Cited by 412Infant Nutrition and HealthBreastfeeding Practices and InfluencesMicrobial Metabolites in Food Biotechnology

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Breast Milk Oligosaccharides: Structure-Function Relationships in the Neonate

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Smilowitz, Jennifer T., Lebrilla, Carlito B., Mills, David A., German, J. Bruce, Freeman, Samara L.·2014·Annual Review of Nutrition

DOI 10.1146/annurev-nutr-071813-105721PMC PMC4348064

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Abstract

In addition to providing complete postnatal nutrition, breast milk is a complex biofluid that delivers bioactive components for the growth and development of the intestinal and immune systems. Lactation is a unique opportunity to understand the role of diet in shaping the intestinal environment including the infant microbiome. Of considerable interest is the diversity and abundance of milk glycans that are energetically costly for the mammary gland to produce yet indigestible by infants. Milk glycans comprise free oligosaccharides, glycoproteins, glycopeptides, and glycolipids. Emerging technological advances are enabling more comprehensive, sensitive, and rapid analyses of these different classes of milk glycans. Understanding the impact of inter- and intraindividual glycan diversity on function is an important step toward interventions aimed at improving health and preventing disease. This review discusses the state of technology for glycan analysis and how specific structure-function knowledge is enhancing our understanding of early nutrition in the neonate.

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“…liquid chromatography coupled with online fluorescence detection (HPLC-FL) and liquid chromatography mass spectrometry (LCMS) are frequently used in HMO studies, where relative or absolute abundances of HMOs can be determined with these methods (Smilowitz et al., 2014; van Leeuwen, 2019).”
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The connection between microbiome and schizophrenia
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Liquid Chromatography–Tandem Mass Spectrometry Approach for Determining Glycosidic Linkages
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Anti-Pathogenic Functions of Non-Digestible Oligosaccharides In Vitro
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“Fucose is present in human milk and the proportion of fucosylated HMOs in term breast milk was recently reported as 35–50% [23].”
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Human milk oligosaccharides and its acid hydrolysate LNT2 show immunomodulatory effects via TLRs in a dose and structure-dependent way
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“HMOs can be found in mother’s milk in concentrations varying between 5 and 20 mg/ mL (Bode, 2012; Petherick, 2010), depending on the stage of lactation and may provide a variety of health-promoting effects (Bode, 2012; Kunz et al., 2000; Smilowitz, Lebrilla, Mills, German, & Freeman, 2014).”
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Prevention of Necrotizing Enterocolitis Through Manipulation of the Intestinal Microbiota of the Premature Infant
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“Taken together, these bioactivities favor the establishment of a protective and healthful intestinal environment (Smilowitz et al., 2014).”
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Recent understanding of human milk oligosaccharides in establishing infant gut microbiome and roles in immune system
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“Human milk oligosaccharides (HMOs) are natural prebiotics because they represent the bifidogenic factors that favour the growth of bifidobacteria, which typically dominate the gut microbiota of breastfed infants (Garrido et al., 2013; Smilowitz et al., 2014).”
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“Most HMO contain 158 lactose at the reducing end and are elongated with galactose and N-acetyglucosamine units to 159 form linear or branched oligosaccharides (Smilowitz et al., 2014).”
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Comparative Genome Analysis of Bifidobacterium longum subsp. infantis Strains Reveals Variation in Human Milk Oligosaccharide Utilization Genes among Commercial Probiotics
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Term Infant Formulas Influencing Gut Microbiota: An Overview
Fabiano, V., Indrio, F., Verduci, E., Calcaterra, V., Pop, T. L., Mari, A., Zuccotti, G., Cokugras, F. C., Pettoello‐Mantovani, M., & Goulet, O. (2021) · Nutrients · doi:10.3390/nu13124200 · Cited by 78
“Compared to formula-fed infants, studies of the “intestinal flora” of BF infants showed differences, especially regarding Bifidobacteria species [9,10].”
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Influence of sulfonated and diet-derived human milk oligosaccharides on the infant microbiome and immune markers
Quin, C., Vicaretti, S. D., Mohtarudin, N. A., Garner, A. M., Vollman, D. M., Gibson, D. L., & Zandberg, W. F. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011351 · Cited by 75
“Obesity (21),malnourishment (7), andhyperglycemia (21) impactboth HMO concentrations and structures; it is possible that these conditions affect the levels of nucleotide-activated GlcNAc and Neu5Ac available forHMObiosynthesis, as obesity and hyperglycemia are both linked to alteredmetabolic flux through the hexosamin…”
Background
How far is it from infant formula to human milk? A look at the human milk oligosaccharides
Li, W., Wang, J., Lin, Y., Li, Y., Ren, F., & Guo, H. (2021) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2021.09.021 · Cited by 74
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Novel Genes and Metabolite Trends in Bifidobacterium longum subsp. infantis Bi-26 Metabolism of Human Milk Oligosaccharide 2′-fucosyllactose
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Prebiotic milk oligosaccharides prevent development of obese phenotype, impairment of gut permeability, and microbial dysbiosis in high fat-fed mice
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“Due to the structure–function relationships of HMOs and other oligosaccharides, correct branching and stereospecific linkages are required for biological function to be preserved (Smilowitz et al., 2014).”
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Infant Complementary Feeding of Prebiotics for the Microbiome and Immunity
McKeen, S., Young, W., Mullaney, J. A., Fraser, K., McNabb, W. C., & Roy, N. C. (2019) · Nutrients · doi:10.3390/nu11020364 · Cited by 66
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Maternal activation of the EGFR prevents translocation of gut-residing pathogenic Escherichia coli in a model of late-onset neonatal sepsis
Knoop, K. A., Coughlin, P. E., Floyd, A. N., Ndao, I. M., Hall-Moore, C. M., Shaikh, N., Gasparrini, A. J., Rusconi, B. A., ESCOBEDO, M. B., Good, M. L., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1912022117 · Cited by 64
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Authors: Smilowitz, J. T., Lebrilla, C. B., Mills, D. A., German, J. B., & Freeman, S. L.
Affiliations: Department of Food Science and Technology,
Department of Chemistry, and
University of California, Davis (US)
ORCID: Smilowitz, Jennifer T.
Lebrilla, Carlito B.
Mills, David A.
German, J. Bruce
Venue: Annual Review of Nutrition
Publisher: Annual Reviews
Published: 2014-07-17
Volume: 34
Issue: 1
Pages: 143-169
ISSN: 0199-9885 (ISSN-L)
1545-4312
DOI: 10.1146/annurev-nutr-071813-105721
PMC: PMC4348064
OpenAlex: W2157542971
Cited by: 410
References: 154
Citations by year: 2026: 15 · 2025: 19 · 2024: 30 · 2023: 33 · 2022: 27 · 2021: 57 · 2020: 64 · 2019: 51 · 2018: 36 · 2017: 29 · 2016: 33 · 2015: 15 · 2014: 1
FWCI: 2.98
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Annual Review of Nutrition (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: Bill and Melinda Gates Foundation
California Dairy Research Foundation
National Institutes of Health
University of California, Davis
National Center for Complementary and Integrative Health (R01AT007079, R21AT006180)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD065122, R01HD061923, R01HD059127)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
Health Sciences › Medicine › Epidemiology › Breastfeeding Practices and Influences
Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
Keywords: human milk oligosaccharides, structure-function relationship, neonatal nutrition, infant microbiome, intestinal development, immune system development, glycoproteins, glycopeptides, glycolipids, lactation
MeSH terms: Bifidobacterium, Breast Feeding, Carbohydrate Sequence, Child Development, Female, Glycolipids, Glycopeptides, Glycoproteins, Humans, Immunity, Innate, Infant, Newborn, Intestinal Mucosa, Lactation, Male, Milk Proteins, Milk, Human, Models, Biological, Oligosaccharides

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Breast Milk Oligosaccharides: Structure-Function Relationships in the Neonate

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