Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Tropical Gastroenterology & Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.
Am J Clin Nutr. 2019 Nov 1;110(5):1240-1252. doi: 10.1093/ajcn/nqz189.
Environmental enteropathy (EE) refers to villus blunting, reduced absorption, and microbial translocation in children and adults in tropical or deprived residential areas. In previous work we observed an effect of micronutrients on villus height (VH).
We aimed to determine, in a randomized controlled trial, if amino acid (AA) or multiple micronutrient (MM) supplementation can improve intestinal structure or barrier dysfunction in Zambian adults with EE.
AA (tryptophan, leucine, and glutamine) and/or MM supplements were given for 16 wk in a 2 × 2 factorial comparison against placebo. Primary outcomes were changes in VH, in vivo small intestinal barrier dysfunction assessed by confocal laser endomicroscopy (CLE), and mechanistic (or mammalian) target of rapamycin complex 1 (MTORC1) nutrient responsiveness in lamina propria CD4+ lymphocytes.
Over 16 wk AA, but not MM, supplementation increased VH by 16% (34.5 μm) compared with placebo (P = 0.04). Fluorescein leak, measured by CLE, improved only in those allocated to both AA and MM supplementation. No effect was seen on MTORC1 activation, but posttreatment MTORC1 and VH were correlated (ρ = 0.51; P = 0.001), and change in MTORC1 was correlated with change in VH in the placebo group (ρ = 0.63; P = 0.03). In secondary analyses no effect was observed on biomarkers of microbial translocation. Metabolomic analyses suggest alterations in a number of microbial- and host-derived metabolites including the leucine metabolite β-hydroxy-β-methylbutyrate, which was increased by AA supplementation and correlated with VH.
In this phase 2 trial, AA supplementation protected against a decline in VH over the supplementation period, and improved barrier function when combined with micronutrients. Leucine and MTORC1 metabolism may be involved in the mechanism of effect. This trial was registered at www.pactr.org as PACTR201505001104412.
环境肠道病（EE）是指热带或贫困地区儿童和成年人的绒毛变钝、吸收减少和微生物易位。在之前的工作中，我们观察到微量营养素对绒毛高度（VH）的影响。
我们旨在通过一项随机对照试验，确定氨基酸（AA）或多种微量营养素（MM）补充是否可以改善赞比亚 EE 成人的肠道结构或屏障功能障碍。
在 2×2 析因比较中，AA（色氨酸、亮氨酸和谷氨酰胺）和/或 MM 补充剂与安慰剂相比，分别进行了 16 周的治疗。主要结局是绒毛高度（VH）的变化、通过共聚焦激光内镜检查（CLE）评估的体内小肠屏障功能障碍以及固有层 CD4+淋巴细胞中机械（或哺乳动物）雷帕霉素靶蛋白复合物 1（MTORC1）对营养素的反应性。
在 16 周的 AA 补充期间，但不是 MM 补充，VH 增加了 16%（34.5 μm），与安慰剂相比（P=0.04）。仅在分配给 AA 和 MM 补充的患者中，荧光素渗漏通过 CLE 改善。MTORC1 激活没有影响，但治疗后 MTORC1 和 VH 呈正相关（ρ=0.51；P=0.001），安慰剂组中 MTORC1 的变化与 VH 的变化相关（ρ=0.63；P=0.03）。在二次分析中，没有观察到对微生物易位的生物标志物的影响。代谢组学分析表明，包括 AA 补充增加的亮氨酸代谢物β-羟基-β-甲基丁酸在内的许多微生物和宿主衍生代谢物发生了改变，并且与 VH 相关。
在这项 2 期试验中，AA 补充剂在补充期间防止 VH 下降，并与微量营养素联合使用时改善了屏障功能。亮氨酸和 MTORC1 代谢可能参与了作用机制。该试验在 pactr.org 上注册，编号为 PACTR201505001104412。
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