Background Enterococcus faecalis (E. faecalis) contributes to persistent endodontic infections through biofilm formation, dentinal tubule invasion, and alkaline resistance, which limits the efficacy of calcium hydroxide. Metformin (Met) attenuates this resistance by interfering with bacterial metabolic adaptation. Combining Met with mesoporous calcium silicate nanoparticles (MCSNs), which possess intrinsic alkaline antibacterial activity and sustained drug-delivery capabilities, may enhance the elimination of alkaline-resistant E. faecalis and promote periapical healing.Methods Metformin-loaded MCSNs (MCSNs-Met) were characterized for physicochemical properties, Met release, alkalinity, cytocompatibility, and dentinal tubule penetration. Antibiofilm activity against highly alkaline-resistant E. faecalis was assessed using infected dentin models. Therapeutic efficacy was further evaluated in a beagle model of E. faecalis-induced apical periodontitis using Micro-CT and histological analyses.Results MCSNs-Met exhibited a uniform mesoporous structure, sustained Met release and alkalinity, favorable cytocompatibility, and enhanced dentinal tubule penetration. Compared with MCSNs alone, MCSNs-Met more effectively disrupted E. faecalis biofilms and reduced viable bacterial signals. In vivo, MCSNs-Met produced the greatest reduction in periapical bone resorption, markedly decreased residual bacterial signals and inflammatory infiltration, reduced osteoclast activity, and enhanced collagen deposition and periapical tissue repair.Conclusions MCSNs-Met integrates sustained Met delivery with the intrinsic alkaline and bioactive properties of calcium silicate nanoparticles, thereby enhancing control of highly alkaline-resistant E. faecalis and promoting periapical healing.
Background Co-infection with Staphylococcus aureus and Candida albicans represents a prevalent, clinically important polymicrobial challenge that can be associated with worse outcomes than monomicrobial infection. Emerging evidence indicates that their synergistic pathogenicity is shaped by quorum sensing (QS) related and other cross-kingdom interactions.Objective To summarize current evidence on cross-kingdom interactions involving the S. aureus agr quorum-sensing system and the C. albicans farnesol signalling pathway and their contributions to polymicrobial pathogenicity.Design This narrative review synthesizes current evidence on QS-related, metabolic, environmental, structural, and host-mediated mechanisms underlying S. aureus - C. albicans interactions.Results Extracellular pH regulation, ribose metabolism, mixed-biofilm architecture, and farnesol-induced stress adaptation modulate bacterial virulence and antimicrobial tolerance. Furthermore, microbial signalling and host innate immune responses interact bidirectionally to shape infection outcomes. Importantly, direct recognition of a C. albicans-derived quorum-sensing molecule by a defined S. aureus QS receptor has not yet been demonstrated.Conclusions QS-targeted and anti-adhesion/anti-virulence strategies may offer therapeutic opportunities, but their efficacy requires further validation in host-relevant oral and systemic infection models.
Background Craniofacial microsomia (CFM) is the second most common congenital craniofacial anomaly. Oral dysbiosis has been described at genus level, but whether it extends beyond the mouth, or relates to the defining alveolar bone deficiency, is unknown.Patients/materials and methods Oral and gut microbiomes of 45 children with CFM and 18 matched controls were profiled at species level by 2bRAD-M, alongside shotgun metagenomes and blood, faecal and oral metabolomes. Alveolar bone loss was quantified on computed tomography against each patient's contralateral side. Centred-log-ratio methods with Benjamini-Hochberg false-discovery-rate (FDR) control were used throughout. Compartment specificity was tested formally by a group-by-compartment interaction model in the 58 participants with paired oral and gut profiles, by sample-size-matched subsampling, and by minimum-detectable-effect calculation.Results Oral alpha diversity was higher in CFM than in controls (Shannon P = 0.014; all three alpha-diversity indices P < 0.05). Four species-level taxa were depleted after false-discovery-rate (FDR) correction (q < 0.05), and 21 interpretable metagenomic pathways differed between groups among 38 FDR-significant pathways. These annotations were enriched for carbohydrate transport, glycan processing and cell-surface or biofilm-related functions, but they are not specific markers of a cariogenic or pathogenic community. No FDR-robust gut or systemic signature was detected. At the species level, the oral and gut analyses were power-matched (minimum detectable |r| = 0.74 at the FDR-equivalent threshold), and the group-by-compartment interaction for Shannon diversity was significant (P = 0.026). This comparison supports an oral-predominant taxonomic pattern but does not establish biological absence of a gut effect. The functional comparison was not power-matched. In the patient-only post hoc analyses, the oral functional pattern was not associated with tooth-brushing frequency, sugary-drink intake or caries burden. Affected-side alveolar bone density was lower than contralateral density (paired P < 0.001) and was not associated with anatomical severity grade.Conclusions CFM was associated with an oral-predominant taxonomic and functional microbiome pattern. The matched-power comparison is informative for taxonomic analyses but does not exclude a biologically meaningful gut effect, and the functional comparison remains underpowered. These observations motivate prospective investigation of local, biofilm-directed interventions and of quantitative alveolar bone assessment as a follow-up endpoint.
Background and Objective Microplastics are widespread environmental contaminants that can enter the body through ingestion. This exploratory study aimed to evaluate whether repeated exposure to polystyrene microplastics (PS-MPs) is associated with alterations in the oral microbial community and gingival metabolome in mice.Design C57BL/6 mice were randomly assigned to receive PS-MPs by daily gavage at 0, 5, 10, or 20 mg/kg body weight for 30 days. Oral microbial communities were characterized by 16S rRNA gene sequencing, and gingival metabolic features were profiled using untargeted liquid chromatography-mass spectrometry. Microbiome and metabolomics data were integrated using correlation-based network analysis.Results PS-MPs exposure, particularly at 10 and 20 mg/kg, was associated with reduced observed oral microbial richness and differences in microbial community composition relative to the control group. Beneficial commensal genera such as Gemella and Lactobacillus were depleted, while opportunistic pathogens including Streptococcus and Rodentibacter were relatively enriched. Metabolomic profiling revealed 206 and 270 differential metabolites in the medium- and high-dose groups versus controls, respectively. KEGG pathway enrichment identified nucleotide metabolism, unsaturated fatty acid biosynthesis, and pantothenate/CoA biosynthesis as candidate pathways. In an exploratory integrated network analysis, the microbial dysbiosis index was highest in the high-dose group, and Gemella and catechin-centred metabolite were among the most connected nodes.Conclusions These findings provide exploratory multi-omics evidence that repeated PS-MPs exposure is associated with changes in oral microbial ecology and gingival metabolic profiles in mice. Larger studies integrating direct periodontal outcomes and mechanistic validation are warranted.
Background Oral mycobiome in children and young adults with type 1 diabetes (T1D) remains poorly characterized.Objective We investigated oral fungal community structure and its associations with bacterial communities and immune mediators in individuals with established T1D compared with healthy controls (HC).Design Oral fungal and bacterial communities were characterized in 68 participants with T1D and 69 HC by ITS and 16S rRNA gene sequencing, alongside multiplex assessment of soluble immune factors. Sequencing data were processed with QIIME 2, immune factors with BioPlex Manager and statistical analyzes with R v.4.3.3.Results Fungal alpha and beta diversity did not differ significantly between groups. However, several taxa were differentially abundant or prevalent in T1D, including Fusarium, Hanseniaspora, Meyerozyma, Cyberlindnera jadinii, Candida albicans, C. dubliniensis and Malassezia globosa. No significant differences emerged by HbA1c category (<7% vs. ≥7%) within T1D. Notably, Cystobasidium/C. slooffiae and Trichoderma, detected exclusively in T1D, showed stronger positive associations with MCP-1/MCAF and IP-10, respectively, than in HC, while several fungal genera were inversely associated with distinct bacterial taxa.Conclusions These findings indicate that T1D is associated with selective, taxon-specific oral mycobiome alterations rather than generalized dysbiosis. The observed fungal-immune and fungal-–bacterial links suggest biological relevance, warranting longitudinal and functional investigation.
