Trivedi Malav S, Shah Jayni S, Al-Mughairy Sara, Hodgson Nathaniel W, Simms Benjamin, Trooskens Geert A, Van Criekinge Wim, Deth Richard C
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium.
J Nutr Biochem. 2014 Oct;25(10):1011-8. doi: 10.1016/j.jnutbio.2014.05.004. Epub 2014 Jun 6.
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.
据报道，无麸质和无酪蛋白饮食等饮食干预措施可改善患有多种疾病患者的肠道、自身免疫和神经症状；然而，此类饮食有益的潜在机制仍不清楚。出生后早期发育过程中发生的表观遗传编程，包括CpG甲基化和组蛋白修饰，可影响后期生活中的疾病风险，并且这种编程可能受到牛奶和小麦等营养因素的调节，尤其是在从单纯以牛奶为基础的饮食过渡到包含其他营养形式的饮食期间。酪蛋白（一种主要的牛奶蛋白）和麦醇溶蛋白（一种小麦衍生蛋白）的水解消化会释放具有阿片样活性的肽，在本研究中，我们证明这些食物来源的富含脯氨酸的阿片样肽通过激活阿片受体来调节培养的人神经元和胃肠道（GI）上皮细胞中的半胱氨酸摄取。半胱氨酸摄取的减少与细胞内抗氧化剂谷胱甘肽和甲基供体S-腺苷甲硫氨酸的变化有关。牛和人酪蛋白衍生的阿片样肽在转录起始位点区域增加了全基因组DNA甲基化，其效力顺序与其对半胱氨酸摄取的抑制作用相似。还观察到参与氧化还原和甲基化稳态的基因表达发生了改变。这些结果说明了牛奶和小麦衍生肽发挥抗氧化和表观遗传变化的潜力，这在出生后从胎盘营养向胃肠道营养的转变过程中可能尤为重要。人乳和牛乳衍生肽之间的差异可能导致母乳喂养和配方奶喂养婴儿的发育差异。由小麦和牛奶衍生的阿片样肽引起的抗氧化能力受限，可能使易感个体易患炎症和全身氧化，部分解释了无麸质或无酪蛋白饮食的益处。
