Journal of Oral Microbiology最新文献

Background: Global demographic aging is intensifying the burden of age-related diseases. Cellular senescence and the accompanying senescence-associated secretory phenotype (SASP) act as key drivers of disease progression by mediating chronic inflammation. As the second largest microbial community in the human body, the oral microbiome occupies a central position in systemic aging pathologies, and its dysbiosis and interaction with SASP are critical in this process. An imbalanced oral microbiota contributes to systemic chronic conditions via metabolic activities, virulence factor release, and immune system activation, while SASP serves as a central molecular mediator linking microbial dysbiosis to chronic inflammation, with well-recognized involvement in inflammatory bowel disease, bone disorders, and neurodegenerative conditions.

Objective: This review aims to examine the mechanism by which oral pathogens directly modulate SASP secretion via microbial metabolites and virulence factors to drive the pathogenesis of age-related diseases, propose a unifying framework of the 'oral microbiome-SASP-aging' axis, summarize therapeutic interventions targeting this axis, and suggest future development directions for precise modulation of the 'microbiome-SASP-aging' cascade.

Design: A narrative review was conducted to synthesize and analyze existing literature on the interplay between the oral microbiome, SASP, and age-related diseases. The review focused on mechanisms of oral pathogen-mediated SASP modulation, therapeutic strategies targeting the 'oral microbiome-SASP-aging' axis, and potential advancements in precise therapeutic delivery and combinatorial therapies.

Results: The 'oral microbiome-SASP-aging' axis serves as a unifying framework for these pathologies. SASP inhibitors, probiotics, and traditional Chinese medicine (TCM) targeting this axis show promise for age-related disease management. Additionally, spatiotemporally precise delivery systems and probiotic-TCM combinatorial therapies are proposed for precise modulation of the 'microbiome-SASP-aging' cascade.

Conclusions: The 'oral microbiome-SASP-aging' axis is a pivotal pathway driving age-related diseases. Therapeutic strategies targeting this axis hold significant promise for clinical management of these diseases. Future advancements in spatiotemporally precise delivery systems and combinatorial therapies are anticipated to enable precise modulation of the 'microbiome-SASP-aging' cascade, offering novel avenues for the prevention and treatment of age-related diseases.

Introduction: Oral microbiota dysbiosis is linked to cardiovascular disease, and oral pathogens have been detected in atherosclerotic plaques. We aimed to investigate the relationship between the oral microbiota and carotid atherosclerosis, and the occurrence of oral pathogens in plaques.

Patients and methods: Oral swab and saliva samples from patients with severe carotid atherosclerosis (≥50% stenosis) were compared with those from controls. The oral microbiome was analyzed by 16S rRNA amplicon sequencing targeting the V3‒V4 region. Carotid plaques were investigated for five oral bacterial species by qRT-PCR.

Results: Compared with controls, patients exhibited different inter-individual (beta) diversity (r = 0.02, p = 0.002), reduced intra-individual (alpha) diversity (p = 0.026) and 22 bacterial genera differed in relative abundance. Furthermore, abundances of five bacterial genera, including Eikenella, were increased in patients with recent cerebrovascular symptoms compared to asymptomatic patients. Eikenella corrodens was detected in all 30 carotid plaques.

Conclusion: Oral microbiota diversity and composition differ between patients with carotid atherosclerosis and controls. A higher relative abundance of the genus Eikenella in symptomatic versus asymptomatic patients and the detection of the species Eikenella corrodens in all carotid plaques, might suggest that Eikenella is important in atherogenesis and plaque instability. Oral Eikenella could possibly serve as a potential new biomarker.

Background/objective: Gastric cancer (GC) is a major cause of cancer mortality worldwide. We evaluated whether oral microbiota could be sensitive, specific, and non-invasive markers for early GC detection.

Materials and methods: Saliva samples were analyzed using 16S rRNA sequencing, and oral microbial markers were validated using an internal validation dataset. Machine learning was used to identify key genera, and functional associations were inferred using Kyoto Encyclopedia of Genes and Genomes pathway and ortholog analyses. Blood samples were also collected, and plasma cytokines were quantified by enzyme-linked immunosorbent assay (ELISA) for pathway-level interpretations.

Results: Eight genera-Lautropia, Megasphaera, Ralstonia, Pseudomonas, Peptostreptococcus, Anaerovorax, Fusobacterium, and Neisseria-were validated as diagnostic microbial markers (area under the receiver operating characteristic curve [AUC] = 0.91). Megasphaera and Ralstonia were enriched in GC, whereas Lautropia was depleted and associated with reduced risk. These genera may be functionally linked to pathways involved in GC progression, including NF-κB, IL-6, STAT3, TGF-β1, and Smad2/3. The proposed classification method effectively identified early-stage and tumor-marker-negative GCs, underscoring its clinical translation potential.

Conclusions: Oral microbial markers, including Ralstonia, Megasphaera, and Lautropia, may serve as non-invasive diagnostic markers for GC and may be related to carcinogenic signaling activity.

Dental caries is a biofilm-mediated disease that arises from polymicrobial dysbiosis in dental plaque. Among these microorganisms, Streptococcus mutans plays a prominent role because of its strong capacity to metabolize fermentable carbohydrates into organic acids that drive enamel demineralization. Central to this process is pyruvate, a key metabolic intermediate that connects glycolysis, energy production, biosynthesis, and stress adaptation. Pyruvate metabolism in S. mutans directs carbon flow into various pathways that contribute to its cariogenic potential, including acidogenesis, biofilm formation, and oxidative stress tolerance. This review explores the multifaceted roles of pyruvate in S. mutans, emphasizing its involvement in the production of lactate, acetate, formate, and branched-chain amino acids. We also discuss the regulatory mechanisms that control pyruvate metabolism, such as the Pta-Ack pathway, LrgAB-mediated pyruvate transport, and transcriptional regulation by CcpA/CodY. Furthermore, we highlight promising strategies for caries prevention, including the targeting of pyruvate metabolism using natural compounds and metabolic inhibitors. Future research should focus on elucidating the regulatory networks governing pyruvate metabolism, the metabolic byproducts, and the impact of disrupting pyruvate-based metabolic crosstalk in polymicrobial biofilms. Understanding how pyruvate functions as a carrier or precursor metabolite in central carbon metabolism of S. mutans and its regulation of survival and metabolic processes will have significant implications for caries prevention.

Background: Chronic intestinal inflammation is a hallmark of inflammatory bowel disease (IBD). Studies suggest that salivary bacteria associated with periodontitis may exacerbate colitis, but the specific contributory microbes and mechanisms remain unclear.

Patients and methods: We analyzed stool samples from 28 IBD patients and 21 controls. Bacterial DNA was extracted and quantified using qPCR targeting Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans). In a murine model, C57BL/6 mice received DSS followed by daily oral gavage with A. actinomycetemcomitans. Disease activity, histopathology and the gut microbiota were evaluated.

Results: Oral administration of A. actinomycetemcomitans exacerbated inflammatory symptoms in DSS-induced colitis. The bacterium was detectable in intestinal tissue transiently following high-dose oral administration during the inflammatory phase. Following high-dose gavage, bacterial DNA was transiently detectable in intestinal tissue during inflammation. This treatment was associated with reduced expression of the tight junction protein ZO-1 and mucin MUC-2, elevated inflammatory mediators, and altered gut microbial community structure, including an expansion of taxa associated with dysbiosis.

Conclusion: In a murine colitis model, A. actinomycetemcomitans exposure was associated with worsened disease severity, coinciding with impaired barrier integrity, heightened inflammation and gut microbiota alterations. These exploratory findings highlight the potential role for specific periodontal microbes in modulating intestinal inflammation and warrant further investigation.

Background: The oral cavity is a known reservoir of antibiotic resistance genes (ARGs), but little is known about their subgingival distribution across health states and regions.

Objective: This study aimed to characterize and compare the subgingival resistome and mobile genetic elements (MGEs) in healthy subjects (HS) and periodontitis patients (PP) from Belgium, Chile, Peru and Spain.

Design: Subgingival samples pooled from the deepest site of each quadrant of 40 HS and 40 PP were analyzed via shotgun metagenomic sequencing. After human DNA depletion, the microbial composition was assessed with MetaPhlAn 4.0; ARGs were identified using MEGAHIT and AMRFinderPlus; and MGEs with MGEfinder.

Results: ARG richness was significantly higher in PP (mean 3.98) than in HS (2.15). PP from Peru showed more ARGs than HS from Chile and Spain. In total, 28 ARGs were found, conferring resistance to eight antibiotic classes. β-lactam, tetracycline and aminoglycoside resistance were more abundant in PP. Macrolide resistance was lower in Chilean samples than in Peruvian and Spanish ones. Additionally, 99 MGE-associated genes were detected, with 16 differing by diagnosis and 78 by country.

Conclusions: Subgingival resistome profiles vary significantly by periodontal status and geography, underscoring the influence of clinical and regional factors on antimicrobial resistance in the oral microbiome.

Background: We previously demonstrated that Streptococcus mitis exhibits anticancer properties in vitro. Here, we sought to validate these findings in vivo. Because mice from different vendors harbor distinct microbiomes that can influence disease susceptibility and experimental outcomes, we also examined whether vendor-specific oral and gut microbiomes affect oral carcinogenesis and response to S. mitis intervention.

Materials and methods: Oral carcinogenesis was induced using 4-NQO in C57BL/6 mice from Jackson Laboratory and Taconic Biosciences (n = 32 per vendor). Mice were randomized to biweekly oral swabbing with S. mitis or vehicle for 28 weeks. Oral and fecal microbiomes were profiled at baseline and week 8. At week 32, tongues were evaluated for tumor development.

Results: Oral and gut microbiomes differed significantly between vendors. 4-NQO exposure induced marked microbial shifts and partial convergence of microbiome profiles. Jackson mice developed a significantly higher squamous cell carcinoma (SCC) burden. Several microbial taxa were associated with SCC, notably Clostridium, which was enriched in oral and fecal samples from Jackson mice. S. mitis reduced SCC burden in both cohorts and was accompanied by decreased Clostridium abundance.

Conclusions: These data support S. mitis as a potential anticancer agent and underscore the importance of microbiome context in preclinical cancer models.

Background: HIV infection alters host immunity, including the oral environment, leading to microbial imbalance and increased risk of opportunistic infections. Although antiretroviral therapy (ART) improves immune function, its effect on the oral microbiome remains unclear, particularly in Indonesia. This study investigated oral microbiome composition in people living with HIV and its associations with ART status, age, and sex.

Methods: In this cross-sectional study, oral rinse samples from 245 adults (115 HIV-on-ART, 15 HIV-ART-naïve, and 115 HIV-negative controls) were analysed using 16S rRNA gene sequencing. Alpha and beta diversity metrics, differential abundance (ANCOM-BC2), and multivariable associations (PERMANOVA) were assessed.

Results: The oral microbiome differed significantly between HIV-positive groups and controls (PERMANOVA p = 0.001, R² = 1.8%). HIV-ART-naïve individuals exhibited the highest alpha diversity and enrichment of pro-inflammatory genera, including Fusobacterium, Alloprevotella, and Staphylococcus. ART-treated individuals displayed a partial shift toward the control profile but retained persistent depletion of bacteria such as Filifactor and (Eubacterium) saphenum. Multivariate analysis identified HIV status, age, and sex as independent contributors to microbial variation.

Conclusion: HIV infection is associated with a distinct oral dysbiosis characterised by an increase in opportunistic pathogens and reduction in commensal bacteria. HIV-on-ART individuals show a transitional shift towards the HIV-negative oral microbiome profiles. Our findings suggest that biological and/or demographic factors coupled to oral microbiome profiles may facilitate targeted interventions in the personalised management of oral health for individuals living with HIV.

Background: Oral microbiome diversity has been associated with general health. However, its association with long-term outcomes in hypertensive individuals remains unclear.

Objectives: This study aimed to investigate whether oral microbiome diversity is associated with all-cause mortality in hypertensive individuals.

Design: Data from 2,669 hypertensive individuals in the National Health and Nutrition Examination Survey (NHANES, 2009-2012) were analyzed. Oral microbiome diversity was assessed using four alpha-diversity metrics: the Simpson index, Shannon-Weiner index, Faith's Phylogenetic Diversity, and observed amplicon sequence variants (ASVs). Weighted multivariable Cox proportional hazards regression and interaction analyses were conducted.

Results: During a mean follow-up of 8.61 years, 268 all-cause deaths occurred. Higher oral microbiome diversity assessed by the Simpson index (hazard ratio [HR] = 0.38; 95% confidence interval [CI], 0.20-0.75; P _trend < 0.01) and Shannon-Weiner index (HR = 0.47; 95% CI, 0.25-0.88; P _trend < 0.05), was significantly associated with reduction in all-cause mortality risk. A potential interaction between sex and oral microbiome diversity on mortality risk was observed.

Conclusions: Higher oral microbiome diversity is an independent protective factor for survival in patients with hypertension, with potential sex-specific differences in this association. These findings suggest that enhancing oral microbiome diversity may potentially help promote overall health in individuals with hypertension.