PDF(Pubmed)
Abstract：
The cervicovaginal microbiome is highly associated with women\'s health, with microbial communities dominated by Lactobacillus species considered optimal. Conversely, a lack of lactobacilli and a high abundance of strict and facultative anaerobes, including Gardnerella vaginalis, have been associated with adverse reproductive outcomes. However, how host-microbial interactions alter specific molecular pathways and impact cervical and vaginal epithelial function remains unclear. Using RNA-sequencing, we characterized the in vitro cervicovaginal epithelial transcriptional response to different vaginal bacteria and their culture supernatants. We showed that G. vaginalis upregulates genes associated with an activated innate immune response. Unexpectedly, G. vaginalis specifically induced inflammasome pathways through activation of NLRP3-mediated increases in caspase-1, IL-1β and cell death, while live L. crispatus had minimal transcriptomic changes on epithelial cells. L. crispatus culture supernatants resulted in a shift in the epigenomic landscape of cervical epithelial cells that was confirmed by ATAC-sequencing showing reduced chromatin accessibility. This study reveals new insights into host-microbe interactions in the lower reproductive tract and suggests potential therapeutic strategies leveraging the vaginal microbiome to improve reproductive health.
摘要：
宫颈阴道菌群与女性健康高度相关，微生物群落以乳酸杆菌为主，被认为是最佳的。相反，缺乏乳酸杆菌和大量的严格和兼性厌氧菌，包括阴道加德纳菌,与不良生殖结局有关。然而,宿主-微生物相互作用如何改变特定分子途径并影响宫颈和阴道上皮功能尚不清楚.使用RNA测序，我们表征了体外宫颈阴道上皮对不同阴道细菌及其培养上清液的转录反应。我们表明，阴道毛虫上调与激活的先天免疫反应相关的基因。出乎意料的是,G.Vaginalis通过激活NLRP3介导的caspase-1，IL-1β和细胞死亡的增加特异性诱导炎症小体途径，而活的卷曲乳杆菌在上皮细胞上的转录变化最小。卷曲乳杆菌培养上清液导致宫颈上皮细胞的表观基因组景观发生变化，这通过ATAC测序证实，显示染色质可及性降低。这项研究揭示了下生殖道宿主-微生物相互作用的新见解，并提出了利用阴道微生物组来改善生殖健康的潜在治疗策略。
