By way of an example, a recent study of a piglet model of digestive immaturity at birth found that feeding with a high-protein formula milk was associated with greater ileal permeability. Altered intestinal permeability and structure during the neonatal period may have immediate and/or ML 171 long-term health impacts. It is increasingly accepted that intestinal barrier dysfunction in neonates contributes to adverse clinical outcomes, and induces susceptibility to infection, inflammation, hypersensitivity and stress in both childhood and adulthood. Chlorpyrifos is an organophosphate insecticide used worldwide to treat fruit and vegetable crops. Chlorpyrifos residues are often detected in food and drinking water. In the European Union, the maximum residue limit for CPF in food corresponds to an average intake of about 1 mg/day in humans. Although the digestive tract is the first organ to come into contact with food contaminants, little is known about CPF��s ML 349 impact on the epithelial barrier. Two studies have shown that CPF increases intestinal permeability: an ex vivo model using the singlepass intestinal perfusion method and an in vitro model based on an enterocyte cell line. In contrast, CPF��s impact on intestinal permeability after chronic in utero and postnatal exposure has not previously been studied. This topic is of particular interest because CPF is known to cross the placental barrier. The present study was designed to evaluate the impact of in utero and postnatal oral low-dose CPF administration on gut maturation. We focused our investigation on gut epithelial permeability, TJ protein expression and bacterial translocation. After birth, maturation of the digestive barrier is particularly important because it enables the gradual maturation of immune cells and prevents the occurrence of intolerance and adverse reactions to food allergens. Lactation is also crucial for the functional development of the digestive system. The progressive closure of the gut epithelium at weaning reflects the ability of the epithelial barrier��s development as a very selective interface between the intestinal lumen and the internal environment. These observations can be compared with the results of a previous study in which we observed that intestinal morphological structures are also affected by CPF-exposure. We also found that CPF-exposure was associated with differences in protein expression in segments of the intestine. The immunohistochemical identification of claudin 4 seems to confirm Chiba et al.��s finding that claudin 4 is more strongly expressed in the small intestine than in the colon. Accordingly, one can hypothesize that CPF has a putative downregulating effect on claudin 4. Many studies have shown that disruption of TJs leads to a rise in epithelial permeability.