Inflammation induced by very low-dose bisphenol-a can be prevented by probiotics

Abstract

Bisphenol-A (BPA) is an endocrine disruptor found in the majority of plastic components with pro-inflammatory effects on adipose tissue, the immune system and the intestine, the first tissue exposed to the effects of BPA. Humans are chronically exposed to BPA through contaminated food and beverages. The aim of this study was to investigate the effect of a very low dose of BPA (0.1 nM) on intestinal epithelial cells during differentiation, compare it with that of a low dose of BPA (1 nM), and determine the role of probiotics in preventing BPA-induced alterations in intestinal permeability and inflammation. Human colon adenocarcinoma-derived cells (Caco2 cells) were treated with 0.1 nM and 1 nM BPA in the presence of G-1 and G15, a specific GPR30 agonist and antagonist, respectively, and probiotics during differentiation, after which transepithelial electrical resistance (TEER) measurements, confocal fluorescence experiments, real-time RT-PCR and Western blot analysis were carried out. Even at a dose of 0.1 nM, BPA significantly reduced TEER in differentiated Caco2 cells. The increased permeability of the enterocyte monolayer and a reduction in Caco2 cell thickness confirmed the effects of BPA. In addition, BPA induced GPR30 expression and ERK1/2 and NF-κB phosphorylation, especially in the early phase of CaCo2 cell differentiation. However, inhibition of GPR30 by G15 reduced the effect of BPA on ERK1/2 and NF-κB phosphorylation. Interestingly, the supernatant of cells grown with the probiotic LGG could prevent the decrease in TEER, alteration of tight junctions (TJs) and induction of pNF-κB. Very low-dose BPA (0.1 nM) and low-dose BPA (1 nM) induced intestinal inflammation and altered intestinal permeability through a mechanism involving GPR30. Treatment with the probiotic LGG reversed the effects of BPA. *Correspondence to: M. Vittoria Barone, Department of Translational Medicine, Federico II University of Naples & ELFID (European Laboratory for the Investigation of Food Induced Disease), Italy, E-mail: mv.barone@unina.it