Metagenomic analysis examines oral microbiome changes and interplay with immune response following prenatal total oral rehabilitation.

BACKGROUND: Suboptimal maternal oral health during pregnancy is potentially associated with adverse birth outcomes and increased dental caries risks in children. This study aimed to assess the oral microbiome and immune response following an innovative clinical regimen, Prenatal Total Oral Rehabilitation (PTOR), that fully restores women's oral health to a "disease-free status" before delivery. METHODS: This prospective cohort study assessed 15 pregnant women at baseline and 3 follow-up visits (1 week, 2 weeks, and 2 months) after receiving PTOR. The salivary and supragingival plaque microbiomes were analyzed using metagenomic sequencing. Multiplexed Luminex cytokine assays were performed to examine immune response following PTOR. The association between salivary immune markers and oral microbiome was further examined. RESULTS: PTOR was associated with a reduction of periodontal pathogens in plaque, for instance, a lower relative abundance of Tannerella forsythia and Treponema denticola at 2 weeks compared to the baseline (p < 0.05). The alpha diversity of plaque microbial community was significantly reduced at the 1-week follow-up (p < 0.05). Furthermore, we observed significant changes in the Actinomyces defective-associated carbohydrate degradation pathway and Streptococcus Gordonii-associated fatty acid biosynthesis pathway. Two immune markers related to adverse birth outcomes significantly differed between baseline and follow-up. ITAC, negatively correlated with preeclampsia severity, significantly increased at 1-week follow-up; MCP-1, positively correlated with gestational age, was elevated at 1-week follow-up. Association modeling between immune markers and microbiome further revealed specific oral microorganisms that are potentially correlated with the host immune response. CONCLUSIONS: PTOR is associated with alteration of the oral microbiome and immune response among a cohort of underserved US pregnant women. Future randomized clinical trials are warranted to comprehensively assess the impact of PTOR on maternal oral flora, birth outcomes, and their offspring's oral health.

Effects of Nystatin oral rinse on oral Candida species and Streptococcus mutans among healthy adults.

OBJECTIVES: To examine the effect of Nystatin oral rinse on oral Candida species and Streptococcus mutans carriage. MATERIALS AND METHODS: Twenty healthy adults with oral candidiasis participated in the single-arm clinical trial and received Nystatin oral rinse for 7 days, 4 applications/day, and 600,000 International Units/application. Demographic-socioeconomic-oral-medical conditions were obtained. Salivary and plaque Candida species and Streptococcus mutans were assessed at baseline and 1-week and 3-month follow-ups. Twenty-four salivary cytokines were assessed. Candida albicans isolates underwent Nystatin susceptibility test. RESULTS: Half of participants (10/20) were free of salivary C. albicans after using Nystatin rinse. Salivary S. mutans was significantly reduced at 3-month follow-up (p < 0.05). Periodontal status reflected by bleeding-on-probing was significantly improved at 1-week and 3-month follow-ups (p < 0.05). Plaque accumulation was significantly reduced at 1-week follow-up (p < 0.05). Interestingly, the responses to Nystatin oral rinse were not associated with race, gender, age, oral hygiene practice, adherence to Nystatin rinse, or sweet consumption (p > 0.05). No C. albicans isolates were resistant to Nystatin. Furthermore, salivary cytokine eotaxin and fractalkine were significantly reduced at 3-month follow-up among participants who responded to Nystatin rinse (p < 0.05). CONCLUSIONS: The study results indicate that oral antifungal treatment had an effect on S. mutans salivary carriage. Future clinical trials are warranted to comprehensively assess the impact of antifungal treatment on the oral flora other than S. mutans and Candida. CLINICAL RELEVANCE: Due to the potential cariogenic role of oral Candida species, antifungal approaches shed new light on the prevention and management of dental caries from a fungal perspective.

Pigment epithelium-derived factor attenuates angiogenesis and collagen deposition in hypertrophic scars.

Scar forming wounds are often characterized by higher levels of vascularity than non-scarring wounds and normal skin, and inhibition of angiogenesis has been shown to inhibit scar formation in some model systems. The rabbit ear hypertrophic scar (HS) model has been widely used to study the mechanisms that underlie the development of HS as well as the effectiveness of various treatments. Although the rabbit ear HS model is well characterized in terms of scar formation, the rate and level of angiogenesis has not been investigated in this model, and the cause-effect relationship between angiogenesis and rabbit HSs has not been examined. In the current study, full-thickness excisional wounds were created on the ventral side of New Zealand White rabbit ears to induce HS formation, and the dynamic pattern of angiogenesis and the expression of angiogenic regulatory factors were examined over time. Blood vessel density was found to peak at 2.7% on day 14 post-wounding, decreasing to 1.7% by day 28. mRNA levels of the proangiogenic factor VEGF-A peaked at day 14, while the expression of the antiangiogenic factors pigment epithelium-derived factor (PEDF) and thrombospondin 1 (TSP1) peaked at day 28 post-wounding. To examine whether inhibition of angiogenesis influences HS formation in this model, wounds were treated with exogenous soluble antiangiogenic agents including recombinant PEDF (rPEDF) and a functional PEDF peptide (PEDF-335). rPEDF and PEDF-335 were administered intradermally from day 4 post-wounding every 3 days until day 19. Intradermal injection of rPEDF or PEDF-335 both led to decreased angiogenesis and decreased collagen deposition at the wound site. The results support the utility of antiangiogenic therapies, including rPEDF/PEDF-335, as a potential new strategy for the prevention or treatment of HSs.

The Health Benefits of Probiotic Lactiplantibacillus plantarum: A Systematic Review and Meta-Analysis.

To ensure effective administration of probiotics in clinical practice, it is crucial to comprehend the specific strains and their association with human health. Therefore, we conducted a systematic review and meta-analysis to evaluate the scientific evidence on the impact of Lactiplantibacillus plantarum probiotic consumption on human health. Out of 11,831 records, 135 studies were assessed qualitatively, and 18 studies were included in the meta-analysis. This systematic review demonstrated that probiotic supplementation with L. plantarum, either alone or in combination, can significantly improve outcomes for patients with specific medical conditions. Meta-analysis revealed notable benefits in periodontal health, evidenced by reduced pocket depth and bleeding on probing (p < 0.001); in gastroenterological health, marked by significant reductions in abdominal pain (p < 0.001); and in infectious disease, through a reduction in C-reactive protein levels (p < 0.001). Cardiovascular benefits included lowered total cholesterol and low-density lipoprotein cholesterol in the L. plantarum intervention group (p < 0.05). Our study's clinical significance highlights the importance of considering probiotic strain and their application to specific diseases when planning future studies and clinical interventions, emphasizing the need for further research in this area.

Racial and oral health disparity associated with perinatal oral health care utilization among underserved US pregnant women.

OBJECTIVE: The study aims to identify specific determinants of dental care utilization during the perinatal period (prenatal and 1-year postnatal) among underserved US women residing in Upstate New York. METHOD AND MATERIALS: The prospective cohort study included 186 low-income US pregnant women. Demographic-socioeconomic parameters and medical-dental conditions were obtained from questionnaires, electronic medical-dental records, and dental examinations. Multivariate regression analyses were used to assess factors associated with perinatal dental care utilization. As an exploratory effort, a separate logistic model assessed factors associated with adverse birth outcomes. RESULTS: The results demonstrated unmet oral health needs among the underserved US pregnant women residing in Upstate New York. Despite an average of 2.7 ± 3.6 untreated decayed teeth per person during pregnancy, only 39.3% and 19.9% utilized prenatal and 1-year postnatal dental care, respectively. Previous dental care utilization was a notable factor contributing to a higher uptake of perinatal dental care at a subsequent period. Prenatal dental care utilization was significantly lower among African American women (odds ratio 0.43 [95% CI 0.19, 0.98], P = .04) and positively associated with dental caries severity (OR 2.40 [1.09, 5.12], P = .03). Postnatal utilization was associated with caries severity (OR 4.70 [1.73, 12.74], P = .002) and prevalent medical conditions (hypertension, diabetes mellitus, and emotional conditions). Pregnant women who achieved prenatal caries-free status had a lower odds of experiencing adverse birth outcomes; however, this was an insignificant finding due to limited adverse birth cases. CONCLUSION: Racial and oral health disparity is associated with perinatal oral health care utilization among underserved US pregnant women in New York. While both prenatal and postnatal dental care utilization was positively associated with oral health status, specifically, postnatal utilization was driven by existing medical conditions such as emotional condition, hypertension, and diabetes mellitus. The results add to existing information on inherent barriers and postulated needs to improve access to perinatal oral care, thereby informing statewide recommendations to maximize utilization. Considering this is a geographically restricted population, the findings are particularly true to this cohort of underserved pregnant women. However, future more robust studies are warranted to assess effective strategies to further improve perinatal dental care utilization among underserved pregnant women.

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 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.