Casein and gluten‐derived opiate peptides affect cysteine uptake and redox status

Abstract

Symptomatic improvement upon dietary exclusion of casein and gluten (GF/CF diet) has been reported for autistic patients. β‐casomorphin‐7 (βCM7) and α‐gliadin‐7 (αG7) peptides are formed during digestion of milk and wheat/rye, respectively, which can activate opiate receptors. Blood and urine samples from autistic and schizophrenic patients contain higher amounts of these peptides, suggesting a possible contribution to these disorders. Systemic oxidative stress and brain neuro‐inflammation have been described in autistic subjects, in association with significantly lower levels of the antioxidant glutathione (GSH). We demonstrate that αG7 and human and bovine forms of βCM‐7 potently inhibit cysteine uptake (a rate‐limiting step for GSH synthesis) in cultured cells, affecting intracellular thiol metabolite levels and decreasing GSH. Bovine βCM‐7 was more potent in inducing these changes. Different signaling pathways were involved in mediating temporal effects of these peptides. Gene expression and site‐specific CpG methylation analyses were also performed. These findings provide a novel mechanistic explanation for the benefit of a GF/CF diet for the treatment of autism and other inflammatory disorders.Funding agency: Autism Research Institute