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

Abstract

IntroductionEndometriosis 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.MethodsIn 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. ResultsWe 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.ConclusionThe current study demonstrates that endometriosis alters the gut microbiota and associated immune metabolism.

Effects of the gut microbiota and its metabolite short-chain fatty acids on endometriosis

“…In addition, recent studies have found a complex relationship between SCFAs and EMS. Metabolomics showed reduced short-chain fatty acids in a mouse model of endometriosis (Alghetaa et al, 2023). Studies by Chadchan et al also found that short-chain fatty acids were reduced in the feces of mice with endometriosis, and treatment with nbutyrate reduced the growth of endometriosis lesions in mice (Chadchan et al, 2021).…”

“…In addition, recent studies have found a complex relationship between SCFAs and EMS. Metabolomics showed reduced short-chain fatty acids in a mouse model of endometriosis ( Alghetaa et al., 2023 ). Studies by Chadchan et al.…”

17β-Estradiol protects female rats from bilateral oophorectomy-induced nonalcoholic fatty liver disease induced by improving linoleic acid metabolism alteration and gut microbiota disturbance

“…Moreover, the physiological significance of gus -enriched bacteria such as Ruminococcus spp. merits attention, given their direct impact on steroid metabolism in the intestinal milieu, thus potentially modulating the pathophysiology of estrogen-related dysfunctions [ 14 ]. More explorations involving more tissue types and bioinformation are needed to reveal these complex mechanisms.…”