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

Cell. 2016 Feb 25;164(5):859-71. doi: 10.1016/j.cell.2016.01.024. Epub 2016 Feb 18.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacteroides fragilis / genetics
  • Bifidobacterium / classification
  • Bifidobacterium / genetics
  • Brain Chemistry
  • Child Development*
  • Disease Models, Animal
  • Escherichia coli / genetics
  • Feces / microbiology
  • Germ-Free Life
  • Humans
  • Infant
  • Malawi
  • Male
  • Malnutrition / diet therapy*
  • Metabolomics
  • Mice
  • Mice, Inbred C57BL
  • Microbiota
  • Milk / chemistry*
  • Milk, Human / chemistry*
  • Oligosaccharides / metabolism*

Substances

  • Oligosaccharides
  • sialooligosaccharides