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

被引:526
作者
Charbonneau, Mark R. [1 ,2 ]
O'Donnell, David [1 ,2 ]
Blanton, Laura V. [1 ,2 ]
Totten, Sarah M. [4 ,5 ]
Davis, Jasmine C. C. [4 ,5 ]
Barratt, Michael J. [1 ,2 ]
Cheng, Jiye [1 ,2 ]
Guruge, Janaki [1 ,2 ]
Talcott, Michael [3 ]
Bain, James R. [8 ,9 ,10 ,11 ]
Muehlbauer, Michael J. [8 ,9 ]
Ilkayeva, Olga [8 ,9 ]
Wu, Chao [12 ]
Struckmeyer, Tedd [12 ]
Barile, Daniela [5 ,6 ]
Mangani, Charles [13 ]
Jorgensen, Josh [7 ]
Fan, Yue-mei [14 ]
Maleta, Kenneth [13 ]
Dewey, Kathryn G. [7 ]
Ashorn, Per [14 ,15 ]
Newgard, Christopher B. [8 ,9 ,10 ,11 ]
Lebrilla, Carlito [4 ,5 ]
Mills, David A. [5 ,6 ]
Gordon, Jeffrey I. [1 ,2 ]
机构
[1] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Ctr Gut Microbiome & Nutr Res, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Div Comparat Med, St Louis, MO 63110 USA
[4] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA
[5] Univ Calif Davis, Foods Hlth Inst, Davis, CA 95616 USA
[6] Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA
[7] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA
[8] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA
[9] Duke Univ, Med Ctr, Duke Mol Physiol Inst, Durham, NC 27710 USA
[10] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[11] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
[12] Hilmar Cheese Co, Hilmar Ingredients, Hilmar, CA 95324 USA
[13] Univ Malawi, Coll Med, Blantyre 3, Malawi
[14] Univ Tampere, Sch Med, Dept Int Hlth, FI-33521 Tampere, Finland
[15] Tampere Univ Hosp, Dept Paediat, FI-33521 Tampere, Finland
基金
芬兰科学院;
关键词
SIALIC-ACID; CHILD UNDERNUTRITION; BONE; BIFIDOBACTERIA; MALNUTRITION; INSULIN; MASS; PIG;
D O I
10.1016/j.cell.2016.01.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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-post-partum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those 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 microbiotadependent 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.
引用
收藏
页码:859 / 871
页数:13
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