Food intolerance at adulthood after perinatal exposure to the endocrine disruptor bisphenol A

Abstract

The food contaminant bisphenol A (BPA) is pointed out as a risk factor in development of food allergy and food intolerance, two adverse food reactions increasing worldwide. We evaluated the consequences of perinatal exposure to low doses of BPA on immune-specific response to the food antigen ovalbumin (OVA) at adulthood. Perinatal exposure to BPA (0.5, 5, or 50 g/kg/d) from 15th day of gravidity to pups weaning resulted in an increase of anti-OVA IgG titers at all BPA dosages in OVA-tolerized rats, and at 5 g/kg/d in OVA-immunized rats compared to control rats treated with vehicle. In BPA-treated and OVAtolerized rats, increased anti-OVA IgG titers were associated with higher IFN␥ secretion by the spleen. This result is in accordance with the increase of activated CD4 ؉ CD44 high CD62L low T lymphocytes observed in spleen of BPA-exposed rats compared to controls. Finally, when BPA-treated OVA-tolerized rats were orally challenged with OVA, colonic inflammation occurred, with neutrophil infiltration, increased IFN␥, and decreased TGF␤. We show that perinatal exposure to BPA altered oral tolerance and immunization to dietary antigens (OVA). In summary, the naive immune system of neonate is vulnerable to low doses of BPA that trigger food intolerance later in life.-Menard, S., Guzylack-Piriou, L., Leveque, M., Braniste, V., Lencina, C., Naturel, M., Moussa, L., Sekkal, S., Harkat, C., Gaultier, E., Theodorou, V., Houdeau, E. Food intolerance at adulthood after perinatal exposure to the endocrine disruptor bisphenol A. FASEB J. 28, 4893-4900 (2014). www.fasebj.org

Early life exposure to bisphenol A investigated in mouse models of airway allergy, food allergy and oral tolerance

“…Interestingly, however, the reduction in this protein, expectedly of intestinal origin (Vaali et al, 2006), suggest that BPA induces a local effect in the intestines after in utero or postnatal peroral exposure. Perinatal BPA exposure at doses relevant for humans has previously been reported to enhance colonic inflammation in adulthood, determined as neutrophil infiltration, increased IFNg and decreased TGFb, after "chronic" OVA challenges in a rat model of food intolerance (IgG, non-allergic) (Menard et al, 2014b). Further, prenatal BPA exposure was recently reported to affect mast cell-mediated production of pro-inflammatory mediators and decreased DNA methylation in bone marrow mast cells from adult mice (O'Brien et al, 2014b).…”

“…BPA exposure, however, did not affect tolerance development, since there were no group differences for any of the endpoints in the tolerized mice, with the exception of reduced serum MMCP-1 levels in the highest BPA exposure groups (as also observed in the food allergy model). Previous studies indicate that BPA may influence development of tolerance, both in terms of partly interrupted immune suppression and accumulation of regulatory T cells after oral ovalbumin administration at tolerogenic doses, and impaired oral tolerance to food antigens (IgG) (Menard et al, 2014b;Ohshima et al, 2007). However, none of these studies tested for food allergy tolerance in vivo.…”

“…The risk of human adverse effects of BPA exposure has recently been critically reviewed by the European Food Safety Authority (EFSA), concluding with a lowering of the recommended tolerable daily intake level of 50 mg/kg body weight per day to 5 mg/kg body weight per day (EFSA, 2015). Recent studies report immune effects at BPA levels at or below this exposure level, supporting the need for further insight into adverse immune effects of BPA (Menard et al, 2014a(Menard et al, , 2014b.…”

“…Also with regard to immunerelated endpoints, epidemiological and experimental studies are inconsistent, but several authors have reported associations between urinary BPA concentrations in mother or child and the incidence of asthma and allergy (Donohue et al, 2013;Gascon et al, 2014;Kim et al, 2014;Spanier et al, 2012;Vaidya and Kulkarni, 2012). In experimental rodent studies, BPA has been reported to enhance allergic airway inflammation in mouse allergy models (Bauer et al, 2012;Midoro-Horiuti et al, 2010;Nakajima et al, 2012;O'Brien et al, 2014a;Petzold et al, 2014), impair non-allergic food tolerance induction (IgG) or certain mechanisms underlying oral food allergy tolerance (Menard et al, 2014b;Ohshima et al, 2007;Yamashita et al, 2003) and accelerate autoimmune diabetes development in non-obese diabetic (NOD) mice (Bodin et al, 2014(Bodin et al, , 2013. However, an impact of BPA on the development of food allergy, or tolerance tested in a food allergy model, have to our knowledge not been investigated.…”

Environmental Immunology: Lessons Learned from Exposure to a Select Panel of Immunotoxicants

“…For example, developmental exposure to BPA modulated innate immunity in adult offspring mice but did not impair the adaptive immune response to influenza A virus infection (113). Perinatal exposure to low doses of BPA rendered the neonatal immune system more susceptible to food intolerance (114), and prenatal, but not postnatal, BPA exposure can enhance the postnatal development of experimental allergic asthma (115). Because BPA has been shown to induce epigenetic regulation (ie DNA methylation, miRNA expression and histone acetylation) in reproductive tissues, it will be interesting to determine if similar effects exist in the developing immune system that may consequently affect the generation of inflammatory or immune-mediated disease (116).…”