In this study, we evaluate the association between vaginal and cervical human papillomavirus infections high-risk types (HPV+H), negative controls (HPV-), the bacterial biota, and urinary metabolites via integration of metagenomics, metabolomics, and bioinformatics analysis. We recently proposed that testing urine as a biofluid could be a non-invasive method for the detection of cervical HPV+H infections by evaluating the association between cervical HPV types and a total of 24 urinary metabolites identified in the samples. As a follow-up study, we expanded the analysis by pairing the urine metabolome data with vaginal and cervical microbiota in selected samples from 19 Puerto Rican women diagnosed with HPV+H infections and HPV- controls, using a novel comprehensive framework, Model-based Integration of Metabolite Observations and Species Abundances 2 (MIMOSA2). This approach enabled us to estimate the functional activities of the cervicovaginal microbiome associated with HPV+H infections. Our results suggest that HPV+H infections could induce changes in physicochemical properties of the genital tract through which niche partitioning may occur. As a result, Lactobacillus sp. enrichment coincided with the depletion of L. iners and Shuttleworthia, which dominate under normal physiological conditions. Changes in the diversity of microbial species in HPV+H groups influence the capacity of new community members to produce or consume metabolites. In particular, the functionalities of four metabolic enzymes were predicted to be associated with the microbiota, including acylphosphatase, prolyl aminopeptidase, prolyl-tRNA synthetase, and threonyl-tRNA synthetase. Such metabolic changes may influence systemic health effects in women at risk of developing cervical cancer. Overall, even assuming the limitation of the power due to the small sample number, our study adds to current knowledge by suggesting how microbial taxonomic and metabolic shifts induced by HPV infections may influence the maintenance of microbial homeostasis and indicate that HPV+H infections may alter the ecological balance of the cervicovaginal microbiota, resulting in higher bacterial diversity.

中文翻译：

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宫颈阴道微生物组和尿液代谢组配对分析揭示了人乳头瘤病毒感染患者微生物群的生态位划分。


在本研究中，我们通过整合宏基因组学、代谢组学和生物信息学分析，评估阴道和宫颈人乳头瘤病毒感染高危型 (HPV+H)、阴性对照 (HPV-)、细菌群和尿液代谢物之间的关联。我们最近提出，通过评估宫颈 HPV 类型与样本中确定的总共 24 种尿液代谢物之间的关联，将尿液作为生物液进行检测可能是检测宫颈 HPV+H 感染的一种非侵入性方法。作为一项后续研究，我们使用一种新颖的综合框架“基于模型”，将尿液代谢组数据与来自 19 名被诊断患有 HPV+H 感染和 HPV-对照的波多黎各女性的选定样本中的阴道和宫颈微生物群进行配对，扩大了分析范围。代谢物观测值和物种丰度的整合 2 (MIMOSA2)。这种方法使我们能够估计与 HPV+H 感染相关的宫颈阴道微生物组的功能活动。我们的结果表明，HPV+H 感染可能会引起生殖道理化特性的变化，从而可能发生生态位划分。结果，乳杆菌属。富集与 L. iners 和 Shuttleworthia 的消耗同时发生，它们在正常生理条件下占主导地位。 HPV+H 群体中微生物物种多样性的变化影响新群落成员产生或消耗代谢物的能力。特别是，四种代谢酶的功能被预测与微生物群相关，包括酰基磷酸酶、脯氨酰氨肽酶、脯氨酰-tRNA 合成酶和苏氨酰-tRNA 合成酶。这种代谢变化可能会影响有患宫颈癌风险的女性的全身健康影响。 总体而言，即使假设由于样本量较小而导致功效有限，我们的研究也增加了当前的知识，表明 HPV 感染引起的微生物分类和代谢变化可能如何影响微生物稳态的维持，并表明 HPV+H 感染可能会改变子宫颈阴道微生物群的生态平衡，导致更高的细菌多样性。