■子宫内膜异位症是一种痛苦的疾病,影响约5%的育龄妇女。在子宫内膜异位症中,异位子宫内膜细胞或接种的子宫内膜碎片在包括腹膜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,慢性盆腔疼痛和经常不孕和症状缓解或手术切除是治疗的主要手段。子宫内膜异位症促进和响应雌激素失衡,导致肠道细菌雌激素失调和随后的炎症诱导。
■在当前的研究中,我们研究了子宫内膜异位症小鼠肠道菌群失调与免疫代谢反应之间的联系。卵巢切除的BALB/c小鼠接受来自OVX供体的子宫内膜组织的腹膜内移植(OVX+END)。对照组包括幼稚小鼠(幼稚),接受子宫内膜移植的原始小鼠(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16srRNA焦磷酸测序,并收集腹膜液以通过流式细胞术确定炎性细胞的表型。
■我们注意到腹膜液细胞数量显著增加,具体来说,T细胞,自然杀伤(NK)细胞,和OVX+END小鼠中的NKT细胞。系统发育分类学分析显示OVX+END小鼠存在显著的生态失调,随着PhylumTenericutes丰度的增加,类Mollicutes,订购无着床,和无精虫属,梭菌菌序的减少,和去盐细菌属,与OVX+VEH对照相比。代谢组学谱显示OVX+END小鼠中一些三羧酸循环(TCA)相关代谢物的增加,伴随短链脂肪酸(SCFA)如丁酸的减少。此外,与OVX+VEH小鼠相比,在OVX+END小鼠中,免疫细胞的线粒体和ATP产生达到最大速率.
■当前的研究表明,子宫内膜异位症改变了肠道微生物群和相关的免疫代谢。
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.
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.
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.
The current study demonstrates that endometriosis alters the gut microbiota and associated immune metabolism.