Annotation and structural elucidation of bovine milk oligosaccharides and determination of novel fucosylated structures
Open accessAbstract
Bovine milk oligosaccharides (BMOs) are recognized by the dairy and food industries, as well as by infant formula manufacturers, as novel, high-potential bioactive food ingredients. Recent studies revealed that bovine milk contains complex oligosaccharides structurally related to those previously thought to be present in only human milk. These BMOs are microbiotic modulators involved in important biological activities, including preventing pathogen binding to the intestinal epithelium and serving as nutrients for a selected class of beneficial bacteria. Only a small number of BMO structures are fully elucidated. To better understand the potential of BMOs as a class of biotherapeutics, their detailed structure analysis is needed. This study initiated the development of a structure library of BMOs and a comprehensive evaluation of structure-related specificity. The bovine milk glycome was profiled by high-performance mass spectrometry and advanced separation techniques to obtain a comprehensive catalog of BMOs, including several novel, lower abundant neutral and fucosylated oligosaccharides that are often overlooked during analysis. Structures were identified using isomer-specific tandem mass spectroscopy and targeted exoglycosidase digestions to produce a BMO library detailing retention time, accurate mass and structure to allow their rapid identification in future studies.
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Bovine colostrum contains a limited amount of milk oligosaccharides that may promote the growth of B. infantis.
“While bovine colostrum not only contains a limited amount of milk oligosaccharides that may promote the growth of this particular bacteria [35, 36], it also contains an abundance of immune proteins, including immunoglobulins, lactoferrin and a range of cytokines, that can further modulate the microbiota [40] and the immune system [40–42].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [36]
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Cites
(1995) · Elsevier eBooks · doi:10.1016/b978-0-12-384430-9.x5000-8 · Cited by 1,153 · see citing works
Oligosaccharides in Human Milk: Structural, Functional, and Metabolic Aspects
Kunz, C., Rudloff, S., Baier, W., Klein, N. J., & Ströbel, S. (2000) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.20.1.699 · Cited by 1,037 · see citing works
A Strategy for Annotating the Human Milk Glycome
Niñonuevo, M. R., Park, Y., Yin, H., Zhang, J., Ward, R. E., Clowers, B. H., German, J. B., Freeman, S. L., Killeen, K., Grimm, R., et al. (2006) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0615810 · Cited by 495 · see citing works
Self-citationFucosylated human milk oligosaccharides vary between individuals and over the course of lactation
Chaturvedi, P., Warren, C. D., Altaye, M., Morrow, A. L., Ruiz-Palacios, G. M., Pickering, L. K., & Newburg, D. S. (2001) · Glycobiology · doi:10.1093/glycob/11.5.365 · Cited by 370 · see citing works
LoCascio, R. G., Ninonuevo, M. R., Freeman, S. L., Sela, D. A., Grimm, R., Lebrilla, C. B., Mills, D. A., & German, J. B. (2007) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0710480 · Cited by 365 · see citing works
Self-citationCoppa, G. V., Zampini, L., Galeazzi, T., Facinelli, B., Ferrante, L., Capretti, R., & Orazio, G. (2006) · Pediatric Research · doi:10.1203/01.pdr.0000200805.45593.17 · Cited by 321 · see citing works
Development of an Annotated Library of Neutral Human Milk Oligosaccharides
Wu, S., Tao, N., German, J. B., Grimm, R., & Lebrilla, C. B. (2010) · Journal of Proteome Research · doi:10.1021/pr100362f · Cited by 312 · see citing works
Self-citationOligosaccharides and glycoconjugates in bovine milk and colostrum
Gopal, P. K., & Gill, H. S. (2000) · British Journal Of Nutrition · doi:10.1017/s0007114500002270 · Cited by 306 · see citing works
Boehm, G., & Stahl, B. (2007) · Journal of Nutrition · doi:10.1093/jn/137.3.847s · Cited by 286 · see citing works
Stahl, B., Thurl, S., Zeng, J. R., Karas, M., Hillenkamp, F., Steup, M., & Sawatzki, G. (1994) · Analytical Biochemistry · doi:10.1006/abio.1994.1577 · Cited by 285 · see citing works
Oligosaccharides of milk and colostrum in non-human mammals
Urashima, T., Saito, T., Nakamura, T., & Messer, M. (2001) · Glycoconjugate Journal · doi:10.1023/a:1014881913541 · Cited by 280 · see citing works
Annotation and Structural Analysis of Sialylated Human Milk Oligosaccharides
Wu, S., Grimm, R., German, J. B., & Lebrilla, C. B. (2010) · Journal of Proteome Research · doi:10.1021/pr101006u · Cited by 268 · see citing works
Self-citationTao, N., DePeters, E. J., Freeman, S., German, J. B., Grimm, R., & Lebrilla, C. B. (2008) · Journal of Dairy Science · doi:10.3168/jds.2008-1305 · Cited by 233 · see citing works
Self-citationThe First Prebiotics in Humans
Coppa, G. V., Bruni, S., Morelli, L., Soldi, S., & Gabrielli, O. (2004) · Journal of Clinical Gastroenterology · doi:10.1097/01.mcg.0000128926.14285.25 · Cited by 202 · see citing works
Relevance and use of capillary coatings in capillary electrophoresis–mass spectrometry
Hühn, C., Ramautar, R., Wuhrer, M., & Somsen, G. W. (2009) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-009-3193-y · Cited by 196 · see citing works
Tao, N., DePeters, E. J., German, J. B., Grimm, R., & Lebrilla, C. B. (2009) · Journal of Dairy Science · doi:10.3168/jds.2008-1642 · Cited by 190 · see citing works
Self-citationStiasny, K., Allison, S. L., Marchler‐Bauer, A., et al. (1996) · Journal of Virology · doi:10.1128/jvi.70.11.8142-8147.1996 · Cited by 184 · see citing works
Bovine Milk as a Source of Functional Oligosaccharides for Improving Human Health
Zivkovic, A. M., & Barile, D. (2011) · Advances in Nutrition · doi:10.3945/an.111.000455 · Cited by 180 · see citing works
Self-citationCarbohydrates in Milks: Analysis, Quantities, and Significance
Newburg, D. S., & Neubauer, S. H. (1995) · Elsevier eBooks · doi:10.1016/b978-012384430-9/50015-9 · Cited by 170 · see citing works
Wuhrer, M., Koeleman, C. A. M., Hokke, C. H., & Deelder, A. M. (2006) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.2509 · Cited by 156 · see citing works
Hua, S. S., An, H. J., Özcan, S., Ro, G. S., Soares, S., White, R. D., & Lebrilla, C. B. (2011) · The Analyst · doi:10.1039/c1an15093f · Cited by 154 · see citing works
Self-citationFong, B., Ma, L., & McJarrow, P. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf202035m · Cited by 146 · see citing works
Mariño, K. V., Lane, J. A., Abrahams, J. L., Struwe, W. B., Harvey, D. J., Marotta, M., Hickey, R. M., & Rudd, P. M. (2011) · Glycobiology · doi:10.1093/glycob/cwr067 · Cited by 143 · see citing works
Ma, Y., Vedernikova, I. V., den Heuvel, H. V., et al. (2000) · Journal of the American Society for Mass Spectrometry · doi:10.1016/s1044-0305(99)00133-6 · Cited by 141 · see citing works
Chu, C. S., Niñonuevo, M. R., Clowers, B. H., et al. (2009) · PROTEOMICS · doi:10.1002/pmic.200800249 · Cited by 140 · see citing works
Veh, R. W., Michalski, J., Corfield, A. P., et al. (1981) · Journal of Chromatography A · doi:10.1016/s0021-9673(01)84044-9 · Cited by 140 · see citing works
Martín‐Sosa, S., Martín, M., & Hueso, P. (2002) · Journal of Nutrition · doi:10.1093/jn/131.10.3067 · Cited by 139 · see citing works
Niñonuevo, M. R., An, H. J., Yin, H., Killeen, K., Grimm, R., Ward, R. E., German, B. J., & Lebrilla, C. B. (2005) · Electrophoresis · doi:10.1002/elps.200500246 · Cited by 132 · see citing works
Self-citationAnnotation of a Serum N-Glycan Library for Rapid Identification of Structures
Aldredge, D. L., An, H. J., Tang, N., Waddell, K., & Lebrilla, C. B. (2012) · Journal of Proteome Research · doi:10.1021/pr2011439 · Cited by 120 · see citing works
Self-citationPfenninger, A., Karas, M., Finke, B., et al. (2002) · Journal of the American Society for Mass Spectrometry · doi:10.1016/s1044-0305(02)00646-3 · Cited by 115 · see citing works
Barile, D., Marotta, M., Chu, C., Mehra, R., Grimm, R., Lebrilla, C. B., & German, J. B. (2010) · Journal of Dairy Science · doi:10.3168/jds.2010-3156 · Cited by 106 · see citing works
Self-citationNiñonuevo, M. R., Perkins, P. D., Francis, J., Lamotte, L. M., LoCascio, R. G., Freeman, S. L., Mills, D. A., German, J. B., Grimm, R., & Lebrilla, C. B. (2007) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf071972u · Cited by 103 · see citing works
Self-citationA Specific Prebiotic Mixture Added to Starting Infant Formula Has Long-Lasting Bifidogenic Effects
Salvini, F. M., Riva, E., Salvatici, E., Boehm, G., Jelinek, J., Banderali, G., & Giovannini, M. (2011) · Journal of Nutrition · doi:10.3945/jn.110.136747 · Cited by 96 · see citing works
Finke, B., Stahl, B., Pfenninger, A., Karas, M., Daniel, H., & Sawatzki, G. (1999) · Analytical Chemistry · doi:10.1021/ac990094z · Cited by 92 · see citing works
Schneir, M., & Rafelson, M. E. (1966) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(66)90002-x · Cited by 90 · see citing works
Milk oligosaccharides: Structural and technological aspects
Mehra, R., & Kelly, P. M. (2006) · International Dairy Journal · doi:10.1016/j.idairyj.2006.06.008 · Cited by 90 · see citing works
CE‐LIF‐MSn profiling of oligosaccharides in human milk and feces of breast‐fed babies
Albrecht, S., Schols, H. A., van den Heuvel, E. G. H. M., Voragen, A. G. J., & Gruppen, H. (2010) · Electrophoresis · doi:10.1002/elps.200900646 · Cited by 86 · see citing works
Blank, D., Dotz, V., Geyer, R., & Kunz, C. (2012) · Advances in Nutrition · doi:10.3945/an.111.001446 · Cited by 83 · see citing works
Chemical structure of three neutral trisaccharides isolated in free form from bovine colostrum
Saito, T., Itoh, T., & Adachi, S. (1987) · Carbohydrate Research · doi:10.1016/0008-6215(87)80076-9 · Cited by 78 · see citing works
Transcriptome Profiling of Bovine Milk Oligosaccharide Metabolism Genes Using RNA-Sequencing
Wickramasinghe, S., Hua, S. S., Rincón, G., Islas‐Trejo, A., German, J. B., Lebrilla, C. B., & Medrano, J. F. F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018895 · Cited by 78 · see citing works
Self-citationUrashima, T., Saito, T., Ohmisya, K., et al. (1991) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(91)90207-w · Cited by 76 · see citing works
High-Performance Capillary Electrophoresis of Sialylated Oligosaccharides of Human Milk
Shen, Z., Warren, C. D., & Newburg, D. S. (2000) · Analytical Biochemistry · doi:10.1006/abio.1999.4448 · Cited by 67 · see citing works
Human and Bovine Milk Oligosaccharides Inhibit Neisseria meningitidis Pili Attachment In Vitro
Hakkarainen, J. J., Toivanen, M., Leinonen, A., Frängsmyr, L., Strömberg, N., Lapinjoki, S., Nassif, X., & Tikkanen‐Kaukanen, C. (2005) · Journal of Nutrition · doi:10.1093/jn/135.10.2445 · Cited by 62 · see citing works
Ernst, B., Müller, D. R., & Richter, W. J. (1997) · International Journal of Mass Spectrometry and Ion Processes · doi:10.1016/s0168-1176(96)04487-4 · Cited by 62 · see citing works
The chemical structure of neutral and acidic sugar chains obtained from bovine colostrum κ-casein
Saito, T., ITOH, T., ADACHI, S., Suzuki, T., & USUI, T. (1981) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(81)90215-4 · Cited by 45 · see citing works
Chai, W., Piskarev, V. E., Zhang, Y., et al. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2004.09.035 · Cited by 44 · see citing works
Broberg, A. (2007) · Carbohydrate Research · doi:10.1016/j.carres.2007.04.020 · Cited by 42 · see citing works
Leo, F., Asakuma, S., Nakamura, T., et al. (2009) · Journal of Chromatography A · doi:10.1016/j.chroma.2009.01.015 · Cited by 38 · see citing works
Structural analysis of three sulfated oligosaccharides isolated from human milk
Guérardel, Y., Morelle, W., Plancke, Y. D., et al. (1999) · Carbohydrate Research · doi:10.1016/s0008-6215(99)00153-6 · Cited by 32 · see citing works
Xie, Y., Tseng, K., Lebrilla, C. B., et al. (2001) · Journal of the American Society for Mass Spectrometry · doi:10.1016/s1044-0305(01)00267-7 · Cited by 28 · see citing works
Self-citationYang, H., Yu, Y., Song, F., & Liu, S. (2011) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-011-0085-0 · Cited by 27 · see citing works
Immunomodulatory Effects of Breast Milk Oligosaccharides
Klein, N. J., Schwertmann, A., Peters, M. J., et al. (2005) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-46830-1_23 · Cited by 25 · see citing works
Strukturelle und funktionelle Aspekte von Oligosacchariden in Frauenmilch
Kunz, C., & Rudloff, S. (1996) · Zeitschrift für Ernährungswissenschaft · doi:10.1007/bf01612024 · Cited by 21 · see citing works
Fragmentation of neutral oligosaccharides using the MALDI LTQ Orbitrap
Rohmer, M., Baeumlisberger, D., Stahl, B., et al. (2010) · International Journal of Mass Spectrometry · doi:10.1016/j.ijms.2010.11.008 · Cited by 17 · see citing works
Biomedical Applications of Biophysics
Jue, T. (2010) · Humana Press eBooks · doi:10.1007/978-1-60327-233-9 · Cited by 14 · see citing works
Examining bioactive components of milk. Sources of complex oligosaccharides (Part 2)
Barile, D., Meyrand, M., Lebrilla, C. B., et al. (2011) · Agro food industry hi-tech · Cited by 8 · see citing works
Self-citationIntroduction to Modern Techniques in Mass Spectrometry
Chu, C. S., & Lebrilla, C. B. (2010) · Humana Press eBooks · doi:10.1007/978-1-60327-233-9_6 · Cited by 1 · see citing works
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Underwood, M. A., German, J. B., Lebrilla, C. B., & Mills, D. A. (2015) · Pediatric Research · doi:10.1038/pr.2014.156 · Cited by 439 · see citing works
Self-citationJost, T., Lacroix, C., Braegger, C., & Chassard, C. (2015) · Nutrition Reviews · doi:10.1093/nutrit/nuu016 · Cited by 267 · see citing works
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- Authors
- Aldredge, D. L., Geronimo, M. R., Hua, S., Nwosu, C. C., Lebrilla, C. B., & Barile, D.
- Affiliations
- University of California, Davis (US)
- Venue
- Glycobiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-02-22
- Volume
- 23
- Issue
- 6
- Pages
- 664-676
- ISSN
- 0959-6658 (ISSN-L)
- 1460-2423
- PMC
- PMC3641798
- OpenAlex
- W2125824345
- Cited by
- 180
- References
- 57
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 17 · 2022: 21 · 2021: 17 · 2020: 23 · 2019: 16 · 2018: 13 · 2017: 12 · 2016: 13 · 2015: 11 · 2014: 15 · 2013: 3
- FWCI
- 12.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Glycobiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- California Dairy Research Foundation
- National Institutes of Health (RR024146)
- National Institute of Child Health and Human Development (HD059127)
- National Center for Research Resources (UL1RR024146)
- National Center for Complementary and Integrative Health (R01AT007079)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD059127, R01HD059127)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- bovine milk oligosaccharides, fucosylated oligosaccharides, tandem mass spectrometry, exoglycosidase digestion, bioactive food ingredients, infant formula, microbiota modulation
- MeSH terms
- Amino Sugars, Animals, Carbohydrate Conformation, Carbohydrate Sequence, Cattle, Chromatography, High Pressure Liquid, Fucose, Galactose, Humans, Isomerism, Lactose, Milk, Milk, Human, Oligosaccharides, Tandem Mass Spectrometry, Molecular Sequence Annotation
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