Journal of Oral Microbiology最新文献

Background: The targeted manipulation of the microbiome using bacteriophages represents a novel approach for addressing antibiotic resistance and polymicrobial diseases.

Objective: To isolate and characterise bacteriophages for key bacteria associated with pathogenic periodontal biofilms.

Design: Using standard microbiological and bioinformatics techniques, this study isolated and characterized lytic (FNU2 and FNU3) and temperate (FNU4) bacteriophages specific to Fusobacterium nucleatum, a key bacterium in oral biofilms linked to periodontitis and a range of cancers.

Results: Morphological and genomic analyses revealed distinct features, with FNU2 and FNU3 classified as Latrobevirus and FNU4 as an unclassified Caudoviricetes. Comparative bioinformatic analysis revealed various defence and anti-defence systems in bacterial hosts and bacteriophages, highlighting complex interactions. Functional assays demonstrated the efficacy of these bacteriophages in disrupting single-species F. nucleatum biofilms and dual-species biofilms of F. nucleatum and Porphyromonas gingivalis.

Conclusion: These findings highlight the potential of F. nucleatum-specific bacteriophages as precise tools for microbiome modulation in chronic diseases such as periodontitis and cancer.

Proper tooth alignment is important for oral and periodontal health, allowing better hygiene and reducing plaque build-up. While traditional braces are effective, clear aligners offer an aesthetic advantage and are also thought to promote better oral hygiene. However, their specific impact on the oral microbiome is not yet fully understood. This longitudinal study used 16S amplicon sequencing to study the oral microbiome (from saliva, subgingival, and supragingival samples) of 11 patients undergoing clear aligner treatment. Samples were collected at three time points: before treatment and at 3 and 6 months during therapy. Our results revealed large differences between the microbiomes of different oral sites but no significant overall changes in the oral microbiome composition due to orthodontic treatment. While some species-specific changes were observed, their effect sizes were very small. Although these results should be confirmed in a larger and more diverse cohort, they suggest that the treatment had a small or negligible impact. Given the observed stability of the oral microbiome in all three studied niches throughout the treatment and the known benefits to oral hygiene, clear aligners may present a favorable therapeutic alternative compared to fixed appliances.

Background: Porphyromonas gingivalis (P. gingivalis) is one of the few bacteria that can produce sphingolipids (SLs). Bacterial SLs have been shown to modulate the host immune response.

Objective: Since neutrophil activation is critical for the pathogenesis of periodontal disease, we hypothesized that SL synthesis by P. gingivalis is important for neutrophil function.

Design: We treated primary human neutrophils with P. gingivalis strains W83 that either produce SL (W83) or lack expression (W83 ΔSPT). We compared the phagocytosis capacity and toll-like receptor 2 (TLR2), TLR4, the adhesion molecule CD62L, and sphingosine 1 phosphate receptor 1 (S1PR1) expressions of the neutrophils. We evaluated the migration speed of neutrophils using microfluidic and transwell systems. We quantified their superoxide formation, measured neutrophil extracellular trap (NET), and inflammatory mediator release.

Results: When P. gingivalis cannot synthesize SLs, this promotes early neutrophil recruitment, higher levels of phagocytosis, and a decrease in bacterial survival. P. gingivalis can stimulate TLR2 expression, prevent S1PR1 expression, and suppress the production of inflammatory mediators in the presence of SL expression.

Conclusions: Our data suggest that SL synthesis is an efficient immune evasion mechanism of P. gingivalis, which dampens the inflammatory response of neutrophils to this endogenous pathogen.

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.