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 #
5R01HD061923-03
Application #
8096559
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
2011-07-01
Budget End
2012-06-30
Support Year
3
Fiscal Year
2011
Total Cost
$324,020
Indirect Cost
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
Davis, Jasmine C C; Lewis, Zachery T; Krishnan, Sridevi et al. (2017) Growth and Morbidity of Gambian Infants are Influenced by Maternal Milk Oligosaccharides and Infant Gut Microbiota. Sci Rep 7:40466
Huang, Jincui; Kailemia, Muchena J; Goonatilleke, Elisha et al. (2017) Quantitation of human milk proteins and their glycoforms using multiple reaction monitoring (MRM). Anal Bioanal Chem 409:589-606
Davis, Jasmine C C; Totten, Sarah M; Huang, Julie O et al. (2016) Identification of Oligosaccharides in Feces of Breast-fed Infants and Their Correlation with the Gut Microbial Community. Mol Cell Proteomics 15:2987-3002
Charbonneau, Mark R; Blanton, Laura V; DiGiulio, Daniel B et al. (2016) A microbial perspective of human developmental biology. Nature 535:48-55
Garrido, Daniel; Ruiz-Moyano, Santiago; Lemay, Danielle G et al. (2015) Erratum: Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria. Sci Rep 5:15311
Pacheco, Alline R; Barile, Daniela; Underwood, Mark A et al. (2015) The impact of the milk glycobiome on the neonate gut microbiota. Annu Rev Anim Biosci 3:419-45
Underwood, Mark A; Gaerlan, Stephanie; De Leoz, Maria Lorna A et al. (2015) Human milk oligosaccharides in premature infants: absorption, excretion, and influence on the intestinal microbiota. Pediatr Res 78:670-7
Garrido, Daniel; Ruiz-Moyano, Santiago; Lemay, Danielle G et al. (2015) Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria. Sci Rep 5:13517
Hong, Qiuting; Ruhaak, L Renee; Stroble, Carol et al. (2015) A Method for Comprehensive Glycosite-Mapping and Direct Quantitation of Serum Glycoproteins. J Proteome Res 14:5179-92
Spevacek, Ann R; Smilowitz, Jennifer T; Chin, Elizabeth L et al. (2015) Infant Maturity at Birth Reveals Minor Differences in the Maternal Milk Metabolome in the First Month of Lactation. J Nutr 145:1698-708

Showing the most recent 10 out of 96 publications