Lipid based complementary foods and gut health in young children

 描述（由申请人提供）：儿童饥饿和营养不良在低收入国家普遍存在，通常在面临长期或季节性粮食短缺或粮食不安全的人口中观察到。在许多低收入和中等收入国家，发育迟缓，即身高或年龄别身高超过国际生长标准中位数的-2 Z分数，仍然是长期贫困的一个难以解决的后果。在成年人中，发育迟缓会损害妇女的生殖结果，降低教育成就，降低社会经济前景，并增加男子和妇女患非传染性疾病的风险。在全球范围内，南亚的发育迟缓人数最多，超过35%的学龄前儿童发育迟缓。24个月时的身高预测成人身高，并且线性生长的最大递减发生在6至24个月龄之间。因此，工作重点是“头1000天”，即从概念到24个月，这被认为是改善增长的关键窗口。然而，迄今为止，仅通过营养干预改善线性生长的努力取得了有限的成果，尽管是积极的成果，这表明在生命的这一阶段改善生长的潜力尚未实现。新一代的脂质为基础的补充食品产品，强化微量营养素，可能提供最好的希望，前瞻性地改善线性增长的设置，补充（或“断奶”）食品的营养多样性和密度差。然而，在这样的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物质的能力，其中最大的问题之一是环境性肠病（EE），或因反复暴露于肠道病原体而对肠道造成的损伤，导致炎症，营养吸收能力受损，以及可能导致病原体移位从而引发全身免疫反应的过度肠道通透性。在孟加拉国西北部农村地区，将在18个月大的儿童中评估EE，在12个月的补充性补充食物后，与单独的营养咨询相比，在四种不同食物配方的生长和发育的随机分组对照试验中。虽然该试验入组了5,300多名儿童，但将对500名儿童（约10%的子样本）进行更深入的研究，以使用肠道炎症的粪便标志物、细菌移位的血清标志物以及甘露醇和乳果糖的相对吸收来表征EE，以分别评估肠道吸收能力和肠道渗透性。我们假设，在过去一年中接受补充食物的儿童比仅接受营养咨询的儿童有更少的EE证据。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及养育做法。[结果将证明通过获得高质量的补充食品来改善饮食是否可以改善EE，并将研究EE与生长轨迹和生长生物介质的关系，为这些儿童的肠道微生物组的未来研究提供支持性数据。

 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.]