Persistent gut microbiota immaturity in malnourished Bangladeshi children.

Persistent gut microbiota immaturity in malnourished Bangladeshi children.
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DOI:
10.1038/nature13421
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发表时间:
2014-06-19
期刊:
影响因子:
64.8
通讯作者:
Gordon, Jeffrey I.
Gordon, Jeffrey I.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Subramanian, Sathish;Huq, Sayeeda;Yatsunenko, Tanya;Haque, Rashidul;Mahfuz, Mustafa;Alam, Mohammed A.;Benezra, Amber;DeStefano, Joseph;Meier, Martin F.;Muegge, Brian D.;Barratt, Michael J.;VanArendonk, Laura G.;Zhang, Qunyuan;Province, Michael A.;Petri, William A., Jr.;Ahmed, Tahmeed;Gordon, Jeffrey I.

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治疗性食品干预措施降低了严重急性营养不良儿童的死亡率,但不完全恢复健康生长仍然是一个主要问题。营养干预的类型、肠道微生物群和治疗反应之间的关系尚不清楚。在目前的研究中,通过将基于机器学习的方法应用于16 S rRNA数据集,确定了其比例代表性定义健康肠道微生物群的细菌物种,因为它在出生后的前两年组装,这些数据集是从出生队列的儿童每月粪便样本中生成的,这些儿童生活在孟加拉国达卡的城市贫民窟,他们表现出持续健康的生长。这些年龄歧视的细菌物种被纳入一个模型,该模型计算“相对微生物群成熟指数”和“年龄微生物群Z分数”,比较儿童粪便微生物群相对于类似年龄的健康儿童的发育(这里定义为成熟)。该模型被应用于双胞胎和三胞胎(以测试这些指数与遗传和环境因素(包括腹泻)的关联),SAM儿童参加了两种食物干预的随机试验,以及中度急性营养不良的儿童。我们的研究结果表明,SAM与显著的相对微生物群不成熟有关,这在两种广泛使用的营养干预措施后仅部分改善。不成熟在不太严重的营养不良中也很明显,这与人体测量有关。微生物群成熟度指数提供了一种衡量人类出生后发育的微生物指标,一种对营养不良状态进行分类的方法,以及一种判断治疗效果的参数。可能需要对现有或新的治疗性食物和/或添加肠道微生物进行更长时间的干预,以实现对儿童营养不良中肠道微生物群不成熟的持久修复,并改善临床结果。
Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM) but incomplete restoration of healthy growth remains a major problem. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S rRNA datasets generated from monthly fecal samples obtained from a birth-cohort of children, living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare development (defined here as maturation) of a child’s fecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors including diarrhea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.
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