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肠道微生物群对宫颈癌病变进展的动态因果效应。

Dynamic causal effects of gut microbiota on cervical Cancer lesion progression.

作者信息

Zhu Fei, Li Li, Zhang Huiqi, Liu Jing, Wu Dongmei, Xu Qin

机构信息

Departments of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Medical University, Fujian Cancer Hospital, Fujian, China.

Department of Obstetrics and Gynecology, The Second People's Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350003, Fujian, China.

出版信息

Sci Rep. 2025 May 3;15(1):15490. doi: 10.1038/s41598-025-00483-8.

DOI:10.1038/s41598-025-00483-8
PMID:40319127
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12049543/
Abstract

Many investigations have highlighted the involvement of the intestinal microbiota in the progression of cervical cancer lesions; however, the causal link between them remains to be confirmed. We employed two-sample Mendelian randomization (MR) as a alternative to randomized controlled trials (RCTs) to explore the association between intestinal microbiota and high-risk Human Papillomavirus (HPV) infection, cervical intraepithelial neoplasia (CIN), and cervical cancer (CC). This method allowed for a detailed investigation of the underlying mechanistic interactions within the gut-cervix axis. The analysis predominantly encompassed the utilization of inverse variance weighting (IVW) and the Wald ratio test. Additionally, various sensitivity analysis methods were employed to validate the findings. We uncovered a total of 17 gut microbial taxa associated with HPV infection, 9 taxa related to CIN, and 7 taxa linked to CC. At different stages of cervical cancer lesions, various gut microbial communities play either protective or promoting roles. However, some microbial communities also act as persistent risk factors in promoting the progression of CC. Our investigation has revealed that the gut microbiota exerts a considerable impact along the entire spectrum of CC progression within the gut-cervix axis. These findings lay a foundation for prospective research focused on the utilization of gut microbiota in cervical cancer screening, prevention, and therapeutic strategies.

摘要

许多研究都强调了肠道微生物群在宫颈癌病变进展中的作用;然而,它们之间的因果关系仍有待证实。我们采用两样本孟德尔随机化(MR)作为随机对照试验(RCT)的替代方法,以探讨肠道微生物群与高危人乳头瘤病毒(HPV)感染、宫颈上皮内瘤变(CIN)和宫颈癌(CC)之间的关联。这种方法能够详细研究肠道-宫颈轴内潜在的机制相互作用。分析主要包括使用逆方差加权(IVW)和 Wald 比率检验。此外,还采用了各种敏感性分析方法来验证研究结果。我们共发现 17 种与 HPV 感染相关的肠道微生物分类群、9 种与 CIN 相关的分类群以及 7 种与 CC 相关的分类群。在宫颈癌病变的不同阶段,各种肠道微生物群落发挥着保护或促进作用。然而,一些微生物群落也作为持续的风险因素促进 CC 的进展。我们的研究表明,肠道微生物群在肠道-宫颈轴内 CC 进展的整个过程中都产生了相当大的影响。这些发现为未来聚焦于利用肠道微生物群进行宫颈癌筛查、预防和治疗策略的研究奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311b/12049543/8ced0d9987a3/41598_2025_483_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311b/12049543/2d9f29a8e4a9/41598_2025_483_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311b/12049543/74ac717f5ed0/41598_2025_483_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311b/12049543/07ef4e9f8425/41598_2025_483_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311b/12049543/8ced0d9987a3/41598_2025_483_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311b/12049543/2d9f29a8e4a9/41598_2025_483_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311b/12049543/74ac717f5ed0/41598_2025_483_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311b/12049543/07ef4e9f8425/41598_2025_483_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311b/12049543/8ced0d9987a3/41598_2025_483_Fig4_HTML.jpg

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