Lipid based complementary foods and gut health in young children

 说明(申请人提供)：儿童饥饿和营养不良在低收入国家很普遍，通常出现在面临长期或季节性粮食短缺或粮食不安全的人口中。在许多低收入和中等收入国家，发育迟缓，即达到国际生长标准中位数-2 Z分数以上的身高或身高，仍然是长期剥夺的一个棘手后果。在成年人中，发育迟缓会导致妇女的生殖结果受损，而在男子和妇女中，则会导致教育成就降低、社会经济前景变差以及患非传染性疾病的风险增加。在全球范围内，发育迟缓的个体数量最多的是南亚，那里超过35%的学龄前儿童发育迟缓。24个月的身高预示着成人的身高，而线性增长的最大减幅出现在6到24个月之间。因此，努力的重点是“头1000天”，即从最初的1000天到24个月，这被认为是改善增长的关键窗口。然而，到目前为止，仅通过营养干预来改善线性增长的努力取得了温和的、尽管是积极的结果，表明在这一生命阶段改善增长的潜力尚未实现。在补充(或“断奶”)食品的营养多样性和密度较差的情况下，添加微量营养素的新一代以脂质为基础的补充食品可能提供最大的希望，有望改善线性增长。然而，这种环境中的儿童也会受到环境暴露的影响，这可能会限制他们利用营养的能力，最令人担忧的问题之一是环境肠病(EE)，即反复暴露于肠道病原体对肠道的损害，导致炎症，营养吸收能力受损，肠道通透性过高，可能导致病原体移位，从而触发全身免疫反应。在孟加拉国西北部农村，将在补充补充食品12个月后对18个月大的儿童进行EE评估，而不是仅进行营养咨询，这是一项关于四种不同食品配方对生长和发育的整群随机对照试验。虽然有5,300多名儿童参加了这项试验，但将对500名儿童进行更深入的研究，约10%的子样本，以分别使用肠道炎症的粪便标记物、细菌易位的血清标记物以及甘露醇和乳果糖的相对吸收来评估肠道吸收能力和肠道通透性。我们假设，在过去一年中接受补充食物的儿童与那些单独接受营养咨询的儿童相比，患上EE的证据更少。这项研究将利用已经收集的生物标本和关于饮食、发病率和人体测量的纵向数据，以及家庭特征和喂养和育儿做法。[结果将证明，通过获得高质量的补充食物来改善饮食是否可以改善EE，并将检查EE与生长轨迹和生长的生物介质的关系，为未来对这些儿童肠道微生物群的研究提供支持数据。]

 DESCRIPTION (provided by applicant): Childhood hunger and under nutrition are prevalent in low income countries, and are typically observed in populations facing states of chronic or seasonal food shortage, or food insecurity. Stunting, attained length or height-for-age beyond -2 Z- scores from the median of the international growth standard, remains an intractable consequence of chronic deprivation in many low and middle income countries. In adults, being stunted contributes to compromised reproductive outcomes in women, and lower educational achievement, poorer socioeconomic prospects, and an increased risk of non-communicable diseases in men and women. Globally, the greatest number of stunted individuals resides in South Asia, where over 35% of preschool age children are stunted. Height at 24 months predicts adult height, and the greatest decrements in linear growth occur between 6 and 24 months of age. Efforts have therefore focused on the "first 1000 days", conception to 24 months, which is considered a critical window for improving growth. However, to date, efforts to improve linear growth through nutrition interventions alone have yielded modest, albeit positive, results, indicating unrealized potential for improving growth during this period of life. A new generation of lipid-based complementary food products, fortified with micronutrients, may offer the best hope of prospectively improving linear growth in settings where complementary (or "weaning") foods are poor in nutrient diversity and density. However, children in such environments are also subject to environmental exposures that may limit their ability to utilize nutrients, with oneof the greatest concerns being environmental enteropathy (EE), or damage to the gut from repeated exposure to enteric pathogens, resulting in inflammation, compromised nutrient absorptive capacity, and excess gut permeability that may lead to the translocation of pathogens that trigger systemic immune responses. In rural northwestern Bangladesh, EE will be assessed in 18 month old children following 12 months of supplemental complementary foods, versus nutrition counseling alone, in the context of a cluster-randomized, controlled trial of four different food formulations on growth and development. While over 5,300 children were enrolled in that trial, a more intensive study of 500 children, a ~10% subsample, will be done to characterize EE using stool markers of gut inflammation, serum markers of bacterial translocation, and the relative absorption of mannitol and lactulose to evaluate gut absorptive capacity and gut permeability, respectively. We hypothesize that children who received supplemental foods for the past year will have less evidence of EE than those who received nutrition counseling alone. This study will take advantage of biospecimens and longitudinal data on diet, morbidity and anthropometry, as well as household characteristics and feeding and parenting practices, which have already been collected. [Results will demonstrate whether improving the diet with access to high quality complementary foods can ameliorate EE, and will examine relationships of EE to growth trajectories and biological mediators of growth, providing supportive data for future study of the gut microbiome in these children.]