Immunomodulatory effects of omega-3 polyunsaturated fatty acids : role in allergy prevention in infancy

在过去的20-30年里，哮喘和过敏性疾病的急剧增加突出了识别相关环境变化的迫切需要，这些变化也可能是疾病预防的合理目标。虽然这可能是多因素的，但在此期间的一个显著变化是西方饮食中抗炎性n-3多不饱和脂肪（PUFA）的摄入量逐渐下降，n-6 PUFA脂肪酸相应增加。我们最近首次表明，在免疫反应完全建立之前，n-3 PUFA可能在生命早期具有更显著的影响。我们证实，母体鱼油补充剂（n-40）导致新生儿的n-3 PUFA水平显着升高（与未补充剂的新生儿相比，n-43），这与对过敏原（如屋尘螨，猫和鸡蛋）的免疫反应降低有关。这些观察结果表明，n-3 PUFA可以改变早期免疫发育。尽管这项先前的研究旨在评估免疫结果（而不是临床结果），但我们收集了用于本申请目的的初步临床数据。我们观察到一个一致的趋势，较少的过敏症状和过敏的补充组。这些观察结果清楚地证明了本拟定研究的必要性，以证实这些临床作用，并更详细地评估作用机制。在这项拟议的研究中，我们将比较鱼油（n-165）或安慰剂（n-165）在婴儿早期（0-6个月大）的影响。这一更大的人群将使我们能够确定增加饮食中的n-3 PUFA是否是降低遗传风险高的家庭中过敏机会的一种方法。在澳大利亚，大约40%的婴儿会患上哮喘或过敏症。像这样降低疾病表达风险（即使是轻微的）或严重程度的策略，可以在全球范围内以相对较小的成本产生巨大的影响。

The dramatic increase in asthma and allergic disease over the last 20-30 years has highlighted the urgent need to identify associated environmental changes that may also be logical targets for disease prevention. Although this is likely to be multifactorial, one significant change during this period has been a progressive decline in the intake of dietary anti-inflammatory n-3 polyunsaturated fats (PUFA) in Western diets, with a corresponding increase in n-6 PUFA fatty acids. We recently showed for the first time that n-3 PUFA may have more significant effects in very early life before immune responses are fully established. We confirmed that maternal fish oil supplementation (n-40) resulted in significantly higher n-3 PUFA levels in newborns (compared to those with no supplements, n-43), and this was related to reduced immune responses to allergens (such as house dust mite, cat and egg). These observations suggest that n-3 PUFA can modify early immune development. Although this previous study was designed to assess immune outcomes (rather than clinical outcomes) we collected preliminary clinical data for the purposes of this application. We observed a consistent trend for less allergic symptoms and sensitisation in the supplementation group. These observations clearly warrant this proposed study to confirm these clinical effects, and to assess the mechanisms of action in considerably more detail. In this proposed study we will compare the effects of fish oil (n-165) or placebo (n-165) in early infancy (from 0-6 months of age). This much larger population will allow us to determine if increasing dietary n-3 PUFA is a way of reducing the chance of allergy in families where there is a high genetic risk. Approximately 40% of infants in Australia will go on to develop asthma or allergies. Strategies such as this that reduce the risk (even slightly) or the severity of disease expression could have enormous impact in this global context at relatively little cost.