Читать книгу Nutrition and Growth - Группа авторов - Страница 14

Cowardin CA^1,2, Ahern PP^1,2, Kung VL^1,2, Hibberd MC^1,2, Cheng J^1,2, Guruge JL^1,2, Sundaresan V^1,2, Head RD^3,4, Barile D^5,6, Mills DA^5,6, Barratt MJ^1,2, Huq S⁷, Ahmed T⁷, Gordon JI^1,2

¹Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA; ²Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO, USA; ³Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; ⁴Genome Technology Access Center, Washington University School of Medicine, St. Louis, MO, USA; ⁵Foods for Health Institute, University of California, Davis, CA, USA; ⁶Department of Food Science and Technology, University of California, Davis, CA, USA; ⁷International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh Proc Natl Acad Sci USA 2019;116:11988–11996

Background: Undernutrition in children is a pressing global health problem, manifested in part by impaired linear growth (stunting). Current nutritional interventions have been largely ineffective in overcoming stunting, emphasizing the need to obtain better understanding of its underlying causes. Treating Bangladeshi children with severe acute malnutrition with therapeutic foods reduced plasma levels of a biomarker of osteoclastic activity without affecting biomarkers of osteoblastic activity or improving their severe stunting.

Methods: To characterize interactions among the gut microbiota, human milk oligosaccharides (HMOs), and osteoclast and osteoblast biology, young germ-free mice were colonized with cultured bacterial strains from a 6-month-old stunted infant and fed a diet mimicking that consumed by the donor population. Adding purified bovine sialylated milk oligosaccharides (S-BMO) with structures similar to those in human milk to this diet increased femoral trabecular bone volume and cortical thickness, reduced osteoclasts and their bone marrow progenitors, and altered regulators of osteoclastogenesis and mediators of Th2 responses. 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 human milk oligosaccharide, 2’-fucosyllactose, failed to elicit these changes in bone biology, highlighting the structural specificity of the S-BMO effects. These results underscore the need to further characterize the balance between, and determinants of, osteoclastic and osteoblastic activity in stunted infants/children, and suggest that certain milk oligosaccharides may have therapeutic utility in this setting.

Reprinted with permission from PNAS.

Comments

Understanding mechanisms associated with childhood undernutrition and growth stunting is of paramount importance in the planning of successful and safe nutritional interventions. As discussed in extent in this systematic review, dairy product supplementation of diet has an important influence on bone mineral content in childhood; the effect on linear growth is, however, still debated [3].In another study, the role of milk oligosaccharides on osteoclast and osteoblast biology was studied in experimental animals, as it was proposed from the epidemiological part of the study that alteration of the osteoclastic activity by nutritional intervention could improve decreased linear growth. Sialylated milk oligosaccharides with structures similar to those in human milk were found to increase femoral trabecular bone volume and cortical thickness, reduced osteoclasts and their bone marrow progenitors, and altered regulators of osteoclastogenesis and mediators of Th2 responses in these mice. These data shed important insights into the mechanisms of bone remodeling and growth and could have an important influence on the composition of foods used in nutritional interventions [4].

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