Background: Candida albicans has been implicated in oral carcinogenesis, but its role in the progression of oral potentially malignant disorders (OPMDs) remains unclear. We investigated whether high Candida burden in OPMD lesions predicts malignant transformation (MT) and whether this association varied by OPMD subtype.
Patients and methods: In a multicenter prospective cohort study across seven hospitals in Taiwan, 734 OPMD patients were followed for a mean of 2.4 years. Oral lesion swabs were cultured on chromogenic agar to quantify Candida albicans level. Cox models were used to estimate hazard ratios (HRs) for MT to oral cancer.
Results: MT occurred in 6.8% of patients. High Candida burden was independently associated with increased MT risk (aHR = 2.84; 95% CI: 1.40-5.75). Patients with oral submucous fibrosis (OSF) or verrucous hyperplasia (VH) also had elevated risk (aHR = 4.99; 95% CI: 1.54-10.38). Interaction analysis revealed strong individual risks for high Candida burden (aHR = 13.83) and OSF/VH (aHR = 13.67), with an attenuating interaction term (aHR = 0.11), yielding a substantial combined risk (HR ≈ 20.8). Stratified analysis showed the strongest effect in leukoplakia (HR = 12.19).
Conclusions: High Candida albicans burden is a significant, subtype-dependent risk factor for malignant progression in OPMDs. These findings underline the role of fungal-host interactions in oral carcinogenesis and support the integration of fungal profiling into routine surveillance of OPMDs.
{"title":"<i><b>Candida albicans</b></i> <b>is a context-dependent risk factor for malignant transformation of oral precancer lesions: a prospective cohort study of 734 Taiwanese patients</b>.","authors":"Shih Sheng Jiang, Chung-Hsing Chen, Fang-Yu Tsai, Yi-Ping Hsieh, Tsung-Te Chung, Jang-Jaer Lee, Mu-Kuan Chen, Yen-Tze Liu, Shun-Fa Yang, Chun-Yi Chuang, Wen-Lun Wang, Chih-Chun Wang, Tze-Ta Huang, I-Chi Chen, Pei-Hua Wu, Yi-Chieh Chen, Ya-Wen Chen, Shine-Gwo Shiah, Li-Hsin Chien, I-Shou Chang, Ching-Yu Yen, Ko-Jiunn Liu","doi":"10.1080/20002297.2025.2598743","DOIUrl":"10.1080/20002297.2025.2598743","url":null,"abstract":"<p><strong>Background: </strong><i>Candida albicans</i> has been implicated in oral carcinogenesis, but its role in the progression of oral potentially malignant disorders (OPMDs) remains unclear. We investigated whether high <i>Candida</i> burden in OPMD lesions predicts malignant transformation (MT) and whether this association varied by OPMD subtype.</p><p><strong>Patients and methods: </strong>In a multicenter prospective cohort study across seven hospitals in Taiwan, 734 OPMD patients were followed for a mean of 2.4 years. Oral lesion swabs were cultured on chromogenic agar to quantify <i>Candida albicans</i> level. Cox models were used to estimate hazard ratios (HRs) for MT to oral cancer.</p><p><strong>Results: </strong>MT occurred in 6.8% of patients. High <i>Candida</i> burden was independently associated with increased MT risk (aHR = 2.84; 95% CI: 1.40-5.75). Patients with oral submucous fibrosis (OSF) or verrucous hyperplasia (VH) also had elevated risk (aHR = 4.99; 95% CI: 1.54-10.38). Interaction analysis revealed strong individual risks for high <i>Candida</i> burden (aHR = 13.83) and OSF/VH (aHR = 13.67), with an attenuating interaction term (aHR = 0.11), yielding a substantial combined risk (HR ≈ 20.8). Stratified analysis showed the strongest effect in leukoplakia (HR = 12.19).</p><p><strong>Conclusions: </strong>High <i>Candida albicans</i> burden is a significant, subtype-dependent risk factor for malignant progression in OPMDs. These findings underline the role of fungal-host interactions in oral carcinogenesis and support the integration of fungal profiling into routine surveillance of OPMDs.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2598743"},"PeriodicalIF":5.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: This study aimed to explore the composition of the tooth-surface plaque (subgingival with marginal supragingival) microbiome in dentate older adults residing in long-term care (LTC) facilities, stratified by clinically assessed oral disease burden (ODB). A total of 196 LTC residents aged ≥62 years underwent oral examinations and microbial sampling from each dentate quadrant. Microbial profiling was performed using 16S rRNA gene sequencing.
Results: Participants were more frequently categorized into Moderate (n = 95, 48%) than Low (n = 32, 16%) or High (n = 69, 35%) ODB groups. Those with High ODB were oldest and had lowest number of remaining teeth. Alpha diversity did not differ between the ODB groups, whereas beta diversity analysis revealed significant differences between groups (Bray-Curtis: P = 0.005; weighted Unifrac: P = 0.025). The Low and Moderate ODB groups were enriched with both commensals and disease-associated genera, such as Ottowia, Lactococcus, Pseudoramibacter, and Anaeroglobus. High ODB group exhibited an increased abundance of genera linked to both oral and systemic diseases, including Cardiobacterium, Leptotrichia, Stomatobaculum, and Pseudopropionibacterium. Among ODB groups, periodontitis was a stronger determinant of oral microbiome composition than caries, whereas caries had a stronger effect on bacterial diversity.
Conclusion: These findings indicate a progressive shift toward a dysbiotic oral microbiome with increasing ODB.
目的:本研究旨在通过临床评估的口腔疾病负担(ODB)进行分层,探讨居住在长期护理(LTC)设施的有齿老年人的牙表面菌斑(龈下和边缘龈上)微生物组的组成。共有196名年龄≥62岁的LTC居民接受了口腔检查和每个齿状象限的微生物采样。采用16S rRNA基因测序进行微生物谱分析。结果:参与者更频繁地被分类为中度(n = 95,48%),而不是低(n = 32, 16%)或高(n = 69, 35%) ODB组。ODB高的人年龄最大,剩余牙齿数量最少。α多样性在ODB组间无差异,而β多样性分析显示组间差异显著(Bray-Curtis: P = 0.005;加权Unifrac: P = 0.025)。低和中等ODB组富含共生菌和疾病相关属,如奥托维亚菌、乳球菌、假弧菌和无氧舌菌。高ODB组显示出与口腔和全身性疾病相关的属的丰度增加,包括心杆菌、细毛菌、口杆菌和假丙酸杆菌。在ODB组中,牙周炎比龋齿对口腔微生物组成的影响更大,而龋齿对细菌多样性的影响更大。结论:这些发现表明,随着ODB的增加,口腔微生物群逐渐转向益生菌群。
{"title":"Tooth-surface plaque microbiome and different levels of oral disease burden among dentate older adults living in long-term care.","authors":"Lina Julkunen, Muhammed Manzoor, Kaija Hiltunen, Riitta Kt Saarela, Kaisu Pitkälä, Pirkko J Pussinen, Päivi Mäntylä","doi":"10.1080/20002297.2025.2602387","DOIUrl":"10.1080/20002297.2025.2602387","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to explore the composition of the tooth-surface plaque (subgingival with marginal supragingival) microbiome in dentate older adults residing in long-term care (LTC) facilities, stratified by clinically assessed oral disease burden (ODB). A total of 196 LTC residents aged ≥62 years underwent oral examinations and microbial sampling from each dentate quadrant. Microbial profiling was performed using 16S rRNA gene sequencing.</p><p><strong>Results: </strong>Participants were more frequently categorized into Moderate (<i>n</i> = 95, 48%) than Low (<i>n</i> = 32, 16%) or High (<i>n</i> = 69, 35%) ODB groups. Those with High ODB were oldest and had lowest number of remaining teeth. Alpha diversity did not differ between the ODB groups, whereas beta diversity analysis revealed significant differences between groups (Bray-Curtis: <i>P</i> = 0.005; weighted Unifrac: <i>P</i> = 0.025). The Low and Moderate ODB groups were enriched with both commensals and disease-associated genera, such as <i>Ottowia, Lactococcus, Pseudoramibacter,</i> and <i>Anaeroglobus</i>. High ODB group exhibited an increased abundance of genera linked to both oral and systemic diseases, including <i>Cardiobacterium</i>, <i>Leptotrichia</i>, <i>Stomatobaculum</i>, and <i>Pseudopropionibacterium</i>. Among ODB groups, periodontitis was a stronger determinant of oral microbiome composition than caries, whereas caries had a stronger effect on bacterial diversity.</p><p><strong>Conclusion: </strong>These findings indicate a progressive shift toward a dysbiotic oral microbiome with increasing ODB.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2602387"},"PeriodicalIF":5.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-14eCollection Date: 2025-01-01DOI: 10.1080/20002297.2025.2600179
Sunjun Wang, Yichao Liu, Beichang Zhang, Joseph Aduse-Opoku, Roberto Buccafusca, Oscar Ayrton, Giulia Mastroianni, Pedro Machado, Mark A J Roberts, Michael A Curtis, James A Garnett
Background:Porphyromonas gingivalis is a Gram-negative bacterium that plays a central role in the development of periodontal disease. It uses a type IX secretion system (T9SS) to export virulence factors to the bacterial surface where they are attached to A-LPS, one of the two forms of lipopolysaccharide (LPS) produced in P. gingivalis, and then packaged into outer membrane vesicles (OMVs). We previously showed that 1-P dephosphorylation of the lipid A component of LPS is regulated by the T9SS outer membrane protein PorV, and this is linked to membrane destabilisation and OMV blebbing/formation. Objective: This study aimed to investigate whether other T9SS outer membrane proteins are required for correct OMV biogenesis. Design: We examined gingipain activity, gingipain secretion, A-LPS production, OMV morphology, and lipid A structure in P. gingivalis W50, T9SS mutant strains, and a lipid A 1-phosphatase (ΔlpxE) mutant strain. Results: A functional T9SS is required for LpxE activity and correct vesicle formation, and this is likely through the function of an exported type IX-cargo protein. Conclusion: This study provides insight into a new mechanism that links type IX cargo sorting with OMV blebbing, which may also be present in other Bacteroidota that colonise the gut and oral cavity.
{"title":"The <i>Porphyromonas gingivalis</i> lipid A 1-phosphatase LpxE requires a functional type IX secretion system for its activity.","authors":"Sunjun Wang, Yichao Liu, Beichang Zhang, Joseph Aduse-Opoku, Roberto Buccafusca, Oscar Ayrton, Giulia Mastroianni, Pedro Machado, Mark A J Roberts, Michael A Curtis, James A Garnett","doi":"10.1080/20002297.2025.2600179","DOIUrl":"10.1080/20002297.2025.2600179","url":null,"abstract":"<p><p><b>Background:</b> <i>Porphyromonas gingivalis</i> is a Gram-negative bacterium that plays a central role in the development of periodontal disease. It uses a type IX secretion system (T9SS) to export virulence factors to the bacterial surface where they are attached to A-LPS, one of the two forms of lipopolysaccharide (LPS) produced in <i>P. gingivalis</i>, and then packaged into outer membrane vesicles (OMVs). We previously showed that 1-P dephosphorylation of the lipid A component of LPS is regulated by the T9SS outer membrane protein PorV, and this is linked to membrane destabilisation and OMV blebbing/formation. <b>Objective:</b> This study aimed to investigate whether other T9SS outer membrane proteins are required for correct OMV biogenesis. <b>Design:</b> We examined gingipain activity, gingipain secretion, A-LPS production, OMV morphology, and lipid A structure in <i>P. gingivalis</i> W50, T9SS mutant strains, and a lipid A 1-phosphatase (Δ<i>lpxE</i>) mutant strain. <b>Results:</b> A functional T9SS is required for LpxE activity and correct vesicle formation, and this is likely through the function of an exported type IX-cargo protein. <b>Conclusion:</b> This study provides insight into a new mechanism that links type IX cargo sorting with OMV blebbing, which may also be present in other <i>Bacteroidota</i> that colonise the gut and oral cavity.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2600179"},"PeriodicalIF":5.5,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Streptococcus suis is a zoonotic pathogen, and its colonization of the host tonsil is believed to be a vital source causing infection, while its mechanism competing for a stable tonsil niche is unknown. Rearrangement hotspot (Rhs) proteins are characterized to facilitate interbacterial competition by their polymorphic C-terminal toxins (CTs) in diverse bacteria, while their distant homologues emerged in S. suis, referred to as wall-associated protein A (WapA), has not been identified.
Methods: Bioinformatics, western blot and interbacterial competition analyses were performed to identify Rhs/WapA toxins and their roles during S. suis infection.
Results: The 350 kDa WapA-CT1, linked with a SecF-like protein and a SrtB sortase, was verified to manipulate the tonsil microbiota for S. suis optimal colonization. The unfolded WapA-CT1 was translocated across the cell membrane via the canonical Sec pathway. Afterward, autocleavage generated four fragments: the N-terminal NCWB fragment, two middle Rhs domains (Rhs1&2) that may fold as a β-barrel structure, and a C-terminal PreT-CT toxin domain. SrtB interacts with the NCWB region, and plays vital roles for the interbacterial antagonism mediated by the toxic CT1.
Conclusion: This discovery underscores the diversity of mechanisms by which pathogens delivering Rhs/WapA polymorphic toxins, and their roles in competing with the host microbiota.
{"title":"<i>Streptococcus suis</i> exports WapA polymorphic toxins to compete with tonsil microbiota for an optimal colonization.","authors":"Xinming Pan, Jianan Liu, Ningyuan Zhong, Ruhui Fan, Zhen Zhang, Caiying Li, Huizhen Wu, Zongfu Wu, Qiankun Bai, Jiale Ma","doi":"10.1080/20002297.2025.2598988","DOIUrl":"10.1080/20002297.2025.2598988","url":null,"abstract":"<p><strong>Background: </strong><i>Streptococcus suis</i> is a zoonotic pathogen, and its colonization of the host tonsil is believed to be a vital source causing infection, while its mechanism competing for a stable tonsil niche is unknown. Rearrangement hotspot (Rhs) proteins are characterized to facilitate interbacterial competition by their polymorphic C-terminal toxins (CTs) in diverse bacteria, while their distant homologues emerged in <i>S. suis</i>, referred to as wall-associated protein A (WapA), has not been identified.</p><p><strong>Methods: </strong>Bioinformatics, western blot and interbacterial competition analyses were performed to identify Rhs/WapA toxins and their roles during <i>S. suis</i> infection.</p><p><strong>Results: </strong>The 350 kDa WapA-CT1, linked with a SecF-like protein and a SrtB sortase, was verified to manipulate the tonsil microbiota for <i>S. suis</i> optimal colonization. The unfolded WapA-CT1 was translocated across the cell membrane via the canonical Sec pathway. Afterward, autocleavage generated four fragments: the N-terminal NCWB fragment, two middle Rhs domains (Rhs1&2) that may fold as a <i>β</i>-barrel structure, and a C-terminal PreT-CT toxin domain. SrtB interacts with the NCWB region, and plays vital roles for the interbacterial antagonism mediated by the toxic CT1.</p><p><strong>Conclusion: </strong>This discovery underscores the diversity of mechanisms by which pathogens delivering Rhs/WapA polymorphic toxins, and their roles in competing with the host microbiota.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2598988"},"PeriodicalIF":5.5,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-07eCollection Date: 2025-01-01DOI: 10.1080/20002297.2025.2595797
Simone Rocco, Adriana Antonina Tempesta, Gaia Vertillo Aluisio, Maria Lina Mezzatesta, Alessandra Romano, Valentina Schiavo, Barbara Pergolizzi, Maria Santagati, Cristina Panuzzo, Gaetano Isola
Background: Chlorhexidine (CHX) is widely used in oral care for its broad-spectrum antimicrobial activity but can cause significant side effects. Sodium DNA has emerged as a potential adjunct capable of modulating cellular responses.
Aim: This study assessed whether sodium DNA enhances the antibacterial and antibiofilm activity of 0.20% and 0.12% CHX mouthwashes against Streptococcus mutans and Escherichia coli, and evaluated their effects on the viability and phagocytic activity of Dictyostelium discoideum, a model for mammalian phagocytes.
Results: All CHX-containing mouthwashes were bactericidal against S.mutans, regardless of sodium DNA, whereas CHX-only formulations were more effective against E.coli in time-kill assays. All formulations inhibited biofilm formation at 50-0.01%. In S. mutans, early biofilms were strongly inhibited (50-0.39%), whereas mature biofilms were less affected. In E. coli, sodium DNA enhanced inhibition of both biofilm formation (50-1.56%) and mature biofilms (50-3.12%). The 0.12% CHX-sodium DNA formulation most effectively modulated D.discoideum viability and phagocytic activity, and metabolomics showed that sodium DNA reduced CHX-induced metabolic stress.
Conclusions: This study integrates antimicrobial, antibiofilm, cellular, and metabolomic analyses to assess CHX with sodium DNA. Sodium DNA reduces CHX-induced cytotoxicity and metabolic stress while maintaining antimicrobial activity, offering insights for optimizing oral hygiene formulations through combined microbial and host-cell evaluation.
{"title":"<b>Antibacterial and cytotoxic effects of chlorhexidine combined with sodium DNA on oral microorganisms: an <i>in vitro</i> study using</b> <i><b>Dictyostelium discoideum</b></i>.","authors":"Simone Rocco, Adriana Antonina Tempesta, Gaia Vertillo Aluisio, Maria Lina Mezzatesta, Alessandra Romano, Valentina Schiavo, Barbara Pergolizzi, Maria Santagati, Cristina Panuzzo, Gaetano Isola","doi":"10.1080/20002297.2025.2595797","DOIUrl":"10.1080/20002297.2025.2595797","url":null,"abstract":"<p><strong>Background: </strong>Chlorhexidine (CHX) is widely used in oral care for its broad-spectrum antimicrobial activity but can cause significant side effects. Sodium DNA has emerged as a potential adjunct capable of modulating cellular responses.</p><p><strong>Aim: </strong>This study assessed whether sodium DNA enhances the antibacterial and antibiofilm activity of 0.20% and 0.12% CHX mouthwashes against <i>Streptococcus mutans</i> and <i>Escherichia coli</i>, and evaluated their effects on the viability and phagocytic activity of <i>Dictyostelium discoideum</i>, a model for mammalian phagocytes.</p><p><strong>Results: </strong>All CHX-containing mouthwashes were bactericidal against <i>S.mutans</i>, regardless of sodium DNA, whereas CHX-only formulations were more effective against <i>E.coli</i> in time-kill assays. All formulations inhibited biofilm formation at 50-0.01%. In <i>S. mutans</i>, early biofilms were strongly inhibited (50-0.39%), whereas mature biofilms were less affected. In <i>E. coli</i>, sodium DNA enhanced inhibition of both biofilm formation (50-1.56%) and mature biofilms (50-3.12%). The 0.12% CHX-sodium DNA formulation most effectively modulated <i>D.discoideum</i> viability and phagocytic activity, and metabolomics showed that sodium DNA reduced CHX-induced metabolic stress.</p><p><strong>Conclusions: </strong>This study integrates antimicrobial, antibiofilm, cellular, and metabolomic analyses to assess CHX with sodium DNA. Sodium DNA reduces CHX-induced cytotoxicity and metabolic stress while maintaining antimicrobial activity, offering insights for optimizing oral hygiene formulations through combined microbial and host-cell evaluation.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2595797"},"PeriodicalIF":5.5,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05eCollection Date: 2025-01-01DOI: 10.1080/20002297.2025.2589656
Supathep Tansirichaiya, Kittikun Songsomboon, Johannes Wigand, Endre Winje, Nichamon Chaianant, Wasawat Leartsiwawinyu, Mohammed Al-Haroni
Background: The oral cavity is an important yet understudied reservoir of antimicrobial resistance genes (ARGs), potentially shaped by geographic variation in antibiotic usage.
Objective: To compare the oral resistomes of healthy adults from Thailand and Norway, two countries with contrasting antimicrobial use practices, using shotgun metagenomic sequencing.
Design: Stimulated saliva samples were collected from healthy adults in Thailand (n = 43) and Norway (n = 50). ARGs were identified with AMRPlusPlus against the MEGARes database, and microbial taxonomy was profiled with KrakenUniq. Diversity metrics, ordination, and clustering analyses assessed resistome and microbiome structures.
Results: Thai samples exhibited significantly greater ARG richness, evenness, and diversity (p < 0.001), driven by higher abundances of multi-biocide, nucleoside, and copper resistance genes. Norwegian samples were enriched in aminoglycoside, sulfonamide, and quaternary ammonium compound resistance genes. Both cohorts shared core oral genera, but Thai samples showed greater taxonomic richness without differences in overall microbiome diversity. Non-metric multidimensional scaling and PERMANOVA revealed stronger geographic separation for resistomes (R² = 0.639) than microbiomes (R² = 0.382). Co-occurrence networks highlighted structured associations between ARG groups and bacterial genera, suggesting ecological influences beyond taxonomic composition.
Conclusions: These results reveal distinct geographic signatures in the oral resistome that are not fully explained by microbiome structure, reflecting the influence of local ecological and societal factors, including antimicrobial exposure. The findings highlight the oral cavity as a dynamic ARG reservoir and support its inclusion in regional antimicrobial resistance surveillance to inform public health strategies.
{"title":"Geographic signatures in the oral resistome: a comparative metagenomic analysis of healthy individuals from Thailand and Norway.","authors":"Supathep Tansirichaiya, Kittikun Songsomboon, Johannes Wigand, Endre Winje, Nichamon Chaianant, Wasawat Leartsiwawinyu, Mohammed Al-Haroni","doi":"10.1080/20002297.2025.2589656","DOIUrl":"10.1080/20002297.2025.2589656","url":null,"abstract":"<p><strong>Background: </strong>The oral cavity is an important yet understudied reservoir of antimicrobial resistance genes (ARGs), potentially shaped by geographic variation in antibiotic usage.</p><p><strong>Objective: </strong>To compare the oral resistomes of healthy adults from Thailand and Norway, two countries with contrasting antimicrobial use practices, using shotgun metagenomic sequencing.</p><p><strong>Design: </strong>Stimulated saliva samples were collected from healthy adults in Thailand (<i>n</i> = 43) and Norway (<i>n</i> = 50). ARGs were identified with AMRPlusPlus against the MEGARes database, and microbial taxonomy was profiled with KrakenUniq. Diversity metrics, ordination, and clustering analyses assessed resistome and microbiome structures.</p><p><strong>Results: </strong>Thai samples exhibited significantly greater ARG richness, evenness, and diversity (<i>p</i> < 0.001), driven by higher abundances of multi-biocide, nucleoside, and copper resistance genes. Norwegian samples were enriched in aminoglycoside, sulfonamide, and quaternary ammonium compound resistance genes. Both cohorts shared core oral genera, but Thai samples showed greater taxonomic richness without differences in overall microbiome diversity. Non-metric multidimensional scaling and PERMANOVA revealed stronger geographic separation for resistomes (R² = 0.639) than microbiomes (R² = 0.382). Co-occurrence networks highlighted structured associations between ARG groups and bacterial genera, suggesting ecological influences beyond taxonomic composition.</p><p><strong>Conclusions: </strong>These results reveal distinct geographic signatures in the oral resistome that are not fully explained by microbiome structure, reflecting the influence of local ecological and societal factors, including antimicrobial exposure. The findings highlight the oral cavity as a dynamic ARG reservoir and support its inclusion in regional antimicrobial resistance surveillance to inform public health strategies.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2589656"},"PeriodicalIF":5.5,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04eCollection Date: 2025-01-01DOI: 10.1080/20002297.2025.2594842
Sung Min Kim, Zeba Praveen, Yeon-Hee Kim, Jae Hee Ko, Yong-Seok Choi, Joo Yong Park, Jong Ho Lee, Sung Weon Choi, Mi Kyung Kim
Background: The pathogenesis of oral squamous cell carcinoma (OSCC) in never-smoking females remains poorly understood, as these patients lack traditional risk factors. This subgroup accounts for an increasing proportion of OSCC cases and may exhibit distinct tumor biology. Here, we investigated the association between the alterations in the salivary microbiome and OSCC in never-smoking female patients.
Materials and methods: Saliva samples from 72 never-smoking female patients with OSCC and 494 never-smoking healthy female controls were analyzed using 16S rRNA gene sequencing. Microbial community structure and function were compared using statistical analyses, machine learning algorithms, and pathway prediction with PICRUSt2.
Results: Patients with OSCC exhibited significantly different microbial diversity and composition compared to controls. The genera Rhodococcus, Slackia, Lactobacillus, and Enterobacterales_g were enriched in the OSCC group, whereas Corynebacterium was more abundant in the Control group. These taxa were associated with oncogenic pathways, including PI3K-Akt signaling and nicotinate/nicotinamide metabolism. Functional inference also indicated enrichment of cancer-related orthologs such as LKB1, NFKB1, ITGAV, and TRAF4.
Conclusions: Salivary microbiome alterations, both taxonomic and functional, are associated with OSCC in never-smoking females. These findings suggest a potential microbial contribution to carcinogenesis in this unique patient population and offer novel insights into disease mechanisms.
{"title":"Functional profiling of the oral microbiome reveals microbial and oncogenic signatures in never-smoking female patients with oral squamous cell carcinoma.","authors":"Sung Min Kim, Zeba Praveen, Yeon-Hee Kim, Jae Hee Ko, Yong-Seok Choi, Joo Yong Park, Jong Ho Lee, Sung Weon Choi, Mi Kyung Kim","doi":"10.1080/20002297.2025.2594842","DOIUrl":"10.1080/20002297.2025.2594842","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of oral squamous cell carcinoma (OSCC) in never-smoking females remains poorly understood, as these patients lack traditional risk factors. This subgroup accounts for an increasing proportion of OSCC cases and may exhibit distinct tumor biology. Here, we investigated the association between the alterations in the salivary microbiome and OSCC in never-smoking female patients.</p><p><strong>Materials and methods: </strong>Saliva samples from 72 never-smoking female patients with OSCC and 494 never-smoking healthy female controls were analyzed using 16S rRNA gene sequencing. Microbial community structure and function were compared using statistical analyses, machine learning algorithms, and pathway prediction with PICRUSt2.</p><p><strong>Results: </strong>Patients with OSCC exhibited significantly different microbial diversity and composition compared to controls. The genera <i>Rhodococcus</i>, <i>Slackia</i>, <i>Lactobacillus</i>, and <i>Enterobacterales_g</i> were enriched in the OSCC group, whereas <i>Corynebacterium</i> was more abundant in the Control group. These taxa were associated with oncogenic pathways, including PI3K-Akt signaling and nicotinate/nicotinamide metabolism. Functional inference also indicated enrichment of cancer-related orthologs such as <i>LKB1, NFKB1, ITGAV</i>, and <i>TRAF4</i>.</p><p><strong>Conclusions: </strong>Salivary microbiome alterations, both taxonomic and functional, are associated with OSCC in never-smoking females. These findings suggest a potential microbial contribution to carcinogenesis in this unique patient population and offer novel insights into disease mechanisms.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2594842"},"PeriodicalIF":5.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04eCollection Date: 2025-01-01DOI: 10.1080/20002297.2025.2593129
Rella P Christensen, Brad J Ploeger, Kaesy R Barker, Wyatt R Hume, Brenda Heaton
Background: Molecular identification of dental caries microbes is advancing rapidly, yet sampling methods remain outdated and imprecise.
Objective: To refine microbe sample harvesting and preserve taxa pre-harvest spatial positions relative to lesion pulpal depth.
Methods: Refinements included a sterile zone surrounding the dissection site and emphasize asepsis, surgical microscope magnification and lighting, and micro-surgical techniques. Retention of taxa pre-harvest spatial positions relative to lesion pulpal depth used shallow-layered dissection (mean 6 mg/layer, SD 2.65 mg), where each layer became a separate sample for molecular identification before sequential reassembly in a layered lesion diagram. To evaluate the method's robustness, 14 lesions varying in severity and type from private dental practices were dissected using the method (7 pit and fissure and 7 facial lesions; 4 untreated, 3 treated).
Results: Pre-harvest taxa detail, not possible previously, showed taxa location, abundance and diversity relative to lesion pulpal depth, as well as absolute abundance per milligram and taxa transitions and fluctuations from superficial through the deepest dissected layers. The method provides these data regardless of lesion type, stage, or complexity, whether untreated or treated.
Conclusions: This method provides new details and perspectives on dental caries taxa that could help develop diagnostic instruments and treatments to halt dental caries progression.
{"title":"Dental caries shallow-layer microbe harvest and data display method shows taxa pre-harvest spatial positions, absolute and relative abundance and diversity related to lesion pulpal depth.","authors":"Rella P Christensen, Brad J Ploeger, Kaesy R Barker, Wyatt R Hume, Brenda Heaton","doi":"10.1080/20002297.2025.2593129","DOIUrl":"10.1080/20002297.2025.2593129","url":null,"abstract":"<p><strong>Background: </strong>Molecular identification of dental caries microbes is advancing rapidly, yet sampling methods remain outdated and imprecise.</p><p><strong>Objective: </strong>To refine microbe sample harvesting and preserve taxa pre-harvest spatial positions relative to lesion pulpal depth.</p><p><strong>Methods: </strong>Refinements included a sterile zone surrounding the dissection site and emphasize asepsis, surgical microscope magnification and lighting, and micro-surgical techniques. Retention of taxa pre-harvest spatial positions relative to lesion pulpal depth used shallow-layered dissection (mean 6 mg/layer, SD 2.65 mg), where each layer became a separate sample for molecular identification before sequential reassembly in a layered lesion diagram. To evaluate the method's robustness, 14 lesions varying in severity and type from private dental practices were dissected using the method (7 pit and fissure and 7 facial lesions; 4 untreated, 3 treated).</p><p><strong>Results: </strong>Pre-harvest taxa detail, not possible previously, showed taxa location, abundance and diversity relative to lesion pulpal depth, as well as absolute abundance per milligram and taxa transitions and fluctuations from superficial through the deepest dissected layers. The method provides these data regardless of lesion type, stage, or complexity, whether untreated or treated.</p><p><strong>Conclusions: </strong>This method provides new details and perspectives on dental caries taxa that could help develop diagnostic instruments and treatments to halt dental caries progression.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2593129"},"PeriodicalIF":5.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04eCollection Date: 2025-01-01DOI: 10.1080/20002297.2025.2591641
Ying Xu, Min Yu, Yuhan Xu, Fengzhen Zhang, Hua Wang, Jie Zhang, Xuemei Gao
Background: Tonsillar hypertrophy (TH) and adenotonsillar hypertrophy (ATH) are primary risk factors for paediatric obstructive sleep apnoea (OSA), but their salivary microbiota differ.
Objective: This study aimed to investigate whether the tonsillar surface and core microbiota resemble the salivary microbiota, and whether these microbial profiles are influenced by adenoid hypertrophy and related clinical factors.
Design: Forty-nine children undergoing tonsillectomy were enrolled, including 21 children with TH and 28 with ATH. Saliva and tonsillar surface swabs were collected preoperatively, and core tissues were obtained intraoperatively. Microbiota were profiled via 16S rRNA sequencing, compared across sites and groups, and correlated with preoperative clinical indicators.
Results: The tonsillar core microbiota was relatively stable across all children, whereas the surface and salivary microbiota shifted with adenoid hypertrophy. Prevotella, Neisseria, Veillonella, Alloprevotella, Lancefieldella and Haemophilus were consistently more abundant on the tonsillar surface compared to the core. Gemella was uniquely enriched on the surface and positively correlated with the obstructive apnoea-hypopnoea index and red cell distribution width in the TH group.
Conclusions: This study reveals distinct microbial profiles between the tonsillar surface and core. In TH, surface microbiota was associated with OSA severity and haematological indicators, suggesting potential relevance that warrants further investigation.
{"title":"Salivary and tonsillar microbiota across multiple sites in paediatric tonsillar hypertrophy and their associations with clinical factors.","authors":"Ying Xu, Min Yu, Yuhan Xu, Fengzhen Zhang, Hua Wang, Jie Zhang, Xuemei Gao","doi":"10.1080/20002297.2025.2591641","DOIUrl":"10.1080/20002297.2025.2591641","url":null,"abstract":"<p><strong>Background: </strong>Tonsillar hypertrophy (TH) and adenotonsillar hypertrophy (ATH) are primary risk factors for paediatric obstructive sleep apnoea (OSA), but their salivary microbiota differ.</p><p><strong>Objective: </strong>This study aimed to investigate whether the tonsillar surface and core microbiota resemble the salivary microbiota, and whether these microbial profiles are influenced by adenoid hypertrophy and related clinical factors.</p><p><strong>Design: </strong>Forty-nine children undergoing tonsillectomy were enrolled, including 21 children with TH and 28 with ATH. Saliva and tonsillar surface swabs were collected preoperatively, and core tissues were obtained intraoperatively. Microbiota were profiled via 16S rRNA sequencing, compared across sites and groups, and correlated with preoperative clinical indicators.</p><p><strong>Results: </strong>The tonsillar core microbiota was relatively stable across all children, whereas the surface and salivary microbiota shifted with adenoid hypertrophy. <i>Prevotella</i>, <i>Neisseria</i>, <i>Veillonella</i>, <i>Alloprevotella</i>, <i>Lancefieldella</i> and <i>Haemophilus</i> were consistently more abundant on the tonsillar surface compared to the core. <i>Gemella</i> was uniquely enriched on the surface and positively correlated with the obstructive apnoea-hypopnoea index and red cell distribution width in the TH group.</p><p><strong>Conclusions: </strong>This study reveals distinct microbial profiles between the tonsillar surface and core. In TH, surface microbiota was associated with OSA severity and haematological indicators, suggesting potential relevance that warrants further investigation.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2591641"},"PeriodicalIF":5.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04eCollection Date: 2025-01-01DOI: 10.1080/20002297.2025.2594296
Yue Xu, Xin Leng, Qi Liu, Qianqian Ji, Jiale Li, Xiaoping Huang, Liuqing Li, Yifan Lin, Ida Karlsson, Yiqiang Zhan
Background: Smoking increases mortality risk and alters the oral microbiome, but its mediating role in the smoking-survival relationship remains unclear. This study examined whether oral microbiome diversity mediates the association between smoking and all-cause mortality.
Methods: We included 8,223 participants from the National Health and Nutrition Examination Survey with linked mortality data through 2019. Oral microbiome diversity was assessed using alpha and beta diversity metrics. Associations between smoking, diversity, and mortality were assessed using Weibull Accelerated Failure Time models. Multivariable linear regression evaluated the relationship between smoking and oral microbiome diversity. Mediation analysis estimated the Natural Direct Effect (NDE) and Natural Indirect Effect (NIE). Sensitivity analyses assessed effect heterogeneity.
Results: Among participants, 429 were deceased. Current smoking was associated with a 42.3% shorter survival time (TR = 0.577). Greater ln-transformed observed Operational Taxonomic Units (OTU) richness was associated with 33.2% longer survival time (TR = 1.332). Smoking was associated with survival time through NIE = 1.013 (95% CI: 1.003, 1.033) and NDE = 0.577 (95% CI: 0.474, 0.697). Sensitivity analyses supported the findings.
Discussion: Oral microbiome diversity partially mediated the association between smoking and mortality. Although smoking shortened survival, its effect on increasing OTU richness modestly suppressed this risk. These results highlight a complex microbial pathway and support further investigation into species-level mechanisms and potential microbiome-targeted interventions.
{"title":"The oral microbiome as mediators in the association between smoking and all-cause mortality.","authors":"Yue Xu, Xin Leng, Qi Liu, Qianqian Ji, Jiale Li, Xiaoping Huang, Liuqing Li, Yifan Lin, Ida Karlsson, Yiqiang Zhan","doi":"10.1080/20002297.2025.2594296","DOIUrl":"10.1080/20002297.2025.2594296","url":null,"abstract":"<p><strong>Background: </strong>Smoking increases mortality risk and alters the oral microbiome, but its mediating role in the smoking-survival relationship remains unclear. This study examined whether oral microbiome diversity mediates the association between smoking and all-cause mortality.</p><p><strong>Methods: </strong>We included 8,223 participants from the National Health and Nutrition Examination Survey with linked mortality data through 2019. Oral microbiome diversity was assessed using alpha and beta diversity metrics. Associations between smoking, diversity, and mortality were assessed using Weibull Accelerated Failure Time models. Multivariable linear regression evaluated the relationship between smoking and oral microbiome diversity. Mediation analysis estimated the Natural Direct Effect (NDE) and Natural Indirect Effect (NIE). Sensitivity analyses assessed effect heterogeneity.</p><p><strong>Results: </strong>Among participants, 429 were deceased. Current smoking was associated with a 42.3% shorter survival time (TR = 0.577). Greater ln-transformed observed Operational Taxonomic Units (OTU) richness was associated with 33.2% longer survival time (TR = 1.332). Smoking was associated with survival time through NIE = 1.013 (95% CI: 1.003, 1.033) and NDE = 0.577 (95% CI: 0.474, 0.697). Sensitivity analyses supported the findings.</p><p><strong>Discussion: </strong>Oral microbiome diversity partially mediated the association between smoking and mortality. Although smoking shortened survival, its effect on increasing OTU richness modestly suppressed this risk. These results highlight a complex microbial pathway and support further investigation into species-level mechanisms and potential microbiome-targeted interventions.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2594296"},"PeriodicalIF":5.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}