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

Mark R. Charbonneau, David O'Donnell, Laura V. Blanton, Sarah M. Totten, Jasmine C.C. Davis, Michael J. Barratt, Jiye Cheng, Janaki Guruge, Michael Talcott, James R. Bain, Michael J. Muehlbauer, Olga Ilkayeva, Chao Wu, Tedd Struckmeyer, Daniela Barile, Charles Mangani, Josh Jorgensen, Yue Mei Fan, Kenneth Maleta, Kathryn G. DeweyPer Ashorn, Christopher B. Newgard, Carlito Lebrilla, David A. Mills, Jeffrey I. Gordon

Research output: Contribution to journalArticle

249 Scopus citations

Abstract

Summary 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 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 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.

Original languageEnglish
Pages (from-to)859-871
Number of pages13
JournalCell
Volume164
Issue number5
DOIs
StatePublished - Feb 25 2016

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    Charbonneau, M. R., O'Donnell, D., Blanton, L. V., Totten, S. M., Davis, J. C. C., Barratt, M. J., Cheng, J., Guruge, J., Talcott, M., Bain, J. R., Muehlbauer, M. J., Ilkayeva, O., Wu, C., Struckmeyer, T., Barile, D., Mangani, C., Jorgensen, J., Fan, Y. M., Maleta, K., ... Gordon, J. I. (2016). Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition. Cell, 164(5), 859-871. https://doi.org/10.1016/j.cell.2016.01.024