Search Results (96)

Background: Dental caries arise from a multifactorial interplay between microbial dysbiosis, host immune responses, and enamel degradation visible on radiographs. Deep learning excels in image-based caries detection; however, integrative analyses that combine radiographic, microbiome, and transcriptomic data remain rare because public cohorts are seldom aligned. Objective: To determine whether three independent deep-learning pipelines—radiographic segmentation, microbiome regression, and transcriptome regression—can be reproducible implemented on non-aligned datasets, and to demonstrate the feasibility of estimating microbiome heritability in a matched twin cohort. Methods: (i) A U-Net with ResNet-18 encoder was trained on 100 annotated panoramic radiographs to generate a continuous caries-severity score from a predicted lesion area. (ii) Feed-forward neural networks (FNNs) were trained on supragingival 16S rRNA profiles (81 samples, 750 taxa) and gingival transcriptomes (247 samples, 54,675 probes) using randomly permuted severity scores as synthetic targets to stress-test preprocessing, training, and SHAP-based interpretability. (iii) In 49 monozygotic and 50 dizygotic twin pairs (n = 198), Bray–Curtis dissimilarity quantified microbial heritability, and an FNN was trained to predict recorded TotalCaries counts. Results: The U-Net achieved IoU = 0.564 (95% CI 0.535–0.594), precision = 0.624 (95% CI 0.583–0.667), recall = 0.877 (95% CI 0.827–0.918), and correlated with manual severity scores (r = 0.62, p < 0.01). The synthetic-target FNNs converged consistently but—as intended—showed no predictive power (R² ≈ −0.15 microbiome; −0.18 transcriptome). Twin analysis revealed greater microbiome similarity in monozygotic versus dizygotic pairs (0.475 ± 0.107 vs. 0.557 ± 0.117; p = 0.0005) and a modest correlation between salivary features and caries burden (r = 0.25). Conclusions: Modular deep-learning pipelines remain computationally robust and interpretable on non-aligned datasets; radiographic severity provides a transferable quantitative anchor. Twin-cohort findings confirm heritable patterns in the oral microbiome and outline a pathway toward future clinical translation once patient-matched multi-omics are available. This framework establishes a scalable, reproducible foundation for integrative caries research. Full article

Background/Objectives: Early diagnosis of periodontitis remains challenging using traditional clinical methods. This systematic review and meta-analysis evaluated the diagnostic accuracy of artificial intelligence (AI) models trained on non-invasive or minimally invasive biomarkers—including saliva, gingival crevicular fluid (GCF), and immunologic profiles—for diagnosing and classifying periodontitis in human subjects. Methods: A comprehensive search of PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and Cochrane CENTRAL was conducted from database inception to June 2025. Eligible studies used AI or machine learning models with patient-derived biomarker data and reported diagnostic performance metrics. Results: Seven studies were included, employing various AI models such as random forest, artificial neural networks, and gradient boosting. Biomarkers were derived from saliva (n = 4), saliva-derived biomarkers from oral rinse (n = 1), immunologic profiles (n = 1), and tissue-based gene expression (n = 1). Reported area under the receiver operating characteristic (ROC) curve (AUC) ranged from 0.83 to 0.96. Meta-analysis of studies with comparable outcomes showed a pooled sensitivity of 0.89 (95% CI: 0.84–0.93), a specificity of 0.87 (95% CI: 0.80–0.92), and a summary AUC of 0.92. Subgroup analysis revealed that models using salivary biomarkers achieved a higher pooled AUC (0.94) than those using GCF or immunologic markers (AUC: 0.89). Sensitivity analyses excluding studies with unclear bias did not significantly alter pooled estimates, affirming robustness. The overall certainty of evidence was rated as moderate to high. Conclusions: AI-based diagnostic models utilizing salivary, microbiome, or immunologic biomarkers demonstrated quantitatively high accuracy; however, the overall certainty of evidence was rated as moderate to high due to limitations in study design and validation. Full article

Introduction: Osteoarthritis (OA) is a chronic degenerative joint disease with limited treatment options focused primarily on symptom management. Emerging evidence suggests that dietary interventions may influence inflammation and pain through modulation of the gut microbiome and metabolome. Methods: We conducted a 4-week open-label pilot trial evaluating the effects of an anti-inflammatory dietary intervention (ITIS diet) in 20 patients with knee OA (ClinicalTrials.gov ID: NCT05559463, registered prior to enrollment; sponsor: University of California, San Diego; responsible party: Monica Guma; study start date: 1 October 2021). The following were assessed before and after the intervention: (1) clinical outcomes; (2) gut and salivary microbiomes; and (3) salivary, stool, and plasma metabolomes. Responders were defined as patients achieving ≥30% reduction in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores. Results: The ITIS diet was well-tolerated, with good adherence (66.2%) and a significant improvement in clinical outcomes, including reduced pain and improved overall health measured with the visual analog scale (VAS). Responders (n = 8) showed distinct gut microbiome and metabolome profiles compared to non-responders (n = 12). Notably, taxa within the Lachnospiraceae family exhibited dynamic, bidirectional shifts post-intervention: Anaerostipes and Limivivens were enriched among responders and negatively correlated with pain scores, while Oliverpabstia and Fusicatenibacter were depleted following dietary intervention. These taxa also showed strong correlations with anti-inflammatory metabolites, including hydroxydecanoic acid derivatives and pyridoxine. Furthermore, subsequent network analysis revealed more structured and selective microbiome–metabolome interactions in responders, specifically post-intervention. Conclusions: This pilot study shows that a short-term anti-inflammatory dietary intervention was associated with meaningful changes in the gut microbiome and metabolome. Members of the Lachnospiraceae family emerged as key taxa associated with pain reduction and anti-inflammatory metabolite production. Our findings suggest that specific microbial responses—rather than global diversity changes—may underlie dietary responsiveness in OA. Although exploratory and limited by sample size, our results support further investigation into personalized, microbiome-informed nutritional strategies for OA management. Full article

The oral microbiota, long recognized for their role in local pathologies, are increasingly implicated in systemic disorders, particularly cardiovascular disease (CVD). This review focuses on emerging evidence linking oral dysbiosis to neuroglial activation and autonomic dysfunction as key mediators of cardiovascular pathology. Pathogen-associated molecular patterns, as well as gingipains and leukotoxin A from Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola, Aggregatibacter actinomycetemcomitans, etc., disrupt the blood–brain barrier, activate glial cells in autonomic centers, and amplify pro-inflammatory signaling. This glia driven sympathetic overactivity fosters hypertension, endothelial injury, and atherosclerosis. Crucially, sex hormones modulate these neuroimmune interactions, with estrogen and testosterone shaping microbial composition, glial reactivity, and cardiovascular outcomes in distinct ways. Female-specific factors such as early menarche, pregnancy, adverse pregnancy outcomes, and menopause exert profound influences on oral microbial ecology, systemic inflammation, and long-term CVD risk. By mapping this oral–brain–heart axis, this review highlights the dual role of oral microbial virulence factors and glial dynamics as mechanistic bridges linking periodontal disease to neurogenic cardiovascular regulation. Integrating salivary microbiome profiling with glial biomarkers [e.g., GFAP (Glial Fibrillary Acidic Protein) and sTREM2 (soluble Triggering Receptor Expressed on Myeloid cells 2)] offers promising avenues for sex-specific precision medicine. This framework not only reframes oral dysbiosis as a modifiable cardiovascular risk factor, but also charts a translational path toward gender tailored diagnostics and therapeutics to reduce the global CVD burden. Full article

Oral squamous cell carcinoma (OSCC) is a malignancy with a poor prognosis, and early diagnosis is essential for improving patient survival and quality of life. This study aimed to develop a non-invasive screening method based on salivary gene expression and microbiome analysis. Unstimulated saliva samples were collected from patients with OSCC, patients with oral potentially malignant disorders, and healthy controls. Microbiome profiling was performed using 16S ribosomal RNA gene sequencing. The OSCC group showed a significant increase in Fusobacterium and Bacteroidetes and a decrease in Streptococcus. LEfSe analysis indicated microbial changes associated with disease progression. Receiver operating characteristic analysis demonstrated high diagnostic accuracy when multiple bacterial species were combined. An increase in Fusobacteria was also associated with a higher risk of recurrence. Gene expression analysis revealed that NUS1, RCN1, CPLANE1, and CCL20 were significantly upregulated in OSCC, as confirmed by qRT-PCR and tissue expression data. Notably, CCL20 expression positively correlated with Fusobacterium abundance. These findings suggest that integrated analysis of the salivary microbiome and gene expression may offer a useful non-invasive approach for early OSCC detection and disease monitoring. Furthermore, we integrated current evidence from the literature to provide a comprehensive overview. Full article

Changes in health, lifestyle, and medication usage significantly impact overall well-being. Aging is associated with an increased need for multiple medications, or polypharmacy. Despite extensive research on how aging and polypharmacy affect the gut microbiome, relatively little is known about their impact on the oral microbiome and how shifts there can contribute to oral and systemic disease. An initial group of 55 saliva donors was formed of individuals with stage 3 periodontal disease and well-characterized for dental decay, both factors that contribute strongly to salivary microbiome identity. Relative levels of saliva bacteria were determined by 16S rRNA amplicon sequencing. Multiple variable analysis was performed to determine taxa associated with polypharmacy after correction for dental decay, tobacco use and gender. A second group, all with stage 3 periodontal disease, over 55 years of age and controlled for caries, served as a validation set. Two differences in taxa were validated as associated with polypharmacy in the elderly group. The tooth surface commensal Corynebacterium durum was lower with polypharmacy, and the dental decay-associated Propionibacterium acidifaciens was elevated. Saliva flow rate differences did not appear to be responsible for the differences seen in these taxa. Additionally, taxa associated with caries level and gender were identified. Polypharmacy associated taxa differences are potentially directly affected by medication usage, or the ailments associated with polypharmacy, and they are strong candidates to contribute to disease in the large group of elderly with poor oral health. Full article

Background: Childhood cancer is considered one of the main causes of mortality and morbidity worldwide. There is strong evidence of the oral toxic effects of oncologic treatments, but their incidence is difficult to determine. The novel therapeutic strategies in Pediatric Oncology have led to increased survival in this population, resulting in an increased incidence of long-term effects, which diminish the patient’s quality of life. Methods: The search for articles started on 5 November 2024 and ended on 5 December 2024. Following the PRISMA Statement, a total of 1266 articles were obtained, from which 13 were selected for review. All articles were considered to be of high quality. The antineoplastic treatments used in them were chemotherapy, radiotherapy, surgery and immune therapy. Results: Most articles were cohorts and case controls. Only one case report was obtained. The results revealed that the most prevalent sequelae in the pediatric population after antineoplastic treatment were enamel alterations, microdontia, dental caries, periodontal disease, gingivitis, hyposalivation, alteration of the oral microbiome, alteration of mandibular bone density and malocclusion. The lesions are different depending on the therapy used. Conclusions: Oncologic treatments in children with cancer cause multiple oral sequelae such as microdontia, dental caries, enamel alterations, salivary gland alterations, mucositis and root resorption. It cannot be concluded which therapy has the most detrimental effect as each has a different mechanism of action in the oral cavity. Full article

Background: Salivary pH plays a critical role in oral health by influencing enamel demineralization, buffering capacity, and the ecology of oral microbiota. Essential oils such as Origanum vulgare (oregano) possess well-documented antimicrobial properties that may reduce acidogenic bacterial activity. However, the effects of edible delivery systems like jellies on salivary pH modulation and their potential interactions with hormonal states remain poorly understood. Methods: This study evaluated the in vitro antimicrobial activity of an oregano-oil-based jelly formulation against standard bacterial (Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli) and fungal (Candida albicans) strains using the Kirby–Bauer disc diffusion method. Additionally, a human trial (n = 91) measured salivary pH before and after administration of the oregano-oil jelly. Participants were characterized by age, smoking status, menopausal status, and presence of menstruation. Multiple linear regression was used to identify predictors of final salivary pH. Results: The oregano-oil jelly demonstrated strong in vitro antimicrobial activity, with inhibition zones up to 8 mm for E. coli and C. albicans. In vivo, mean unstimulated salivary pH increased from 6.94 to 7.07 overall, indicating a mild alkalinizing effect. However, menstruating participants showed a significant decrease in final pH (from 7.03 to 6.78). Multiple regression identified menstruation as a significant negative predictor (β = −0.377, p < 0.001) and initial pH as a positive predictor (β = +0.275, p = 0.002). Menopausal status was not a significant predictor, likely due to the small sample size. Conclusions: Oregano-oil jellies may represent a promising natural approach to support oral health by increasing salivary pH and providing strong antimicrobial activity. However, physiological states such as menstruation can significantly modulate this response, underscoring the importance of personalized or phase-aware oral care strategies. Further studies with larger, diverse cohorts and controlled hormonal assessments are needed to validate these findings and optimize product formulations. Full article

Three-dimensional (3D) scaffold systems have proven instrumental in advancing our understanding of polymicrobial biofilm dynamics and probiotic interactions within the oral environment. Among oral probiotics, Streptococcus salivarius K12 (Ssk12) has shown considerable promise in modulating microbial homeostasis; however, its long-term therapeutic benefits are contingent upon successful and sustained colonization of the oral mucosa. Despite its clinical relevance, the molecular mechanisms underlying the adhesion, persistence, and integration of Ssk12 into the native oral microbiome/biofilm remain inadequately characterized. In this pilot study, we explored the temporal colonization dynamics of Ssk12 and its impact on the structure and functional profiles of salivary-derived biofilms cultivated on melt-electrowritten poly(ε-caprolactone) (MEW-mPCL) scaffolds, which emulate the native oral niche. Colonization was monitored via fluorescence in situ hybridization (smFISH), confocal microscopy, and RT-qPCR, while shifts in community composition and function were assessed using 16S rRNA sequencing and meta-transcriptomics. A single administration of Ssk12 exhibited transient colonization lasting up to 7 days, with detectable presence diminishing by day 10. This was accompanied by short-term increases in Lactobacillus and Bifidobacterium populations. Functional analyses revealed increased transcriptional signatures linked to oxidative stress resistance and metabolic adaptation. These findings suggest that even short-term probiotic colonization induces significant functional changes, underscoring the need for strategies to enhance probiotic persistence. Full article

Background: Halitosis is frequently observed in patients undergoing orthodontic treatment with multibracket appliances, primarily due to volatile sulfur compounds (VSCs) produced by oral anaerobic bacteria. Cetylpyridinium chloride (CPC) is a widely used antimicrobial agent in oral care products and may help alleviate halitosis.This study aimed to evaluate the effects of 0.05% CPC mouthwash on halitosis, oral hygiene indices, and the tongue microbiota in orthodontic patients with elevated VSC levels. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 30 orthodontic patients with elevated VSCs (≥150 ppb) were assigned to a CPC mouthwash group or a placebo group. Participants used the assigned mouthwash three times daily for 1 month. Halitosis was quantitatively assessed by gas chromatography (Oral Chroma™), and oral hygiene parameters including Plaque Index (PI), Gingival Index (GI), Tongue Coating Index (TCI), and unstimulated salivary flow rate were evaluated at baseline and after the intervention. The tongue microbiota was analyzed by 16S rRNA sequencing. Results: The CPC mouthwash group showed significant reductions in total VSCs, hydrogen sulfide, methyl mercaptan, PI, GI, and TCI (p < 0.05), while salivary flow rate and dimethyl sulfide remained unchanged. Microbiome analysis revealed decreases in halitosis-associated genera (Actinomyces, Corynebacterium, Tannerella) and increases in beneficial species such as Streptococcus salivarius. Conclusions: CPC mouthwash (0.05%) effectively reduced halitosis and improved oral hygiene parameters in orthodontic patients, likely through modulation of the tongue microbiota. This mouthwash may serve as a safe and practical adjunct to conventional oral hygiene practices during orthodontic treatment. Full article

Background and Objectives: Infant feeding practices play a crucial role in shaping the oral microbiome, modulating inflammatory responses, and maintaining epithelial health during the first year of life. Breastfeeding promotes the growth of beneficial bacteria and supports a diverse, stable microbial community. In contrast, formula feeding is associated with increased colonization by potentially pathogenic bacteria, such as Staphylococcus and Escherichia coli, which may elevate the risk of infections, oral diseases, and inflammation. This study investigates the effects of breastfeeding versus formula feeding on oral bacterial growth, epithelial cell integrity, and interleukin-17 (IL-17) expression in infants aged 1–12 months. Materials and Methods: A total of 60 infants (30 breastfed and 30 formula-fed) were recruited from pediatric clinics in the Qassim region. Microbial cultures quantified bacterial colony-forming units (CFUs), and epithelial cell morphology was assessed through the microscopic analysis of mucosal scrapings. IL-17 concentrations were quantified from the oral mucosa through enzyme-linked immunosorbent assay. Statistical analyses, including t-tests and chi-square tests, compared bacterial loads, IL-17 levels, and indicators of epithelial health between groups. Adjustment for potential confounders was achieved through multivariate statistical analysis. Results: Formula-fed infants showed significantly higher IL-17 levels than breastfed infants (p < 0.001), indicating a stronger pro-inflammatory profile. Breastfed infants exhibited lower inflammation, improved epithelial health, and reduced cellular debris compared to formula-fed infants, who had higher bacterial loads. A significant correlation was found between epithelial health and bacterial clustering, with clearer epithelial cells associated with lower bacterial colonization. Conclusions: Formula feeding was associated with increased salivary IL-17 levels, greater bacterial colonization, and compromised epithelial integrity, indicating a heightened pro-inflammatory state and potential vulnerability to mucosal irritation or infection. Breastfeeding appeared to confer protective effects by promoting healthier microbial balance, epithelial integrity, and reducing inflammatory responses. These findings underscore the immunological and microbial benefits of breastfeeding in supporting oral health during infancy. Full article

Background: This study explores the link between oral biofluids, microbial dysbiosis, and Alzheimer’s disease (AD), highlighting saliva and gingival crevicular fluid (GCF) as non-invasive diagnostic sources. AD onset and progression appear to be influenced not only by genetic and environmental factors but also by changes in the oral microbiome and related inflammatory and metabolic alterations. As global populations age, the incidence of AD is projected to rise significantly. Emerging evidence implicates the oral microbiome and salivary metabolites in neurodegenerative pathways, suggesting that oral health may mirror or influence brain pathology. Materials and Methods: A systematic review of recent multi-omics studies was performed, focusing on salivary and GCF analysis in patients with AD, those with mild cognitive impairment (MCI), and cognitively healthy individuals. Databases searched included PubMed, Web of Science, and Scopus, following PRISMA guidelines. Results: Across the 11 included studies, significant alterations were reported in both the salivary microbiome and metabolome in AD patients. Notable microbial shifts involved increased abundance of Veillonella parvula and Porphyromonas gingivalis, while key metabolites such as L-tyrosine, galactinol, and mannitol were consistently dysregulated. These biomarkers correlated with cognitive performance and systemic inflammation. Conclusions: Oral biofluids represent promising, accessible sources of biomarkers for early AD detection. Multi-omics integration reveals the oral–brain axis as a potential target for diagnosis, monitoring, and therapeutic strategies. Full article

Background/Purpose: Coronavirus disease 2019 (COVID-19) has become the cause of a global health crisis during the pandemic. This research aimed to study the impact of symptomatic COVID-19 on children’s oral health indices and salivary microbiome composition during the post-COVID-19 period. Methods: An observational, cross-sectional study was conducted in Tbilisi (Georgia) among children aged 7–12 years. A total of 421 children included in the study had a history of laboratory-confirmed COVID-19 within one year of exposure. No participants met the criteria for comorbid conditions or for PCC. A stratified simple random selection of schools and among selected clusters was used. The selected children were divided into two groups: the exposed group, who were patients with a history of symptomatic COVID-19, and the control group, who were patients with a history of asymptomatic COVID-19. The data were collected from August 2022 to December 2023. Oral screening, microbiological examination of saliva, and administration of questionnaires were also performed. Logistic regression was used to calculate ORs with 95% confidence intervals. The statistical processing of the data was performed with SPSS 23.0. This study was approved by the Biomedical Research Ethical Council of the University of Georgia (UGREC–04–22/9 March 2022). Results: Statistically significant differences in the means of the oral health indicators between the studied groups were detected (exposed: DMFT + deft = 5.9; MGI = 0.92; S-OHI = 1.9; control: DMFT + deft = 3.8; MGI = 0.56; S-OHI = 1.4). According to the logistic regression, symptomatic COVID-19 had a significant effect on the following oral health indicators: DMFT + deft (OR = 1.26; 95% CI = 1.14–1.39), MGI (OR = 2.31; 95% CI = 1.50–3.55), and S-OHI (OR = 3.43; 95% CI = 2.03–5.76). The effect of symptomatic COVID-19 on the frequency of eradication of the studied microbiome was also significant (OR = 2.12; 95% CI = 1.23–3.63). Conclusions: A close association was established between symptomatic COVID-19 and microbiome changes in the oral saliva of children, as well as between oral health indicators and symptomatic COVID-19. Considering the research results, it is assumed that a symptomatic course of COVID-19 may be an additional risk factor associated with poor oral health in the pediatric population in the post-COVID-19 period. Full article

Histatin peptides are a family of small histidine-rich cationic polypeptides produced by two genes, HTN1 and HTN3. They are found in salivary secretions from the parotid, sublingual, and submandibular salivary glands. These peptides undergo proteolytic cleavages to produce different histatin fragments which play multiple roles including wound healing, maintenance of enamel, and regulation of balance in the oral microbiome. In this review, we explored the expression, structural characteristics, and metal-ion-binding capacities of these peptides and how their functions are modulated by their structure. We also provide here an insight into the potential use of histatins as biomarkers and therapeutic peptides in the management of oral and non-oral diseases including cancer. Potential gaps in the current understanding of histatins that warrant further research have also been highlighted. Full article

Background and Objectives: Menopause is a natural physiological process involving hormone production changes, affecting many functions and systems. This scoping review offers a contemporary outlook on oral issues related to menopause, such as saliva production, periodontal and alveolar bone issues, and changes in the microbiome, and it also investigates the effects of hormonal therapy. Materials and Methods: A literature search from 2019 to 2024 was conducted according to PRISMA-ScR guidelines. Articles investigating the oral effects of menopause were included. Results: A total of 30 studies were covered; 8 focused on salivary alterations, 5 on periodontal issues, 7 on bone, 3 on the microbiome, and 7 on multiple oral problems, showing that xerostomia and altered taste are the most common oral manifestations, followed by indirect causal effects on periodontitis. Many of these alterations can be contained through regular consultations and adequate hygiene. Some alveolar bone changes may occur after menopause and are associated with osteoporosis. Conclusions: Postmenopausal women experience notable reductions in salivary flow, pH levels, and taste sensitivity, which are associated with hormonal fluctuations as well as factors such as age, medication use, and treatments for climacteric symptoms. This population is at increased risk for periodontitis, tooth loss, altered taste, lichen planus, candidiasis, and decreased bone mineral density, which also affect the peri-implant area. Osteoporosis and hormonal changes can play a significant role in causing these increased risks. Maintaining proper oral hygiene and consistently monitoring bone health are essential. While changes in the oral microbiome are more heavily influenced by reductions in salivary flow than by menopause itself, hormone therapy may help improve periodontal health by reducing harmful bacteria and fostering a more balanced microbial environment. The intricate impact of hormones on oral health highlights the necessity for further research. Full article