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. Dewey, Per Ashorn, Christopher B. Newgard, Carlito Lebrilla, David A. Mills, Jeffrey I. Gordon
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.