Undernutrition in children is a major global health problem that partly manifests as reduced growth, or stunting. Nutritional interventions aimed at treating stunting have been largely ineffective, highlighting the need for a greater understanding of the mechanisms that promote growth.

Researchers measured circulating biomarkers of bone resorption by osteoclasts and bone formation by osteoblasts in 54 stunted children with severe acute malnutrition and found evidence for elevated osteoclastic activity.

Based on an earlier finding that some mothers of stunted children have reduced levels of sialylated breast milk oligosaccharides, the authors colonized young mice raised in a germ-free environment with a consortium of bacterial strains cultured from the gut microbial community of a severely stunted malnourished 6-month-old infant.

Gnotobiotic mice exhibited decreased bone resorption when given a diet resembling that of the infant but supplemented with a purified bovine oligosaccharide mixture dominated by sialylated structures found in human breast milk (S-BMO). Supplementation decreased osteoclastogenesis while sparing osteoblast activity.

Comparisons of germ-free and colonized mice revealed S-BMO-dependent and microbiota-dependent increases in cecal levels of succinate, increased numbers of small intestinal tuft cells, and evidence for activation of a succinate-induced tuft cell signaling pathway linked to Th2 immune responses. A prominent fucosylated HMO, 2′-fucosyllactose, failed to elicit these changes in bone biology, highlighting the structural specificity of the S-BMO effects.

The findings suggest that interactions between milk oligosaccharides, the gut microbiota, and the immune system may uncover potential therapeutic targets for overcoming stunting in undernourished children, according to the authors.

https://www.pnas.org/content/early/2019/05/21/1821770116

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