具核梭杆菌促进结直肠癌发生发展机制研究进展

具核梭杆菌(Fusobacterium nucleatum)是一种人体共生菌,尤其富集于口腔,在特定情况下可导致机会感染.近年来,随着微生物群与健康或疾病相关性研究的深入,具核梭杆菌与结直肠癌(colorectal cancer,CRC)之间的关联性研究备受关注.大量临床研究表明,具核梭杆菌在CRC中更为富集,且进一步...     

具核梭杆菌与结直肠癌关系的研究进展

结直肠癌(Colorectal cancer,CRC)是世界第三大癌症,涉及因素众多,而肠道菌群失调、菌群致病性与结直肠癌的发生、发展有着密不可分的关系。近期的研究发现具核梭杆菌(Fusobacterium nucleatum,F.nucleatum)与结直肠癌的发生存在显著的相关性。具核梭杆菌为革兰阴性厌氧菌,广泛存在于人体肠道中。分子机制研究发现,其能影响宿主细胞因子水平,促进血管生成、巨噬细胞M2极化和抑制机体免疫调节能力,进而增强肿瘤细胞增殖、侵袭及转移。本文就具核梭杆菌与结直肠癌相关机制研究进展作一综述。     

肠道中特异性菌群与结直肠癌的发生发展关系

结直肠癌（colorectal cancer,CRC）是常见的恶性肿瘤之一,并且发病率有逐年上升的趋势。建立有效的早期筛查方法是当今防治结直肠癌的首要任务。随着肠道菌群研究的深入,越来越多的研究结果显示肠道菌群与CRC的发生发展有一定的关系,尤其是具核梭杆菌、产肠毒素脆弱拟杆菌、大肠埃希菌等这些特异性菌群与CRC的发展密切相关。本文结合国内外最新研究进展,就这些特异性菌群在CRC发病机制中的作用作一综述,为进一步研究CRC和实现对其早期筛查提供新的思路。     

白介素-22与具核梭杆菌在结直肠癌发生发展中的协同作用

结直肠癌是威胁全球和我国公民健康的恶性肿瘤之一.近年来,越来越多的报道揭示了肠道微生物和免疫微环境在维持肠稳态中的重要作用;其中,具核梭杆菌介导的肠道微生态失调和免疫紊乱是近期研究热点之一.但是,少有研究关注肠道细菌和免疫炎症因子在致癌过程中的相互作用.本课题组发现,具核梭杆菌可以增高白介素-6(IL-6)和IL-22等免疫因子的表达,从而参与大肠癌的发生发展,且与大肠癌化疗疗效相关.IL-22和具核梭杆菌可能有协同促癌作用.     

肠道具核梭杆菌与结直肠癌的关系及其致病机制的研究进展

结直肠癌(colorectal cancer, CRC)为全球第三大常见癌症,死亡率位居第二。随着微生物组学技术的发展,近年来,研究发现,具核梭杆菌(Fusobacterium nucleatum,Fn)不仅参与口腔疾病和脑膜炎、心内膜炎、化脓性关节炎等口腔外感染性疾病的发生、发展,还可能通过促进结直肠上皮细胞增殖、促进机体炎症微环境、免疫调节等多种机制参与CRC的发生、发展,但具体致病机制还亟待阐明。基于此,现就Fn与CRC的关系和相关致病机制作一概述,为未来深入探究CRC生物预防及治疗提供理论依据。     

口腔菌群与肠道健康

人类口腔栖息着细菌、古生菌和病毒等多种微生物,口腔菌群是人体微生物组的重要组成部分。口腔中的条件致病菌,尤其是牙龈卟啉单胞菌和具核梭杆菌等,不仅充当着牙周病原体的传统角色,还可以通过各种方式进入肠道。越来越多的研究表明,口腔菌群与肠道菌群主要以协同或合作的方式致病,这些微生物群与人体的生理状态密切相关。本文就口腔菌群与肠道菌群的相互作用及其在炎症性疾病和结肠癌等肠道疾病发病中的作用进行综述。     

结直肠癌与肠道菌群

肠道是集消化、吸收、内分泌、免疫、屏障等功能为一体的重要器官,肠道菌群的结构和功能与人体的健康、疾病的发生发展及机体的快速康复息息相关。结直肠癌变是个逐步发生发展的过程,从局部炎性反应、腺瘤、癌前病变到恶化的过程可达数年甚至数十年之久。结肠癌早期临床症状不明显且潜伏期较长,容易造成漏诊和误诊,贻误最佳治疗时机。近年来,国内外多项研究显示大肠埃希菌、粪肠球菌、脆弱拟杆菌、解没食子酸链球菌、具核梭杆菌等细菌与结直肠癌的发生发展关系密切,这为我们从另外一个角度来进行结直肠癌早期诊断提供了新思路和新途径。     

具核梭杆菌通过调节肠道代谢产物丁酸钠上调Cdk1促进结直肠癌发展

该文探讨了肠道微生物具核梭杆菌(Fusobacterium nucleatum,Fn)通过调节代谢产物丁酸钠(NaB)对结直肠癌(CRC)发生发展的影响及其分子机制.提取临床组织RNA和蛋白,RT-qPCR和Western blot检测肿瘤组织与正常/癌旁组织Cdk1的mRNA及蛋白表达,同时检测具核梭杆菌的mRNA的...     

核梭杆菌与其它口腔细菌共聚及共聚抑制

目的：探讨核梭杆菌与其它口腔细菌共聚模式及共聚抑制的方法。方法：通过目测、比色和电镜进行观察。结果：证实细菌共聚具特异性。核梭杆菌能与牙龈卟啉菌、血链球菌和变链球菌发生共聚,可形成共聚桥,证实核梭杆菌是早、晚期定植菌的的粘接桥。经热处理后,核梭杆菌丧失共聚能力,而后三菌均保持原有的共聚能力。乳糖和Ｌ－鼠李糖对它们有解聚作用。结论：牙菌斑中存在细菌共聚,经过一定处理后共聚可解除。本研究为生态防治牙周病提供理论依据。     

具核梭杆菌通过Toll样受体促进口腔鳞状细胞癌发生发展的研究进展

口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)是常见的恶性肿瘤,其发病率和致死率位于口腔肿瘤的首位。目前,世界范围内约四分之一的恶性肿瘤与微生物感染相关。牙周主要致病菌具核梭杆菌(Fusobacterium nucleatum,F.nucleatum)可促进食管癌和结直肠癌恶性转化,并且与口腔鳞状细胞癌的发生发展密切相关。F.nucleaum通过与OSCC细胞外膜受体的相互作用,上调Toll样受体表达,调节免疫因子IL-6、IL-8等,实现对OSCC发生发展的影响。本研究将对Toll样受体在F.nucleaum促进OSCC发生发展中的作用机制作一综述。     

具核梭杆菌与全身疾病相关性的研究进展

具核梭杆菌(Fusobacterium nucleatum,F.nucleatum)是在口腔微生态环境中常驻的一种革兰阴性专性厌氧菌,近来研究发现F.nucleatum不仅与口腔感染性疾病如牙周病、根尖周病等的发生、发展密切相关,而且与早产低体重儿、结直肠癌、呼吸道感染等全身疾病密切相关。本研究对F.nucleatum生物学功能及与口腔感染、全身疾病相关性的研究进展作一综述。     

具核梭杆菌促进结直肠癌发生发展机制的研究进展

结直肠癌（colorectal cancer,CRC）是一种全球高发的恶性肿瘤,肠道菌群失调作为潜在致病因素逐渐受到关注。大量的研究发现具核梭杆菌（Fusobacterium nucleatum,F. nucleatum）在CRC组织中丰度显著升高,与CRC的发生有关,目前其具体的作用机制尚不明确。分子及细胞学研究表明F. nucleatum能够破坏肠道上皮屏障、损伤细胞DNA、影响肿瘤相关microRNAs的表达和促进肿瘤细胞转移。本文就F. nucleatum促进CRC发生发展的机制及相关研究进展作一综述。

     

Identification and characterization of a novel adhesin unique to oral fusobacteria

Fusobacterium nucleatum is a gram-negative anaerobe that is prevalent in periodontal disease and infections of different parts of the body. The organism has remarkable adherence properties, binding to partners ranging from eukaryotic and prokaryotic cells to extracellular macromolecules. Understanding its adherence is important for understanding the pathogenesis of F. nucleatum. In this study, a novel adhesin, FadA (Fusobacterium adhesin A), was demonstrated to bind to the surface proteins of the oral mucosal KB cells. FadA is composed of 129 amino acid (aa) residues, including an 18-aa signal peptide, with calculated molecular masses of 13.6 kDa for the intact form and 12.6 kDa for the secreted form. It is highly conserved among F. nucleatum, Fusobacterium periodonticum, and Fusobacterium simiae, the three most closely related oral species, but is absent in the nonoral species, including Fusobacterium gonidiaformans, Fusobacterium mortiferum, Fusobacterium naviforme, Fusobacterium russii, and Fusobacterium ulcerans. In addition to FadA, F. nucleatum ATCC 25586 and ATCC 49256 also encode two paralogues, FN1529 and FNV2159, each sharing 31% identity with FadA. A double-crossover fadA deletion mutant, F. nucleatum 12230-US1, was constructed by utilizing a novel sonoporation procedure. The mutant had a slightly slower growth rate, yet its binding to KB and Chinese hamster ovarian cells was reduced by 70 to 80% compared to that of the wild type, indicating that FadA plays an important role in fusobacterial colonization in the host. Furthermore, due to its uniqueness to oral Fusobacterium species, fadA may be used as a marker to detect orally related fusobacteria. F. nucleatum isolated from other parts of the body may originate from the oral cavity.     

口源性口臭患者主要厌氧菌的分布

目的分析口臭患者龈下菌斑和舌苔上主要相关厌氧菌的分布情况。方法选择口腔门诊中口臭患者29例,鼻闻法来确定产臭部位和非产臭部位;分别采集龈下菌斑和舌苔标本接种在非选择性培养基和核梭杆菌选择性培养基,厌氧培养5d后记录非选择性培养基上生长的细菌总数、产黑色素细菌总数及核梭杆菌选择性培养基上生长的目的菌总数。结果29例患者中,15例患者的口臭主要来源于龈缘菌斑,10例主要来源于舌苔,4例患者的口臭由龈缘菌斑和舌苔共同产生;产臭部位和非产臭部位相比,细菌总数、产黑色素菌和具核梭杆菌数都明显上升（P〈0．01）。结论口源性口臭患者口气变化与产黑色素细菌、核梭杆菌相关。     

Fluorescence based measurements of Fusobacterium nucleatum coaggregation and of fusobacterial attachment to mammalian cells

Fusobacterium nucleatum is a common oral anaerobe associated with gingivitis, periodontal disease and preterm deliveries. Coaggregation among oral bacteria is considered to be a significant factor in dental plaque development. Adhesion to host cells was suggested to be important for the F. nucleatum virulence associated with oral inflammation and with preterm births. An uncharacterized fusobacterial galactose inhibitible adhesin mediates coaggregation of F. nucleatum 12230 and F. nucleatum PK1594 with the periodontal pathogen Porphyromonas gingivalis. This adhesin is also involved with the attachment of both fusobacterial strains to host cells. However, it has been suggested that additional unidentified fusobacterial adhesins are involved in F. nucleatum virulence associated with preterm births. In this study, a fluorescence-based high throughput sensitive and reproducible method was developed for measuring bacterial coaggregation and bacterial attachment to mammalian cells. Using this method we found that coaggregation of F. nucleatum 4H with P. gingivalis and its attachment to murine macrophages is less inhibitible by galactose than that of F. nucleatum PK1594. These findings suggest that F. nucleatum 4H can serve as a model organism for identifying nongalactose inhibitible F. nucleatum adhesins considered to be involved in fusobacterial attachment to mammalian cells.     

Genotypic and phenotypic characterization of fusobacteria from Chinese and European patients with inflammatory periodontal diseases

Phylogenetic and antigenic studies were performed on 48 human oral Fusobacterium strains from Chinese patients with either necrotizing ulcerative gingivitis (NUG) or gingivitis and on 23 Fusobacterium nucleatum or Fusobacterium periodonticum strains from European periodontitis patients. Alignment of partial 16S rRNA gene sequences resulted in a phylogenetic tree that corresponded well with the current classification of oral fusobacteria into F. periodonticum and several subspecies of F. nucleatum, in spite of much minor genetic variability. F. periodonticum, F. nucleatum subsp. animalis and a previously undescribed phylogenetic cluster (C4), that may represent an additional F. nucleatum subspecies, constituted discrete clusters distinct from the remainder of F. nucleatum with high bootstrap values. Chinese and European strains differed markedly with regard to their respective classification patterns, suggesting a predominance of F. peridonticum and F. nucleatum susp. animalis over F. nucleatum subsp. nucleatum and F. nucleatum subsp. fusiforme/vincentii in samples from China. Antigenic typing enabled the association of many previously described serovars with distinct phylogenetic clusters and when applied directly to uncultured clinical samples confirmed the differential distribution of oral Fusobacterium taxa in Chinese and European samples. Bacteria from cluster C4 and F. nucleatum subsp. animalis were significantly more prevalent and accounted for higher cell numbers in NUG than in gingivitis samples, suggesting a possible association of these rarely observed taxa with NUG in Chinese patients.     

Intracellular degradation of Fusobacterium nucleatum in human gingival epithelial cells

The role of Fusobacterium nucleatum in oral health and disease is controversial. We have previously shown that F. nucleatum invades gingival epithelial cells. However, the destiny of the internalized F. nucleatum is not clear. In the present study, the intracellular destiny of F. nucleatum and its cytopathic effect on gingival epithelial cells were studied. The ability of F. nucleatum and seven other oral bacterial species to invade immortalized human gingival epithelial (HOK-16B) cells were compared by confocal microscopy and flow cytometry. F. nucleatum had the highest invasive capacity, comparable to that of Porphyromonas gingivalis, a periodontal pathogen. Confocal microscopic examination revealed colocalization of internalized F. nucleatum with endosomes and lysosomes. Examination by transmission electron microscopy revealed that most intracellular F. nucleatum was located within vesicular structures with single enclosed membranes. Furthermore, F. nucleatum could not survive within gingival epithelial cells and had no cytopathic effects on host cells. Interestingly, endosomal maturation played a role in induction of the antimicrobial peptides human beta defensin (HBD)-2 and -3 by F. nucleatum from gingival epithelial cells. F. nucleatum is destined to enter an endocytic degradation pathway after invasion and has no cytopathic effect on gingival epithelial cells, which may cast new light on the role of F. nucleatum in the pathogenesis of periodontitis.