雌激素组失调与子宫内膜异位症小鼠模型中免疫代谢的改变有关。

Estrobolome dysregulation is associated with altered immunometabolism in a mouse model of endometriosis.

机构信息

Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States.

出版信息

Front Endocrinol (Lausanne). 2023 Dec 8;14:1261781. doi: 10.3389/fendo.2023.1261781. eCollection 2023.

DOI:10.3389/fendo.2023.1261781

PMID:38144564

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10748389/

Abstract

INTRODUCTION

Endometriosis is a painful disease that affects around 5% of women of reproductive age. In endometriosis, ectopic endometrial cells or seeded endometrial debris grow in abnormal locations including the peritoneal cavity. Common manifestations of endometriosis include dyspareunia, dysmenorrhea, chronic pelvic pain and often infertility and symptomatic relief or surgical removal are mainstays of treatment. Endometriosis both promotes and responds to estrogen imbalance, leading to intestinal bacterial estrobolome dysregulation and a subsequent induction of inflammation.

METHODS

In the current study, we investigated the linkage between gut dysbiosis and immune metabolic response in endometriotic mice. Ovariectomized BALB/c mice received intraperitoneal transplantation of endometrial tissue from OVX donors (OVX+END). Control groups included naïve mice (Naïve), naïve mice that received endometrial transplants (Naive+END) and OVX mice that received the vehicle (OVX+VEH). Colonic content was collected 2 weeks post-transplantation for 16s rRNA pyrosequencing and peritoneal fluid was collected to determine the phenotype of inflammatory cells by flow cytometry.

RESULTS

We noted a significant increase in the number of peritoneal fluid cells, specifically, T cells, natural killer (NK) cells, and NKT cells in OVX+END mice. Phylogenetic taxonomy analysis showed significant dysbiosis in OVX+END mice, with an increase in abundance of Phylum Tenericutes, Class Mollicutes, Order Aneroplasmatales, and Genus Aneroplasma, and a decrease in Order Clostridiales, and Genus Dehalobacterium, when compared to OVX+VEH controls. The metabolomic profile showed an increase in some tricarboxylic acid cycle (TCA)-related metabolites accompanied by a reduction in short-chain fatty acids (SCFA) such as butyric acid in OVX+END mice. Additionally, the mitochondrial and ATP production of immune cells was enforced to a maximal rate in OVX+END mice when compared to OVX+VEH mice.

CONCLUSION

The current study demonstrates that endometriosis alters the gut microbiota and associated immune metabolism.

摘要

简介

子宫内膜异位症是一种影响生育期妇女 5%左右的疼痛性疾病。在子宫内膜异位症中，异位的子宫内膜细胞或播散的子宫内膜碎片在包括腹腔在内的异常位置生长。子宫内膜异位症的常见表现包括性交困难、痛经、慢性盆腔疼痛，常伴有不孕，治疗的主要方法是症状缓解或手术切除。子宫内膜异位症既能促进又能响应雌激素失衡，导致肠道细菌雌激素组失调和随后的炎症诱导。

方法

在目前的研究中，我们研究了肠道菌群失调与子宫内膜异位症小鼠免疫代谢反应之间的联系。去卵巢 BALB/c 小鼠接受来自 OVX 供体的子宫内膜组织的腹腔内移植（OVX+END）。对照组包括未处理的小鼠（Naive）、接受子宫内膜移植的未处理的小鼠（Naive+END）和接受载体的 OVX 小鼠（OVX+VEH）。移植后 2 周收集结肠内容物进行 16s rRNA 焦磷酸测序，收集腹腔液通过流式细胞术确定炎症细胞的表型。

结果

我们注意到 OVX+END 小鼠腹腔液细胞数量显著增加，特别是 T 细胞、自然杀伤（NK）细胞和 NKT 细胞。系统发育分类分析显示，与 OVX+VEH 对照组相比，OVX+END 小鼠存在显著的菌群失调，厚壁菌门、软壁菌门、厌氧原体目和 Aneroplasma 属丰度增加，梭状芽胞杆菌目和 Dehalobacterium 属丰度减少。代谢组学图谱显示，与 OVX+VEH 对照组相比，OVX+END 小鼠中一些三羧酸循环（TCA）相关代谢物增加，而短链脂肪酸（SCFA）如丁酸减少。此外，与 OVX+VEH 小鼠相比，OVX+END 小鼠的免疫细胞的线粒体和 ATP 产生被强制提高到最大速率。