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与HPV感染和宫颈上皮内瘤变相关的微生物和代谢谱:一项多组学研究。

Microbial and metabolic profiles associated with HPV infection and cervical intraepithelial neoplasia: a multi-omics study.

作者信息

Pu Xiaowen, Wang Xiao, Wang Jingjing, Gu Zhengrong, Zhu Haiyan, Li Chao

机构信息

Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.

Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

Microbiol Spectr. 2025 Jun 3;13(6):e0019225. doi: 10.1128/spectrum.00192-25. Epub 2025 Apr 30.

DOI:10.1128/spectrum.00192-25
PMID:40304477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12131762/
Abstract

UNLABELLED

Cervical cancer is the most common malignancy of the female reproductive system, with the incidence of human papillomavirus (HPV) being a crucial factor in its pathogenesis. Emerging evidence indicates that cervicovaginal microbiota may influence HPV persistence and cervical intraepithelial neoplasia (CIN). However, the interplay between cervicovaginal and cervical tissue microbiomes and their association with HPV infection and CIN remains poorly understood. In this cross-sectional study, we analyzed the microbiota profiles of cervicovaginal and cervical tissue via five-region 16S rRNA gene metabarcoding, along with cervicovaginal metabolites, including short-chain fatty acids (SCFAs) and non-targeted metabolomic data, from 94 women. Key species, particularly and various anaerobes, are vital components of the microbiota found in both cervicovaginal secretions and cervical tissue, despite notable differences in microbial composition. The CIN group exhibited significant differences in microbial diversity and composition compared to the control groups, with key species such as and associated with HPV status and CIN progression. Metabolomic analysis revealed alterations in glycerophospholipid metabolism, but not in SCFAs, with correlations observed between metabolites and HPV status. Notable associations, including -PE(18:1/0:0)-HPV and -PI(40:6)-HPV, were identified. Our findings emphasize the critical roles of cervicovaginal and cervical tissue microbiomes in HPV infection and CIN development, highlighting specific microbial species and metabolic pathways for early detection and therapeutic targets.

IMPORTANCE

Cervical cancer is the most prevalent malignancy in the female reproductive system, with human papillomavirus (HPV) persistency being a critical factor in its pathogenesis. This study highlights the significant yet often overlooked role of cervicovaginal secretion and cervical tissue microbiota in influencing HPV infection and the progression of cervical intraepithelial neoplasia (CIN). By employing a multi-omics approach, we elucidated distinct microbiota profiles in cervical tissues compared to cervicovaginal secretions, revealing a complex interplay between specific bacterial species (notably and anaerobes) and metabolomic changes associated with glycerophospholipid metabolism. Our findings address a significant gap in understanding the interplay between cervicovaginal secretion and cervical intratissue microbiomes, HPV infection, and CIN.

摘要

未标注

宫颈癌是女性生殖系统最常见的恶性肿瘤,人乳头瘤病毒(HPV)感染率是其发病机制中的关键因素。新出现的证据表明,宫颈阴道微生物群可能影响HPV持续感染和宫颈上皮内瘤变(CIN)。然而,宫颈阴道和宫颈组织微生物群之间的相互作用及其与HPV感染和CIN的关联仍知之甚少。在这项横断面研究中,我们通过五区域16S rRNA基因元条形码分析了94名女性的宫颈阴道和宫颈组织的微生物群谱,以及宫颈阴道代谢物,包括短链脂肪酸(SCFAs)和非靶向代谢组学数据。关键物种,特别是[具体物种未给出]和各种厌氧菌,是宫颈阴道分泌物和宫颈组织中微生物群的重要组成部分,尽管微生物组成存在显著差异。与对照组相比,CIN组在微生物多样性和组成上表现出显著差异,[具体物种未给出]等关键物种与HPV状态和CIN进展相关。代谢组学分析显示甘油磷脂代谢发生改变,但SCFAs未改变,且代谢物与HPV状态之间存在相关性。确定了显著关联,包括-PE(18:1/0:0)-HPV和-PI(40:6)-HPV。我们的研究结果强调了宫颈阴道和宫颈组织微生物群在HPV感染和CIN发展中的关键作用,突出了特定微生物物种和代谢途径作为早期检测和治疗靶点的重要性。

重要性

宫颈癌是女性生殖系统中最普遍的恶性肿瘤,人乳头瘤病毒(HPV)持续感染是其发病机制中的关键因素。本研究强调了宫颈阴道分泌物和宫颈组织微生物群在影响HPV感染和宫颈上皮内瘤变(CIN)进展方面重要但常被忽视的作用。通过采用多组学方法,我们阐明了与宫颈阴道分泌物相比宫颈组织中不同的微生物群谱,揭示了特定细菌物种(特别是[具体物种未给出]和厌氧菌)与甘油磷脂代谢相关的代谢组学变化之间的复杂相互作用。我们的研究结果填补了在理解宫颈阴道分泌物和宫颈组织内微生物群之间的相互作用、HPV感染和CIN方面的重大空白。

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