Background Periodontitis is a chronic inflammatory disease affecting more than 50% of the global population, resulting in irreversible gum damage, alveolar bone loss and ultimately tooth loss. Periodontitis arises from stable, multi-species biofilms whose pathogenicity is driven by emergent ecological interactions persistent to antimicrobial perturbations. Fusobacterium spp. are considered key microbial components that provide scaffolding for this ecological niche, which includes the pathobionts Tannerella forsythia, Prevotella intermedia and Porphyromonas gingivalis.Objectives To examined how oral microbial interactions shape periodontal biofilms and whether selectively targeting Fusobacterium polymorphum by bacteriophages can disrupt this pathogenic community structure.Materials and methods In vitro biofilms were established using (i) F. polymorphum, T. forsythia and P. intermedia on their own, (ii) T. forsythia and P. intermedia in dual-species biofilms with F. polymorphum and (iii) four-species complex biofilms involving F. polymorphum, T. forsythia, P. intermedia and P. gingivalis. The biofilms were then exposed to the F. polymorphum-specific bacteriophage FNU1 to assess the ecological impact of targeted viral predation on a single member of the biofilm community. Biofilm formation, spatial organisation and microbial interactions were visualised by confocal laser scanning microscopy using CellTrace™ proliferation assays and live-dead staining. Community biofilm biomass was quantified using 0.1% crystal violet staining.Results Multi-species biofilms displayed enhanced biomass and increased cell density relative to simpler communities. Disruption of F. polymorphum by bacteriophage FNU1 led to significant reductions in total biofilm biomass and altered cell density in the single-species F. polymorphum biofilm as well as dual- and four-species complex biofilms.Conclusion Our findings support a role for F. polymorphum-specific bacteriophages in destabilising complex biofilms of periodontal pathobionts. They highlight the importance of F. polymorphum in community dynamics in microbial biofilms and that its precision targeting results in ecological perturbation with the potential to reverse dysbiosis in chronic inflammation in periodontitis.
Background Cross-infection may occur if alginate impressions are not disinfected. Available chlorine (AC), though common, poses safety risks. Chlorogenic acid (CA), a natural compound, shows effective disinfection and, as we previously verified, inhibits pathogens without damaging impressions.Objective This study investigates the influence of CA and AC on the oral microbial community of alginate impressions from a community-ecology perspective.Methods The maxillary impressions of 60 participants were randomly assigned to four groups (n = 15). The NS-AC group received a normal saline (NS) rinse and a 2,000 mg/L AC spray. The NS-CA group got an NS rinse and a CA (10 mg/mL mix + 60 mg/mL spray). The CA-AC group obtained a 10 mg/mL CA rinse and a 2,000 mg/L AC spray. The CA-CA group acquired a CA (10 mg/mL rinse & mix + 60 mg/mL spray). An analysis of 16S rRNA sequencing was conducted on the samples that were collected.Results The NS-CA group exhibited substantially higher Chao1, Shannon and Simpson indices than the NS-AC group (p < 0.05), and the PCoA revealed a centralized clustering pattern. As the primary biomarkers in the NS-CA, Neisseria, Porphyromonas and Prevotella were identified through LEfSe analysis and a random forest model (LDA > 4, AUC = 0.911). A synchronous decrease in the NS-CA was predicted by FAPROTAX functional prediction in relation to aromatic_compound_degradation and human_pathogens_all. The NS-CA and CA-CA did not exhibit any significant differences in alpha diversity or FAPROTAX (p > 0.05), and the PCoA showed that the two groups were closely clustered.Conclusion The stabilization and maturation of oral microbiota on the surface of alginate impressions are facilitated by CA disinfection. Of all the groups, the NS-CA group demonstrates specific cost-effectiveness advantages and has the potential to serve as an alternative to conventional AC disinfection.
Background:Oral squamous cell carcinoma accounts for over 90% of oral neoplasms. Despite therapeutic advances, the lack of reliable, non-invasive biomarkers and delayed diagnosis continues to impede effective clinical management. By combining paired lesion and non-lesion sampling with predictive metagenomics analysis, our study addresses this gap and advances the current understanding of microbiome‒tumor interactions. Methods:We analyzed 92 buccal swab samples from 39 OSCC patients and 14 healthy controls using 16S rRNA gene (V3-V4) sequencing. Taxonomic profiling was conducted using QIIME2 and SILVA/eHOMD databases, functional pathways were predicted using PICRUSt2, and hub taxa were identified through co-abundance network analysis. Results:Microbial community structure differed significantly across lesion, non-lesion, and healthy sites (PERMANOVA, p = 0.001). Lesions were enriched with Selenomonas infelix and Treponema vincentii, while healthy controls harbored Streptococcus oralis and Gemella haemolysans. Co-abundance network analysis revealed lesion-specific hub species, notably T. vincentii, strongly correlated with predicted activation of pyrimidine biosynthesis pathways (r = 0.69, q < 1E-6), suggesting predicted metabolic alterations in the tumor microenvironment. Non-lesion sites were also characterized by two hub species, Prevotella melaninogenica and Segatella oulorum. Conclusion:Our findings define a lesion-specific microbial signature of OSCC characterized by the depletion of health-associated taxa, enrichment of pro-inflammatory pathobionts, and predicted associations with metabolic pathways implicated in carcinogenesis. These alterations reflect a predicted functionally altered tumor microenvironment.
Objective:To investigate the bidirectional causal associations between genetically predicted oral microbial taxa and allergic rhinitis (AR) in East Asian populations. Methods:We used summary-level genome-wide association study (GWAS) data from East Asian populations to conduct a bidirectional two-sample Mendelian randomization (MR) analysis. The inverse-variance weighted (IVW) method was the primary method. Bayesian weighted Mendelian randomization (BWMR) was used to assess the robustness of taxa that remained significant after IVW-based FDR correction. Cochran's Q test, the MR-Egger intercept test, and MR-PRESSO were used to assess heterogeneity and horizontal pleiotropy. Results:In the forward MR analysis, 16 tongue dorsum and 22 salivary microbial taxa were associated with AR risk. BWMR supported associations for 15 tongue dorsum and 17 salivary taxa, with effect directions generally consistent with those obtained using IVW. Representative associations included a positive association between genetically predicted salivary Campylobacter_A_mgs_1095 abundance and AR risk (OR = 1.381), and an inverse association between tongue dorsum Streptococcus_mgs_1057 abundance and AR risk (OR = 0.767).Sensitivity analyses indicated no substantial heterogeneity or horizontal pleiotropy for most taxa. Conclusions:Genetically predicted abundances of several tongue dorsum and salivary microbial taxa were associated with AR risk in East Asian GWAS datasets.These findings require validation in larger independent cohorts and experimental studies.
Backgroud Dental fluorosis is a prevalent endemic condition, yet its impact on the oral microbiota structure and resistance in children remains understudied.Objective To assess the microbial composition, diversity, functional pathways and co-occurrence patterns among urinary fluoride (UF), bacterial taxa and antibiotic resistance genes in relation to fluorosis severity. Design: Metagenomic analysis of dental plaque was conducted on 96 school-aged children, who were grouped into normal, dubious, very mild, mild, moderate and severe base on fluorosis severity.Results Microbial diversity increased with fluorosis severity. Actinomyces sp. HMT 175, Actinomyces oris and Corynebacterium matruchotii, Fusobacterium nucleatum and Rothia dentocariosa were significantly enriched in the moderate and severe groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed a reduced relative abundance of genes involved in carbohydrate metabolism and genetic information processing in moderate and severe groups. Network analysis revealed positive correlations among Actinomyces sp. HMT 175, UF levels and GRD33_1 (a carbapenem resistance gene).Conclusions These findings highlight severity-dependent shifts in the oral microbiota and resistance, warranting further investigation into fluoride's public health implications.
Background:Prior studies have linked oral microbial diversity to separate cardiometabolic endpoints, yet none have applied the cardiovascular-kidney-metabolic (CKM) framework. Objective:This study aimed to evaluate the association between oral microbiome α-diversity and advanced CKM, mortality, and potential mediators. Design:We analyzed 6,044 adults (≥30 years) from NHANES 2009-2012. 402 all-cause deaths (144 CVD deaths) were recorded. Four α-diversity metrics (observed amplicon sequence variants (ASVs), Faith's PD, Shannon-Weiner index, Simpson index) from 16S rRNA sequencing of oral rinse samples were used to assess associations with advanced CKM (logistic regression) and all-cause/CVD mortality (Cox regression). Restricted cubic splines (RCS) and generalized additive models (GAM) characterized dose-response shapes. The findings were verified through four sets of sensitivity analyses. Mediation analyses examined two candidate mediators-a 49-item frailty index and the systemic immune-inflammation index (SII). Results:Higher α-diversity was inversely associated with advanced CKM (strongest for Faith's PD, per 1-SD: OR = 0.91, 95% CI 0.86-0.98, Q4 vs Q1 OR = 0.70, 95% CI 0.58-0.84, p-trend < 0.001). All four α-diversity metrics were inversely associated with all-cause mortality, with Observed ASVs and Faith's PD exhibiting L-shaped dose-response patterns (p-nonlinear = 0.017 and 0.012, respectively), the Shannon-Weiner index exhibited a strictly linear inverse association (p-nonlinear = 0.445; EDF = 1.00), and the Simpson index showed a near-linear pattern (p-nonlinear = 0.05, p-overall < 0.001, EDF = 1.92). For CVD mortality, Shannon-Weiner index (per 1-SD: HR = 0.79, 95% CI 0.68-0.92, Q4 vs Q1 HR = 0.62, 95% CI 0.39-1.00, p-trend = 0.018) and Simpson index (HR = 0.82, 95% CI 0.72-0.93, Q4 vs Q1 HR = 0.57, 95% CI 0.35-0.93, p-trend = 0.024) maintained the most robust associations. Findings were robust across four sensitivity analyses. Exploratory mediation analyses estimated that the indirect effect of frailty on mortality was 14.30%-37.20%. Conclusion:This study suggests that oral microbiome α-diversity may be associated with CKM risk, and frailty may represent a potential mediator.
Background:Hyperuricemia (Hu) is a systemic metabolic disorder implicated in inflammatory conditions and has been epidemiologically associated with an increased prevalence of periodontitis. However, whether Hu is associated with periodontal microbial dysbiosis in experimental periodontitis remains unclear. Objective:This exploratory pilot study aimed to investigate whether Hu is associated with periodontal dysbiosis in experimental periodontitis by characterizing the diversity, taxonomic composition, and predicted functional potential of ligature-associated microbiota using 16S rRNA sequencing. Methods:A mouse model combining potassium oxonate-induced Hu with ligature-induced periodontitis was established. Male C57BL/6 mice were allocated to normouricemia with periodontitis (NuP), hyperuricemia with periodontitis (HuP), and allopurinol-treated hyperuricemia with periodontitis (HuP+Allo) groups. Ligature-associated microbiota were analyzed by 16S rRNA gene sequencing. Correlations between microbial alterations and biochemical parameters were evaluated using redundancy analysis. Results:Hu significantly increased microbial diversity and evenness, as indicated by higher Shannon index (P = 0.007) and Shannoneven index (P = 0.002), but did not affect community richness. At the phylum level, Hu increased the Firmicutes/Bacteroidota ratio and Proteobacteria abundance while decreasing Bacteroidota and Actinobacteriota. At the genus level, Hu enriched potentially pathogenic taxa, including Streptococcus and Escherichia-Shigella. Allopurinol partially reversed these changes. Redundancy analysis revealed that microbial shifts were significantly correlated with serum uric acid (R2 = 0.711, P = 0.040) and creatinine (R2 = 0.695, P = 0.035). Functional prediction suggested that Hu was associated with higher predicted abundances of NOD-like receptor signalling and lower predicted abundance of IL-17 signalling pathways. Conclusion:These exploratory findings suggest that Hu may be associated with dysbiotic remodeling of the periodontal ligature microbiota in experimental periodontitis, linking systemic metabolic disturbance with local microbial imbalance and inflammatory pathway alteration. These alterations were partially reversed by allopurinol and correlated with serum uric acid and creatinine, providing mechanistic insight into how Hu may aggravate periodontal tissue destruction.
Background:Periodontal pathogens are associated with cardiovascular disease, but clinical evidence linking Porphyromonas gingivalis (Pg) detection with coronary heart disease (CHD) and gut microbiota features remains limited. This study evaluated associations between oral and peripheral blood Pg detection status, CHD prevalence and exploratory gut microbiota characteristics in participants undergoing coronary angiography (CAG). Materials and methods:This analytical cross-sectional study included 165 CAG participants, including 124 patients with CAG-confirmed CHD and 41 non-CHD controls. Oral and peripheral blood Pg were detected by TaqMan quantitative polymerase chain reaction. Modified Poisson regression with robust standard errors was used to estimate adjusted prevalence ratios (PRs). Gut microbiota profiles were assessed by 16S rRNA gene sequencing. Results:Oral Pg positivity was more frequent in CHD participants than in non-CHD controls and remained associated with CHD in the primary adjusted model (PR = 1.237, 95% CI 1.044-1.465). The oral+/blood+ group showed the strongest association with CHD prevalence (PR = 1.362, 95% CI 1.099-1.688). Five FDR-significant ASVs were enriched in oral Pg-positive participants, whereas predicted pathways were not significant after FDR correction. Conclusions:Oral Pg positivity, especially combined oral and peripheral blood Pg nucleic acid positivity, was associated with CHD prevalence in this CAG-defined cohort.
Background:Metabolic syndrome (MetS) is associated with a higher risk of mortality. Oral microbiome diversity is related to health outcomes, but its role in forecasting MetS prognosis and the relevant pathogenic mechanisms is still largely unexplored. Methods:Data from 1,769 MetS patients were extracted from the National Health and Nutrition Examination Survey (NHANES) 2009-2012 cycle. To evaluate alpha diversity, the Shannon index, Faith's phylogenetic diversity (PD), observed operational taxonomic units (OTUs), and the Inverse Simpson index were determined. ALDEx2 was employed for differential abundance analysis in the high-diversity subgroup. Co-occurrence network analysis was subsequently conducted, followed by partitioning around medoids (PAM) clustering for community typing. Prognostic associations were validated through Cox regression. Results:Both the Shannon index (hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63-0.96) and the Inverse Simpson index (HR = 0.84, 95% CI: 0.74-0.96) were inversely associated with mortality. In the high-diversity subgroup, differential abundance analysis did not identify any OTU whose relative abundance differed significantly by survival status. According to network analysis, the deceased group exhibited a higher density of positive co-occurrences (283 vs. 224 edges) alongside a notable expansion of negative interactions (71 vs. 15 edges), which was a hallmark of declining community stability. Two clusters were identified through community typing, yet this classification was not significantly related to survival outcomes (CType_2 vs. CType_1: HR = 1.05, 95% CI: 0.73-1.49). Conclusions:Oral microbiome diversity exhibits a negative association with mortality among MetS patients. However, in the high-diversity subgroup, ecological network disruption, rather than alpha diversity or differential taxonomic richness, differentiates the deceased patients from the alive counterparts. This suggests that community structure is a promising risk marker with a higher sensitivity than diversity alone.
Background:Prior studies have linked the microbiota to brain diseases, whereas the longitudinal effects of the oral microbiota on cortical thinning and cognitive impairments in cerebral small vessel disease (CSVD) remain unexplored. Methods:We recruited 120 CSVD patients and 40 healthy controls (HCs). The subgingival plaque microbiota was sequenced by a metagenomic approach. Cortical thickness was assessed using GM-centile, an age- and sex-normalized MRI metric. Differential microbial taxa and KEGG orthologs (KOs) between groups were identified using MaAsLin2. Associations between key differential taxa with CSVD-specific cortical thinning were examined using the Spearman test, and those with MoCA score and plasma inflammatory markers (CRP and lymphocyte counts) were examined by linear regression models. Mediation models evaluated the indirect role of cortical thinning in the relationship between microbial abundance and cognitive function. Generalized estimation equations validated the longitudinal effects of the microbiota on cortical thinning progression. Result:We identified distinct oral microbiota dysbiosis in CSVD, including depletion of g_Selenomonas and g_Leptotrichia and enrichment of g_Treponema. The abundance of these microbes was correlated with longitudinal cortical thinning in the frontal gyrus, insular lobes, and inferotemporal gyrus. Enrichment analysis revealed that CSVD-enriched KOs were linked to the upregulation of LPS-mediated pro-inflammatory pathways, while those depleted were associated with the reduced biosynthesis of neuroprotective short-chain fatty acids (SCFAs). g_Leptotrichia abundance showed negatively correlation with CRP (p = 0.045). Mediation analyses indicated that the association between g_Leptotrichia depletion and baseline cognitive impairment was mediated by bilateral insular cortical thinning (both p < 0.05). Additionally, the association between g_Leptotrichia depletion and one-year cognitive decline was mediated by superior frontal cortical thinning (p = 0.033). Conclusions:Oral microbiota dysbiosis in CSVD patients reflects a pro-inflammatory state, characterized by enhanced LPS synthesis and reduced SCFAs production. This dysbiosis is associated with CSVD-specific cortical thinning in regions vulnerable to neuroinflammation, which in turn mediates cognitive impairment.
Background Post-oncological maxillary defects are commonly rehabilitated with obturator prostheses. This study compared the oral microbiota of post-oncological patients using obturators with that of control subjects wearing conventional removable dentures, focusing on clinically relevant, cultivable microorganisms.Methods Post-oncological obturator users and denture-wearing controls were examined. Swabs from the oral mucosa, prosthesis surfaces, and resection sites were analyzed using culture-based microbiological methods, including species identification and antimicrobial susceptibility testing. Microbial, demographic, and clinical data were statistically analyzed.Results Obturator users harbored a more pathogenic and antimicrobial-resistant oral microbiota than controls, with increased colonization by opportunistic pathogens such as Staphylococcus aureus (including MRSA), Gram-negative rods (Klebsiella pneumoniae), and yeast-like fungi. S. aureus remained significantly more prevalent in obturator users regardless of radiotherapy status. Candida spp. were prevalent in both groups, with Candida albicans predominating and Candida tropicalis more frequent among obturator users.Conclusions Culture-based analysis demonstrated increased colonization with antimicrobial-resistant opportunistic pathogens in post-oncological patients using obturator prostheses, highlighting the need for intensified hygiene and preventive care.
Objective:We aimed to identify significantly reduced metabolites (SRMs) in saliva by filtration and to analyze their associations with oral microorganisms. Methods:A total of 423 volunteers were assigned into two cohorts. Paired saliva samples were collected from cohort 1 (n = 60) and underwent metabolomics analysis before and after filtration. SRMs were identified based on the following thresholds: variable importance in projection ≥1, false discovery rate <0.05, and fold change ≥10. The pre-filtration samples from Cohort 1 were subjected to microbiome analysis. Saliva samples collected from cohort 2 (n = 334) underwent metabolomic and microbiome analyses, but were not filtered. Results:Principal coordinates analysis revealed a clear separation between pre- and post-filtration samples. The filtered saliva samples had approximately 5.8% fewer detectable metabolites. Notably, over half of the SRMs had an unknown origin, indicating significant knowledge gaps in oral metabolites. Prevotella melaninogenica and Veillonella parvula were core species associated with the SRMs (hypoxanthine and phosphatidylcholine), with purine metabolism identified as enriched pathway for Prevotella melaninogenica. Conclusions:Filtration can reshape saliva metabolite profiles. This study combined key metabolite filtration with integrated multi-omics and functional analyses, providing new insights into saliva metabolism and microbe-metabolite interactions.
Objectives:This pilot study aimed to determine whether adjunctive photobiomodulation (PBM) alters dental plaque microbiota and clinical parameters in periodontitis patients during orthodontic retention. Methods:Six stage IV, grade C periodontitis patients entering orthodontic retention were enrolled in this split-mouth study. One arch side received monthly PBM therapy (GaAlAs diode laser) for six months; the contralateral side received sham irradiation. Periodontal examinations were performed. Supragingival and subgingival plaque samples were evaluated at appliance removal (Ti), 6 months (Tii) and 12 months (Tiii) using 16S rRNA sequencing. Results:No significant differences were observed in periodontal clinical parameters between PBM and placebo sites at any time point (P > 0.05). Microbiome analysis showed similar alpha and beta diversity in supragingival and subgingival microbiota between the groups (P > 0.05). Exploratory genus-level differences were limited, with Treponema enriched in placebo supragingival plaque and Aggregatibacter in placebo subgingival plaque at Tii, while Catonella differed in time-pooled supragingival comparisons. No headline differential genera were detected at Ti and Tiii. Conclusion:Adjunctive PBM did not significantly alter overall plaque microbial community structure or clinical periodontal parameters. However, a few periodontitis-associated genera showed nominal, exploratory differences. These hypothesis-generating signals warrant confirmation in adequately powered trials.
Background:Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen can alter the gut microbial composition, serum metabolites and systemic immune status in mice. However, the role of its sialidase in modulating these parameters remains unexplored. Objective:This study aims to investigate the effects of P. gingivalis sialidase on gut microbiota, serum metabolites and their correlations with systemic immune responses. Design:C57BL/6 mice were orally inoculated with P. gingivalis W83, its sialidase-deficient ΔPG0352 mutant or PBS twice weekly following antibiotic pretreatment. After 40 days, spleen samples were collected for histological examination and cytokine analysis. Faecal samples were collected for 16S rRNA sequencing, and the serum samples were analysed by untargeted metabolomics. Results:P. gingivalis W83 group exhibited severe splenic inflammation and higher inflammatory cytokine levels than the other two groups. 16S rRNA gene analysis identified 19 differential bacterial genera (including Staphylococcus and Prevotellaceae_UCG-001) between the P. gingivalis W83 and ∆PG0352 groups. Metabolomics detected 12 key differential metabolites mainly involved in energy metabolism and amino acid biosynthesis pathways. Correlation analysis revealed phosphatidylcholine as a central metabolite, positively correlated with Staphylococcus, Prevotellaceae_UCG-001 and IL-1β, confirming its hub role linking metabolic shifts to immune activation. Conclusions:P. gingivalis sialidase exacerbated systemic inflammation by reshaping gut microbiota, driving phosphatidylcholine-centred metabolic reprogramming and amplifying splenic immunity.
Background:Several studies have investigated the possible links between oral yeast infections and oral cancer. However, many of these studies concentrate on single species or genera and the overall oral mycobial profiles of oral cancer patients are not well known. Objective:We examined the salivary mycobial profiles of oral squamous cell carcinoma (OSCC) patients before and after cancer treatment and compared them with those of non-cancer controls. Additionally, we tested the recently introduced concept of two salivary mycotypes-one driven by the genus Candida and one by the genus Malassezia-in the context of OSCC. Design:Paraffin-stimulated saliva from OSCC patients before cancer treatment (n = 75), after a mean follow-up of 4 years (n = 27) and from non-cancer controls (n = 81) was analysed using ITS2 amplicon sequencing. Results:The OSCC patients had lower alpha-diversity (p = 0.001, Shannon diversity index) and higher relative abundance of OTU1 Candida albicans compared with controls. No significant difference in beta-diversity or in differential abundance of OTUs was found between the paired pre-treatment OSCC and follow-up samples or the follow-up samples and controls. Baseline OSCC patients had higher prevalence of the Candida-mycotype compared with controls (p = 0.019). The prevalence of the Malassezia-mycotype increased from baseline OSCC to follow-up. Conclusions:Our results suggest that OSCC patients have a Candida-dominated salivary mycobiota that differs significantly from that of non-cancer controls and shifts towards an increased prevalence of Malazzesia after cancer is treated.
Background Porphyromonas gingivalis (P. gingivalis) is a key pathogen in the initiation and progression of chronic periodontitis. As a heme auxotrophic bacterium, P. gingivalis must acquire heme from the host environment as a source of both iron and the porphyrin ring. The scarcity of heme in healthy periodontal tissues and during the early stages of periodontitis serves as a critical factor governing the viability and pathogenic potential of P. gingivalis. The unique heme uptake pathway supports targeted treatment development.Objective This review systematically summarizes the adaptive mechanisms of P. gingivalis in nutrient-restricted environments, its crosstalk with oral microbes, and related therapeutic strategies.Design We review the published literature and elucidate the survival mechanisms of P. gingivalis in nutrient-restricted environments from five dimensions: growth morphology, virulence phenotype, heme transport system, metabolic enzyme activity, and transcriptional regulatory network. We also explore the possible mechanisms by which P. gingivalis disrupts immune homeostasis, leading to microbial dysbiosis, and analyze its synergistic interactions with other oral microorganisms. Based on the unique heme acquisition mechanism of P. gingivalis, we summary novel therapeutic strategies reported in existing research.Results Heme limitation reshapes P. gingivalis morphology, virulence, metabolism and heme acquisition systems. Interactions with S. gordonii and C. albicans boost its pathogenicity and trigger microbial dysbiosis. Porphyrin-conjugated antibiotics, antimicrobial photodynamic therapy and vaccines are promising heme-targeted therapies.Conclusions Heme scarcity is a decisive environmental factor regulating the survival and pathogenic transformation of P. gingivalis. Under heme-limited conditions, the bacterium activates a complete set of adaptive survival programs and interacts with other oral microbes to disrupt tissue immune balance and trigger microbial dysbiosis. Targeting its distinctive heme acquisition system is a feasible and promising direction for developing novel therapies against chronic periodontitis.
Background Periodontal diseases may influence systemic health through the oral-gut axis, with three mechanistic pathways proposed. Periodontitis-associated gut dysbiosis has been repeatedly observed and may plausibly extend to effects on drug metabolism, yet the literature on periodontitis-associated dysbiosis and that on its potential effects on medicine pharmacokinetics have not previsouly been bridged.Objective To synthesise the available human evidence for each of the three pathways with a distinct focus on the interventional evidence, and to position the evidence to its clinical context alongside downstream outcomes and the implications for patients and clinicians. Our secondary aim was to connect the dysbiosis and pharmacokinetic literatures in a hypothesis-generating section.Design This systematic review was registered on PROSPERO. PubMed and Scopus were searched and eligibility restricted to human studies.Results A total of 76 studies were included following full-text assessment by two independent reviewers. Across the three pathways, the human evidence was placed in clinical context with its downstream outcomes. Direct evidence that periodontitis modeifies drug response in humans was not identified, however, we were able to provide a hypothesis-generating section that identifies four drug classes for which a periodontitis-mediated modification of drug response would be most clinically relevant.Conclusions The oral-gut axis is a biologically plausible but, currently, under-evidenced route from periodontal disease to systemic and pharmacological outcomes. Future reserach should prioritise prospective comparative pharmacokinetic studies in periodontitis-affected popualtions and field-wide standardisation of methodology across oral-gut microbiome research.
