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.
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.
|Newburg, David S; Grave, Gilman (2014) Recent advances in human milk glycobiology. Pediatr Res 75:675-9|
|Tan, Ming; Jiang, Xi (2014) Subviral particle as vaccine and vaccine platform. Curr Opin Virol 6:24-33|
|He, Y; Liu, S; Leone, S et al. (2014) Human colostrum oligosaccharides modulate major immunologic pathways of immature human intestine. Mucosal Immunol 7:1326-39|
|Farkas, Tibor; Lun, Cindy Wong Ping; Fey, Brittney (2014) Relationship between genotypes and serotypes of genogroup 1 recoviruses: a model for human norovirus antigenic diversity. J Gen Virol 95:1469-78|
|Tan, Ming; Jiang, Xi (2014) Vaccine against norovirus. Hum Vaccin Immunother 10:1449-56|
|Tan, Ming; Jiang, Xi (2014) Histo-blood group antigens: a common niche for norovirus and rotavirus. Expert Rev Mol Med 16:e5|
|Greenwood, Corryn; Morrow, Ardythe L; Lagomarcino, Anne J et al. (2014) Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. J Pediatr 165:23-9|
|Van Trang, Nguyen; Vu, Hau ThiBich; Le, Nhung ThiHong et al. (2014) Association between norovirus and rotavirus infection and histo-blood group antigen types in Vietnamese children. J Clin Microbiol 52:1366-74|
|Wang, Leyi; Xia, Ming; Huang, Pengwei et al. (2014) Branched-linear and agglomerate protein polymers as vaccine platforms. Biomaterials 35:8427-38|
|Lemay, Danielle G; Ballard, Olivia A; Hughes, Maria A et al. (2013) RNA sequencing of the human milk fat layer transcriptome reveals distinct gene expression profiles at three stages of lactation. PLoS One 8:e67531|
Showing the most recent 10 out of 261 publications