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Meta-omics reveals subgingival plaque reconstruction dynamics. 元组学揭示龈下菌斑重建动态。
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-10-13 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2569528
Fangjie Zhou, Yajie Wu, Biao Ren, Yuchuan Liu, Kaihua Luo, Qinyang Li, Fangting Huang, Xian Peng, Yuqing Li, Zhifei Su, Jiyao Li

Background: The homeostasis of the subgingival microbiome is crucial for periodontal health, although the dynamics governing its community variation remain insufficiently studied. This study aims to investigate the dynamics of subgingival microbiota reassembly after disruption, focusing on core taxa, functions, and driving forces.

Methods: 339 subgingival plaques in periodontally healthy states were collected before and after ultrasonic cleaning across 12 timepoints for 1 year. All samples underwent full-length 16S rRNA sequencing; 30 were selected for metagenomic sequencing.

Results: Our findings revealed that disturbed subgingival microbiota underwent short-term disruptions but subsequently reverted to baseline, maintaining stability within a year. Homogeneous selection dominated assembly, driving convergent structure under consistent pressure. Such a recovery process was accompanied by key taxa increased sequentially: Pseudomonas fluorescens early, Haemophilus parainfluenzae mid-stage, and Capnocytophaga spp. late. Functionally, reconstruction began with energy metabolism, expanded via biofilm formation and LPS biosynthesis mid-stage, and involved late apoptosis and complex amino acid metabolism. Microbial interactions, including positive regulation from Veillonella HMT 780 to Fusobacterium HMT 248, internally drove community assembly.

Conclusion: Our study clarifies species and functional dynamics during subgingival microbiota reconstruction and maps time-directed networks among stage-specific bacteria, offering a theoretical basis for targeted microbiome regulation.

背景:牙龈下微生物群的动态平衡对牙周健康至关重要,尽管其群落变化的动力学控制仍未得到充分研究。本研究旨在探讨牙龈下微生物群在破坏后的重组动态,重点关注核心分类群、功能和驱动力。方法:收集超声清洁前后12个时间点牙周健康状态的龈下斑块339个,为期1年。所有样本均进行16S rRNA全长测序;选取30例进行宏基因组测序。结果:我们的研究结果显示,受到干扰的牙龈下微生物群经历了短期的破坏,但随后恢复到基线,并在一年内保持稳定。均匀选择主导装配,在一致压力下驱动收敛结构。这种恢复过程伴随着关键类群的顺序增加:早期荧光假单胞菌,中期副流感嗜血杆菌,晚期嗜碳细胞吞噬菌。功能上,重建始于能量代谢,中期通过生物膜形成和LPS生物合成扩展,并涉及晚期凋亡和复杂氨基酸代谢。微生物的相互作用,包括从细孔菌HMT 780到梭杆菌HMT 248的正调控,在内部推动了群落的聚集。结论:我们的研究阐明了牙龈下菌群重建过程中的物种和功能动态,并绘制了特定阶段细菌之间的时间导向网络,为针对性地调节微生物群提供了理论基础。
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引用次数: 0
The role of oral microbiota in digestive system diseases: current advances and perspectives. 口腔微生物群在消化系统疾病中的作用:目前的进展和观点。
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-10-13 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2566403
Yaqi Li, Yiping Xin, Wenlu Zong, Xiaoyu Li

The oral microbiota is intimately linked to human health and various disease states. With the advent of the Human Microbiome Project, our comprehension of the oral microbiota has substantially improved. This microbial community is not only associated with a range of oral diseases, such as dental caries and periodontal diseases, but also with numerous digestive disorders, as demonstrated by recent clinical studies. Specific bacteria residing in the oral cavity, such as Porphyromonas gingivalis, Fusobacterium species and Streptococcus species, have been shown to translocate to the gastrointestinal tract, thereby establishing a potential connection between the oral and gut microbiota. The transfer and ectopic colonization of oral microbiota within the gastrointestinal tract may contribute to both the onset and exacerbation of gastrointestinal diseases. Following the principles of dysregulation characteristics, mechanism research and innovative treatment, this paper systematically reviews the association between the oral microbiota and various digestive system diseases. This paper explores how specific oral microbiota drive digestive system diseases mechanisms and evaluates treatments including probiotics, prebiotics, fecal microbiota transplantation, and targeted antimicrobial therapies. By clarifying the oral-gut microbiota-disease link, it highlights oral microbiota monitoring as a promising tool for early detection, diagnosis, and therapy.

口腔微生物群与人类健康和各种疾病状态密切相关。随着人类微生物组计划的出现,我们对口腔微生物群的理解有了很大的提高。最近的临床研究表明,这种微生物群落不仅与一系列口腔疾病(如龋齿和牙周病)有关,而且与许多消化系统疾病有关。居住在口腔中的特定细菌,如牙龈卟啉单胞菌、梭杆菌和链球菌,已被证明可以转移到胃肠道,从而在口腔和肠道微生物群之间建立了潜在的联系。胃肠道内口腔微生物群的转移和异位定植可能导致胃肠道疾病的发生和恶化。本文遵循失调特征、机制研究和创新治疗的原则,系统综述了口腔微生物群与各种消化系统疾病的关系。本文探讨了特定的口腔微生物群驱动消化系统疾病的机制,并评估了包括益生菌、益生元、粪便微生物群移植和靶向抗菌治疗在内的治疗方法。通过阐明口腔-肠道微生物群-疾病之间的联系,它强调了口腔微生物群监测作为早期发现、诊断和治疗的一种有前途的工具。
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引用次数: 0
Water-insoluble exopolysaccharide synthesized by glucosyltransferases mediates the antibacterial activity of ClyR against Streptococcus mutans. 葡萄糖基转移酶合成的水不溶性外多糖介导了ClyR对变形链球菌的抗菌活性。
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-10-09 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2566894
Qizhao Ma, Xiaowan Wang, Mai Xu, Ziyi Yang, Dian Zhang, Jiamin Chen, Tao Gong, Hang Yang, Yuqing Li

Background: Dental caries is a widespread global health issue strongly associated with Streptococcus mutans. Bacteriophage-derived lytic enzymes such as ClyR hold considerable promise as antibacterial potential, but the molecular mechanisms underlying their activity against S. mutans remain unclear.

Objective: This study aimed to determine the role of water-insoluble exopolysaccharides (EPS) in mediating the antibacterial activity of ClyR against S. mutans.

Design: We compared the antibacterial effects of ClyR on S. mutans UA159 and its ΔgtfB mutant, which is characterized by reduced synthesis of water-insoluble EPS. Biofilm architecture and susceptibility were assessed using scanning electron microscopy, confocal laser scanning microscopy, and biomass quantification. Adsorption assays were conducted to evaluate the interaction between ClyR and water-insoluble EPS.

Results: The ΔgtfB mutant exhibited significantly higher resistance to ClyR than S. mutans UA159, with reduced biofilm disruption and bacterial loss after treatment. In vitro assays confirmed that water-insoluble EPS specifically adsorbed ClyR, with binding localized to its catalytic PlyCAC domain.

Conclusions: Water-insoluble EPS synthesized by S. mutans glucosyltransferases plays a critical role in modulating bacterial susceptibility to ClyR. These findings reveal a novel mechanism underlying bacteriophage lysin activity and highlight EPS as a potential target for enhancing ClyR efficacy against cariogenic biofilms.

背景:龋齿是一种与变形链球菌密切相关的全球性健康问题。噬菌体衍生的裂解酶如ClyR具有相当大的抗菌潜力,但其对变形链球菌活性的分子机制尚不清楚。目的:研究水不溶性外多糖(water-insoluble exopolysaccharides, EPS)在介导菌株clr对变形链球菌的抑菌活性中的作用。设计:我们比较了ClyR对S. mutans UA159及其ΔgtfB突变体的抑菌效果,该突变体的特点是减少了水不溶性EPS的合成。利用扫描电子显微镜、共聚焦激光扫描显微镜和生物量定量评估生物膜结构和敏感性。采用吸附法评价了ClyR与水不溶性EPS之间的相互作用。结果:ΔgtfB突变体对ClyR的抗性明显高于S. mutans UA159,治疗后生物膜破坏和细菌损失减少。体外实验证实,不溶于水的EPS特异性吸附了ClyR,其结合定位于其催化结构域PlyCAC。结论:变形链球菌糖基转移酶合成的水不溶性EPS在调节细菌对ClyR的敏感性中起关键作用。这些发现揭示了噬菌体溶酶活性的新机制,并突出了EPS作为增强ClyR对龋齿生物膜的功效的潜在靶点。
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引用次数: 0
Antifungal efficacy of caffeic acid and nano-caffeic acid particles against candidiasis: an in vitro study. 咖啡酸和纳米咖啡酸颗粒抗念珠菌病的体外研究。
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2564690
Maede Salehi, Iman Haghani, Majid Saeedi, Katayoun Morteza-Semnani, Reza Negarandeh, Abolfazl Hosseinnataj, Ali Jafari, Anahita Lotfizadeh, Anahita Rafiei, Tahereh Molania

Background/purpose: Candidiasis is the most common oral fungal infection. Several medications have been introduced to manage this infection. This study investigated the antifungal effect of caffeic acid and nano-caffeic acid.

Materials and methods: The size and particle dispersion index (PDI) of caffeic acid-containing niosome vesicles were measured after their production. The zeta potential was measured using a Zetasizer Nano ZS, and the amount of nano-caffeic acid released from the vesicles was measured. Candida isolates were cultured in Malt Extract Agar medium. Nystatin, fluconazole, caffeic acid and nano-caffeic acid were studied according to the Clinical and Laboratory Standards Institute (CLSI) protocol (M27-A3/S4), a broth microdilution test was performed, and the minimum inhibitory concentration (MIC) was determined. The data were analyzed using the Mann‒Whitney and Kruskal‒Wallis tests.

Results: The optimal formulation had 100 mg Tween 60, 100 mg Span 60, 200 mg cholesterol, a size of 271.83 ± 3.11 nm, a PDI of 0.21 ± 0.02, a zeta potential of 5.58 ± 0.47 mV and an encapsulation efficiency (EE%) of 42.34 ± 4.34%. The size, absolute zeta potential and EE% increased significantly with increasing cholesterol content from zero to 200  mg (P < 0.05). Caffeic acid, nano-caffeic acid, carrier, fluconazole and nystatin had the lowest to highest antifungal activity, respectively.

Conclusion: According to the MIC50 and MIC90 values, nystatin, fluconazole, carrier, nano-caffeic acid and caffeic acid had the highest to lowest inhibitory efficiency against Candida species, respectively.

背景/目的:念珠菌病是最常见的口腔真菌感染。已经引入了几种药物来控制这种感染。研究了咖啡酸和纳米咖啡酸的抗真菌作用。材料与方法:制备咖啡酸溶囊体后,测定其粒径和颗粒分散指数(PDI)。采用Zetasizer Nano ZS测定zeta电位,并测定微泡中纳米咖啡酸的释放量。假丝酵母分离株在麦芽提取物琼脂培养基中培养。根据临床与实验室标准协会(CLSI)的方案(M27-A3/S4)对制霉菌素、氟康唑、咖啡酸和纳米咖啡酸进行研究,并进行肉汤微量稀释试验,确定最低抑菌浓度(MIC)。使用Mann-Whitney和Kruskal-Wallis检验对数据进行分析。结果:最佳处方为Tween 60 100 mg、Span 60 100 mg、胆固醇200 mg,粒径为271.83±3.11 nm, PDI为0.21±0.02,zeta电位为5.58±0.47 mV,包封效率(EE%)为42.34±4.34%。结论:根据MIC50和MIC90值,制霉菌素、氟康唑、载体、纳米咖啡酸和咖啡酸对念珠菌的抑制效果分别为最高和最低。
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引用次数: 0
Streptococcus cristatus reduces cariogenicity of saliva-derived microcosms under pH-dependent conditions. 在ph依赖的条件下,冠状链球菌降低了唾液衍生的微生物的龋齿性。
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2565450
Yanling Cai, Lijing Wu, Bernd W Brandt, Mark J Buijs, Xi Wei, Hongyan Liu, Dongmei Deng

Background: The study aims to investigate Streptococcus cristatus, an oral commensal bacterium, as a probiotic for dental caries prevention by modulating the oral microbiome.

Methods: Saliva from four healthy donors was used to establish 24-h microcosm biofilms in an in vitro 96-well peg model. The preformed biofilms were then exposed to biofilm medium containing 0.2% sucrose (BM), with or without S. cristatus. They were grown for 48 h under two conditions: a constant pH-neutral regime (BM supplemented with 76 mM K2HPO4 and 15 mM KH2PO4, pH 7.0) or cariogenic pH-cycling regime (8 h pH-neutral and 16 h in BM containing 100 mM acetic acid, pH 5.5). Phosphate and acetate buffers were used to control pH. After 72 h, the biofilms were analyzed for biomass, lactic acid production, hydrogen peroxide (HP) concentrations, and microbial composition via 16S rRNA gene sequencing.

Results: S. cristatus successfully integrated into 24-h preformed microcosm biofilms derived from individual saliva. Under pH-neutral conditions, it reduced biofilm biomass and lactate production while increasing hydrogen peroxide (HP) generation in a donor-dependent manner. Conversely, under cariogenic pH-cycling conditions, these inhibitory effects on biomass and lactate production were consistent across all donors, although HP was undetectable. Microbiome analysis revealed that S. cristatus increased species richness and mitigated the compositional shifts caused by pH-cycling. This was achieved by inhibiting Streptococcus salivarius/vestibularis across all donors, while promoting Streptococcus mitis group and Streptococcus anginosus in a donor-dependent manner.

Conclusions: S. cristatus represents a promising microbiome modulator with the potential to substantially mitigate the cariogenicity of oral microcosms.

背景:本研究旨在探讨口腔共生细菌cristatus链球菌通过调节口腔微生物群作为益生菌预防龋齿的作用。方法:采用4例健康供体唾液建立体外96孔peg模型24 h微生物生物膜。然后将预成型的生物膜暴露于含有0.2%蔗糖(BM)的生物膜培养基中,含或不含葡萄球菌。它们在两种条件下生长48小时:恒定的pH中性状态(BM中添加76 mM K2HPO4和15 mM KH2PO4, pH 7.0)或致龋性pH循环状态(8 h pH中性,16 h BM中添加100 mM乙酸,pH 5.5)。使用磷酸盐和醋酸盐缓冲液控制ph。72 h后,通过16S rRNA基因测序分析生物膜的生物量、乳酸产量、过氧化氢(HP)浓度和微生物组成。结果:棘球菌成功整合到24小时预成型的个体唾液微生物生物膜中。在ph中性条件下,它减少了生物膜生物量和乳酸产量,同时以供体依赖的方式增加了过氧化氢(HP)的产生。相反,在致龋性ph循环条件下,尽管HP检测不到,但这些对生物量和乳酸产量的抑制作用在所有供体中都是一致的。微生物组学分析表明,凤尾花增加了物种丰富度,减轻了ph循环引起的组成变化。这是通过抑制所有供体中的唾液链球菌/前庭链球菌来实现的,同时以供体依赖的方式促进炎链球菌组和血管链球菌。结论:葡萄球菌是一种很有前途的微生物组调节剂,具有显著减轻口腔微生物致龋性的潜力。
{"title":"Streptococcus cristatus reduces cariogenicity of saliva-derived microcosms under pH-dependent conditions.","authors":"Yanling Cai, Lijing Wu, Bernd W Brandt, Mark J Buijs, Xi Wei, Hongyan Liu, Dongmei Deng","doi":"10.1080/20002297.2025.2565450","DOIUrl":"10.1080/20002297.2025.2565450","url":null,"abstract":"<p><strong>Background: </strong>The study aims to investigate <i>Streptococcus cristatus</i>, an oral commensal bacterium, as a probiotic for dental caries prevention by modulating the oral microbiome.</p><p><strong>Methods: </strong>Saliva from four healthy donors was used to establish 24-h microcosm biofilms in an <i>in vitro</i> 96-well peg model. The preformed biofilms were then exposed to biofilm medium containing 0.2% sucrose (BM), with or without <i>S. cristatus</i>. They were grown for 48 h under two conditions: a constant pH-neutral regime (BM supplemented with 76 mM K<sub>2</sub>HPO<sub>4</sub> and 15 mM KH<sub>2</sub>PO<sub>4</sub>, pH 7.0) or cariogenic pH-cycling regime (8 h pH-neutral and 16 h in BM containing 100 mM acetic acid, pH 5.5). Phosphate and acetate buffers were used to control pH. After 72 h, the biofilms were analyzed for biomass, lactic acid production, hydrogen peroxide (HP) concentrations, and microbial composition via 16S rRNA gene sequencing.</p><p><strong>Results: </strong><i>S. cristatus</i> successfully integrated into 24-h preformed microcosm biofilms derived from individual saliva. Under pH-neutral conditions, it reduced biofilm biomass and lactate production while increasing hydrogen peroxide (HP) generation in a donor-dependent manner. Conversely, under cariogenic pH-cycling conditions, these inhibitory effects on biomass and lactate production were consistent across all donors, although HP was undetectable. Microbiome analysis revealed that <i>S. cristatus</i> increased species richness and mitigated the compositional shifts caused by pH-cycling. This was achieved by inhibiting <i>Streptococcus salivarius/vestibularis</i> across all donors, while promoting <i>Streptococcus mitis</i> group and <i>Streptococcus anginosus</i> in a donor-dependent manner.</p><p><strong>Conclusions: </strong><i>S. cristatus</i> represents a promising microbiome modulator with the potential to substantially mitigate the cariogenicity of oral microcosms.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2565450"},"PeriodicalIF":5.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258295","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}
引用次数: 0
Sepsis and septic shock caused by Porphyromonas gingivalis: a case report. 牙龈卟啉单胞菌致脓毒症及感染性休克1例。
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-10-05 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2564692
Meifang Lin, Guang Yang, Cong Shen, Yinglun Xiao, Cha Chen, Xuan Zhang

Background: Porphyromonas gingivalis is a predominant pathogen in periodontitis and is closely associated with the progression of chronic obstructive pulmonary disease (COPD).

Objective: This case report aims to describe a case of sepsis caused by P. gingivalis in a patient with COPD and a history of dental pain, highlighting the diagnostic challenges and clinical implications.

Design: This single case report was based on clinical data collected from medical records, with the pathogen identified from blood cultures by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). A comparative analysis was performed between the present case and previously reported cases of P. gingivalis bacteremia or sepsis based on a literature review. The patient was discharged after his general condition improved as a result of the potentially effective antimicrobial agents and anti-infective treatments through literature review.

Results: A 73-year-old man with COPD and a prolonged history of dental pain presented with a 30-year history of recurrent cough, expectoration, and dyspnoea, with symptoms exacerbating over the past 3 d and the recent onset of high fever for 1 d. Clinical evaluation revealed sepsis with rapid progression to septic shock. Blood cultures confirmed the presence of P. gingivalis.

Conclusions: This case highlights the need to consider anaerobes like P. gingivalis in septic patients with poor oral health, especially for patients with dental pain or periodontitis, and highlights the diagnostic challenges associated with slow-growing pathogens.

背景:牙龈卟啉单胞菌是牙周炎的主要病原体,与慢性阻塞性肺疾病(COPD)的进展密切相关。目的:本病例报告旨在描述一例慢性阻塞性肺病患者因牙龈假单胞菌引起的脓毒症,并有牙痛史,强调诊断挑战和临床意义。设计:本病例报告基于从医疗记录中收集的临床数据,通过基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)从血液培养物中鉴定病原体。在文献综述的基础上,对本病例和先前报道的牙龈卟啉卟啉菌血症或败血症进行了比较分析。通过文献查阅,患者在使用抗菌药物和抗感染治疗后,一般情况好转,出院。结果:73岁男性,慢性阻塞性肺病患者,长期牙痛病史,30年复发性咳嗽、咳痰、呼吸困难,过去3 d症状加重,近期出现高热1 d。临床评估显示败血症迅速发展为感染性休克。血液培养证实了牙龈假单胞菌的存在。结论:本病例强调了在口腔健康状况不佳的脓毒症患者,特别是牙痛或牙周炎患者中,需要考虑像牙龈卟啉卟啉菌这样的厌氧菌,并强调了与生长缓慢的病原体相关的诊断挑战。
{"title":"Sepsis and septic shock caused by <i>Porphyromonas gingivalis</i>: a case report.","authors":"Meifang Lin, Guang Yang, Cong Shen, Yinglun Xiao, Cha Chen, Xuan Zhang","doi":"10.1080/20002297.2025.2564692","DOIUrl":"10.1080/20002297.2025.2564692","url":null,"abstract":"<p><strong>Background: </strong><i>Porphyromonas gingivalis</i> is a predominant pathogen in periodontitis and is closely associated with the progression of chronic obstructive pulmonary disease (COPD).</p><p><strong>Objective: </strong>This case report aims to describe a case of sepsis caused by <i>P. gingivalis</i> in a patient with COPD and a history of dental pain, highlighting the diagnostic challenges and clinical implications.</p><p><strong>Design: </strong>This single case report was based on clinical data collected from medical records, with the pathogen identified from blood cultures by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). A comparative analysis was performed between the present case and previously reported cases of <i>P. gingivalis</i> bacteremia or sepsis based on a literature review. The patient was discharged after his general condition improved as a result of the potentially effective antimicrobial agents and anti-infective treatments through literature review.</p><p><strong>Results: </strong>A 73-year-old man with COPD and a prolonged history of dental pain presented with a 30-year history of recurrent cough, expectoration, and dyspnoea, with symptoms exacerbating over the past 3 d and the recent onset of high fever for 1 d. Clinical evaluation revealed sepsis with rapid progression to septic shock. Blood cultures confirmed the presence of <i>P. gingivalis</i>.</p><p><strong>Conclusions: </strong>This case highlights the need to consider anaerobes like <i>P. gingivalis</i> in septic patients with poor oral health, especially for patients with dental pain or periodontitis, and highlights the diagnostic challenges associated with slow-growing pathogens.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2564692"},"PeriodicalIF":5.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244646","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}
引用次数: 0
Novel biomarker identification for oral squamous cell carcinoma development in nonsmoker, nondrinker, and nonchewer patients using third-generation sequencing of oral microbiome. 利用第三代口腔微生物组测序技术鉴定不吸烟、不饮酒和不咀嚼患者口腔鳞状细胞癌发展的新生物标志物。
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-10-02 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2565452
Wei-Ni Lyu, Cheng-Ying Shen, Yung-Hua Lee, Shin-Kuang Chen, Eric Y Chuang, Pei-Jen Lou, Mong-Hsun Tsai

Background/objective: Oral squamous cell carcinoma (OSCC) in patients without tobacco, alcohol, or betel-quid habits is poorly understood and difficult to detect early. This study aimed to identify microbial biomarkers specific to this habit-free population using third-generation sequencing (TGS).

Patients/materials and methods: Twenty-seven habit-free OSCC patients were recruited at National Taiwan University Hospital (NTUH). Paired tumor and adjacent normal tissues were collected with informed consent and NTUH Research Ethics Committee approval (IRB 201902080RINC, 201304078RIND). Full-length 16S rRNA sequencing (PacBio Sequel IIe) was processed with DADA2 and SILVA. Biomarkers were identified using sparse partial least squares discriminant analysis (sPLS-DA) and random forest with cross-validation, and validated against three public OSCC cohorts.

Results: A three-species panel-Eikenella corrodens, Slackia exigua, and Eggerthia catenaformis-discriminated tumor from normal tissues (AUC = 0.905 training; 0.733 testing). Functional and network analyses showed tumor-enriched taxa forming pro-inflammatory clusters linked to lipid and glutamine metabolism, while commensals correlated with homeostatic pathways. Cross-cohort comparison confirmed this panel's specificity to habit-free OSCC.

Conclusions: Using TGS, we revealed distinct microbial signatures in habit-free OSCC that may aid early diagnosis and underscore the role of microbiome-host interactions in carcinogenesis.

背景/目的:口腔鳞状细胞癌(OSCC)在没有吸烟、饮酒或饮用槟榔习惯的患者中,人们对其了解甚少,难以早期发现。本研究旨在利用第三代测序技术(TGS)鉴定这种无习惯人群特有的微生物生物标志物。经知情同意和NTUH研究伦理委员会批准(IRB 201902080RINC, 201304078RIND),收集配对肿瘤和邻近正常组织。采用DADA2和SILVA进行16S rRNA全长测序(PacBio Sequel IIe)。使用稀疏偏最小二乘判别分析(sPLS-DA)和随机森林进行交叉验证,并对三个公共OSCC队列进行验证。结果:艾肯氏菌(eikenella)、艾肯氏菌(Slackia exigua)和链状埃格氏菌(Eggerthia catenaformia)三种组与正常组织区分肿瘤(训练AUC = 0.905,检测AUC = 0.733)。功能和网络分析显示,肿瘤富集的分类群形成的促炎簇与脂质和谷氨酰胺代谢有关,而共生体与稳态途径相关。跨队列比较证实了该小组对无习惯OSCC的特异性。结论:使用TGS,我们揭示了无习惯OSCC中不同的微生物特征,这可能有助于早期诊断,并强调了微生物组-宿主相互作用在癌变中的作用。
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引用次数: 0
CRISPR cas7 influences the host-pathogen interaction of Porphyromonas gingivalis. CRISPR cas7对牙龈卟啉单胞菌宿主-病原体相互作用的影响
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-09-30 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2561790
Nicole de Mello Fiallos, Muhammad Irfan, Jose Solbiati, Alejandro R Walker, Jorge Frias-Lopez, Frank C Gibson

Introduction: Porphyromonas gingivalis, a Gram-negative anaerobe, is a key contributor to periodontal disease. Emerging evidence suggests a role for the P. gingivalis CRISPR-Cas system in disease progression, although the specific roles of its components remain unclear.

Objectives: Here we investigate the role of cas7, a Class 1 type I-B CRISPR-Cas system component, in P. gingivalis physiology and host interaction.

Methods: We compared P. gingivalis wild-type and ∆cas7 strains for growth, biofilm formation, oxidative stress resistance, and hemagglutination. Host interactions were assessed using THP-1 macrophage-like cells to evaluate intracellular survival and cytokine response. Dual RNA-seq enabled host and microbe transcriptomic profiling during cellular infection, and Galleria mellonella was used to assess virulence.

Results: The ∆cas7 mutant showed similar planktonic growth and biofilm formation compared to wild-type but was more sensitive to oxidative stress and had reduced hemagglutination. Although intracellular survival was unaffected, ∆cas7 altered the host cytokine production profile. Transcriptomic analysis revealed differential gene expression linked to oxidative stress and disease progression. In vivo, ∆cas7 infection led to a trend of increased larval mortality.

Conclusion: These findings reveal a previously unrecognized role for cas7 in modulating P. gingivalis virulence, offering new insights into CRISPR-Cas system functions in bacterial pathogenesis.

简介:牙龈卟啉单胞菌是一种革兰氏阴性厌氧菌,是导致牙周病的主要原因。新出现的证据表明牙龈假单胞菌CRISPR-Cas系统在疾病进展中起作用,尽管其成分的具体作用尚不清楚。目的:研究1类I-B型CRISPR-Cas系统组分cas7在牙龈假单胞菌生理和宿主相互作用中的作用。方法:比较牙龈假单胞菌野生型和∆cas7菌株的生长、生物膜形成、氧化应激抗性和血凝能力。使用THP-1巨噬细胞样细胞评估宿主相互作用,以评估细胞内存活和细胞因子反应。在细胞感染期间,双RNA-seq使宿主和微生物转录组分析成为可能,并使用mellonella Galleria来评估毒力。结果:与野生型相比,∆cas7突变体的浮游生物生长和生物膜形成相似,但对氧化应激更敏感,血凝反应降低。虽然细胞内存活不受影响,但∆cas7改变了宿主细胞因子的产生谱。转录组学分析揭示了与氧化应激和疾病进展相关的差异基因表达。体内感染∆cas7后,幼虫死亡率呈上升趋势。结论:这些发现揭示了以前未被认识到的cas7在调节牙龈卟啉卟啉毒力中的作用,为CRISPR-Cas系统在细菌发病机制中的功能提供了新的见解。
{"title":"CRISPR <i>cas7</i> influences the host-pathogen interaction of <i>Porphyromonas gingivalis</i>.","authors":"Nicole de Mello Fiallos, Muhammad Irfan, Jose Solbiati, Alejandro R Walker, Jorge Frias-Lopez, Frank C Gibson","doi":"10.1080/20002297.2025.2561790","DOIUrl":"10.1080/20002297.2025.2561790","url":null,"abstract":"<p><strong>Introduction: </strong><i>Porphyromonas gingivalis</i>, a Gram-negative anaerobe, is a key contributor to periodontal disease. Emerging evidence suggests a role for the <i>P. gingivalis</i> CRISPR-Cas system in disease progression, although the specific roles of its components remain unclear.</p><p><strong>Objectives: </strong>Here we investigate the role of <i>cas7</i>, a Class 1 type I-B CRISPR-Cas system component, in <i>P. gingivalis</i> physiology and host interaction.</p><p><strong>Methods: </strong>We compared <i>P. gingivalis</i> wild-type and ∆<i>cas7</i> strains for growth, biofilm formation, oxidative stress resistance, and hemagglutination. Host interactions were assessed using THP-1 macrophage-like cells to evaluate intracellular survival and cytokine response. Dual RNA-seq enabled host and microbe transcriptomic profiling during cellular infection, and <i>Galleria mellonella</i> was used to assess virulence.</p><p><strong>Results: </strong>The ∆<i>cas7</i> mutant showed similar planktonic growth and biofilm formation compared to wild-type but was more sensitive to oxidative stress and had reduced hemagglutination. Although intracellular survival was unaffected, ∆<i>cas7</i> altered the host cytokine production profile. Transcriptomic analysis revealed differential gene expression linked to oxidative stress and disease progression. In vivo, ∆<i>cas7</i> infection led to a trend of increased larval mortality.</p><p><strong>Conclusion: </strong>These findings reveal a previously unrecognized role for <i>cas7</i> in modulating <i>P. gingivalis</i> virulence, offering new insights into CRISPR-Cas system functions in bacterial pathogenesis.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2561790"},"PeriodicalIF":5.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212991","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}
引用次数: 0
Is Candida albicans a promoting factor, rather than an inducing factor for oral cancer? 白色念珠菌是口腔癌的促进因子,而不是诱发因子?
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-09-29 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2564694
Xu Wang, Xinming Zhang, Shuangshuang Wu, Wenqing Zhang, Zhimin Yan

Background: Candida albicans (C. albicans) is closely associated with cancer. Whether C. albicanscan directly induce the occurrence of oral cancer remains undetermined.

Objective: This study aimed to explore the carcinogenic potential of C. albicans in oral cancer.

Methods: Transcriptome sequencing (mRNAseq) and whole exome sequencing (WES) were performed to reveal the effects of long-term C. albicans stimulation on oral mucosa in mouse models. 4-nitroquinoline-1-oxide (4NQO), a mutagenic substance that mimics tobacco, was used to examine the combined role of tobacco smoking and C. albicans in oral carcinogenesis. Additionally, the somatic mutation landscape of chronic hyperplastic candidiasis (CHC)-a variant of oral candidiasis typically presenting with dysplasia-was characterized in biopsy tissues.

Results: Long-term C. albicans stimulation didn't directly induce oral cancer in mouse models but significantly upregulated the expression of genes related to cell proliferation and cancer development in the oral epithelium (e.g. Mki67, Kif11, Ccna2, Ckap2, Fos, Ccnb1; P < 0.05). Analysis of somatic mutations in CHC revealed that Candida and smoking might co-contribute to this type of precancerous lesion. Furthermore, C. albicans stimulation activated signaling pathways involved in inflammation and immune response, and promoted cancer formation in mice pre-treated with 4NQO.

Conclusion: C. albicans alone rarely induces carcinogenesis directly but can accelerate the malignant transformation of oral mucosa when combined with smoking.

背景:白色念珠菌(C. albicans)与癌症密切相关。白色念珠菌是否能直接诱发口腔癌的发生尚不清楚。目的:探讨白色念珠菌在口腔癌中的致癌性。方法:采用转录组测序(mRNAseq)和全外显子组测序(WES)研究长期刺激白色念珠菌对小鼠口腔黏膜的影响。4-硝基喹啉-1-氧化物(4NQO)是一种类似烟草的致突变物质,用于研究吸烟和白色假丝酵母菌在口腔致癌中的联合作用。此外,慢性增生性念珠菌病(CHC)——口腔念珠菌病的一种变体,通常表现为发育不良——的体细胞突变景观在活检组织中得到了表征。结果:在小鼠模型中,长期刺激白色念珠菌不会直接诱发口腔癌,但会显著上调口腔上皮细胞增殖和癌变相关基因(如Mki67、Kif11、Ccna2、Ckap2、Fos、Ccnb1等)的表达;P念珠菌和吸烟可能是导致这类癌前病变的共同因素。此外,白色念珠菌刺激激活了参与炎症和免疫反应的信号通路,并促进了4NQO预处理小鼠的癌症形成。结论:单纯白色念珠菌很少直接致癌,但与吸烟联合可加速口腔黏膜的恶性转化。
{"title":"Is <i>Candida albicans</i> a promoting factor, rather than an inducing factor for oral cancer?","authors":"Xu Wang, Xinming Zhang, Shuangshuang Wu, Wenqing Zhang, Zhimin Yan","doi":"10.1080/20002297.2025.2564694","DOIUrl":"10.1080/20002297.2025.2564694","url":null,"abstract":"<p><strong>Background: </strong><i>Candida albicans</i> (<i>C. albicans</i>) is closely associated with cancer. Whether <i>C. albicans</i>can directly induce the occurrence of oral cancer remains undetermined.</p><p><strong>Objective: </strong>This study aimed to explore the carcinogenic potential of <i>C. albicans</i> in oral cancer.</p><p><strong>Methods: </strong>Transcriptome sequencing (mRNAseq) and whole exome sequencing (WES) were performed to reveal the effects of long-term <i>C. albicans</i> stimulation on oral mucosa in mouse models. 4-nitroquinoline-1-oxide (4NQO), a mutagenic substance that mimics tobacco, was used to examine the combined role of tobacco smoking and <i>C. albicans</i> in oral carcinogenesis. Additionally, the somatic mutation landscape of chronic hyperplastic candidiasis (CHC)-a variant of oral candidiasis typically presenting with dysplasia-was characterized in biopsy tissues.</p><p><strong>Results: </strong>Long-term <i>C. albicans</i> stimulation didn't directly induce oral cancer in mouse models but significantly upregulated the expression of genes related to cell proliferation and cancer development in the oral epithelium (e.g. <i>Mki67</i>, <i>Kif11</i>, <i>Ccna2</i>, <i>Ckap2</i>, <i>Fos</i>, <i>Ccnb1</i>; <i>P </i>< 0.05). Analysis of somatic mutations in CHC revealed that <i>Candida</i> and smoking might co-contribute to this type of precancerous lesion. Furthermore, <i>C. albicans</i> stimulation activated signaling pathways involved in inflammation and immune response, and promoted cancer formation in mice pre-treated with 4NQO.</p><p><strong>Conclusion: </strong><i>C. albicans</i> alone rarely induces carcinogenesis directly but can accelerate the malignant transformation of oral mucosa when combined with smoking.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2564694"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206735","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}
引用次数: 0
Impact of bovine lactoferrin supplementation and reduced iron in formula on infant oral microbiome: a randomized controlled trial. 在配方奶中添加牛乳铁蛋白和减少铁对婴儿口腔微生物组的影响:一项随机对照试验。
IF 5.5 2区 医学 Q2 MICROBIOLOGY Pub Date : 2025-09-24 eCollection Date: 2025-01-01 DOI: 10.1080/20002297.2025.2561212
Cynthia Anticona, Anders Esberg, Staffan K Berglund, Maria Björmsjö, Olle Hernell, Bo Lönnerdal, Ingegerd Johansson, Pernilla Lif Holgerson

Introduction: Infant formulas with reduced iron levels and lactoferrin (Lf) supplementation might mimic the beneficial effects of breast milk on the oral microbiome. This study aimed to investigate the impact of a bovine Lf-supplemented and iron-reduced formula on the oral microbiota in infants at 4, 6 and 12 months.

Methods: In a double-blind controlled trial, 6-week-old formula-fed infants were randomized to receive either a formula with reduced iron levels (2 mg/L) and Lf supplementation (1 g/L) (n = 72), the same formula without Lf (n = 72), or a standard formula (8 mg iron/L) (n = 36). A breast-fed reference group (n = 72) was also included. The oral microbiota was analyzed at 4 (n = 244), 6 (n = 216) and 12 (n = 229) months of age using the Oxford Nanopore Technology of the 16S rRNA gene annotation (eHOMD database).

Results: Neither the within- or between-group diversities nor overall microbiota pattern assessment revealed any statistically significant differences in microbiota composition between the formula groups. However, single species were significantly associated with specific formula-fed groups. At 6 months, breast-fed infants exhibited significantly lower species richness and distinct microbiota composition compared to the formula-fed groups.

Conclusions: The effects of reduced iron levels and lactoferrin supplementation of infant formula on the oral microbiome were inconclusive.

婴儿配方奶粉中铁含量降低和乳铁蛋白(Lf)的补充可能模仿母乳对口腔微生物群的有益影响。本研究旨在研究补充低铁和减少铁的牛配方奶粉对4、6和12个月婴儿口腔微生物群的影响。方法:在一项双盲对照试验中,6周大的配方奶喂养的婴儿随机接受低铁(2 mg/L)和添加铁(1 g/L)的配方奶(n = 72),不添加铁的相同配方奶(n = 72),或标准配方奶(8 mg铁/L) (n = 36)。还包括母乳喂养参照组(n = 72)。在4 (n = 244)、6 (n = 216)和12 (n = 229)月龄时,采用牛津纳米孔技术对16S rRNA基因注释(eHOMD数据库)进行口腔微生物群分析。结果:无论是组内或组间的多样性,还是总体微生物群模式评估,都没有显示配方奶粉组之间微生物群组成有统计学上的显著差异。然而,单一物种与特定配方饲料组显著相关。在6个月时,与配方奶喂养组相比,母乳喂养的婴儿表现出明显较低的物种丰富度和独特的微生物群组成。结论:婴儿配方奶粉中降低铁水平和添加乳铁蛋白对口腔微生物群的影响尚无定论。
{"title":"Impact of bovine lactoferrin supplementation and reduced iron in formula on infant oral microbiome: a randomized controlled trial.","authors":"Cynthia Anticona, Anders Esberg, Staffan K Berglund, Maria Björmsjö, Olle Hernell, Bo Lönnerdal, Ingegerd Johansson, Pernilla Lif Holgerson","doi":"10.1080/20002297.2025.2561212","DOIUrl":"10.1080/20002297.2025.2561212","url":null,"abstract":"<p><strong>Introduction: </strong>Infant formulas with reduced iron levels and lactoferrin (Lf) supplementation might mimic the beneficial effects of breast milk on the oral microbiome. This study aimed to investigate the impact of a bovine Lf-supplemented and iron-reduced formula on the oral microbiota in infants at 4, 6 and 12 months.</p><p><strong>Methods: </strong>In a double-blind controlled trial, 6-week-old formula-fed infants were randomized to receive either a formula with reduced iron levels (2 mg/L) and Lf supplementation (1 g/L) (<i>n</i> = 72), the same formula without Lf (<i>n</i> = 72), or a standard formula (8 mg iron/L) (<i>n</i> = 36). A breast-fed reference group (<i>n</i> = 72) was also included. The oral microbiota was analyzed at 4 (<i>n</i> = 244), 6 (<i>n</i> = 216) and 12 (<i>n</i> = 229) months of age using the Oxford Nanopore Technology of the 16S rRNA gene annotation (<i>e</i>HOMD database).</p><p><strong>Results: </strong>Neither the within- or between-group diversities nor overall microbiota pattern assessment revealed any statistically significant differences in microbiota composition between the formula groups. However, single species were significantly associated with specific formula-fed groups. At 6 months, breast-fed infants exhibited significantly lower species richness and distinct microbiota composition compared to the formula-fed groups.</p><p><strong>Conclusions: </strong>The effects of reduced iron levels and lactoferrin supplementation of infant formula on the oral microbiome were inconclusive.</p>","PeriodicalId":16598,"journal":{"name":"Journal of Oral Microbiology","volume":"17 1","pages":"2561212"},"PeriodicalIF":5.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186158","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}
引用次数: 0
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Journal of Oral Microbiology
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