Globally, severe acute malnutrition (SAM), defined as a weight-for-length z -score more than three SDs below a reference mean (WLZ < −3), affects 14 million children under 5 years of age. Complete anthropometric recovery after standard, short-term interventions is rare, with children often left with moderate acute malnutrition (MAM; WLZ −2 to −3). We conducted a randomized controlled trial (RCT) involving 12- to 18-month-old Bangladeshi children from urban and rural sites, who, after initial hospital-based treatment for SAM, received a 3-month intervention with a microbiome-directed complementary food (MDCF-2) or a calorically more dense, standard ready-to-use supplementary food (RUSF). The rate of WLZ improvement was significantly greater in MDCF-2–treated children ( P = 8.73 × 10 −3 ), similar to our previous RCT of Bangladeshi children with MAM without antecedent SAM ( P = 0.032). A correlated meta-analysis of plasma levels of 4520 proteins in both RCTs revealed 215 positively associated with WLZ (largely representing musculoskeletal and central nervous system development) and 44 negatively associated (primarily related to immune activation). Moreover, the positively associated proteins were significantly enriched by MDCF-2 ( q = 1.1 × 10 −6 ). Characterizing the abundances of 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome and how, during treatment for MAM, specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and anthropometric recovery. These results provide a rationale for further testing the generalizability of MDCF efficacy and for identifying biomarkers to define treatment responses.

中文翻译：

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一种以微生物组为导向的治疗性食品，适用于严重急性营养不良康复儿童


在全球范围内，严重急性营养不良 （SAM） 定义为身长别体重 z 评分比参考平均值 （WLZ < -3） 低 3 个标准差以上，影响了 1400 万名 5 岁以下儿童。在标准的短期干预后，人体测量学的完全恢复很少见，儿童通常患有中度急性营养不良 （MAM;WLZ −2 到 −3）。我们进行了一项随机对照试验 （RCT），涉及来自城市和农村地区的 12 至 18 个月大的孟加拉国儿童，他们在医院接受 SAM 的初始治疗后，接受了为期 3 个月的干预，使用微生物组导向的补充食品 （MDCF-2） 或热量更高的标准即食补充食品 （RUSF）。MDCF-2 治疗儿童的 WLZ 改善率显着更高 （P = 8.73 × 10 −3 ），类似于我们之前对孟加拉国 MAM 儿童的 RCT 没有前科 SAM （P = 0.032）。对两项 RCT 中 4520 种蛋白质血浆水平的相关荟萃分析显示，215 种与 WLZ 呈正相关（主要代表肌肉骨骼和中枢神经系统发育），44 种与 WLZ 呈负相关（主要与免疫激活相关）。此外，MDCF-2 显著富集了正相关蛋白 （ q = 1.1 × 10 − 6 ）。在连续收集的粪便样本中表征 754 个细菌宏基因组组装基因组的丰度，揭示了 SAM 急性康复对微生物组的影响，以及在 MAM 治疗期间，Prevotella copri 的特定菌株如何在 MDCF-2 聚糖代谢和人体测量恢复之间的交叉点发挥作用。这些结果为进一步测试 MDCF 疗效的普遍性和识别生物标志物以定义治疗反应提供了理论依据。