Advanced analytical strategies for measuring free bioactive milk sugars: from composition and concentrations to human metabolic response
Our daily food intake provides the nutrients to maintain health. However, in addition to the nutritional values, food can promote health and be beneficial in preventing diseases. Human milk is a unique food source that contains essential nutrients in the right balance and other bioactive factors that make it the ideal food for all healthy term infants. Human milk oligosaccharides (HMOs) play an important role in health, at several levels: acting as prebiotics promoting the growth of beneficial bacterial strains, preventing the growth of pathogenic bacteria in the intestine, and modulating the immune response against bacterial infections. However, despite their biological relevance and the advances made in the analytical field, very few studies have been carried out to better understand HMOs bioactivity mechanisms or to examine human metabolic response to dietary supplementation. This review describes the state-of-the-art of glycomics strategies, recent analytical methods, and future trends for the identification and discovery of bioactive sugars, the known mechanisms of action, and discusses findings of some recent human intervention trials.
KeywordsGlycomics Human milk oligosaccharides Mass spectrometry Ion mobility Nutrition
Josep Rubert thanks the Joint Action Biomarkers in Nutrition and Health, Project Food Biomarkers Alliance (FoodBall) of the Joint Programming Initiative a Healthy Diet for a Healthy Life (JPI HDHL) and the respective national funding organization, Ministry of Education, University and Research (MIUR).
Compliance with ethical standards
Conflict of interest
- 7.Galeotti F, Coppa GV, Zampini L, MacCari F, Galeazzi T, Padella L, et al. On-line high-performance liquid chromatography-fluorescence detection-electrospray ionization-mass spectrometry profiling of human milk oligosaccharides derivatized with 2-aminoacridone. Anal Biochem. 2012;430:97–104.CrossRefGoogle Scholar
- 8.Xu G, Davis JCC, Goonatilleke E, Smilowitz JT, German JB, Lebrilla CB. Absolute quantitation of human milk oligosaccharides reveals phenotypic variations during lactation. J Nutr. 2017;1:1–8.Google Scholar
- 12.Balogh R, Jankovics P, Béni S. Qualitative and quantitative analysis of N-acetyllactosamine and lacto-N-biose, the two major building blocks of human milk oligosaccharides in human milk samples by high-performance liquid chromatography-tandem mass spectrometry using a porous graphitic. J Chromatogr A. 2015b;1422:140–6.CrossRefGoogle Scholar
- 13.Oursel S, Cholet S, Junot C, Fenaille F. Comparative analysis of native and permethylated human milk oligosaccharides by liquid chromatography coupled to high resolution mass spectrometry. J Chromatogr B. 2017; https://doi.org/10.1016/j.jchromb.2017.03.028.
- 16.Berendsen BJ, Meijer T, Mol HG, van Ginkel L, Nielen MWF. A global inter-laboratory study to assess acquisition modes for multi-compound confirmatory analysis of veterinary drugs using liquid chromatography coupled to triple quadrupole, time of flight and Orbitrap mass spectrometry. Anal Chim Acta. 2017;962:60–72.CrossRefGoogle Scholar
- 19.Commission Decision 2002/657/EC implementing Council Directive 96/23/EC concerning the performance of analytical methods and the interpretation of results. Official J. Eur Commun L221 (2002), pp. 8–36Google Scholar
- 20.SANTE/11813/2017. Implemented by 01.01.2018. Guidance document on analytical quality control and method validation procedures for pesticide residues and analysis in food and feed. European Commission, Brussels (2017) Available at: https://ec.europa.eu/food/sites/food/files/plant/docs/pesticides_mrl_guidelines_wrkdoc_2017-11813.pdf
- 21.Food and Drug Administration. Final Guidance for Industry: Mass Spectrometry for Confirmation of the Identity of Animal Drug Residues Division of Residue Chemistry, Office of Research, Center for Veterinary Medicine, Rockville, MD (2003)Google Scholar
- 22.SANTE/11945/2015. 30 November–1 December 2015, Rev. 0, Guidance Document on Analytical Quality Control and Method Validation Procedures for Pesticide Residues Analysis in Food and Feed. European Commission, Brussels (2015) Available at: https://ec.europa.eu/food/sites/food/files/plant/docs/pesticides_mrl_guidelines_wrkdoc_11945.pdf
- 23.European Commission Health and Consumer Protection. Health and Consumer Protection Directorate, SANCO/12571/2013 Guidance Document on analytical quality control and validation procedures for pesticide residues analysis in food and feed.Google Scholar
- 39.D'Atri V, Porrini M, Rosu F, Gabelica V. Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure. J Mass Spectrom. 2015;50:711–26.Google Scholar
- 53.De Leoz MLA, Kalanetre KM, Bokulich NA, Strum JS, Underwood MA, German JB, et al. Human milk glycomics and gut microbial genomics in infant feces show a correlation between human milk oligosaccharides and gut microbiota: a proof-of-concept study. J Proteome Res. 2015;14(1):491–502.CrossRefGoogle Scholar
- 65.Autran CA, Kellman BP, Kim JH, Asztalos E, Blood AB, Spence EC, Patel AL, Hou J, Lewis NE, Bode L (2017) Gut published online first: 05 April 2017. doi: https://doi.org/10.1136/gutjnl-2016-312819.
- 68.Comstock SS, Donovan SM. Human milk oligosaccharides as modulators of intestinal and systemic immunity. In: prebiotics and probiotics in human milk: origins and functions of milk-borne oligosaccharides and bacteria. Ann Nutr Metab. 2016;69(Suppl 2):42–51.Google Scholar
- 70.El-Hawiet A, Chen Y, Shams-Ud-Doha K, Kitova EN, Kitov PI, Bode L, Hage N, Falcone FH, Klassen JS, (2017) Screening natural libraries of human milk oligosaccharides against lectins using CaR-ESI-MS. Analyst published online first: 27 November 2017. doi: https://doi.org/10.1039/C7AN01397C
- 85.Simeoni U, Berger B, Junick J, Blaut M, Pecquet S, Rezzonico E, et al. Gut microbiota analysis reveals a marked shift to bifidobacteria by a starter infant formula containing a synbiotic of bovine milk-derived oligosaccharides and Bifidobacterium animalis Subsp. lactis Cncm I-3446. Environ Microbiol. 2016;18:2185–95.CrossRefGoogle Scholar