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阴道微生物群、代谢组与伴有高级别宫颈上皮内瘤变的持续性人乳头瘤病毒感染之间的推断性双向相互作用。

Inferred bi-directional interactions between vaginal microbiota, metabolome and persistent HPV infection accompanied by high-grade cervical intraepithelial neoplasia.

作者信息

Yang Qin, Dai Wenkui, Wu Di, Xu Ruinan, Li Changzhong, Wu Ruifang, Du Hui

机构信息

Shantou University Medical College, Shantou, China.

Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China.

出版信息

BMC Microbiol. 2025 Jul 2;25(1):404. doi: 10.1186/s12866-025-04126-w.

DOI:10.1186/s12866-025-04126-w
PMID:40604390
Abstract

BACKGROUND

Vaginal microbiota (VM) links to the risk of persistent HPV infection and the progression of cervical intraepithelial neoplasia (CIN). However, a comprehensive understanding of concurrent alterations in VM and metabolome associated with that risk remains elusive in population-based studies, particularly among Chinese women.

METHODS

This study conducted an extensive analysis of VM and metabolome profiles in a cohort of 56 Chinese women, classified into HPV_C (natural clearance of HPV, n = 18) and HPV_PH(persistent HPV infection accompanied by high-grade CIN, n = 38), based on the result of 3-6 months follow-up visits.

RESULTS

Our analysis revealed a higher prevalence of Lactobacillus-dominated samples in the HPV_C cohort. Notably, the vaginal metabolome exhibited a significant interaction with VM, with Lactobacillus emerging as a pivotal influencer. We identified 386 metabolites that significantly differentiated between HPV_C and HPV_PH groups, of which 364 were associated with VM components such as Lactobacillus, Hoylesella, Fannyhessea and Megasphaera. Further examination showed that 66 of these 364 metabolites positively correlated with Lactobacillus, including citric acid, DL-beta-Leucine, Xanoic acid and Norcholic acid. Conversely, 19 metabolites, including HPV_PH enriched maltotriose and N-Acetyl-L-aspartic acid, negatively correlated with Lactobacillus. Further analysis suggested potential bi-directional modulation between VM and persistent HPV infection accompanied by high-grade, being partially mediated by vaginal metabolites.

CONCLUSIONS

This study provides additional insights into the correlations between concurrent alterations in VM and metabolome associated with persistent HPV infection accompanied by high-grade CIN.

摘要

背景

阴道微生物群(VM)与持续性人乳头瘤病毒(HPV)感染风险及宫颈上皮内瘤变(CIN)进展相关。然而,在基于人群的研究中,尤其是中国女性中,对于与该风险相关的VM和代谢组同时发生的变化仍缺乏全面了解。

方法

本研究对56名中国女性队列的VM和代谢组谱进行了广泛分析,根据3至6个月随访结果将其分为HPV_C组(HPV自然清除,n = 18)和HPV_PH组(伴有高级别CIN的持续性HPV感染,n = 38)。

结果

我们的分析显示HPV_C队列中以乳酸杆菌为主的样本患病率更高。值得注意的是,阴道代谢组与VM表现出显著相互作用,乳酸杆菌成为关键影响因素。我们鉴定出386种在HPV_C组和HPV_PH组之间有显著差异的代谢物,其中364种与VM成分如乳酸杆菌、霍伊尔斯菌属、范尼海斯菌属和巨球形菌属相关。进一步检查表明,这364种代谢物中有66种与乳酸杆菌呈正相关,包括柠檬酸、DL-β-亮氨酸、黄原酸和降胆酸。相反,19种代谢物,包括HPV_PH组富集的麦芽三糖和N-乙酰-L-天冬氨酸,与乳酸杆菌呈负相关。进一步分析表明VM与伴有高级别病变的持续性HPV感染之间存在潜在的双向调节,部分由阴道代谢物介导。

结论

本研究为与伴有高级别CIN的持续性HPV感染相关的VM和代谢组同时发生的变化之间的相关性提供了更多见解。

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有和无宫颈发育不良的女性阴道微生物群的组成和功能差异。
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Metabolic profiles outperform the microbiota in assessing the response of vaginal microenvironments to the changed state of HPV infection.代谢谱在评估 HPV 感染状态改变对阴道微环境的反应方面优于微生物组。
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