Female Pelvic Floor Urinary Reconstructive Center, Dalian Women and Children's Medical Group, Dalian, China.
Department of Engineering Mechanics, Dalian University of Technology, Dalian, China.
Front Cell Infect Microbiol. 2024 Oct 10;14:1457216. doi: 10.3389/fcimb.2024.1457216. eCollection 2024.
Emerging evidence suggests that the vaginal microbiota is closely associated with cervical cancer. However, little is known about the relationships among the vaginal microbiota, vaginal metabolites, and cervical lesion progression in women undergoing cervical dysplasia.
In this study, to understand vaginal microbiota signatures and vaginal metabolite changes in women with cervical lesions of different grades and cancer, individuals with normal or cervical dysplasia were recruited and divided into healthy controls (HC) group, low-grade squamous intraepithelial lesions (LSIL) group, high-grade squamous intraepithelial lesions (HSIL) group, and cervical cancer (CC) group. Vaginal secretion samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics, and integrated analysis.
The results demonstrated that bacterial richness and diversity were greater in the CC group than the other three groups. Additionally, was found to be negatively associated with bacterial diversity and bacterial metabolic functions, which increased with the degree of cervical lesions and cancer. Metabolomic analysis revealed that distinct metabolites were enriched in these metabolite pathways, including tryptophan metabolism, retinol metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, as well as citrate cycle (TCA cycle). Correlation analysis revealed positive associations between CC group-decreased abundance and CC group-decreased metabolites. was both negative to and genes, the predicted abundance of which was significantly higher in the CC group. The linear regression model showed that the combination of the vaginal microbiota and vaginal metabolites has good diagnostic performance for cervical cancer.
Our results indicated a clear difference in the vaginal microbiota and vaginal metabolites of women with cervical dysplasia. Specifically altered bacteria and metabolites were closely associated with the degree of cervical lesions and cancer, indicating the potential of the vaginal microbiota and vaginal metabolites as modifiable factors and therapeutic targets for preventing cervical cancer.
新出现的证据表明，阴道微生物群与宫颈癌密切相关。然而，对于阴道微生物群、阴道代谢物与宫颈病变进展之间的关系，在接受宫颈上皮内瘤变的女性中知之甚少。
在这项研究中，为了了解不同分级宫颈病变和宫颈癌患者阴道微生物群特征和阴道代谢物变化，招募了正常或宫颈上皮内瘤变的个体，并分为健康对照组（HC）、低级别鳞状上皮内病变（LSIL）组、高级别鳞状上皮内病变（HSIL）组和宫颈癌（CC）组。收集阴道分泌物样本进行 16S rRNA 基因测序、基于液相色谱与质谱联用（LC-MS）的代谢组学和综合分析。
结果表明，CC 组的细菌丰富度和多样性大于其他三组。此外，发现与细菌多样性和细菌代谢功能呈负相关，随着宫颈病变和癌症程度的增加而增加。代谢组学分析表明，这些代谢途径中存在独特的代谢物，包括色氨酸代谢、视黄醇代谢、谷胱甘肽代谢、丙氨酸、天冬氨酸和谷氨酸代谢以及柠檬酸循环（TCA 循环）。相关性分析表明，CC 组减少的丰度与 CC 组减少的代谢物之间存在正相关。与 CC 组减少的 丰度呈负相关，并且与 CC 组预测丰度显著增加的 基因和 基因呈负相关。线性回归模型表明，阴道微生物群和阴道代谢物的组合对宫颈癌具有良好的诊断性能。
我们的研究结果表明，宫颈上皮内瘤变患者的阴道微生物群和阴道代谢物存在明显差异。具体来说，改变的细菌和代谢物与宫颈病变的严重程度密切相关，表明阴道微生物群和阴道代谢物作为可改变的因素和治疗靶点预防宫颈癌的潜力。
