子宫内膜微生物失调和代谢改变促进子宫内膜癌的发展。

Endometrial microbial dysbiosis and metabolic alteration promote the development of endometrial cancer.

机构信息

Clinical School of Obstetrics and Gynecology Center, Tianjin Medical University, Tianjin, China.

Department of Obstetrics and Gynecology, Tianjin First Center Hospital, Tianjin, China.

出版信息

Int J Gynaecol Obstet. 2024 Nov;167(2):810-822. doi: 10.1002/ijgo.15718. Epub 2024 Jun 4.

DOI:10.1002/ijgo.15718

PMID:38837368

Abstract

OBJECTIVE

Emerging evidence suggests that the endometrial microbiome plays important roles in the development of endometrial cancer (EC). Here, we evaluate stage-specific roles of microbial dysbiosis and metabolic disorders in patients with EC, patients with endometrial hyperplasia (EH), and patients afflicted with benign uterine conditions (CK).

METHODS

This prospective cohort study included 33 women with EC, 15 women with endometrial EH, and 15 women with benign uterine conditions (CK) from November 2022 to September 2023. Different typical endometrial samples were imaged with a scanning electron microscope and a transmission electron microscope. The endometrial microbiome was assessed by sequencing the V3-V4 region of the 16S rRNA gene and the ITS1 to fill the gap in relation to the study of the uterine fungal microbiome. Moreover, liquid chromatography-mass spectrometry-based metabolomics was used to identify and quantify metabolic changes among these groups.

RESULTS

The endometrial microbiome revealed that there is a structural microbiome shift and an increase in the α-diversity in the EC and EH cases, distinguishable from the benign cases, especially the fungal community structure. The fungal microbiome from patients with EC and EH was altered relative to controls and dominated by Penicillium sp. By contrast, Sarocladium was more abundant in controls. Significant differences were observed in the composition and content of compounds between benign cases and EC, especially estradiol-like metabolism-related substances. Altered microbiota was correlated with the concentrations of interleukin-6 (IL-6), IL-11, transforming growth factor-beta, and β-glucuronidase activity especially the relative abundance increase of Penicillium sp.

CONCLUSIONS

This study suggested that the endometrial microbiome is complicit in modulating the development of EC such as estrogen activity and a pro-inflammatory response. Our work provides a new insight into the endometrial microbiome from a perspective of stages, which opens up new avenues for EC prognosis and therapy.

摘要

目的

新出现的证据表明，子宫内膜微生物组在子宫内膜癌（EC）的发展中起着重要作用。在这里，我们评估了微生物失调和代谢紊乱在 EC 患者、子宫内膜增生（EH）患者和良性子宫疾病（CK）患者中的特定阶段的作用。

方法

本前瞻性队列研究纳入了 2022 年 11 月至 2023 年 9 月期间的 33 名 EC 患者、15 名子宫内膜 EH 患者和 15 名良性子宫疾病（CK）患者。使用扫描电子显微镜和透射电子显微镜对不同典型的子宫内膜样本进行成像。通过对 16S rRNA 基因 V3-V4 区和 ITS1 进行测序来评估子宫内膜微生物组，以填补与子宫真菌微生物组研究相关的空白。此外，还使用基于液相色谱-质谱的代谢组学来鉴定和量化这些组之间的代谢变化。

结果

子宫内膜微生物组显示，EC 和 EH 病例存在结构微生物组转移和 α 多样性增加，与良性病例不同，尤其是真菌群落结构。与对照组相比，EC 和 EH 患者的真菌微生物组发生了改变，并且以 Penicillium sp.为主。相比之下，Sarocladium 在对照组中更为丰富。良性病例和 EC 之间的化合物组成和含量存在显著差异，特别是与雌二醇样代谢相关的物质。改变的微生物群与白细胞介素-6 (IL-6)、IL-11、转化生长因子-β和β-葡萄糖醛酸酶活性的浓度相关，特别是 Penicillium sp. 的相对丰度增加。