Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.

Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.
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DOI:
10.1016/j.cell.2016.01.024
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发表时间:
2016-02-25
期刊:
影响因子:
64.5
通讯作者:
Gordon JI
Gordon JI
中科院分区:
生物学1区
文献类型:
--
作者:
Charbonneau MR;O'Donnell D;Blanton LV;Totten SM;Davis JC;Barratt MJ;Cheng J;Guruge J;Talcott M;Bain JR;Muehlbauer MJ;Ilkayeva O;Wu C;Struckmeyer T;Barile D;Mangani C;Jorgensen J;Fan YM;Maleta K;Dewey KG;Ashorn P;Newgard CB;Lebrilla C;Mills DA;Gordon JI

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确定更有效地促进营养不良儿童健康成长的干预措施是一项紧迫的全球卫生目标。对两个马拉维出生队列中产后6个月母亲的母乳低聚糖(HMO)进行分析,结果显示,患有严重发育不良婴儿的母亲中唾液酸化HMO的含量明显较低。为了探索这种关联,我们用从6个月大发育不良的马拉维婴儿的粪便微生物群培养的细菌菌株的财团定殖年轻的无菌小鼠,并给受体动物喂食含有或不含有纯化的唾液酸化牛乳低聚糖(S-BMO)的原型马拉维饮食。S-BMO产生了瘦体重增加的微生物群依赖性增加,改变了骨形态,改变了肝脏、肌肉和大脑的代谢,表明了更大的利用营养物质的能力。这些影响也记录在gnotobiotic仔猪使用相同的财团和马拉维饮食。这些临床前模型表明,S-BMO和生长促进之间存在因果关系和微生物群依赖性关系。
Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month postpartum mothers in two Malawian birth-cohorts revealed that sialylated HMOs are significantly less abundant in mothers with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology and altered liver, muscle and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.