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PubMed2026

Association of Socioeconomic Factors With Oral Health in Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Oral diseases remain disproportionately prevalent among older adults. However, evidence on oral health inequalities among older adults remains dispersed across studies that have used different socioeconomic indicators and oral health measures and has not been synthesised. OBJECTIVE: To synthesise the evidence on the association between socioeconomic factors and oral health among older adults aged 75 years and older. METHODS: A systematic review and meta-analysis was conducted following PRISMA guidelines. The Medline, Embase, and CENTRAL databases were searched. Studies reporting socioeconomic factors (education, income, occupation, area-level deprivation, and multi-aspect socioeconomic position) and oral health (dentition status, dental caries, periodontal disease, dry mouth, oral function, oral health behaviours, and oral health-related quality of life (OHRQoL)) among older adults were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Sixty-eight studies were included. Meta-analyses showed that socioeconomic disadvantage in older adults was associated with: (1) poor dentition status: fewer natural teeth, higher prevalence of edentulism, and lacking a functional dentition; (2) more teeth with decay; (3) irregular dental attendance; and (4) poorer OHRQoL. Similar patterns were generally observed for periodontal disease, dry mouth, and oral function, although no meta-analysis could be performed due to limited evidence and heterogeneous oral health measures. CONCLUSION: Socioeconomic disadvantage was consistently associated with poor oral health in older adults. Associations were more pronounced for dentition status, reflecting the cumulative socioeconomic disadvantage over the life course. Socioeconomic factors should be considered to inform prevention, clinical decision-making and oral healthcare planning for the ageing population. TRIAL REGISTRATION: PROSPERO Registration CRD420251231319.

Aged↗

PubMed2026

Nutrition and Diet-Related Training and Curriculum in the US Predoctoral Dental Programs.

PURPOSE: Nutrition and diet are vital for oral and systemic health. It is unclear how well US predoctoral dental programs prepare students in nutrition screening and counseling. This study analyzed US dental school curricula on these topics. METHODS: A cross-sectional online survey was sent to the publicly available email addresses of 67 of 72 academic dental deans at US Commission on Dental Accreditation-accredited dental schools. Items assessed availability, modes and hours of instruction, curricular topics, clinical integration, and instructors. Descriptive statistics summarized responses. RESULTS: A total of 21 academic deans responded, for an overall response rate of 29%. Most (85%) of responding academic dental deans reported that nutrition and diet education was mandatory, with none treating it as optional. Of these schools, 83% offered both classroom and clinical training, while 17% provided only didactic teaching. Didactic hours varied; 42% reported 10 or fewer hours. Foundational nutrition topics were common, although dietary guidelines such as MyPlate were reported less often (66%). Oral health-related nutrition content was broadly covered, with all respondents reporting instruction related to caries, erosion, periodontal disease, and oral dysfunction. Counseling content was less consistent, particularly public health nutrition (67%) and the impact of oral dysfunction on diet and nutrition (72%). CONCLUSION(S): Most responding academic dental deans report including nutrition and diet education in their curricula. However, it remains uncertain whether these topics are incorporated at schools that did not participate in the survey. Variability in curricular time, counseling, and teaching highlights the need for clearer competencies and more clinical training. Improving this could better prepare future dentists for common dietary risks affecting oral and systemic health.

dental caries↗

PubMed2024

Deciphering the molecular nexus of BTG2 in periodontitis and diabetic kidney disease.

OBJECTIVE: To investigate the role of BTG2 in periodontitis and diabetic kidney disease (DKD) and its potential underlying mechanism. METHODS: Gene expression data for periodontitis and DKD were acquired from the Gene Expression Omnibus (GEO) database. Differential expression analysis identified co-expressed genes between these conditions. The Nephroseq V5 online nephropathy database validated the role of these genes in DKD. Pearson correlation analysis identified genes associated with our target gene. We employed Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) networks to elucidate potential mechanisms. Expression levels of BTG2 mRNA were examined using quantitative polymerase Chain Reaction (qPCR) and immunofluorescence assays. Western blotting quantified proteins involved in epithelial-to-mesenchymal transition (EMT), apoptosis, mTORC1 signaling, and autophagy. Additionally, wound healing and flow cytometric apoptosis assays evaluated podocyte migration and apoptosis, respectively. RESULTS: Analysis of GEO database data revealed BTG2 as a commonly differentially expressed gene in both DKD and periodontitis. BTG2 expression was reduced in DKD compared to normal conditions and correlated with proteinuria. GSEA indicated enrichment of BTG2 in the EMT and mTORC1 signaling pathways. The PPI network highlighted BTG2's relevance to S100A9, S100A12, and FPR1. Immunofluorescence assays demonstrated significantly lower BTG2 expression in podocytes under high glucose (HG) conditions. Reduced BTG2 expression in HG-treated podocytes led to increased levels of EMT markers (α-SMA, vimentin) and the apoptotic protein Bim, alongside a decrease in nephrin. Lower BTG2 levels were associated with increased podocyte mobility and apoptosis, as well as elevated RPS6KB1 and mTOR levels, but reduced autophagy marker LC3. CONCLUSION: Our findings suggest that BTG2 is a crucial intermediary gene linking DKD and periodontitis. Modulating autophagy via inhibition of the mTORC1 signaling pathway, and consequently suppressing EMT, may be pivotal in the interplay between periodontitis and DKD.

Periodontitis↗

PubMed2026

Dental wastewater reveals a hidden reservoir of oral bacteriophage diversity.

Bacteriophages (phages) are being explored as alternatives or complements to antibiotics because of their ability to selectively kill bacterial pathogens. However, phages that infect many oral bacteria remain undiscovered. Here, we discovered that dental wastewater harbors previously underexplored phage diversity. Viral particles concentrated from dental wastewater displayed diverse morphologies, including abundant filamentous phage-like particles. Deep long-read metagenomic sequencing of concentrated viral particles generated 7.4 billion bases of sequence data and yielded 255 medium- to high-quality viral operational taxonomic units (vOTUs), including 46 predicted complete genomes. Comparison with large phage databases revealed that 63 of these 255 vOTUs had no detectable match, indicating that extensive sequencing of dental wastewater substantially expands the number of potential bacteriophages associated with the human oral microbiome. Host prediction linked many vOTUs to oral-associated bacterial taxa, including species with few or no previously reported phages, such as Porphyromonas gingivalis, Tannerella forsythia, and Candidatus Saccharibacteria. Functional annotation identified diverse genes associated with antiphage defense systems within a subset of vOTUs, suggesting that oral phages may contribute to the movement of genes encoding bacterial immune functions within the oral microbiome. Together, these findings expand the known oral phageome and show that dental wastewater contains a largely untapped diversity of phages.IMPORTANCEThe human oral cavity contains a diverse microbial community, but the bacteriophages (phages) that infect many oral bacteria remain poorly characterized. This gap limits our understanding of how phages shape oral microbial communities. Here, we show that dental wastewater is an underexplored source of oral phage diversity. Deep long-read metagenomic sequencing revealed 255 medium- to high-quality phage operational taxonomic units, many of which are not present in existing oral phage databases. These genomes include predicted phages of periodontal disease-associated bacteria and other oral taxa with few or no known phages. Dental wastewater therefore expands the known human oral phageome and reveals candidate phages linked to bacteria associated with oral health and disease.

Bacteriophages↗

PubMed2026

The Oral Microbiome of King Richard III of England.

OBJECTIVES: Metagenomic investigations of ancient dental calculus provide insights into oral health, disease, and diet. Here, we analyze the dental calculus metagenome of King Richard III of England (1452-1485). MATERIALS AND METHODS: Dental calculus DNA was extracted from three teeth of King Richard III and shotgun sequenced to a depth of nearly 400 million reads. The metagenomic data were taxonomically profiled and compared to new and previously published dental calculus metagenomes from England, Ireland, the Netherlands, and Germany spanning the Neolithic to the present. Sequencing data were de novo assembled, and metagenome-assembled genomes assigned to the genus Tannerella were investigated for phylogenetic relatedness and virulence. Putative dietary DNA was assessed for authenticity. RESULTS: The dental calculus of King Richard III was well-preserved and yielded an exceptionally high quantity of DNA. Oral microbiome species diversity fell within the range previously observed among other northern European populations, suggesting that a royal lifestyle and a rich diet did not substantially impact his oral microbiota. The reconstructed Tannerella genomes contained many virulence factors found today among oral Tannerella species. No putative dietary DNA could be authenticated. DISCUSSION: The dental calculus of King Richard III produced one of the richest ancient oral metagenomes published to date, yet the species diversity was indistinguishable from that of commoners living in northern Europe over the last 7000 years. Insufficient plant and animal DNA were recovered to investigate diet, suggesting that dental calculus may not be a sufficient source of dietary DNA even when exceptionally well-preserved.

Humans↗

PubMed2025

GWAS for Periodontitis Phenotypes Using Multi-Ancestry All of Us Research Platform.

Periodontitis is a multifactorial inflammatory disease whose pathogenesis is associated with intricate interactions between genetic and environmental factors. Leveraging electronic health records data from the All of Us Research Program, we stratified periodontitis by clinically relevant dimensions: stage, grade, and extent. Based on these phenotypes, we performed a multi-ancestry genome-wide association study, focusing on predominant ancestry populations of African, European, and Admixed American. Our study cohort comprised 3,881 periodontitis patients and a control group of 10,760 patients with dental caries and without periodontitis. Ancestry-specific GWAS revealed significant genetic associations (P<5×10-8) in periodontitis grade phenotypes at the LINC00294 and CLMN loci in the African ancestry population and also confirmed via the multi-ancestry meta-analysis. In addition, the XYLT1 locus emerged as a significant signal associated with periodontitis grade phenotype in the admixed American GWAS. Our GWAS comparing periodontitis to dental caries in the admixed American population identified several significant loci, including RABGAP1L, previously linked to immune regulation, DCHS2, a cadherin-related gene involved in bone mineralization and tissue morphogenesis, and OSTM1, known to be crucial for bone remodeling. The findings of our study highlight the potential of integrating EHR and genomic data from large-scale biobanks to achieve informative dental phenotyping, uncover novel molecular insights into periodontal disease, and personalize treatment approaches.

Journal Article↗

PubMed2025

Ferroptosis in Oral Cancer: Mechanistic Insights and Clinical Prospects.

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a pivotal vulnerability in oral squamous cell carcinoma (OSCC). This review provides an overview of ferroptosis mechanisms and their implications for OSCC pathobiology and therapy. OSCC cells exhibit heightened reliance on anti-ferroptotic defenses such as GPX4, SLC7A11, FSP1, and Nrf2, and disrupting these pathways suppresses tumor growth and restores sensitivity to chemotherapy, radiotherapy, and immunotherapy. Genetic and epigenetic regulators, including p53, PER1, circ_0000140, and STARD4-AS1, critically modulate ferroptotic sensitivity, while metabolic enzymes such as ACSL4, LPCAT3, and TPI1 link ferroptosis to cellular plasticity and resistance. Preclinical studies highlight the promise of small-molecule inhibitors, repurposed agents (e.g., sorafenib, artesunate, trifluoperazine), natural compounds (e.g., piperlongumine, Evodia lepta, quercetin), and nanomedicine platforms for targeted ferroptosis induction. We further address ferroptosis within the tumor microenvironment, highlighting its immunogenic and context-dependent dual roles, and summarize genomic and transcriptomic evidence linking ferroptosis-related genes to patient prognosis. Beyond cancer, ferroptosis also contributes to non-malignant oral diseases, including pulpitis, periodontitis, and infection-associated inflammation, where inhibitors may protect tissues. Despite these advances, clinical translation is constrained by the lack of safe ferroptosis inducers and validated biomarkers. Future research should focus on developing pharmacologically viable GPX4 inhibitors, refining biomarker-driven patient stratification, and designing multimodal regimens that combine ferroptosis induction with standard therapies while preserving immune and tissue integrity. Ferroptosis therefore represents both a mechanistic framework and a translational opportunity to reshape oral oncology and broader oral disease management.

Humans↗

PubMed2026

Challenges and future directions in AI-driven biomaterials for microbiome-associated oral infectious diseases: A systematic review.

Oral biofilm-induced antimicrobial resistance is the core pathogenic mechanism of microbiome-associated oral infectious diseases (dental caries, periodontitis, peri-implantitis, and endodontic infection). Traditional therapies and biomaterials are limited by poor biofilm penetration, drug resistance induction, single functionality, and inadequate adaptation to dynamic oral microenvironmental changes (e.g., pH fluctuations, salivary rinsing, masticatory stimulation). Artificial intelligence (AI) has transformed the field by integrating materials science, microbiology, and stomatology data. Via machine learning, deep learning, and multi-physics simulation, AI optimizes biomaterial physicochemical properties, decodes microenvironmental signals, constructs precise sensing-response loops, and supports the full chain of material design, performance prediction, and action simulation, advancing treatment from empirical intervention to precision regulation. This systematic review retrieved literature from PubMed, Embase, and Web of Science (January 2016-January 2026) using keywords across three dimensions: AI, biomaterials, and oral microbiome. Following inclusion/exclusion criteria, 99 articles were included. It elaborates on five core mechanisms of AI-driven oral biomaterials (precise oral microbiome analysis, targeted material design/optimization, performance prediction/simulation, targeted delivery/intervention, effect evaluation/dynamic regulation), analyzes their applications in microbiome-targeted biomaterial research and development (R&D) and clinical practice for the four major oral infectious diseases, addresses technical bottlenecks (insufficient targeting specificity and precision of biomaterials, poor stability and durability in complex oral microenvironments, inadequate biofilm disruption capacity, and clinical translation obstacles), and proposes future directions (multimodal design to enhance targeting specificity, structural and component optimization to improve stability/durability, development of multi-mechanism synergistic biofilm disruption strategies, strengthening translational research for clinical application, and deep integration of AI in the full chain of biomaterial R&D). This work provides comprehensive theoretical and practical support for the R&D, optimization, and clinical translation of AI-driven microbiome-targeted oral biomaterials.

Humans↗

PubMed2026

Markerless gene deletion in Porphyromonas gingivalis using a pheS*-based counterselection system.

Porphyromonas gingivalis is an oral pathobiont implicated in periodontitis and several systemic diseases and serves as an important model organism. However, the routine generation of markerless mutants in P. gingivalis has remained challenging due to the lack of an efficient counterselection system for the double cross-over approach. Markerless gene deletion is crucial for bacterial genetic manipulations, in particular for generating multiple gene deletions or introducing point mutations. In this study, a counterselection system for P. gingivalis was established by placing the pheS* gene under the control of a P. gingivalis promoter enabling efficient expression. The construct was delivered to P. gingivalis via a suicide plasmid by conjugation. Using PG0719 as a representative target gene, first cross-over recombinants were selected using erythromycin resistance encoded on the suicide plasmid. Cells were then subjected to counterselection in the presence of p-chloro-phenylalanine (p-Cl-Phe). Retention of pheS* in the genome reduced viability, thereby enriching recombinants that had undergone a second recombination event and loss of the plasmid sequence. Candidate clones were screened by colony PCR analysis to confirm the loss of the gene of interest. A markerless PG0719 mutant was generated and further validated by Sanger sequencing, demonstrating a practical approach for markerless gene deletion in P. gingivalis and providing a framework for further genome modifications in the organism.IMPORTANCEAlthough Porphyromonas gingivalis is a widely studied model organism, the genetic manipulation of this bacterium has remained limited by the lack of efficient tools for markerless genome editing. Here, we established a counterselection system based on pheS∗ that enables markerless gene deletion in P. gingivalis. This approach addresses a technical limitation in the field and provides a practical and broadly applicable framework for advanced genetic manipulation in this important oral pathobiont.

Porphyromonas gingivalis↗

PubMed2025

Cross-talk between NLRP3 and AIM2 inflammasomes in macrophage activation by LPS and titanium ions.

BACKGROUND: Periodontitis and peri-implantitis are chronic inflammatory diseases that contribute to tissue destruction and bone loss. Periodontitis is triggered by pathogenic bacteria, while peri-implantitis also involves metallic particles, which increase the inflammatory response. Both conditions are linked to the activation of inflammasomes, such as NLRP3 and AIM2, which facilitate the release of pro-inflammatory cytokines like IL-1β and IL-18 and induce pyroptosis. This study aims to investigate the activation of NLRP3 and AIM2 inflammasomes in macrophages exposed to bacterial and metallic components, as well as to explore the potential interplay between these two signaling pathways. METHODS: Human THP-1-derived macrophages were treated with bacterial lipopolysaccharide (LPS) and titanium ions to evaluate inflammasome activation. IL-1β secretion, ROS production, mitochondrial DNA release and pyroptosis were assessed. Additionally, macrophages deficient in NLRP3 and AIM2 were used to examine the roles of these inflammasomes in inflammatory responses. RESULTS: LPS and titanium ions synergistically activated NLRP3, resulting in increased IL-1β secretion, ROS production, and pyroptosis. Under these conditions, AIM2 was indirectly activated, as indicated by elevated mitochondrial DNA release. Notably, AIM2 expression was reduced in wild-type macrophages treated with LPS and titanium ions compared to LPS alone, however, in NLRP3-deficient cells, AIM2 expression was increased following LPS and titanium ions treatment. This upregulation of AIM2 in NLRP3-deficient cells was further reduced by ROS inhibition, which decreased mitochondrial DNA release. Additionally, NLRP3 knockout had a more pronounced effect on reducing IL-1β secretion and pyroptosis compared to AIM2 knockout, indicating a greater role of NLRP3 in these inflammatory responses. CONCLUSIONS: This study demonstrates that bacterial and metallic components drive the activation of both NLRP3 and AIM2 inflammasomes in macrophages, highlighting their roles in the inflammatory responses associated with periodontitis and peri-implantitis. The findings reveal a regulatory relationship between NLRP3 and AIM2, where the absence of one inflammasome can enhance the activity of the other. These results provide new insights into the mechanisms underlying inflammasome-mediated inflammation and suggest potential therapeutic targets for managing inflammatory diseases.

NLR Family, Pyrin Domain-Containing 3 Protein↗

PubMed2025

A high-quality genomic catalog of the human oral microbiome broadens its phylogeny and clinical insights.

The oral microbiome is increasingly linked to human health. To further examine this microbial community, we present the human reference oral microbiome (HROM), with 72,641 high-quality genomes from 3,426 species, including 2,019 previously unidentified species, improving metagenomic sequence read classification over existing catalogs. Notably, HROM unveils 1,137 previously uncharacterized candidate phyla radiation (CPR) species, establishing Patescibacteria as the most prevalent phylum in the oral microbiota and distinct from environmental Patescibacteria. Additionally, an oral CPR subclade is associated with periodontitis, complementing Porphyromonas gingivalis in predicting disease. Finally, comparing HROM with reference genomes of the gut microbiome reveals taxonomic and functional divergence between these microbiomes. HROM contains 42 ectopic oral species, and their relative abundance in gut microbiota is predictive of intestinal, cardiovascular, and liver diseases. Thus, HROM offers an expanded view of the oral microbiome and highlights the clinical importance of further examining the links between oral microbes and systemic disorders.

Humans↗

PubMed2026

Causal effect of chloride intracellular channel protein 5 on chronic periodontitis: A Mendelian randomization study.

This study aimed to evaluate the potential causal effect of chloride intracellular channel protein 5 (CLIC5) on the risk of chronic periodontitis (CP) using a Mendelian randomization (MR) approach. MR analysis was conducted utilizing publicly available summary statistics from genome-wide association studies summary statistics for CLIC5 and CP. Multiple MR methods, including inverse variance weighted, MR Egger, weighted median and weighted mode, were employed to estimate the causal effects. Sensitivity analyses, comprising leave-one-out and heterogeneity assessments were performed to evaluate the robustness of our findings. This MR analysis consistently revealed a negative association between CLIC5 and CP, with statistical significance achieved using the inverse variance weighted and weighted median methods. The concordant effect estimates obtained from all methodological approaches collectively indicated a potential protective effect of CLIC5 against CP. The sensitivity analyses further confirmed the robustness of these findings. This study provides genetic evidence suggesting a potential causal association between increased CLIC5 levels and decreased risk of CP. These findings augment the existing literature implicating chloride channel proteins in modulating the inflammatory processes pertinent to periodontal health. Further investigation is warranted to decipher the underlying biological mechanisms and to explore the potential of CLIC5 as a therapeutic target for CP.

Chloride Channels↗

PubMed2026

Molecular and Genomic Mechanisms Linking Diabetes Mellitus and Periodontitis: From Pathogenesis to Translational Opportunities.

Diabetes mellitus and periodontitis are bidirectionally associated chronic disorders linked through metabolic dysregulation, host inflammation, microbial dysbiosis, and impaired tissue remodeling. This review summarizes clinical, molecular, cellular, genomic, epigenomic, transcriptomic, and microbial evidence concerning the mechanisms underlying this relationship and their potential translational relevance. Chronic hyperglycemia is associated with advanced glycation end product signaling through the receptor for advanced glycation end products, mitogen-activated protein kinase/nuclear factor-κB activation, reactive oxygen species production, oxidative stress, and NLR family pyrin domain-containing 3 inflammasome activation, which may contribute to enhanced cytokine responses and periodontal tissue injury. Diabetes is also associated with altered neutrophil and macrophage function, increased T helper 17/interleukin-17 signaling, and an elevated receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio, thereby favoring osteoclastogenesis and alveolar bone loss. Conversely, periodontal inflammation and microbial products may contribute to systemic low-grade inflammation, insulin resistance, and metabolic dysregulation. Multi-omics studies have identified shared susceptibility loci, regulatory networks, and disease-associated cell states, although their causal and clinical significance remains incompletely defined. These findings suggest potential roles for integrated medical-dental care, glycemic screening in dental settings, periodontal inflammation control, host-modulatory therapies, and regenerative biomaterials. Further longitudinal and experimental studies are needed to determine their clinical applicability.

Humans↗

PubMed2025

Cerebrospinal fluid microbiome revisited: no evidence of resident bacteria in archived samples.

UNLABELLED: DNA from oral bacteria has been detected in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease and related dementias (AD/ADRD). We hypothesized that examination of archived CSF samples from donors with variable cognitive status would reveal evidence of a resident microbiome. 176 CSF samples harvested from community-dwelling individuals (77% between 61 and 80 years old) were analyzed; 57% originated from donors with impaired cognitive status. DNA was extracted after adding microbial spike-in controls, and libraries were prepared and sequenced on an Illumina-MiSeq platform. 16S rRNA sequences were processed, and a taxonomic classification was performed. Spike-in bacteria were consistently detected, and Streptococcus pneumoniae was found in a positive control sample from a patient with bacterial meningitis. However, very few reads mapping to other bacterial taxa were detected across samples, suggesting a negligible bacterial content consistent with occasional contamination or sequencing errors. CSF is a privileged, sterile environment that does not harbor a resident microbiome in elderly people with various morbidities, including AD/ADRD. IMPORTANCE: Recent reports have suggested that DNA from oral bacteria has been found in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease and related dementias (AD/ADRD). We hypothesized that examination of archived CSF samples from donors with variable cognitive status would reveal evidence of a resident microbiome. We thus analyzed 176 CSF samples harvested from community-dwelling individuals including donors with impaired cognitive status. While our findings suggested the presence of occasional bacterial contamination, they provided no evidence of a resident microbiome. We thus conclude that the CSF is indeed a privileged, sterile environment that does not harbor a resident microbiome in elderly people with various morbidities including AD/ADRD.

Humans↗