Department of Pediatrics Division of Genetics and Metabolism

How does gluten and casein relate to the problem of autism?

A good starting place in thinking about gluten toxicity is to review what is known about a condition termed gluten sensitive enteropathy, or celiac disease. We now know that this condition is basically an inflammatory problem of the intestines in response to certain small peptides that represent the incompletely digested product of the large gluten protein molecule. The diagram below explains this phenomenal toxicity problem and it is a compelling example of how a genetic liability (in this case, individuals who have the HLA genotype termed DQ2) can interact with an environmental factor (in this case, a small peptide derived from gluten) to produce a human disease. Actually in the case of celiac disease, a small peptide probably no greater than nine amino acids in length is able to cross the intestinal microvillus border. It is unknown how this peptide gains access to the intracellular space but it clearly does. As the diagram shows, once the peptide is in the intracellular space, and once it has been specifically processed by a transglutaminase enzyme, it is able to interact with certain immunological cells to then produce a cytotoxic inflammatory problem.

Celiac disease peptide mechanism

Now in terms of autism, the situation is somewhat different because children with autism generally do not have celiac disease and do not have the DQ2 genotype problem. Whereas the problem of celiac disease is well proven in scientific studies, the problem with gluten sensitivity in autism is less well studied. The autism hypothesis involves, like celiac disease, the toxic effects of small peptides, generally in the range of five to seven amino acids in length (termed casomorphin and gliadorphin, as noted below). It is believed that these peptides from gluten, as well as certain peptides from cow milk protein (casein), can somehow cross the intestinal microvillus barrier and reach the blood stream. The theory purports that these peptides can then gain access into the brain by getting past the blood brain barrier. In the brain, certain amino acid sequences of these peptides then compete with the natural peptides (e.g., hormone/neurotransmitter peptides) of the body that bind to opioid receptors. Opioid receptors are G-protein receptors that are on the cell membrane surfaces of neurons and they have far reaching signaling effects. As the theory goes, binding to these opioid receptors leads to a perturbation of neuronal function that ultimately causes or contributes to the problem of autism.

Autism: Casein and Giadin Peptide Theory