In this revised application, we seek competitive renewal of our program project, """"""""The Role of Human Milk in Infant Nutrition and Health,"""""""" which is now entering its 31st year. This is a unique research program on human milk bioactive factors that addresses a long-standing priority of NICHD. Our program project involves a highly interactive, interdisciplinary team of senior and junior investigators with cores and projects at Cincinnati, Mexico, and Boston. Breastfeeding conveys potent bioactive factors that protect child health. During the current grant cycle we have shown that the human milk glycans, particularly, the a1,2 fucosyl (""""""""secretor"""""""") oligosaccharides and their high molecular weight glycoconjugates, are a major new class of antimicrobial agents. We have achieved initial synthesis of human milk secretor oligosaccharide analogs (H- 2 on LNneoT) in bioengineered bacteria. In this competitive renewal, we focus on the human milk glycans as novel antimicrobials with three major functions - pathogen-binding inhibition, prebiotic activity, and antiinflammatory activity - that protect breastfeeding children against enteric infectious and inflammatory diseases, three projects are proposed pertaining to the human milk glycans: 1) Inhibition of bacterial gastroenteritis;2) Inhibition of viral gastroenteritis;and 3) Modulation of inflammation, colonization, and mucosal development. In each project, we propose basic, clinical and translational research. Two complementary lines of translational research will be pursued: 1) Developing and testing human milk glycan analogs as novel antimicrobials and 2) testing the secretor phenotype as a novel clinical biomarker for enteric infectious and inflammatory diseases. The projects will be supported by cores in Biometry (Epidemiology, Biostatistics, and Informatics);Glycobiology;and Molecular Biology. Our focus and approach addresses NIH Road Map 2008 priorities pertaining to inflammation, the microbiome, and phenotyping.

Public Health Relevance

The research proposed in this application is designed to transform our fundamental understanding of human milk glycans and infant glycans in relation to disease risk and translate our discoveries into novel therapeutics, dietary interventions, and diagnostic tools that improve infant and child health.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-DSR-A (MA))
Program Officer
Grave, Gilman D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Cincinnati Children's Hospital Medical Center
United States
Zip Code
Ward, Doyle V; Scholz, Matthias; Zolfo, Moreno et al. (2016) Metagenomic Sequencing with Strain-Level Resolution Implicates Uropathogenic E. coli in Necrotizing Enterocolitis and Mortality in Preterm Infants. Cell Rep 14:2912-24
Newburg, David S; Ko, Jae Sung; Leone, Serena et al. (2016) Human Milk Oligosaccharides and Synthetic Galactosyloligosaccharides Contain 3'-, 4-, and 6'-Galactosyllactose and Attenuate Inflammation in Human T84, NCM-460, and H4 Cells and Intestinal Tissue Ex Vivo. J Nutr 146:358-67
He, YingYing; Lawlor, Nathan T; Newburg, David S (2016) Human Milk Components Modulate Toll-Like Receptor-Mediated Inflammation. Adv Nutr 7:102-11
Payne, Daniel C; Currier, Rebecca L; Staat, Mary A et al. (2015) Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States. JAMA Pediatr 169:1040-5
Newburg, David S; He, Yingying (2015) Neonatal Gut Microbiota and Human Milk Glycans Cooperate to Attenuate Infection and Inflammation. Clin Obstet Gynecol 58:814-26
Tan, Ming; Wei, Chao; Huang, Pengwei et al. (2015) Tulane virus recognizes sialic acids as cellular receptors. Sci Rep 5:11784
Jin, Miao; Tan, Ming; Xia, Ming et al. (2015) Strain-specific interaction of a GII.10 Norovirus with HBGAs. Virology 476:386-94
Newburg, David S; Morelli, Lorenzo (2015) Human milk and infant intestinal mucosal glycans guide succession of the neonatal intestinal microbiota. Pediatr Res 77:115-20
Dai, Ying-Chun; Zhang, Xu-Fu; Xia, Ming et al. (2015) Antigenic Relatedness of Norovirus GII.4 Variants Determined by Human Challenge Sera. PLoS One 10:e0124945
Taft, Diana H; Ambalavanan, Namasivayam; Schibler, Kurt R et al. (2015) Center Variation in Intestinal Microbiota Prior to Late-Onset Sepsis in Preterm Infants. PLoS One 10:e0130604

Showing the most recent 10 out of 286 publications