detection of S. mutans and Candida and a higher plaque index. This proof-of-concept study demonstrates the significant impact machine learning could have in prevention and diagnostic advancements for tooth decay, as well as the importance of considering fungal and demographic–environmental factors.« less
  3. Chua Chin Heng, Matthew (Ed.)
    Early Childhood Caries (ECC) is the most common childhood disease worldwide and a health disparity among underserved children. ECC is preventable and reversible if detected early. However, many children from low-income families encounter barriers to dental care. An at-home caries detection technology could potentially improve access to dental care regardless of patients’ economic status and address the overwhelming prevalence of ECC. Our team has developed a smartphone application (app), AICaries, that uses artificial intelligence (AI)-powered technology to detect caries using children’s teeth photos. We used mixed methods to assess the acceptance, usability, and feasibility of the AICaries app among underserved parent-child dyads. We conducted moderated usability testing (Step 1) with ten parent-child dyads using "Think-aloud" methods to assess the flow and functionality of the app and analyze the data to refine the app and procedures. Next, we conducted unmoderated field testing (Step 2) with 32 parent-child dyads to test the app within their natural environment (home) over two weeks. We administered the System Usability Scale (SUS) and conducted semi-structured individual interviews with parents and conducted thematic analyses. AICaries app received a 78.4 SUS score from the participants, indicating an excellent acceptance. Notably, the majority (78.5%) of parent-taken photos of children’smore »teeth were satisfactory in quality for detection of caries using the AI app. Parents suggested using community health workers to provide training to parents needing assistance in taking high quality photos of their young child’s teeth. Perceived benefits from using the AICaries app include convenient at-home caries screening, informative on caries risk and education, and engaging family members. Data from this study support future clinical trial that evaluates the real-world impact of using this innovative smartphone app on early detection and prevention of ECC among low-income children.« less
  4. Tooth decay is one of the most common chronic infectious diseases worldwide. Bacteria from the oral biofilm create a local acidic environment that demineralizes the enamel in the caries disease process. By optically imaging plaque pH in pits and fissures and contacting surfaces of teeth, then medicinal therapies can be accurately applied to prevent or monitor the reversal of caries. To achieve this goal, the fluorescence emission from an aqueous solution of sodium fluorescein was measured using a multimodal scanning fiber endoscope (mmSFE). The 1.6-millimeter diameter mmSFE scans 424nm laser light and collects wide-field reflectance for navigational purposes in grayscale at 30 Hz. Two fluorescence channels centered at 520 and 549 nm are acquired and ratiometric analysis produces a pseudo-color overlay of pH. In vitro measurements calibrate the pH heat maps in the range 4.7 to 7.2 pH (0.2 standard deviation). In vivo measurements of a single case study provides informative images of interproximal biofilm before and after a sugar rinse. Post processing a time series of images provides a method that calculates the average pH changes of oral biofilm, replicating the Stephan Curve. These spatio-temporal records of oral biofilm pH can provide a new method of assessing the riskmore »of tooth decay, guide the application of preventative therapies, and provide a quantitative monitor of overall oral health. The non-contact in vivo optical imaging of pH may be extended to measurements of wound healing, tumor environment, and other food processing surfaces since it relies on low power laser light and a US FDA approved dye.« less
  5. Biswas, Indranil (Ed.)
    ABSTRACT The genus Streptococcus encompasses a large bacterial taxon that commonly colonizes mucosal surfaces of vertebrates and is capable of disease etiologies originating from diverse body sites, including the respiratory, digestive, and reproductive tracts. Identifying new modes of treating infections is of increasing importance, as antibiotic resistance has escalated. Streptococcus mutans is an important opportunistic pathogen that is an agent of dental caries and is capable of systemic diseases such as endocarditis. As such, understanding how it regulates virulence and competes in the oral niche is a priority in developing strategies to defend from these pathogens. We determined that S. mutans UA159 possesses a bona fide short hydrophobic peptide (SHP)/Rgg quorum-sensing system that regulates a specialized biosynthetic operon featuring a radical-SAM ( S -adenosyl- l -methionine) (RaS) enzyme and produces a ribosomally synthesized and posttranslationally modified peptide (RiPP). The pairing of SHP/Rgg regulatory systems with RaS biosynthetic operons is conserved across streptococci, and a locus similar to that in S. mutans is found in Streptococcus ferus , an oral streptococcus isolated from wild rats. We identified the RaS-RiPP product from this operon and solved its structure using a combination of analytical methods; we term these RiPPs tryglysin A and Bmore »for the unusual Trp-Gly-Lys linkage. We report that tryglysins specifically inhibit the growth of other streptococci, but not other Gram-positive bacteria such as Enterococcus faecalis or Lactococcus lactis . We predict that tryglysin is produced by S. mutans in its oral niche, thus inhibiting the growth of competing species, including several medically relevant streptococci. IMPORTANCE Bacteria interact and compete with a large community of organisms in their natural environment. Streptococcus mutans is one such organism, and it is an important member of the oral microbiota. We found that S. mutans uses a quorum-sensing system to regulate production of a novel posttranslationally modified peptide capable of inhibiting growth of several streptococcal species. We find inhibitory properties of a similar peptide produced by S. ferus and predict that these peptides play a role in interspecies competition in the oral niche.« less