Walsh Kevin, Calder Nuala, Olupot-Olupot Peter, Ssenyondo Tonny, Okiror William, Okalebo Charles Bernard, Muhindo Rita, Mpoya Ayub, Holmes Elaine, Marchesi Julian, Delamare de la Villenaise de Chenevarin Gael, Frost Gary, Maitland Kathryn
Department of Paediatrics, Imperial College, London, W2 1PG, UK.
Section for Nutrition Research, Department of Medicine, Imperial College, London, W12 ONN, UK.
Wellcome Open Res. 2018 Aug 2;3:95. doi: 10.12688/wellcomeopenres.14706.1. eCollection 2018.
Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome. We will investigate in an open-label trial in 160 Ugandan children with SAM, defined by mid-upper arm circumference <11.5cm and/or presence of kwashiorkor. Children will be randomised to a lactose-free, chickpea-enriched feed containing 2 kcal/ml, provided in quantities to match usual energy provision (experimental) or WHO standard treatment F75 (0.75 kcal/ml) and F100 (1 kcal/ml) feeds on a 1:1 basis, conducted at Mbale Regional Referral Hospital nutritional rehabilitation unit. The primary outcomes are change in MUAC at day 90 and survival to day 90. Secondary outcomes include: i) moderate to good weight gain (>5 g/kg/day), ii) development of diarrhoea (>3 loose stools/day), iii) time to diarrhoea resolution (if >3 loose stools/day), and iv) time to oedema resolution (if kwashiorkor) and change in intestinal biomarkers (faecal calprotectin). We hypothesize that, if introduced early in the management of malnutrition, such lactose-free, fermentable carbohydrate-based feeds, could safely and cheaply improve global outcome by reducing lactose intolerance-related diarrhoea, improving mucosal integrity and enhancing immunity, and limiting the risk of systemic infection and associated broad-spectrum antibiotic resistance. ISRCTN 10309022.
严重急性营养不良（SAM）会导致肠道黏膜完整性和肠道微生物平衡发生变化，进而导致治疗失败和不良临床结局（革兰氏阴性菌败血症、腹泻和高病死率）。由于肠道刷状缘乳糖酶丧失导致的短暂乳糖不耐受，也会使SAM病情复杂化，因此以牛奶为基础的喂养方式可能并非营养康复的最佳选择。鉴于肠道上皮屏障可由特定可发酵碳水化合物经微生物群发酵产生的短链脂肪酸来支持，我们推测，一种由豆类可发酵碳水化合物组成的能量密集型营养饲料，与世界卫生组织（WHO）标准F75/F100营养饲料的无乳糖版本相结合，将增强营养不良儿童的上皮屏障功能，减少并促进腹泻的缓解，改善总体结局。我们将在160名乌干达SAM儿童中开展一项开放标签试验，这些儿童通过上臂中部周长<11.5cm和/或存在夸希奥科病来定义。儿童将被随机分配到一种每毫升含2千卡能量、富含鹰嘴豆的无乳糖饲料组，提供的量与通常的能量供应相匹配（试验组），或按1:1的比例分配到WHO标准治疗用F75（每毫升0.75千卡）和F100（每毫升1千卡）饲料组，试验在姆巴莱地区转诊医院营养康复科进行。主要结局指标为第90天时上臂中部周长的变化以及至第90天的存活情况。次要结局指标包括：i）中度至良好的体重增加（>5克/千克/天），ii）腹泻的发生（>3次稀便/天），iii）腹泻缓解时间（如果>3次稀便/天），iv）水肿缓解时间（如果是夸希奥科病）以及肠道生物标志物（粪便钙卫蛋白）的变化。我们假设，如果在营养不良管理早期引入这种无乳糖、基于可发酵碳水化合物的饲料，可通过减少与乳糖不耐受相关的腹泻、改善黏膜完整性和增强免疫力，以及限制全身感染风险和相关的广谱抗生素耐药性，安全且低成本地改善总体结局。国际标准随机对照试验编号：ISRCTN 10309022。
