Bisphenol A in the Gut: Another Break in the Wall?
From animal studies, a consensus exists that the synthetic estrogen bisphenol A (BPA), a plastic monomer widely used in the food-packaging industry, is able to disrupt endocrine signalling pathways during development, with persisting effects later in life. Although the fetal and then the adult gut expresses functional estrogen receptors (ERs), the endocrine impact of BPA on the intestinal barrier function remains largely unexplored. The intestinal epithelium and mucosal immune cells provide a first line of defence designed to restrict the passage of harmful substances from the lumen. Intestinal permeability is high at birth, permitting lumen-to-mucosa exchanges involved in the maturation process of the gut immune system. As a barrier to the external environment, gut epithelium is renewed constantly during life. Renewal of gut epithelial cells occurs in less than ~96 h, starting from fetal stage, and is dependent on controlled cell stimulation and proliferation by various signalling pathways. Lessons learned from ER-deficient mice underline the importance of estrogen signalling in growth, organization and maintenance of a normal epithelial barrier. In rats, BPA was recently shown to interact with ERs in the adult gut by mimicking the estradiol-mediated decrease of epithelial permeability through genomic pathways. This effect also occurs in neonates when low doses of BPA (5 μg/kg BW/day: tenfold below the tolerable daily intake for humans) are orally administered to pregnant and then lactating rats. A perinatal exposure to BPA also reduces epithelial cell proliferation in the colon of neonates, while the overall decrease of intestinal permeability remains apparent in adulthood only in female offspring. As a consequence, adult females perinatally exposed to BPA have been shown to develop severe inflammatory responses in a rat model of inflammatory bowel disease, demonstrating enhanced expression and production of T-Helper 1 cytokines in inflamed areas. In mice, a mother-to-infant transport of maternal BPA is consistent with the ability of the chemical to reach the fetus through the placental barrier: BPA is present in the amniotic fluid and accumulates in the maturing gut. Although BPA, once absorbed by maternal gut, is rapidly deactivated by first pass conjugation in the liver, recent studies emphasize that BPA at low, environmentally relevant levels can transfer across the human placenta, mainly in an estrogen-active, unconjugated form. It is now thought that BPA ingested by dams has repercussions on the education of the immune system by reducing intestinal permeability from fetal stages and promotes severe inflammatory response later in life.
KeywordsIntestinal Permeability Endocrine Disruptor Intestinal Barrier Function Perinatal Exposure Severe Inflammatory Response
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