Food-derived opioid peptides (from gliadin and casein) inhibit cysteine uptake with redox and epigenetic consequences.

Dietary interventions like gluten-free and casein-free diets have been
reported to improve intestinal, autoimmune and neurological symptoms in
patients with a variety of conditions; however, the underlying mechanism
of benefit for such diets remains unclear. Epigenetic programming,
including CpG methylation and histone modifications, occurring during
early postnatal development can influence the risk of disease in later
life, and such programming may be modulated by nutritional factors such
as milk and wheat, especially during the transition from a solely
milk-based diet to one that includes other forms of nutrition. The
hydrolytic digestion of casein (a major milk protein) and gliadin (a
wheat-derived protein) releases peptides with opioid activity, and in
the present study, we demonstrate that these food-derived proline-rich
opioid peptides modulate cysteine uptake in cultured human neuronal and
gastrointestinal (GI) epithelial cells via activation of opioid
receptors. Decreases in cysteine uptake were associated with changes in
the intracellular antioxidant glutathione and the methyl donor
S-adenosylmethionine. Bovine and human casein-derived opioid peptides
increased genome-wide DNA methylation in the transcription start site
region with a potency order similar to their inhibition of cysteine
uptake. Altered expression of genes involved in redox and methylation
homeostasis was also observed. These results illustrate the potential of
milk- and wheat-derived peptides to exert antioxidant and epigenetic
changes that may be particularly important during the postnatal
transition from placental to GI nutrition. Differences between peptides
derived from human and bovine milk may contribute to developmental
differences between breastfed and formula-fed infants. Restricted
antioxidant capacity, caused by wheat- and milk-derived opioid peptides,
may predispose susceptible individuals to inflammation and systemic
oxidation, partly explaining the benefits of gluten-free or casein-free

No comments: