Food and Behaviour Research

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β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis

Fiedorowicz E, Kaczmarski M, Cieślińska A, Sienkiewicz-Szłapka E, Jarmołowska B, Chwała B, Kostyra E (2014) Peptides 2014 62 144-9. doi: 10.1016/j.peptides.2014.09.020. 

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Atopic dermatitis (AD) is a chronic inflammatory skin disease with heterogeneous clinical phenotypes reflecting genetic predisposition and exposure to environmental factors. Reactions to food may play a significant role especially in young children.

Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 (BCM7, Tyr-Pro-Phe-Pro-Gly-Pro-Ile). BCM7 exerts its influence on nervous, digestive, and immune functions via the μ-opioid receptor (MOR). Proline dipeptidyl peptidase IV (DPPIV; EC appears to be the primary degrading enzyme of BCM7. Moreover, DPPIV is known to restrict activity of proinflammatory peptides. BCM7 is considered to modulate an immune response by affecting MOR and DPPIV genes expression.

In this study, we determined the MOR and DPPIV genes expression in children diagnosed with a severe form of AD. 40 healthy children and 62 children diagnosed with severe AD (AD score ≥60) were included in the study. Peripheral blood mononuclear cells (PBMCs) from the studied subjects were incubated with the peptide extracts of raw and hydrolysed cow milk with defined β-casein genotypes (A1A1, A2A2 and A1A2) and MOR and DPPIV genes expression was determined with real-time PCR.

Incubation PBMCs with peptide extracts from cow milk caused an increase of the MOR gene expression (p<0.05; p<0.001) in AD children with a simultaneous decrease in the DPPIV gene expression (p<0.001). The obtained results supplement the knowledge on the BCM7 participation in AD etiology and provide an important diagnostic tool.

Copyright © 2014 Elsevier Inc. All rights reserved.


This study adds to the evidence that beta-casomorphin-7 (BCM-7), an opioid-like peptide arising from the digestion of cows' milk - but not human or other mammal milks - could play some role in allergic conditions including eczema (atopic dermatitis), and allergic rhinitis (chronic stuffy nose).

In children with atopic dermatitis, the researchers report that the consumption of cows' milk led to an increase in gene expression for both a key opiate receptor, and an enzyme important for breaking down the opioid peptide BCM-7.

Eczema and other allergies are particularly common in chldren with Austistic Spectrum Disorders and related developmental conditions including ADHD, dyslexia and dyspraxia (DCD). 

It is therefore notable that an unusual sensitivity to opioid peptides - which arise from the digestion of gluten, as well as from standard cows' milk (which contains the A1 form of beta-casein that gives rise to BCM-7) - has been proposed as a possible contributory factor in some individuals with these conditions, although research evidence for this still remains limited.

For more information on the differences between A1 and A2 milk, see: