Different terms are synonomyously used to describe human milk oligosaccharide structures, and are summarised here. Human milk oligosaccharides are composed of five building blocks and always contain lactose, which is depicted with a residue. Based on the residue, human milk oligosaccharides are classified into different categories: fucosylated human milk oligosaccharides, sialylated or acidic human milk oligosaccharides, and non-fucosylated neutral human milk oligosaccharides.
The literature on human milk oligosaccharides (HMO) is diverse and stretches over many decades. Certain terms are used synonymously. We summarised these terms here:
All human milk oligosaccharides (HMO) can be described with an equation such as this:
To break down this complicated seeming equation, we start with the three to five monosaccharides or monomers that are the building blocks of HMO (Figure 412-3). Depending on the way these five building blocks are combined together with a number of different structural ways to connect, they form more than 200 HMO isoforms (Thurl et al. 2010).
The disaccharide lactose is a combination of D‑glucose (Glu, blue circle Figures 412-3 and 412-4) with D-galactose (Gal, yellow circle, Figures 412-3 and 412-4) connected via a β1-4 bond (Figure 412-5). As free disaccharide or dimer, lactose is the major carbohydrate in mother's milk and thus called milk sugar. Lactose is a core component of all HMO isoforms. It is located at the terminal end of all HMO and further modified by the addition of galactose, N‑acetyllactosamine, fucose, or sialic acid, elongated and branched in various ways to form the multitude of known HMO isoforms (Figure 412-4) (Bode. 2012).
The type of connection ‑ that is the glucoside bond ‑ plays a crucial role in HMO formation. It can define the 3D structure, thus determine interaction of the HMO to microorganisms (decoy receptor) or access of enzymes and other metabolites, and therefore affect functionality of the HMO isoform that was synthesised.
The disaccharide lactose is a combination of D‑glucose (Glu, blue circle Figures 412-3 and 412-4) with D-galactose (Gal, yellow circle, Figures 412-3 and 412-4) connected via a β1-4 bond (Figure 412-5). As free disaccharide or dimer, lactose is the major carbohydrate in mother's milk and thus called milk sugar. Lactose is a core component of all HMO isoforms: It is located at the terminal end of all HMO and further modified by the addition of galactose, N‑acetyllactosamine, fucose, or sialic acid, elongated and branched in various ways to form the multitude of known HMO isoforms (Figure 412-4) (Bode. 2012).
Human milk oligosaccharides structures are described by a basic blueprint (Figure 412-3): Lactose is a core component linked with at least one further residue or unit. Based on the presence of these residues, HMO can be sorted into three different categories:
Fucosylated HMO (Figure 412-6) are linked with at least one L-fucose residue.
Sialylated or acidic HMO (Figure 412-7) are oligosaccharides linked with at least one sialic acid residue.
Non-fucosylated or neutral HMO (Figure 412-8) are linked with at least one galactose, N‑acetyllactosamine, or lacto‑N‑biose unit. They are neither linked with fucose nor sialic acid (Ayechu-Muruzabal et al. 2018; Kunz et al. 2000).
Non-fucosylated neutral human milk oligosaccharides are the most diverse and extensive category representing between 42 ‑ 55% of the entire human milk oligosaccharide fraction, followed by fucosylated human milk oligosaccharides with 35 ‑ 50%. Sialylated, acidic human milk oligosaccharides are the least extensive category, representing approx. 13% of total human milk oligosaccharides (Donovan and Comstock. 2016).
Ayechu-Muruzabal V, van Stigt AH, Mank M, Willemsen LEM, Stahl B, Garssen J, Van't Land B. Diversity of Human Milk Oligosaccharides and Effects on Early Life Immune Development. Frontiers in pediatrics 2018; 6:239. at: www.ncbi.nlm.nih.gov/pubmed//30250836
Donovan SM, Comstock SS. Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity. Annals of nutrition & metabolism 2016; 69 Suppl 2:42–51. at: www.ncbi.nlm.nih.gov/pubmed/28103609
Kunz C, Rudloff S, Baier W, Klein N, Strobel S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annual review of nutrition 2000; 20:699–722. at: www.ncbi.nlm.nih.gov/pubmed/10940350
Neelamegham S, Aoki-Kinoshita K, Bolton E, Frank M, Lisacek F, Lütteke T, O'Boyle N, Packer NH, Stanley P, Toukach P, Varki A, Woods RJ. Updates to the Symbol Nomenclature for Glycans guidelines. Glycobiology 2019; 29(9):620–4. at: https://pubmed.ncbi.nlm.nih.gov/31184695/
Newburg DS, Ko JS, Leone S, Nanthakumar NN. Human Milk Oligosaccharides and Synthetic Galactosyloligosaccharides Contain 3'-, 4-, and 6'-Galactosyllactose and Attenuate Inflammation in Human T84, NCM-460, and H4 Cells and Intestinal Tissue Ex Vivo. The Journal of nutrition 2016; 146(2):358–67. at: www.ncbi.nlm.nih.gov/pubmed/26701795
Thurl S, Munzert M, Boehm G, Matthews C, Stahl B. Systematic review of the concentrations of oligosaccharides in human milk. Nutrition reviews 2017; 75(11):920–33. at: https://pubmed.ncbi.nlm.nih.gov/29053807
Thurl S, Munzert M, Henker J, Boehm G, Müller-Werner B, Jelinek J, Stahl B. Variation of human milk oligosaccharides in relation to milk groups and lactational periods. The British journal of nutrition 2010; 104(9):1261–71. at: www.ncbi.nlm.nih.gov/pubmed/20522272back