Prescott Susan L
Nestle Nutr Inst Workshop Ser. 2016;85:1-17. doi: 10.1159/000439477. Epub 2016 Apr 18.
Early-life nutritional exposures are significant determinants of the development and future health of all organ systems. The dramatic rise in infant immune diseases, most notably allergy, indicates the specific vulnerability of the immune system to early environmental changes. Dietary changes are at the center of the emerging epigenetic paradigms that underpin the rise in many modern inflammatory and metabolic diseases. There is growing evidence that exposures in pregnancy and the early postnatal period can modify gene expression and disease susceptibility. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also interest in the developmental effects of specific nutrients. Oligosaccharides (soluble fiber), antioxidants, polyunsaturated fatty acids, folate and other vitamins have documented effects on immune function as well as metabolism. Some have also been implicated in modified risk of allergic diseases in observational studies. Intervention studies are largely limited to trials with polyunsaturated fatty acids and oligosaccharides, showing preliminary but yet unconfirmed benefits in allergy prevention. Understanding how environmental influences disrupt the finely balanced development of immune and metabolic programming is of critical importance. Diet-sensitive pathways are likely to be crucial in these processes. While an epigenetic mechanism provides a strong explanation of how nutritional exposures can affect fetal gene expression and subsequent disease risk, other diet-induced tissue compositional changes may also contribute directly to altered immune and metabolic function--including diet-induced changes in the microbiome. A better understanding of nutritional programming of immune health, nutritional epigenetics and the biological processes sensitive to nutritional exposures early in life may lead to dietary strategies that provide more tolerogenic conditions during early immune programming and reduce the burden of many inflammatory diseases--not just allergy.
生命早期的营养暴露是所有器官系统发育和未来健康的重要决定因素。婴儿免疫疾病,尤其是过敏症的急剧增加,表明免疫系统对早期环境变化具有特殊的易感性。饮食变化是新兴表观遗传范式的核心,这些范式支撑着许多现代炎症和代谢疾病的增加。越来越多的证据表明,孕期和出生后早期的暴露会改变基因表达和疾病易感性。尽管现代饮食变化复杂,涉及多种营养素模式的改变,但人们也对特定营养素的发育影响感兴趣。寡糖(可溶性纤维)、抗氧化剂、多不饱和脂肪酸、叶酸和其他维生素已被证明对免疫功能以及新陈代谢有影响。在观察性研究中,一些物质还与过敏性疾病风险的改变有关。干预研究主要限于多不饱和脂肪酸和寡糖试验,在预防过敏方面显示出初步但尚未得到证实的益处。了解环境影响如何扰乱免疫和代谢编程的精细平衡发展至关重要。饮食敏感途径可能在这些过程中起关键作用。虽然表观遗传机制有力地解释了营养暴露如何影响胎儿基因表达和随后的疾病风险,但其他饮食诱导的组织成分变化也可能直接导致免疫和代谢功能改变——包括饮食诱导的微生物群变化。更好地理解免疫健康的营养编程、营养表观遗传学以及生命早期对营养暴露敏感的生物学过程,可能会带来饮食策略,在早期免疫编程期间提供更具耐受性的条件,并减轻许多炎症性疾病——不仅仅是过敏症的负担。