Abstract

Campylobacter is one of the most common cause of diarrhea worldwide. Human milk protects young infants against Campylobacter diarrhea by several factors including fucosylated oligosaccharides. However, there is a lack of understanding of the chemical structure of these components and their mechanism of interaction with Campylobacter virulence traits associated with attachment to gut mucosa.
The specific aims of this project are: 1) define the virulence markers of Campylobacter associated with attachment to epithelial cells; 2) characterize and purify milk glycoconjugates that inhibit Campylobacter infection; 3) assess passive protection in breast- fed children and experimentally in transgenic mice carrying a human fucoslytransferase gene expressed mainly in mammary tissue; 4) develop strategies for large-scale synthesis of fucosylated glycoconjugates active against Campylobacter infection; and 5) conduct clinical trials on safety and protection of fucosylated glycoconjugates against Campylobacter diarrhea. The long-term goal of this project is to develop methods for prevention and treatment of Campylobacter infection through understanding at the cellular and molecular level the mechanism of protection conferred by human milk against Campylobacter infection.

  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 #
7P01HD013021-24
Application #
6505584
Study Section
Project Start
2001-09-01
Project End
2002-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
24
Fiscal Year
2001
Total Cost
$172,411
Indirect Cost

  Institution

Name
Eastern Virginia Medical School
Department
Type
DUNS #
City
Norfolk
State
VA
Country
United States
Zip Code
23501

  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
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
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
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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