Exploratory observational study of therapeutic feeds used to treat intestinal inflammation in Malawian children with severe acute malnutrition (SAM)

用于治疗马拉维严重急性营养不良 (SAM) 儿童肠道炎症的治疗性饲料的探索性观察研究

• 批准号: MR/M022390/1
• 负责人: Stephen Allen
• 金额: $ 18.28万
• 依托单位: Liverpool School of Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM022390%2F1
• 关键词: Exploratory; observational; study; therapeutic; feeds

Despite interventions to prevent malnutrition, SAM, encompassing both marasmus (severe wasting) and kwashiorkor, occurred in 19m under fives in 2011 and accounted for 7% of all under 5 deaths. Many children with SAM are managed in the community using Ready-to-Use Therapeutic Food (RUTF). However, about 20% requires in-patient care because of inability to take adequate feeds, complications such as infection or diarrhoea or failure to improve under community management. The in-patient management of children with SAM is extremely challenging. Despite following a well-established WHO protocol, case fatality often exceeds 20% and many of the survivors die following discharge home. Amongst long-term survivors, stunting, the recurrence of wasting and re-admission to hospital are common. It has long been recognized that children with SAM have intestinal inflammation, termed "environmental" or "tropical" enteropathy. Although of unknown cause, it is thought to result from poor sanitation increasing exposure to microbial pathogens in the gut. Studies of the small intestine have shown that the marked reduction in surface area impairs food digestion and nutrient absorption. Also, the mucosa is "leaky" which likely allows bacteria to enter the tissues and blood stream causing sepsis and exposes the gut immune cells to microbial and food antigens resulting in persistence of the inflammation and consequent gut damage. Children who also have HIV infection may have even more severe enteropathy because HIV itself damages the intestinal mucosa. After initial stabilisation of the child's condition, the current management of SAM focuses on re-feeding and treating infections. The feeds used (RUTF, F100) contain micronutrients such as vitamin A and zinc that are known to be important for mucosal health. However, these feeds would not be expected to improve the intestinal inflammation and this may underlie the poor response to treatment and poor long-term outcomes in many cases. The inflammation in the intestine in SAM is very similar to that which occurs in food intolerance and Crohn's disease. In contrast to SAM, the treatment of these conditions targets the gut inflammation. In children, recommended treatments are with an extensively hydrolysed or elemental formula (food intolerance) or polymeric or elemental formula (Crohn's disease). These are complete feeds that promote healing of the intestinal mucosa and nutritional recovery and are free of significant adverse effects. In children with active Crohn's disease, about 60% achieve clinical remission and another 30% improve with these feeds. The similarity in the gut inflammation across these conditions raises the possibility that treatments that effectively reduce the gut inflammation in food intolerance and Crohn's disease may also be effective in SAM. We aim to undertake a pilot study to see if an extensively hydrolysed, elemental and/or polymeric formula are tolerated by children with SAM and to see if they reduce the intestinal inflammation. If we find that one or more of these feeds are likely to be effective, they would need to be evaluated in a larger study. If confirmed in a larger study, our findings would establish the necessity of specifically treating the intestinal inflammation in SAM. This could then be included in standard clinical management protocols. Researchers would be encouraged to consider how these alternative therapeutic feeds could be adapted to make them practical and cost-effective in low resource settings perhaps by using local ingredients and formulation as a paste for use at home. Also, it would be important to explore potential alternative approaches to treating the enteropathy - possibly also including children with less severe malnutrition managed in the community.

尽管采取了预防营养不良的干预措施，但 2011 年 1,900 万 5 岁以下儿童中仍出现 SAM（包括严重消瘦）和恶性营养不良，占所有 5 岁以下死亡人数的 7%。许多患有 SAM 的儿童在社区中使用即用治疗食品 (RUTF) 进行管理。然而，约20%的人因无法摄入足够的食物、感染或腹泻等并发症或在社区管理下未能改善而需要住院治疗。 SAM 儿童的住院管理极具挑战性。尽管遵循了世卫组织完善的方案，但病死率往往超过 20%，许多幸存者在出院回家后死亡。在长期幸存者中，发育迟缓、消瘦复发和再次入院很常见。人们很早就认识到患有 SAM 的儿童患有肠道炎症，称为“环境”或“热带”肠病。尽管原因不明，但据认为是由于卫生条件差，肠道内微生物病原体的暴露增加所致。小肠的研究表明，表面积的显着减少会损害食物消化和营养吸收。此外，粘膜是“渗漏的”，这可能会让细菌进入组织和血流，导致败血症，并使肠道免疫细胞暴露于微生物和食物抗原，导致炎症持续存在和随后的肠道损伤。同时感染艾滋病毒的儿童可能会出现更严重的肠病，因为艾滋病毒本身会损害肠粘膜。在孩子的病情初步稳定后，目前 SAM 的治疗重点是重新喂养和治疗感染。使用的饲料（RUTF、F100）含有维生素 A 和锌等微量营养素，已知这些营养素对粘膜健康很重要。然而，这些饲料预计不会改善肠道炎症，这可能是许多情况下治疗反应不佳和长期结果不佳的原因。 SAM 中的肠道炎症与食物不耐受和克罗恩病中发生的炎症非常相似。与 SAM 不同，这些病症的治疗目标是肠道炎症。对于儿童，推荐的治疗方法是使用深度水解或元素配方（食物不耐受）或聚合或元素配方（克罗恩病）。这些是全价饲料，可以促进肠粘膜愈合和营养恢复，并且没有明显的副作用。在患有活动性克罗恩病的儿童中，大约 60% 的儿童通过这些饲料获得临床缓解，另外 30% 的儿童病情有所改善。这些疾病中肠道炎症的相似性表明，有效减少食物不耐受和克罗恩病引起的肠道炎症的治疗方法也可能对 SAM 有效。我们的目标是进行一项试点研究，看看患有 SAM 的儿童是否能够耐受深度水解的元素和/或聚合配方奶粉，并看看它们是否可以减轻肠道炎症。如果我们发现这些饲料中的一种或多种可能有效，则需要在更大规模的研究中对其进行评估。如果在更大规模的研究中得到证实，我们的研究结果将确定专门治疗 SAM 肠道炎症的必要性。然后可以将其纳入标准临床管理方案中。我们将鼓励研究人员考虑如何调整这些替代治疗性饲料，使其在资源匮乏的环境中实用且具有成本效益，或许可以使用当地成分和配方作为在家使用的糊剂。此外，探索治疗肠病的潜在替代方法也很重要——可能还包括社区管理的不太严重营养不良的儿童。

项目成果

Hypoallergenic and anti-inflammatory feeds in children with complicated severe acute malnutrition: an open randomised controlled 3-arm intervention trial in Malawi.

患有复杂性严重急性营养不良的儿童的低过敏性和抗炎饲料：马拉维的一项开放随机对照三臂干预试验。

• DOI: 10.1038/s41598-019-38690-9
• 发表时间: 2019
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Bartels RH

Metabolic derangements identified through untargeted metabolomics in a cross-sectional study of Nigerian children with severe acute malnutrition

• DOI: 10.1007/s11306-016-1150-2
• 发表时间: 2017-02-01
• 期刊: METABOLOMICS
• 影响因子: 3.6
• 作者: McMillan, Amy;Orimadegun, Adebola E.;Allen, Stephen J.
• 通讯作者: Allen, Stephen J.