Journal of Oral Microbiology最新文献

Background: Porphyromonas gingivalis, a keystone oral pathogen, secretes the enzyme peptidylarginine deiminase (PPAD), which catalyzes protein citrullination and is implicated in both dental biofilm formation and the pathogenesis of systemic inflammatory diseases.

Objective: This review aims to synthesize current knowledge on PPAD, with a specific focus on its mechanistic roles in oral biofilm dynamics and its potential contribution to the development of periodontitis and rheumatoid arthritis (RA).

Design: A comprehensive literature search was conducted using the PubMed database up to August 2025, employing keywords including 'PPAD', 'Porphyromonas gingivalis', 'citrullination', 'dental biofilm', 'periodontitis', and 'rheumatoid arthritis'.

Results: PPAD contributes critically to biofilm pathogenicity by modulating microbial pH, citrullinating virulence factors, and facilitating polymicrobial interactions. It promotes bacterial adhesion, disrupts host immunity, and sustains local inflammation. Systemically, PPAD-generated citrullinated antigens may trigger autoimmune responses, potentially linking periodontitis to RA.

Conclusion: PPAD represents a promising biomarker and therapeutic target for mitigating oral-systemic disease progression. Future research should prioritize elucidating its spatiotemporal regulation within biofilms and its immune-dysregulating effects to guide precision interventions.

Background: Periodontitisis a chronic inflammatory disease of the oral cavity, primarily driven by periodontopathogens such as Porphyromonas gingivalis (Pg)."

Objective: We investigated the therapeutic potential of BTK and SYK inhibitors on the pathological processes induced by two Pg strains, ATCC 33277 and W83, in human monocyte-derived macrophages (hMDMs) and human gingival fibroblasts (hGFs).

Design: hMDM and hGF were infected with Pg strains and assessed for viability, inflammatory activation, and phenotype, with or without the BTK inhibitor ibrutinib or SYK inhibitor R406, under acute and chronic infection conditions.

Results: Ibrutinib and R406 suppressed Pg infection-induced activation of the NLRP3-dependent pyroptosis pathway and IL-1β secretion in hMDMs. Both compounds also significantly reduced IL-6, IL-8, and TNFα release by hMDM in both infection models, regardless of differences between ATCC 33277 and W83 Pg strains. Ibrutinib and R406 potently suppressed inflammatory activation of hGFs, including IL-6 and IL-8 production, and NF-κB p65 phosphorylation triggered by the more immunostimulatory ATCC 33277 strain.

Conclusions: The pharmacological inhibition of BTK or SYK mitigates the pyroptotic pathway in hMDMs and exerts a broad anti-inflammatory effect in both hMDMs and hGFs. These results highlight the anti-inflammatory potential of BTK and SYK inhibitors for the treatment of periodontal disease.

Objectives: Polypharmacy has been linked to alterations in gut microbiota, but its effects on the oral microbiome remain underexplored. This study aimed to examine the association of polypharmacy and anticholinergic burden with oral microbiome diversity and composition.

Methods: We conducted a cross-sectional analysis using data from NHANES 2009-2012, including participants aged 55-69 years who reported at least one prescription medication. Polypharmacy was defined as the concurrent use of five or more medications. Anticholinergic burden was quantified by the Anticholinergic Cognitive Burden scale and the Anticholinergic Drug Scale. Oral microbiome profiling comprised alpha diversity, beta diversity, and taxonomic composition at multiple phylogenetic levels. Associations were analyzed via weighted multivariable linear regression, principal coordinate analysis (PCoA), and multivariate analysis of variance.

Results: Among 1,596 participants, 29.2% reported polypharmacy, which correlated with higher anticholinergic burden. Both polypharmacy and anticholinergic burden were inversely associated with alpha diversity across multiple measures. Taxonomic analyses showed heterogeneous associations, with Porphyromonadaceae negatively linked to both exposures. PCoA indicated significant differences in community structure by polypharmacy status (Bray-Curtis: R² = 0.35%, P < .001).

Conclusions: Among middle-aged and older U.S. adults, both polypharmacy and anticholinergic burden were inversely associated with oral microbiome diversity and linked to distinct microbiome composition.

Objectives: To investigate whether systemic inflammation mediates the relationship between oral microbiome alterations and oral squamous cell carcinoma (OSCC) through multi-omics integration analyses.

Methods: Metagenomic sequencing of unstimulated saliva samples from 65 OSCC patients and 65 matched controls was performed. Plasma levels of 34 inflammatory cytokines were profiled using Luminex assay. Six machine learning models identified potential diagnostic microbial markers. Mediation analysis assessed whether inflammation serves as a mechanistic link between oral microbiota and OSCC.

Results: OSCC patients exhibited reduced species richness and significant beta diversity alterations. Among 155 differential species identified, 25 were enriched in OSCC, including Capnocytophaga sputigena, Gemella haemolysans, Staphylococcus aureus, and several Streptococcus species, with higher abundance in poor oral hygiene conditions. The Boruta-CatBoost model achieved exceptional diagnostic performance (bootstrap AUC = 0.991; 5-fold cross-validation AUC = 0.947). Functional profiling revealed 22 metabolic pathways over-represented in OSCC, notably lipopolysaccharide biosynthesis. Nine circulating cytokines (IL-22, IL-6, IL-2, CCL5, GM-CSF, IL-1β, TNF-α, IL-18, IFN-α) were significantly elevated in OSCC patients. Mediation analysis revealed that IL-22 partially mediated the effect of Staphylococcus aureus on OSCC risk, while CCL5 mediated associations of Gemella haemolysans and Streptococcus species with OSCC (mediation proportions: 29.9-50.1%).

Conclusion: Our multi-omics integration suggests that systemic inflammation, particularly through IL-22 and CCL5 upregulation, serves as a mechanistic link between specific oral bacteria and OSCC risk, which could provide new strategies for OSCC prevention and early intervention.

Background: Mucin degradation is essential for understanding oral microbial adaptation, yet the enzymes involved remain incompletely understood. Herein, we have characterised two mucin-degrading proteases, MdpS and MdpS2, from the oral commensal Streptococcus oralis.

Materials and methods: MdpS2 was characterised using physicochemical assays and substrate profiling and was compared to MdpS. Further Mdp characterisation included structural modelling, and functional assays analysing the gene expression during biofilm growth on salivary MUC5B, enzyme-induced biofilm dispersal, and mucus degradation analysed through nanoLC-MS/MS, sedimentation profiling, and microrheology.

Results: MdpS2 shared conformational homology with MdpS despite low sequence identity and showed greater tolerance to pH and sodium chloride. Both genes were significantly upregulated during late stationary biofilm phase. MdpS and MdpS2 hydrolysed MUC5B extensively, with overlapping but distinct hydrolysis patterns. MdpS2 promoted biofilm dispersal and caused a pronounced reduction in MUC5B size and compactness. Microrheology showed selective modulation of MUC5B-rich mucus by MdpS2, while MdpS affected both MUC5B and MUC5AC networks.

Conclusions: MdpS and MdpS2 exhibit complementary biochemical and functional profiles, supporting their roles in mucin degradation and biofilm remodelling. These findings advance our understanding of how early colonizing streptococci may interact with mucosal surfaces, influence biofilm dynamics and oral ecology, and suggest potential applications in targeting mucus-related disorders.

Background: Oral microbes modulate the gut microbiota. Haemophilus parainfluenzae, a core human oral commensal with immunomodulatory properties, is reduced in autoimmune diseases, while mitigating Sjögren's syndrome-like disease with improved oral microbiota in female NOD mice. However, whether it modulates the gut microbiota remains unknown.

Objective: To study the modulatory effect of oral H. parainfluenzae inoculation on the gut microbiota.

Design: Female NOD mice were orally inoculated with H. parainfluenzae following antibiotic treatment. Fecal samples were collected pre- and post-inoculation for 16S rRNA gene sequencing. Splenic antigen-presenting cells were analyzed for systemic immunomodulation.

Results: Despite prominent convergence of diversity and beta dissimilarity within each group, H. parainfluenzae led to distinct core microbiota and overall microbial community. While reducing the Firmicutes-to-Bacteroidetes ratio, H. parainfluenzae enriched Bacteroidaceae and its genus Bacteroides. Bacteroides acidifaciens, a beneficial gut commensal, was enriched in ASV-level analyses. The splenic dendritic cells were reduced. Notably, neither did H. parainfluenzae establish ectopic gut colonization, nor was sustained oral colonization required, indicating that non-viable microbes may be sufficient to direct these responses.

Conclusions: H. parainfluenzae drives a distinct gut microbiota reconstitution trajectory, characterized by B. acidifaciens enrichment without establishing notable colonizations, supporting its role in the oral-gut axis and warranting future postbiotic research.

Background: Oral squamous cell carcinoma (OSCC) represents more than 90% of all oral cancers. Among the known risk factors, periodontal diseases are a significant contributor to OSCC development. The balance between the various components of the oral microbial community contributes to oral and systemic health, while an altered balance leads to dysbiosis, with an excessive growth of pathogens. The OSCC microbiota is characterized by increased expression of genes related to bacterial chemotaxis, flagellar assembly, lipopolysaccharide biosynthesis and the metabolism of cofactors and vitamins.

Objective: The production of carcinogens, induction of an immune-mediated inflammatory response or immune suppression, cell proliferation and anti-apoptotic activity represent the mechanisms of oral microbe-mediated carcinogenesis. Interventions aimed at modifying the oral microbiota for inhibiting the development of OSCC should be performed; polyphenols and probiotics have demonstrated promising opportunities in cancer models and patients.

Design: We performed an extensive search on the link between OSCC and the oral microbiota accessing the main scientific databases.

Results: The aim of the present review is to describe the role of the oral microbiota in health and disease, including OSCC development, and its relationship with oral bacteria. Emphasis should also be placed on antibiotics, which may represent an additional risk factor for oral cancers. Interventions with natural products will be illustrated.

Conclusions: Current literature show a clear role of the oral microbiota in determining and control the evolution of OSCC. Specific interventions on the oral microbiota will help the prevention and management of OSCC in the next future.

Background: This systematic review and meta-analysis aim to assess the diagnostic accuracy of the oral microbiome in detecting pancreatic cancer.

Methods: A comprehensive search of relevant studies was conducted using key terms across multiple databases. The methodological quality of the included studies was assessed using the Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2). Diagnostic accuracy metrics were calculated including specificity, sensitivity, likelihood ratios, and diagnostic odds ratio (DOR). Subgroup analyses were performed to explore the effects of oral sample collection methods, bacterial taxonomy, and oral microbiome classifications.

Results: This systematic review included nine studies, comprising 188 study units with 6601 subjects The pooled specificity, sensitivity, and diagnostic odds ratio (DOR) for the use of a single oral microbiome were 0.70 (95% CI: 0.68-0.71), 0.65 (95% CI: 0.64-0.67), and 4.85 (95% CI: 4.11-5.74), respectively. Subgroup meta-analysis revealed that using multiple oral microbiome approaches could increase the DOR to 16.33. Subgroup analysis was performed based on bacterial phylum classification, multiple oral microbiomes, sampling methods, bacterial taxonomy, and subgenus-level taxonomy (g_Streptococcus and g_Prevotella).

Conclusions: Oral microbiome holds promise as a diagnostic biomarker for pancreatic cancer, supporting its potential as a noninvasive tool for the screening and early detection of this malignancy.

Background: Oropharyngeal candidiasis (OPC) is a prevalent fungal infection primarily caused by Candida species, notably Candida albicans, posing significant health challenges. Traditional Chinese medicine (TCM) has gained attention due to its multifaceted pharmacological properties and lower incidence of adverse effects compared to conventional treatments.

Objective: This article aims to explore the application of TCM in OPC therapy and elucidate the potential molecular mechanisms underlying its efficacy.

Design: A comprehensive analysis of relevant studies and research findings was conducted to investigate the bioactive components of TCM and their mechanisms of action.

Results: The analysis reveals that TCM exerts beneficial effects through inhibition of fungal growth, regulation of immune responses, and enhancement of oral microecological balance.

Conclusions: TCM offers a holistic approach to managing OPC, leveraging its multifaceted mechanisms to address this common yet troublesome infection effectively.

Background: COVID-19 has been strongly associated with alterations in the oropharyngeal microbiota, yet the microbial features linked to disease severity remain unclear.

Objective: This study aimed to elucidate the microbial signatures associated with COVID-19 disease severity.

Design: 16S rRNA gene sequencing was employed to profile the oropharyngeal microbiota of patients with varying degrees of COVID-19 severity.

Results: A significant reduction in alpha diversity suggests a major microbial dysbiosis in critically ill patients compared to less severe cases and healthy individuals, whereas beta diversity analysis revealed a broadly conserved community structure across different groups. Comparative analysis showed significant depletion of the phylum Fusobacteriota and enrichment of bacterial families, including Corynebacteriaceae, Methylobacteriaceae, Acetobacteraceae, Bradyrhizobiaceae, Lactobacillaceae, Staphylococcaceae, Propionibacteriaceae, and Moraxellaceae. Rothia mucilaginosa was notably enriched in patients with severe respiratory symptoms, and many of the enriched taxa are known opportunistic pathogens associated with respiratory infections.

Conclusion: The marked dysbiosis and enrichment of opportunistic pathogens in the oropharyngeal microbiota of critically ill patients indicate their possible role in respiratory complications. The identified microbial patterns highlight the potential of microbiome profiling as a tool for disease prognosis and guide further research into the role of microbes in COVID-19 pathogenesis and implications for treatment protocols.