title: Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.
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.
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Charbonneau
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: David
authors.initials: D
authors.lastname: O'Donnell
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Laura V
authors.initials: LV
authors.lastname: Blanton
authors.affiliation: Department of Chemistry, University of California at Davis, Davis, CA 95616, USA; Foods for Health Institute, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Totten
authors.affiliation: Department of Chemistry, University of California at Davis, Davis, CA 95616, USA; Foods for Health Institute, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Jasmine C C
authors.initials: JC
authors.lastname: Davis
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Barratt
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jiye
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Janaki
authors.initials: J
authors.lastname: Guruge
authors.affiliation: Division of Comparative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Talcott
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Bain
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Muehlbauer
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Ilkayeva
authors.affiliation: Hilmar Ingredients, Hilmar Cheese Company, Hilmar, CA 95324, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Hilmar Ingredients, Hilmar Cheese Company, Hilmar, CA 95324, USA.
authors.forename: Tedd
authors.initials: T
authors.lastname: Struckmeyer
authors.affiliation: Foods for Health Institute, University of California at Davis, Davis, CA 95616, USA; Department of Food Science and Technology, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Barile
authors.affiliation: College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi.
authors.forename: Charles
authors.initials: C
authors.lastname: Mangani
authors.affiliation: Department of Nutrition, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Josh
authors.initials: J
authors.lastname: Jorgensen
authors.affiliation: Department of International Health, School of Medicine, University of Tampere, FI-33521 Tampere, Finland.
authors.forename: Yue-mei
authors.initials: YM
authors.lastname: Fan
authors.affiliation: College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Maleta
authors.affiliation: Department of Nutrition, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Dewey
authors.affiliation: Department of International Health, School of Medicine, University of Tampere, FI-33521 Tampere, Finland; Department of Paediatrics, Tampere University Hospital, FI-33521 Tampere, Finland.
authors.forename: Per
authors.initials: P
authors.lastname: Ashorn
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.affiliation: Department of Chemistry, University of California at Davis, Davis, CA 95616, USA; Foods for Health Institute, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Carlito
authors.initials: C
authors.lastname: Lebrilla
authors.affiliation: Foods for Health Institute, University of California at Davis, Davis, CA 95616, USA; Department of Food Science and Technology, University of California at Davis, Davis, CA 95616, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Mills
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: jgordon@wustl.edu.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001441:Bacteroides fragilis / Q000235:genetics; D001644:Bifidobacterium / Q000145:classification / Q000235:genetics; D001923:Brain Chemistry; D002657:Child Development; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005856:Germ-Free Life; D006801:Humans; D007223:Infant; D008295:Malawi; D008297:Male; D044342:Malnutrition / Q000178:diet therapy*; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D008892:Milk / Q000737:chemistry*; D008895:Milk, Human / Q000737:chemistry*; D009844:Oligosaccharides / Q000378:metabolism*
chemical_list: D009844:Oligosaccharides; C016735:sialooligosaccharides