In postmenopausal women, the prevalence of MetS increases varying between 30 and 70% compared to 14-45% in younger women, depending on ethnicity and other confounding factors such as lifestyle and eating habits [11]. Since women live at least one-third of their life after menopause, it is important to understand the mechanisms behind the development of metabolic diseases occurring during the menopausal transition in order to design prevention strategies. Although imperfect, ovariectomy is a very common and accepted model developed in rodents to mimic post-menopausal conditions. Indeed, ovariectomized rodents develop the majority of MetS risk factors such as insulin resistance, visceral obesity, and inflammation [12], especially if the mice are fed with a high-fat diet since it accelerates the progression of menopausal symptoms compared to a low-fat diet [13]. Interestingly, previous studies suggested that ovariectomy can modulate intestinal permeability and inflammation and is accompanied by a state of dysbiosis associated with MetS [12], favoring the development and progression of non-alcoholic fatty liver disease (NAFLD) through the gut-liver axis [14]. However, the intestine has been little explored in mice exposed to pollutants [15; 16] and not at all in ovariectomized mice. Yet, the gut is the second detoxifying tissue after the liver expressing various xenobiotic receptors and processing genes [17]. In the present study, we took benefit of an in vivo protocol previously carried out in female mice allowing the exploration of the metabolic consequences of ovarian withdrawal and E2 replacement along with investigating the impact of a mixture of pollutants exhibiting estrogen-mimetic properties [18; 19]. The mixture consisted of archetypal endocrine disruptors among which only bisphenol A (BPA) is considered as an xenoestrogen [7]. They were each present at a dose close to the tolerable daily intake (TDI) dose as defined by the European Food Safety Agency (EFSA), and which is derived from the low or non-observed adverse effect levels (LOAEL/NOAEL) determined in experimental studies [20]. Specifically, it contained a dioxin and polychlorinated biphenyl (PCB153), two persistent chemicals that bioaccumulate in the food chain being particularly present in fatty foods of animal origin (meat, milk, fish) and characterized by half-lives of several years in humans [21]. The mixture also contained two short-lived chemicals, a phthalate and BPA massively used in plastic goods, the leaching from packaging causes contamination resulting in chronic exposure [22; 23]. Interestingly, the mixture of pollutants triggers sex-dependent metabolic alterations in the liver and adipose tissue of chronically exposed mice, suggesting an interaction with estrogen signaling [24; 25]. The overall objective of the present investigation was to identify changes in intestinal gene expression caused by exposure to low doses of pollutants that could act as early markers of chronic adverse effects, in order to better understand the mechanisms of toxicity and the role of estrogen. To this end, we undertook an extensive qPCR analysis of genes encoding estrogen receptors, xenobiotic processing genes, and genes related to nutrient uptake, gut permeability, and bile acid biosynthesis, using samples collected from different regions of the intestinal tract.