Background In the cervicovaginal environment, HPV acquisition and cervical cancer progression are linked to non-Lactobacillus dominance, of which Atopobiaceae are key taxa. We hypothesize that Atopobiaceae modulates the cervicovaginal microenvironment to promote HPV persistence and progression to cancer. However, the extent to which Atopobiaceae impact the immunometabolic microenvironment is poorly understood. Methods We investigated Atopobiaceae in a cohort of primarily Hispanic and non-Hispanic White women who were HPV-negative (n=20), HPV-positive (n=31) without dysplasia, diagnosed with cervical dysplasia (n=38), or newly diagnosed with invasive cervical carcinoma (n=9). Microbiome data was integrated with clinical and demographic surveys, immunoproteomics, and metabolomics data. Results Atopobiaceae identified were Fannyhessea vaginae, Fannyhessea massiliense, Fannyhessea species type 2, Lancefieldella deltae, and an unclassified species. A higher prevalence of Atopobiaceae was observed in women who were Hispanic and had higher gravidity and parity. F. species type 2 and F. vaginae were observed with infections of high-risk HPV genotypes 31 and 52. Atopobiacaeae were negatively correlated with Lactobacillus and positively correlated to Sneathia, Dialister, Anaerococcus, Prevotella, and Bifidobacterium/Gardnerella. Proinflammatory cytokines (IL-1α, IL-1β, IL-12, TNFα), immune checkpoint proteins (PD-L1, LAG3), and cancer biomarkers (CEA, MIF, TRAIL) were positively associated with Atopobiaceae-rich profiles. Pro-oncogenic metabolites, including 4-hydroxybutyrate and sphingosine, were also elevated in women colonized by Atopobiaceae. Conclusions Our data implicate Atopobiaceae in lipid modulation, oxidative stress, inflammatory responses, and immune evasion, which may contribute to cancer. This study highlights a key family of pathogenic cervicovaginal bacteria that could be exploited to monitor HPV persistence and/or targeted to prevent HPV-mediated cancer.

中文翻译：

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Atopobiaceae 家族成员在人瘤病毒感染、宫颈发育不良和癌症中的免疫代谢贡献


背景 在宫颈阴道环境中，HPV 获得和宫颈癌进展与非乳酸菌优势有关，其中 Atopobiaceae 是关键分类群。我们假设 Atopobiaceae 调节宫颈阴道微环境以促进 HPV 持续存在和进展为癌症。然而，Atopobiaceae 对免疫代谢微环境的影响程度知之甚少。方法 我们调查了一组主要由西班牙裔和非西班牙裔白人女性组成的队列，这些女性是 HPV 阴性 （n=20）、HPV 阳性 （n=31） 无异型增生、诊断为宫颈发育不良 （n=38） 或新诊断为浸润性宫颈癌 （n=9）。微生物组数据与临床和人口统计调查、免疫蛋白质组学和代谢组学数据相结合。结果 鉴定出的 Atopobiaceae 为 Fannyhessea vaginae、Fannyhessea massiliense、Fannyhessea 物种类型 2、Lancefieldella deltae 和一个未分类的物种。在西班牙裔女性中观察到 Atopobiaceae 的患病率较高，并且具有较高的重力和胎次。观察到 F. 物种 2 型和阴道 F. 菌感染高危 HPV 基因型 31 和 52。Atopobiacaeae 与 Lactobacillus 呈负相关，与 Sneathia 、 Dialister 、 Anaerococcus、Prevotella 和 Bifidobacterium/Gardnerella 呈正相关。促炎细胞因子 （IL-1α 、 IL-1β 、 IL-12 、 TNFα ）、免疫检查点蛋白 （PD-L1 、 LAG3） 和癌症生物标志物 （CEA、MIF、TRAIL） 与富含 Atopobiaceae 的特征呈正相关。促癌代谢物，包括 4-羟基丁酸酯和鞘氨醇，在 Atopobiaceae 定植的女性中也升高。 结论 我们的数据表明 Atopobiaceae 与脂质调节、氧化应激、炎症反应和免疫逃避有关，这可能导致癌症。本研究强调了一个关键的致病性宫颈阴道细菌家族，可用于监测 HPV 持久性和/或靶向预防 HPV 介导的癌症。