Complex oligosaccharides have been proposed to exert important biological properties for human health. However, despite advances in the commercialization of simple plant oligosaccharides and polysaccharides, these products of plant metabolism are unable to substantially alter the human gut microbial ecology nor its metabolism nor the physiology and disease risks of humans. Human milk, on the other hand, is an attractive source of oligosaccharides precisely because human milk produces a unique microbiota whose persistence yields scientifically established evidence of benefits to human infants. The free oligosaccharides in human milk have emerged through evolution in remarkable abundance and with significant structural diversity. Research in the collaborating laboratories has demonstrated that these oligosaccharides constitute a symbiotic system in human infants stimulating the competitive growth of commensal bifidobacteria. In this project we propose to build the analytic, genetic and biological tools to establish the structures and functions of the oligosaccharides in human milk as thematic principles to guide the development, research and industrialization of bioactive oligosaccharides for human health. To achieve this goal, we will: (A) elucidate in precise chemical detail the entire human milk glycome and categorize a diverse pool of human lactating subjects differing in the composition of expressed oligosaccharides, (B) develop analytical tools to rapidly determine human secretor versus non- secretor status based on the oligosaccharide profile and link maternal secretor status to milk oligosaccharide composition and microbiota diversity, and (C) establish the genetic basis of bifidobacterial selection by the specific structures in the ensemble of human milk oligosaccharides using whole genomic analysis of a range of bifidobacterial strains, relating specific oligosaccharide consumption by bacteria to functional analysis of genes and proteins in and on bacterial surfaces.

Public Health Relevance

Lebrilla, Carlito B. Title: Structures, Functions, and Genetic Diversity of the Complex Oligosaccharides Present in Human Milk NARRATIVE Human milk will be examined as a source of prebiotic oligosaccharides that are beneficial food for gut bacteria. The prebiotic oligosaccharides are sugar chains with little nutritional value to the infant but select the growth of certain bacteria. We will determine whether there is a genetic correlation between the types of oligosaccharides produced by the mother and those that are consumed by the infant's gut bacteria.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD061923-05
Application #
8487419
Study Section
Special Emphasis Panel (ZHD1-DSR-Z (04))
Program Officer
Grave, Gilman D
Project Start
2009-09-15
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$308,054
Indirect Cost
$105,120
Name
University of California Davis
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Guerrero, Andres; Lerno, Larry; Barile, Daniela et al. (2015) Top-down analysis of highly post-translationally modified peptides by Fourier transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom 26:453-9
Smilowitz, Jennifer T; Lebrilla, Carlito B; Mills, David A et al. (2014) Breast milk oligosaccharides: structure-function relationships in the neonate. Annu Rev Nutr 34:143-69
German, J Bruce (2014) The future of yogurt: scientific and regulatory needs. Am J Clin Nutr 99:1271S-8S
Joslin, A C; Green, R; German, J B et al. (2014) Concept mapping One-Carbon Metabolism to model future ontologies for nutrient-gene-phenotype interactions. Genes Nutr 9:419
Huang, Jincui; Lee, Hyeyoung; Zivkovic, Angela M et al. (2014) Glycomic analysis of high density lipoprotein shows a highly sialylated particle. J Proteome Res 13:681-91
Hong, Qiuting; Ruhaak, L Renee; Totten, Sarah M et al. (2014) Label-free absolute quantitation of oligosaccharides using multiple reaction monitoring. Anal Chem 86:2640-7
Garay, Luis A; Boundy-Mills, Kyria L; German, J Bruce (2014) Accumulation of high-value lipids in single-cell microorganisms: a mechanistic approach and future perspectives. J Agric Food Chem 62:2709-27
Kailemia, Muchena J; Ruhaak, L Renee; Lebrilla, Carlito B et al. (2014) Oligosaccharide analysis by mass spectrometry: a review of recent developments. Anal Chem 86:196-212
Dallas, David C; Guerrero, Andres; Khaldi, Nora et al. (2013) Extensive in vivo human milk peptidomics reveals specific proteolysis yielding protective antimicrobial peptides. J Proteome Res 12:2295-304
Lewis, Zachery T; Bokulich, Nicholas A; Kalanetra, Karen M et al. (2013) Use of bifidobacterial specific terminal restriction fragment length polymorphisms to complement next generation sequence profiling of infant gut communities. Anaerobe 19:62-9

Showing the most recent 10 out of 49 publications