A Microbiota-Directed Food Intervention for Undernourished Children.

A Microbiota-Directed Food Intervention for Undernourished Children.
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DOI:
10.1056/nejmoa2023294
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发表时间:
2021-04-22
期刊:
The New England journal of medicine
影响因子:
--
通讯作者:
Gordon JI
Gordon JI
中科院分区:
其他
文献类型:
--
作者:
Chen RY;Mostafa I;Hibberd MC;Das S;Mahfuz M;Naila NN;Islam MM;Huq S;Alam MA;Zaman MU;Raman AS;Webber D;Zhou C;Sundaresan V;Ahsan K;Meier MF;Barratt MJ;Ahmed T;Gordon JI

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全世界有3000多万儿童患有中度急性营养不良(MAM)。目前的治疗方法疗效有限,发病机制尚不清楚。患有MAM的儿童表现出肠道微生物区系发育受扰。居住在贫民窟的12至18个月的孟加拉儿童患有中度急性营养不良(n=124),他们接受微生物区系辅助食品(MDCF-2)或现有的即用补充食品(RUSF),每天两次,为期三个月,然后进行一个月的监测。我们在基线和每两周一次,共四个月,获得长度体重、年龄体重、年龄长度Z分数和上臂中段周长。我们比较了基线和三个月以及基线和四个月之间这些相关表型的变化率。我们还测量了血浆中4977种蛋白质的水平以及粪便样本中的209种细菌分类群。118名儿童完成干预(n=59/ARM)。在包括一个月随访的研究过程中,长度体重Z分数(β-WLZ)、年龄体重Z分数和上臂中部周长的变化率与MDCF2对生长的益处是一致的。Mdcf-2的接受与70个β-wlz正相关血浆蛋白水平的变化有关,包括骨生长、神经发育和炎症的介质(基因集浓缩分析0.001)和23个wlz相关细菌分类群的丰度(gsea;p<0.001)。这些发现为进一步临床研究MDCF-2作为患有MAM的幼儿的膳食补充提供了支持,并为这种微生物区系成分的靶向操纵可能与生长有关的机制提供了洞察。(由比尔和梅林达·盖茨基金会和美国国立卫生研究院支持;ClinicalTrials.gov标识符:NCT04015999)
More than 30 million children worldwide suffer from moderate acute malnutrition (MAM). Current treatments have limited effectiveness and much remains unknown about pathogenesis. Children with MAM exhibit perturbed development of their gut microbiota. Slum-dwelling Bangladeshi children, aged 12 to 18 months, with moderate acute malnutrition (n=124) received a microbiota-directed complementary food (MDCF-2) or an existing ready-to-use supplementary food (RUSF), twice daily for three months followed by a 1-month period of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age Z-scores and mid-upper arm circumference at baseline and fortnightly, through four months. We compared the rate of change of these related phenotypes between baseline and three months, and between baseline and four months. We also measured levels of 4,977 proteins in plasma plus 209 bacterial taxa in fecal samples. 118 children completed the intervention (n=59/arm). The rate of change in weight-for-length Z-score (β-WLZ), weight-for-age Z-score, and mid upper arm circumference is consistent with a benefit of MDCF-2 on growth over the course of the study including the one-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 β-WLZ-positively correlated plasma proteins including mediators of bone growth, neurodevelopment and inflammation (gene set enrichment analysis [GSEA];p<0.001) and the abundances of 23 WLZ-associated bacterial taxa (GSEA;p<0.001). These findings provide support for further clinical investigation of MDCF-2 as a dietary supplement for young children with MAM and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the NIH; ClinicalTrials.gov identifier:NCT04015999)