Press release. 15/12/2009

Bisphenol-A affects intestinal function, scientists find

Researchers at INRA-Toulouse have demonstrated for the first time that exposure to Bisphenol A (BPA) affects intestinal function. BPA, a component of many plastic food containers, is often detected in the systems of most people regardless of age. However, it is an endocrine disruptor that can mimic oestrogens, the female sex hormones, which not only play a crucial role in reproduction but are also vital to organ development, including the brain and the cardiovascular system. INRA scientists have shown that the rat's gastrointestinal system is highly sensitive to low doses of BPA, which affects intestinal permeability, visceral pain, and immune response to gut inflammation. They have also shown how pre- and post-natal exposure of these animals to BPA can weaken their adult intestinal barrier function. Their work breaks new ground in assessing the risks of exposure to endocrine disruptors. Their findings are published in the online PNAS Early Edition of 14-18 December 2009.

Bisphenol A is a food contaminant widely used in the industrial production of polycarbonate plastic containers such as baby bottles. It is also found in the resins of the inner coating used in food and beverage cans. However, trace levels of BPA can migrate spontaneously from these plastics and resins, especially when they are heated. BPA can be detected in the urine, blood and amniotic fluid of a large majority of the European population. The European Food Safety Authority (EFSA) and the French Agency for Food Safety (AFSSA) have set the acceptable daily intake (ADI) for BPA at 0.05 mg/kg body weight.

This threshold was chosen because the molecule is toxic to the reproduction and development of laboratory animals. BPA can bind to receptors of oestrogen, the female sex hormone, and mimic its effects. To date, the studies aimed at evaluating its effects on the human body have focused on reproduction and brain development.

For the first time, scientists have studied the effects of BPA on the intestine, the first organ to come into contact with ingested contaminants. Researchers at the Neurogastroenterology and Nutrition laboratory of INRA-Toulouse fed low doses of BPA to rats whose ovaries, which produce natural oestrogens, were removed. They found that intestinal function was affected by BPA at doses as low as a tenth of the acceptable daily intake thought very safe for humans.

First, they found that BPA decreased the permeability of intestinal epithelium, which allows the exchange of water and mineral salts (or ions) needed to maintain physiological balance. Intestinal permeability is determined by junction proteins between the epithelial cells. The scientists found that in rats and cultured human intestinal cells, BPA was capable of activating oestrogen receptors found in these epithelial cells. This led to increased protein synthesis and a tightening of the junction between intestinal cells, limiting natural exchanges at intestinal walls and contributing to water retention in the body. They also found that BPA affected inflammatory response in the colon and made the intestine more sensitive to pain.

In newborn rats, the researchers showed that exposure to BPA in utero and during breastfeeding increased the risk of developing a severe intestinal inflammation in adulthood. These effects were observed mainly in female offspring, which are naturally more sensitive to oestrogen than males. This predisposition to the development of inflammatory gut diseases could be the result of imperfect maturation of the parts of the immune system located in the intestinal mucosa. The intestine is practically sterile at birth, then colonised progressively by bacteria from food and the environment, which participate in "training" the gut immune system. The scientists postulate that pre- and post-natal exposure to BPA could hinder the development of intestinal immune defences, thereby altering their future capacity to recognise potentially harmful substances.

These findings illustrate the intestine's great sensitivity to Bisphenol A and open new research paths for characterising and evaluating the effects of endocrine disruptors from food. They may also contribute to risk assessment and the determination of new acceptable exposure thresholds for these molecules.

For more information:
Impact of oral Bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats. PNAS.
Viorica Braniste^a, Aurore Jouault^a, Eric Gaultier^a, Arnaud Polizzi^b, Claire Buisson-Brenac^a, Mathilde Leveque^a, Pascal G. Martin^b, Vassilia Theodorou^a, Jean Fioramonti^a, and Eric Houdeau^a.
^a Neuro-Gastroenterology and Nutrition Unit, Joint Research Unit 1054
^b Pharmacology and Toxicology Laboratory, Research Unit 66,
ToxAlim Research Center, National Institute for Agricultural Research, 31027 Toulouse cedex 3, France

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