子宫内膜异位症中新出现的口腔微生物-宿主轴:具核梭杆菌的系统综述。
完整摘要 · 中文译文
背景:具核梭杆菌是一种与多种口外疾病相关的口腔相关细菌,近来被提出可能通过微生物易位、炎症和纤维化参与子宫内膜异位症的发生。然而,这种关联的一致性及临床意义仍不确定。本系统综述评估了将具核梭杆菌与子宫内膜异位症联系起来的人体和实验证据,并评估了所提出的口腔微生物-宿主轴的可信性。 方法:按照PRISMA 2020指南,检索了PubMed/MEDLINE、Embase、Web of Science和Google Scholar自建库至2026年8月31日的文献。纳入报告具核梭杆菌或历史上相关的具核梭杆菌复合群分类群与子宫内膜异位症关系的人体和动物研究。偏倚风险采用预先设定的、改编的ROBINS-I框架评估人体观察性研究,采用SYRCLE评估动物研究。由于解剖部位、检测方法和结局存在显著异质性,不宜进行荟萃分析,故对研究结果进行定性综合。 结果:共纳入4项人体研究,在研究层面涵盖384名参与者,但各分析的特异分母有所不同。直接组织证据来自两项研究且结果相互矛盾:Muraoka等人在42例对42例的组织亚组中报告,子宫内膜异位症女性子宫内膜样本的梭杆菌阳性率为64.3%,而对照组为7.1%;而Graciano-España等人在55 病例和37名对照。间接微生物组研究报告,在中度/重度子宫内膜异位症中口腔梭杆菌属富集,在伴有子宫内膜异位症的慢性盆腔疼痛中阴道F. animalis耗竭。所有人体研究均被判定为总体偏倚风险严重,证据确定性极低。提示TGF-β介导的病灶生长和纤维化的实验证据主要来源于一项转化研究,且缺乏独立重复。 结论:当前证据支持生物学合理性,但不支持具核梭杆菌与子宫内膜异位症之间存在一致或因果关系。直接组织证据仅限于两项相互矛盾的研究,而非组织微生物组发现均为间接证据。在能够确立微生物易位、时间性、因果关系或抗菌治疗之前,需要进行标准化的污染控制采样、配对的解剖部位采样、菌株水平分析以及纵向研究。 系统综述注册:https://www.crd.york.ac.uk/PROSPERO/view/CRD420261337885。
完整摘要 · 英文原文
BACKGROUND: Fusobacterium nucleatum, an oral-associated bacterium implicated in several extraoral diseases, has recently been proposed as a potential contributor to endometriosis through microbial translocation, inflammation, and fibrosis. However, the consistency and clinical significance of this association remain uncertain. This systematic review evaluated the human and experimental evidence linking F. nucleatum with endometriosis and assessed the plausibility of a proposed oral microbe-host axis. METHODS: PubMed/MEDLINE, Embase, Web of Science, and Google Scholar were searched from inception through August 31, 2026, following PRISMA 2020 guidelines. Human and animal studies reporting F. nucleatum or historically related F. nucleatum-complex taxa in relation to endometriosis were included. Risk of bias was assessed using a prespecified adapted ROBINS-I framework for human observational studies and SYRCLE for animal studies. Owing to substantial heterogeneity in anatomical compartments, detection methods, and outcomes, meta-analysis was not appropriate and findings were synthesized qualitatively. RESULTS: Four human studies encompassing 384 participants at the study level were included, although analysis-specific denominators varied. Direct tissue evidence came from two studies and was conflicting: Muraoka et al. reported Fusobacterium positivity in 64.3% of endometrial samples from women with endometriosis versus 7.1% of controls in a 42-versus-42 tissue subset, whereas Graciano-España et al. found no significant case-control difference in F. nucleatum abundance among 55 cases and 37 controls. Indirect microbiome studies reported oral Fusobacterium enrichment in moderate/severe endometriosis and vaginal F. animalis depletion in chronic pelvic pain with endometriosis. All human studies were judged at serious overall risk of bias, and certainty of evidence was very low. Experimental evidence suggesting TGF-β-mediated lesion growth and fibrosis derived principally from one translational study and lacked independent replication. CONCLUSIONS: Current evidence supports biological plausibility but not a consistent or causal association between F. nucleatum and endometriosis. Direct tissue evidence is limited to two conflicting studies, while non-tissue microbiome findings are indirect. Standardized contamination-controlled sampling, paired anatomical-site sampling, strain-level analyses, and longitudinal studies are required before microbial translocation, temporality, causality, or antimicrobial treatment can be established. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261337885.