Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.
Gut Microbes. 2023 Jan-Dec;15(1):2221093. doi: 10.1080/19490976.2023.2221093.
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, which remains a threat to female health at all ages. Hypotheses for EOC development include the continuous presence of inflammation, in which microbiota and inflammatory cytokines participate in cancer-related signaling pathway activation. Hedgehog (Hh) signaling is prominent for EOC progression, and interacts with inflammation response related to gut microbiota (GM). However, the precise roles of GM during this process are unknown. Here, we showed that the GM from patients with EOC differed from that of healthy women and had GM dysbiosis. We found that EOC modeling may lead to GM changes in mice, and it restored after the administration of GM from healthy controls, while GM from patients with EOC further exacerbated GM dysbiosis. Furthermore, we found that GM from EOC markedly promoted tumor progression and activated Hh signaling; meanwhile, it increased the extent of inflammation and activated NF-κB signaling, but GM from healthy controls improved them. Our results demonstrate how GM dysbiosis promoted EOC progression by activating Hh signaling mediated by TLR4/NF-κB signaling. We anticipate our assay to be a new thought for exploring the role of GM in EOC development. Furthermore, improving GM dysbiosis is a novel therapeutic approach for delaying EOC development.
上皮性卵巢癌（EOC）是最致命的妇科癌症，仍然是所有年龄段女性健康的威胁。EOC 发展的假设包括炎症的持续存在，其中微生物群和炎症细胞因子参与癌症相关信号通路的激活。Hedgehog（Hh）信号在 EOC 进展中很突出，并与与肠道微生物群（GM）相关的炎症反应相互作用。然而，GM 在这一过程中的精确作用尚不清楚。在这里，我们表明 EOC 患者的 GM 与健康女性不同，存在 GM 失调。我们发现 EOC 建模可能导致小鼠 GM 发生变化，而来自健康对照的 GM 给药后恢复正常，而来自 EOC 患者的 GM 进一步加剧 GM 失调。此外，我们发现 GM 从 EOC 显著促进肿瘤进展并激活 Hh 信号；同时，它增加了炎症的程度并激活了 NF-κB 信号，但来自健康对照的 GM 改善了它们。我们的结果表明 GM 失调如何通过 TLR4/NF-κB 信号转导激活 Hh 信号来促进 EOC 进展。我们期望我们的测定方法成为探索 GM 在 EOC 发展中的作用的新思维。此外，改善 GM 失调是延缓 EOC 发展的一种新的治疗方法。
