Abstract

In this project, the PMN function altering and anti-inflammatory characteristics of human colostrum/milk will be examined. The studies proposed will characterize the colostrum/milk components responsible for altering human PMN function and the mechanisms by which these effects occur. In addressing mechanisms, changes in both cellular phenotype and gene expression that result from colostrum exposure will be examined. Studies will also characterize the anti-inflammatory components of human colostrum/milk using a rat model of acute inflammation, and examine the mechanisms by which the anti-inflammatory effects are mediated. These mechanistic studies will focus on (but not be limited to) neutralization of pro-inflammatory cytokine activities. Field studies will be used to prospectively examine the relationship between the content and activity of milk anti-inflammatory components and the occurrence of asymptomatic, mild-symptomatic and inflammatory-symptomatic enteric infections. By completion of these studies, we will concretely associate the PMN function-altering and anti-inflammatory characteristics of human colostrum/milk with protection against inflammatory enteric diseases in breastfed infants.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD013021-18
Application #
5212507
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Reed, Benjamin D; Schibler, Kurt R; Deshmukh, Hitesh et al. (2018) The Impact of Maternal Antibiotics on Neonatal Disease. J Pediatr 197:97-103.e3
Dingess, Kelly A; Valentine, Christina J; Ollberding, Nicholas J et al. (2017) Branched-chain fatty acid composition of human milk and the impact of maternal diet: the Global Exploration of Human Milk (GEHM) Study. Am J Clin Nutr 105:177-184
Young, Bridget E; Patinkin, Zachary W; Pyle, Laura et al. (2017) Markers of Oxidative Stress in Human Milk do not Differ by Maternal BMI But are Related to Infant Growth Trajectories. Matern Child Health J 21:1367-1376
He, YingYing; Lawlor, Nathan T; Newburg, David S (2016) Human Milk Components Modulate Toll-Like Receptor-Mediated Inflammation. Adv Nutr 7:102-11
Vanchiere, John A; Carillo, Berenice; Morrow, Ardythe L et al. (2016) Fecal Polyomavirus Excretion in Infancy. J Pediatric Infect Dis Soc 5:210-3
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; Liu, ShuBai; Kling, David E et al. (2016) The human milk oligosaccharide 2'-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation. Gut 65:33-46
Currier, Rebecca L; Payne, Daniel C; Staat, Mary A et al. (2015) Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population. Clin Infect Dis 60:1631-8
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

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