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
diets.
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
diets.
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