Oral dysbiosis plays an important role in the pathogenesis of oral squamous cell carcinoma (OSCC). Our study aimed to perform a pairwise comparison of the oral microbiota, especially the bacteriome, from OSCC tumoral surface vs other oral samples and evaluate the association of a novel bacteriome-based Oral Dysbiosis Index (bbODI) with the OSCC surface. This pilot observational study used 84 patient-matched samples from the OSCC tumoral surface (swabs and biopsies), healthy oral mucosa (tongue and buccal swabs), and supragingival dental plaque swabs. Bacteriomes were analyzed by 16S rRNA amplicon sequencing. The presence of microscopic fungi and selected viruses was also evaluated. The relative abundance of the genus Fusobacterium, the ratio of the relative abundances of gram-negative to gram-positive bacterial genera, and the bbODI on the tumour surface significantly differed from patient-matched healthy oral mucosa (both buccal and tongue swabs) and supragingival dental plaque samples. Oral candidosis was found in 25% of patients; all patients were negative for cytomegalovirus and Epstein-Barr virus. Certain characteristics of the bacteriome composition of the OSCC surface differ from patient-matched samples of healthy oral mucosa and supragingival dental plaque. The proposed bbODI appears to be a promising non-invasive tool for the identification of bacteriome disruption on the OSCC surface. A novel index (bbODI) was introduced based on the ratio of selected bacteria.The bbODI provides a comprehensive single-value characteristic of the oral bacteriome.The bbODI was significantly higher in swabs from OSCC than from healthy oral mucosa.
Streptococcus mutans (S. mutans) is the primary pathogen of dental caries and one of the pioneer colonizers of dental plaque biofilms. The normoxic stress experienced by S. mutans during initial adhesion is detrimental to biofilm formation. Membrane vesicles (MVs) can modulate the stress adaptability and biofilm formation of parental bacteria. However, it remains unclear whether normoxic stress influences the secretion, composition and function of MVs. We conducted characterization, omics analysis, and functional validation of MVs secreted by S. mutans under normoxic and hypoxic conditions. Furthermore, we performed a comparative analysis of protein expression profiles between MVs and their parental bacteria under normoxic stress. Compared with those of hypoxic MVs, the secretion of normoxic MVs is increased approximately 100-fold, and significantly enrich the adhesion proteins GtfC and SpaP. Normoxic MVs promote the initial adhesion and early biofilm formation of S. mutans through enhancing glucan synthesis, self-aggregation and the surface adhesion force. On the contrary, the magnitude of expression changes of GtfC and SpaP at the transcriptional and cellular levels under normoxic stress are modest. Normoxic stress enhances the secretion of adhesion-promoting MVs by S. mutans. The cargo composition of S. mutans MVs may dynamically modulate in response to environmental stresses to facilitate their colonization. Successful adhesion under normoxic stress is a prerequisite for biofilm formation of S. mutans. MVs play a crucial role in regulating stress adaptation and biofilm formation in bacteria.Normoxic stress enhances S. mutans MVs secretion and promotes initial adhesion as well as early biofilm formation of S. mutans.Developing MV-targeted strategies to prevent the colonization of S. mutans, and the formation of cariogenic biofilms is promising.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
This study investigated the antibacterial action of photo-liberated nitric oxide (NO) from primary and tertiary S-nitrosothiol-modified mesoporous silica nanoparticles (1° RSNO-MSNs and 3° RSNO-MSNs, respectively) against planktonic periodontal pathogens and ex vivo subgingival periodontal biofilms. The antibacterial and antibiofilm efficacy of photo-liberated NO release from 1° RSNO-MSNs and 3° RSNO-MSNs was evaluated as a function of wavelength (405 and 455 nm), irradiance (400-1000 mW cm-2), and time (0-15 min) against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and ex vivo subgingival biofilms. Time course, biofilm dispersion, and biofilm eradication assays were employed to evaluate the synergistic impact of antibacterial blue light therapy (aBLT) and photo-liberated NO. The addition of photo-initiated NO release with aBLT significantly improved antibiofilm activity, with irradiation of 405 nm at 1000 mW cm-2 demonstrating the most efficacious NO liberation from both 1° RSNO-MSNs and 3° RSNO-MSNs. While aBLT demonstrated antibacterial activity alone, the addition of NO was crucial for biofilm dispersal and eradication. The in vitro and ex vivo results demonstrate, for the first time, the utility of a dual-action aBLT and NO-releasing system for treating periodontal pathogens and biofilms. Photo-initiated nitric oxide (NO) release from RSNO-modified mesoporous silica nanoparticles enables wavelength- and irradiance-dependent control over NO-release kinetics and payloads, allowing precise modulation of antibacterial activity.Antibacterial efficacy against dental biofilms is governed not only by total NO payload but by NO-release kinetics, with sustained NO release enabling superior biofilm penetration and eradication compared to rapid, high-flux release at equivalent NO doses.Combining antimicrobial blue light therapy with photo-initiated NO delivery overcomes intrinsic biofilm protective mechanisms, enabling effective eradication of resilient periodontal biofilms under clinically relevant irradiation conditions.
Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanoscale membrane-bound structures that mediate intercellular communication through the transfer of proteins, lipids, and nucleic acids. In the oral cavity, EVs are present in saliva and gingival crevicular fluid, where they contribute to immune regulation, epithelial barrier integrity, and host-microbiome interactions. This review aimed to critically summarize current knowledge regarding EV biogenesis, molecular composition, cellular and microbial sources, and their roles in oral homeostasis and disease pathogenesis. Current evidence demonstrates that EVs derived from host cells and oral microorganisms actively regulate inflammatory responses, biofilm dynamics, tissue regeneration, and microbial colonization. Dysregulation of EV-mediated communication has been implicated in the development and progression of periodontal disease, oral candidiasis, and oral squamous cell carcinoma (OSCC). In addition, salivary EVs have emerged as promising non-invasive biomarkers and potential therapeutic tools in oral medicine. However, important methodological limitations remain, particularly regarding EV isolation, characterization, and standardization. EVs represent central mediators of communication within the oral microenvironment and play dual roles in maintaining oral homeostasis and promoting disease progression. Further standardized and clinically relevant studies are required to better define EV biology and facilitate the translation of EV-based diagnostic and therapeutic strategies into clinical oral medicine.
Oral pathogens play a significant role in the pathogenesis of Alzheimer's disease (AD) via the oral-brain axis and oral-gut-brain axis. However, how Prevotella intermedia (P. intermedia) affect the development of AD remains unclear. To investigate the effects of P. intermedia infection on neuroinflammation and cognitive function. Sixty C57BL/6 mice were divided into two cohorts and infected with P. intermedia via gingival injection or oral gavage, mimicking pathogen invasion. The microbiota changes of saliva collected from 5 AD patients and 5 healthy individuals were analyzed by 16S rRNA sequencing. Gingival injection resulted in cognitive impairment, neuronal loss in the hippocampal CA1/CA3 regions (p < 0.05), overactivation of microglia and increased expression of proinflammatory cytokines (IL-1β and TNF-α, p < 0.05) and NF-κB in hippocampus (p < 0.05). Similar cognitive impairments and cerebral changes were noted after oral gavaging. Additionally, oral gavage induced gut microbiota dysbiosis, intestinal inflammation and decreased expression of tight junction in intestinal barrier and blood-brain barrier (ZO-1, Occludin, Claudin-1 and Claudin-5, p < 0.05). Furthermore, AD patients exhibited oral microbiota dysbiosis, with a higher relative abundance of P. intermedia (p < 0.05). P. intermedia is associated with cognitive impairment and AD-related neuroinflammation via the oral-brain and oral-gut-brain axes. P. intermedia induces neuroinflammation via the oral‒brain axis, leading to cognitive impairment in mice.P. intermedia induces cognitive impairment and neuroinflammation in mice via the oral–gut–brain axis, which is associated with gut microbiota dysbiosis and disruption of both the intestinal barrier and blood–brain barrier.Patients with AD exhibit alterations in the oral microbiota, with P. intermedia being a key species demonstrating significant differential abundance.
The oral cavity harbours a complex and transcriptionally active antibiotic resistance gene (ARG) reservoir shaped by polymicrobial biofilm ecology. Whether probiotic-mediated ecological modulation can remodel the active resistome without promoting horizontal gene transfer remains poorly understood. To investigate the impact of Streptococcus salivarius K12 (Ssk12) colonisation on active resistome dynamics within saliva derived polymicrobial biofilms and determine whether probiotic driven ecological restructuring transiently alters resistance-associated transcriptional signatures. Saliva-derived polymicrobial biofilms were established on three-dimensional melt electrowritten poly(ε-caprolactone) (MEW-mPCL) scaffolds and exposed to Ssk12. Metatranscriptomic profiling was performed across four time points (Baseline, Day 4, Day 7, and Day 10), complemented by quantitative PCR validation and ARG-mobile genetic element (MGE) co-localisation analysis to characterise resistome restructuring during probiotic colonisation and decolonisation. Baseline biofilms contained 27 ARGs spanning 16 antibiotic classes, predominantly ermB, tet(M), and tet(W). During peak Ssk12 colonisation (Days 4-7), total ARG abundance declined to approximately 17% of baseline levels, with marked reductions in efflux-associated and β-lactam/fluoroquinolone resistance-associated transcripts. Partial resistome recovery occurred by Day 10 (~32% of baseline), indicating reversible ecological modulation rather than permanent dysbiotic restructuring. ARG dynamics were primarily reshaped by ARG-bearing taxa rather than enrichment of high-confidence putatively mobile resistance determinants. S. salivarius K12 transiently remodelled the transcriptionally active oral resistome within structured polymicrobial biofilms without evidence of enhanced putative horizontal resistance gene mobilisation. These findings support a proof-of-concept model in which probiotic driven ecological restructuring may create a transient resistome state potentially associated with altered responsiveness to selected antibiotic classes.
Oral biofilm-derived diseases pose a significant clinical challenge due to their persistent nature and increasing drug resistance, contributing to a substantial global economic burden. Conventional treatments-such as mechanical debridement, antiseptic agents, and laser therapy-though partially effective, often lack specificity, resulting in non-targeted microbial killing and disruption of the ecological balance. This review provides an updated overview of the application of precision antimicrobial therapies against oral biofilms, with a particular focus on pH-responsive materials and bacteriophage-based strategies. A comprehensive literature search was conducted across PubMed and Google Scholar databases from January 2016 to January 2026. A total of 84 full-text articles were included for qualitative synthesis. The collective findings demonstrate that multiple precision-targeting strategies-spanning from bacteriophage therapy to pH-responsive antimicrobial materials-exhibit distinct advantages in combating oral biofilms. The common core principle underpinning these approaches lies in their 'precision-targeting' capability: the ability to identify and interfere with specific targets or biological processes. This attribute not only significantly enhances therapeutic efficacy but also paves the way for developing personalized, microbiome-preserving strategies for the prevention and management of oral diseases.
Diagnosis of oral epithelial dysplasia (OED), particularly grading, is challenging as it shows inter- and intra-observer variability. New technologies to assist pathologists are needed to decrease variability and enhance reproducibility. AI has brought about a new wave of increased precision in oncological pathology. High accuracy and objectivity in OED grading may now be attainable in histopathology because of AI tools such as deep learning. A deep learning model, Densenet121, was developed for automated and reliable grading of OED according to the 2017 WHO classification (mild, moderate, and severe). The dataset comprised 1500 images, and slides were digitised at 4×, 10× and 40× magnification. We developed and trained a classification model. Overall performance of the Densenet 121 model was good, with accuracy above 80% across all magnifications. However, the 10× magnification yielded a good accuracy of 92.7%, precision of 92.8% and recall of 92.5%. For classification into mild, moderate, and severe categories, accuracy reached 91%, with good precision and recall. DenseNet121 achieves high accuracy making it computationally efficient. This model was able to distinguish between normal epithelium and different grades of OED. These findings support the potential role of AI-based tools in reducing variability in grading dysplasia.
Objectives: To evaluate the clinical effectiveness and safety of adjunctive corticosteroid versus standard treatment alone in facial infections. Eligibility criteria: Included clinical comparative studies (randomized or non-randomized) evaluating adjunctive corticosteroids versus standard care in patients with bacterial facial infections such as odontogenic/facial space infections, dental abscesses, orbital cellulitis, periorbital cellulitis, and Ludwig's angina. An unrestricted literature search of five databases was conducted up to December 15, 2025. Risk of bias: The quality assessment of the studies was conducted using the Cochrane Risk of Bias Tool (ROBINS-I) for non-randomized and a new risk of bias tool (RoB-2) for randomized studies. Random effects meta-analyses using mean difference (MD) or standardized mean differences (SMDs) were performed, followed by sensitivity analyses, and assessment of the quality of evidence using GRADE. Included studies: Fifteen comparative studies (three randomized and 12 non-randomized) including 13,905 patients with bacterial facial infections (61.5% male) were included. Low-certainty evidence showed that the use of adjunctive steroids significantly reduced hospital stay compared with standard treatment alone (10 studies; MD = -1.61 [-3.17, -0.05] days; p = 0.04; I2 = 99.3%). Low-certainty evidence also showed that pre-treatment CRP was higher in the steroid groups (3 studies; SMD = 0.33 [0.09, 0.58]; p = 0.03; I2 = 0%). Low-certainty evidence indicated no significant difference in the number of surgeries (p = 0.13), while very low-certainty evidence showed no significant differences in intensive care unit admissions (p = 0.07) or airway compromise (p = 0.18). Sensitivity and subgroup analyses showed no significant differences by study design, infection type, or risk of bias, confirming robust results; only ethnicity had a significant effect on hospital stay (p = 0.0027). Limitations of evidence: Certainty of evidence was low to very low for all outcomes, with hospital stay rated low due to methodological limitations, high risk of bias, and the predominance of non-randomized studies. The low level of evidence suggests that adjunctive corticosteroids may provide a reduction in hospital length of stay for patients with bacterial facial infections. Further well-designed, randomized, and prospective comparative studies are needed to confirm these findings. PROPSERO Registration Number: (CRD420261329331).
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. In 2023, approximately 1·3 billion (95% uncertainty interval [UI] 1·2 to 1·4) individuals were estimated to be living with MASLD (ie, 16·1% of the global population), with an age-standardised prevalence rate of 14 429·3 (95% UI 13 268·3 to 15 990·6) per 100 000 population, representing a percentage increase of 142·7% (95% UI 139·2 to 146·7) in crude numbers from 1990 (0·5 billion [0·5 to 0·6]) and of 28·6% (27·8 to 29·5) in the rate (11 217·2 [10 276·8 to 12 467·0] per 100 000 in 1990). An estimated 3·6 million (2·8 to 4·5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39·6 (31·2 to 49·9) per 100 000 population. Despite a 116·3% (93·3 to 139·4) increase in crude DALYs (from 1·7 million [1·3 to 2·1] in 1990), its age-standardised estimate remained consistent (1·8% [-8·6 to 12·8]) from 1990 (38·9 [30·1 to 49·8] per 100 000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29 246·1 [26 848·3 to 32 048·7] per 100 000) and Andean Latin America showed the highest DALY rate (152·3 [114·1 to 194·7] per 100 000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653·5 [7923·7 to 9592·8] per 100 000) and east Asia had the lowest DALY rate (16·3 [13·5 to 19·9] per 100 000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15 616·4 [14 349·2 to 17 263·3] per 100 000 people in 2023) than in females (13 245·2 [12 132·0 to 14 692·6] per 100 000 people), and peaked at age 80-84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35-39 years for males and age 55-59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2·2 [95% UI 1·6 to 3·1] per 100 000 people), followed by high BMI (1·4 [0·6 to 2·4] per 100 000 people) and smoking (1·0 [0·3 to 1·8] per 100 000 people). Our forecasting model estimates that 1·8 billion (95% UI 1·6 to 2·0) individuals are likely to have MASLD by 2050, representing a 42·0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15 774·9 (95% UI 14 613·9 to 17 336·2) per 100 000 people in 2050, representing an average annual percentage change of 0·3% (95% UI 0·3-0·3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. With a global prevalence of 16·1% and approximately 1·3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Gates Foundation.
The frozen section technique is a vital intraoperative diagnostic tool that enables rapid microscopic assessment of tissues, providing immediate information to guide surgical decision-making, including evaluation of tumor margins, disease extent, and metastatic involvement. Given the high risk of positive surgical margins in oral squamous cell carcinoma (OSCC), achieving margin-negative resection is critical to minimizing recurrence. This systematic review and meta-analysis evaluates the reliability of frozen section analysis in detecting tumor-free margins in OSCC. A comprehensive literature search was performed across PubMed, Scopus, Embase, and Science Direct, yielding 1082 records. After removing duplicates and screening titles, abstracts, and full texts, 19 studies met the criteria for qualitative synthesis. Of these, 9 studies with complete 2 × 2 data were included in the quantitative meta-analysis. Under the random-effects model, frozen section demonstrated a pooled sensitivity of 0.78 (95% CI: 0.55-0.91) and a pooled specificity of 0.98 (95% CI: 0.96-0.99). The common-effect estimates were lower due to the influence of larger studies. The SROC curve from the Reitsma bivariate model showed excellent overall diagnostic performance with an AUC of 0.955, confirming strong discriminative ability in distinguishing positive from negative margins. Frozen section demonstrates high specificity and acceptable sensitivity in detecting margin status in OSCC. The strong overall diagnostic performance supports its value as a reliable intraoperative tool. Incorporating frozen section assessment may improve surgical precision and reduce the risk of residual disease.
Most studies of the oral microbiome during pregnancy have focused on the second and third trimesters (T2, T3, respectively). To date, no large-scale longitudinal study has examined oral microbiome development across all three trimesters, leaving early gestational dynamics largely unexplored. We conducted a longitudinal analysis of 346 pregnant Israeli women, validated in an independent cohort of 154 Russian women. In Israel, saliva samples were collected during T1 (11-14 weeks), T2 (24-28 weeks), and T3 (32-38 weeks); in Russia, samples were collected during T2 and T3 at similar gestational ages. Microbial profiles were analyzed for differential abundance and associations with maternal nutrition and lifestyle. Significant shifts in oral microbial composition were observed as early as the transition from T1 to T2. Alpha diversity decreased progressively across pregnancy. Taxonomic changes included a reduction in Verrucomicrobiota and an increase in Synergistota. Gluten-free diet showed the strongest associations with microbiome composition across all trimesters, followed by smoking history and conception method. This study provides the first large-scale evidence of significant oral microbiome changes beginning in early-mid pregnancy, characterized by reduced diversity and a directional shift toward inflammation-associated communities. Strong associations between gluten consumption and smoking suggest a lifestyle effect on the oral microbiome.
Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy of the oral cavity, frequently preceded by oral potentially malignant disorder (OPMD). Despite therapeutic advances, survival rates remain unsatisfactory, primarily due to late diagnosis, recurrence, and molecular alterations in histologically tumor-free surgical margins. Programmed cell death ligand-1 (PD-L1), an immune checkpoint molecule, contributes to tumor immune evasion and has been implicated in cancer progression. Its expression in OPMDs and OSCC surgical margins may serve as an early indicator of malignant transformation and recurrence risk. This study aims to assess PD-L1 expression in OPMDs and histologically negative surgical margins of OSCC and evaluate their association with 3-year survival outcomes. This retrospective cross-sectional study will be conducted over 12 months at a tertiary care hospital in Sawangi Meghe, Wardha, India. Archived formalin-fixed, paraffin-embedded samples of OPMDs and tumor-free surgical margins from OSCC cases (2018-2020) will be retrieved. Immunohistochemistry for PD-L1 will be performed using the SP263 clone, and expression will be evaluated using the combined positive score. Demographic, clinical, and survival data will be collected from patient records. Statistical analysis will determine correlations among PD-L1 expression, clinicopathological variables, and 3-year survival. The study is expected to provide insights into the role of PD-L1 as a biomarker for early detection, prognostication, and risk stratification in patients with OPMDs and OSCC. Data collection and immunohistochemical analysis have not yet commenced at the time of submission. By evaluating PD-L1 expression in premalignant lesions and histologically negative margins, this study aims to identify molecular predictors of OSCC progression and survival. The findings may help establish PD-L1 as a prognostic biomarker and support its integration into precision oncology and immunotherapy strategies.
Periodontitis is a chronic inflammatory disease driven by oral microbial dysbiosis. Although the oral microbiome has been characterized in diverse populations, comprehensive profiling across periodontal disease stages defined by the 2018 AAP/EFP classification remains limited in Korean adults. In this pilot prospective cross-sectional study, oral microbiome profiles were characterized in 74 participants classified into three groups: healthy controls (n = 24), Stage I-II periodontitis (n = 12), and Stage III-IV periodontitis (n = 38). Mouthwash samples were collected and subjected to 16S rRNA gene sequencing of the V3-V4 hypervariable region. Alpha diversity, beta diversity (PERMANOVA with sequential covariate adjustment for age, sex, and smoking), differential abundance (MaAsLin2), and core microbiome analyses were performed. Stage III-IV periodontitis was associated with significantly higher Shannon diversity, Simpson diversity, and Pielou's evenness compared to both healthy and Stage I-II groups, indicating increased evenness rather than species richness. Beta diversity analyses revealed significant community-level separation across groups after adjustment for demographic confounders (allp = 0.001). Differential abundance analysis identified 14 genera significantly associated with disease status. Twelve genera were enriched in Stage III-IV, including established periodontal pathogens Tannerella and Treponema, as well as emerging pathobionts Filifactor and Fretibacterium. Rothia and Kingella were enriched in periodontal health, consistent with their roles in nitrate reduction and maintenance of a health-compatible oral environment. Core microbiome analysis identified 40 universally present genera, with Anaeroglobus detected exclusively in Stage III-IV at 100% prevalence. These findings support the polymicrobial synergy and dysbiosis model of periodontitis pathogenesis and provide a foundation for developing microbiome-based diagnostic tools for periodontal disease assessment in Korean populations.
This systematic review aimed to assess the association between the oral microbiota and polycystic ovary syndrome (PCOS) and elucidate its potential clinical significance. A comprehensive search of eight databases and other sources from inception to 13 January 2026, identified 10 eligible studies from 310 records, involving 334 PCOS patients and analyzed oral microbiota species and their clinical parameters correlation. Oral microbiota alterations in PCOS women showed consistent and heterogeneous features, with Fusobacterium elevation as the most robust finding. However, the results for Porphyromonas gingivalis and Fusobacterium nucleatum varied with periodontal status. Specific oral microbial changes are correlated with core systemic features of PCOS, including hormonal dysregulation (e.g. elevated testosterone and luteinizing hormone) and metabolic disturbances (e.g. dyslipidemia and insulin resistance). Oral microbiota alterations in PCOS are characterized by consistent Fusobacterium elevation and heterogeneous changes associated with systemic inflammation, metabolic‒endocrine disturbances and poor periodontal health. Despite the limited current evidence, the oral microbiota may serve as a novel entry point for PCOS management. Large, high‑quality prospective studies are warranted to clarify the causal relationship between the oral microbiota and PCOS, and to explore the feasibility of modulating the oral microbiota as a novel therapeutic strategy. Consistent alteration in the oral microbiota of women with PCOS is the elevated abundance of Fusobacterium.Levels of Porphyromonas gingivalis and Fusobacterium nucleatum in women with PCOS vary with periodontal status.Oral microbial changes in women with PCOS are associated with metabolic and endocrine disturbances.
Bronchiectasis (BE) is a chronic respiratory disease characterized by damage to the bronchial wall structure and permanent dilation of the bronchi. The symptoms include a persistent cough, excessive production of purulent sputum, and recurrent hemoptysis. Dysbiosis of the microbiome plays a crucial role in the progression of BE. An increased abundance of pathogenic bacteria, along with viral and fungal infections, is closely associated with disease severity and clinical outcomes. Next-generation sequencing technology has significantly enhanced the sensitivity and resolution of the airway microbiome, providing powerful tools for a more detailed characterization of the microecology of BE. However, certain challenges still exist in clinical applications of this technology. In addition, extra-airway microbiomes, such as the gut and oral microbiome, may participate in airway inflammation and immune regulation through the gut-lung axis and oral-lung axis. In this review, we summarize the characteristics of microbiome dysbiosis in BE and highlight the potential value of related biomarkers in disease classification, severity assessment, and prognosis. We also provide an overview of recent treatment advancements. A deeper understanding of the microbiome's role in BE may facilitate early diagnosis and the optimization of individualized treatment strategies. Microbiome and its role in bronchiectasisThe microbiome refers to the collection of microorganisms, including bacteria, fungi, viruses, and other microbes. A healthy microbiome is essential for overall well-being, as it plays a crucial role in protecting against infections and supporting bodily functions. However, this balance can be disrupted by various diseases. Dysbiosis of the microbiome plays a significant role in the progression of BE, characterized by reduced microbial diversity and increased abundance of pathogenic bacteria. In this review, we summarize how the microbiome interacts with the immune system and influences disease severity. It also highlights emerging biomarkers and new therapies, including DPP-1 inhibitors, inhaled antibiotics, biologics that target specific immune pathways, and innovative approaches like phage therapy. However, research on extra-airway microbiomes is still limited. Furthermore, variations across different regions and populations make it challenging to apply findings universally. A better understanding of the microbiome could lead to more accurate diagnoses, personalized treatments, and ultimately better long-term outcomes for patients.
Oral microbial implications for lung cancer outcomes and association with clinical markers are largely unknown. This work aimed to characterize the oral microbiome in relation to clinical indicators and identify oral microbial biomarkers associated with lung cancer outcomes in patients with non-small cell lung cancer (NSCLC). This is an observational prospective study of saliva samples from patients undergoing curative surgery for NSCLC. Taxonomic and composition profiles were generated using full-length 16S rRNA gene sequencing (n=64). Differences in bacterial diversity and composition with cancer stage, histological subtype, overall survival (OS), and event-free survival (EFS) were examined. Most alpha diversity measures were lower with stage III cancer compared to stage I. All other clinical features were not statistically associated with alpha diversity (P>0.05). The relative abundance of Haemophilus and Solobacterium was detected as significantly differentially abundant in participants with stage III NSCLC by at least 2 differentially abundant tools and an FDR-corrected p-value<0.1. This study shows a significant association between cancer stage with oral bacterial diversity and the relative abundance of specific genera in relation to OS in participants with resectable NSCLC. This study is limited by sample size and needs to be confirmed in larger studies.
This study investigated socioeconomic, psychosocial, behavioral, and clinical factors directly and indirectly associated with subjective happiness among recruits from southern Brazil. This cross-sectional study included a sample of recruits performing mandatory military service at two military bases in southern Brazil. Questionnaires were administered to collect socioeconomic data (mother's education, family income, and participant education level), behavioral habits (toothbrushing frequency and flossing), and psychosocial variables, such as sense of coherence (SoC-13 scale), oral health-related quality of life (OHRQoL), assessed using the Oral Health Impact Profile (OHIP-14), and degree of happiness (Subjective Happiness Scale). A clinical dental examination was performed by a single trained and calibrated examiner to determine the gingival bleeding index and dental caries experience (DMFT, number of decayed, missing due to caries, or filled permanent teeth). Pathway analysis was conducted to test the direct and indirect paths linking socioeconomic, psychosocial, behavioral, and clinical factors to happiness (Stata software). Results are presented as beta coefficients (β) and p values. A total of 499 recruits aged 18-19 years were evaluated. High levels of SoC were directly associated with greater happiness (β = 0.49, p < 0.001), whereas higher OHIP-14 scores, indicating poorer OHRQoL, were directly associated with lower happiness (β = -0.09, p < 0.05). Untreated dental caries was indirectly associated with lower happiness (β = -0.03, p < 0.05) via OHRQoL. No significant paths were observed from socioeconomic or behavioral variables to happiness. In conclusion, psychosocial and clinical factors were associated with happiness levels among Brazilian Army recruits.
Periodontitis (PD) is a chronic infectious disease driven by bacterial biofilms, yet the oral virome's role in pathogenesis remains poorly understood. This cross-cohort meta-analysis aims to define PD-associated viral signatures, characterize predicted virus-host interactions, and evaluate the diagnostic potential of viral biomarkers. We integrated 89 saliva (44 PD, 45 healthy) and 86 subgingival plaque (48 PD, 38 healthy) metagenomes from six public cohorts for a unified virome analysis. We identified 156 viral operational taxonomic units (vOTUs) significantly associated with PD (105 in saliva, 66 in subgingival plaque and 15 shared). PD-enriched vOTUs were predicted to target periodontal pathogens including Porphyromonas gingivalis, whereas Streptococcus-targeting phages were decreased. PD-associated vOTUs harbored diverse bacterial defense and anti-defense systems, with those enriched in PD overrepresenting lysozyme and replication-associated genes. Diagnostic models based on key viral markers achieved robust performance, with AUCs of 0.95 (saliva) and 0.92 (subgingival plaque) for classifying PD. This study delineates a distinct oral virome profile in PD, highlights predicted virus-host interactions, and underscores the potential of viral biomarkers for PD diagnosis,providing a basis for future investigations into viral ecology and phage-based interventions. The oral virome undergoes a significant and consistent shift in periodontitis, characterized by the increase of bacteriophages targeting periodontal pathogens and the reduction of others. The PD-associated oral vOTUs are predominantly temperate and harbor a diverse arsenal of defense and anti-defense systems, with the subset enriched in disease exhibiting significant overrepresentation of lysozyme and a parallel trend for DNA replication-associated genes, suggesting a complex interplay with bacterial hosts in the periodontal niche. Viral biomarkers demonstrate promising preliminary potential as non-invasive diagnostic aids for periodontitis.