Human milk oligosaccharides

Editor/ Takane Katayama, Tadasu Urashima


The current manufacturing process and business development of human milk oligosaccharide products

Tetsuro Ujihara / Yanashima Kentaro

last updated 2022/06/01 (Glycoforum. 2022 Vol.25 (3), A7)  

Human milk oligosaccharides (HMOs) is the general term for the complex sugar molecules (oligosaccharides) in human breast milk. HMOs are known to be important nutrients for infants because of their great abundance in human colostrum but only trace amount in bovine milk (Fig. 1). Therefore, efficient large-scale production of HMOs is desired to enhance the nutritional value of infant formula. However, HMO production was not easy. Limited numbers of HMOs can be obtained by using natural extraction methods. Although there are several reports on the chemical synthesis of HMOs including 2'-FL, chemical synthesis of HMOs is still inefficient for industrial production purposes. HMOs consist of saccharide moieties with numerous hydroxy groups and should be attached in a stereospecific manner. In order to reduce the synthesis of unexpected byproducts, protection of the hydroxy groups is required, further complicating synthesis. Enzymes which evolved over time can be used to easily produce complicated oligosaccharide chains with position-dependent activity in a stereospecific manner. So, nowadays, most HMOs are produced biologically. ...and more

Sialic acid impact on the gut microbiome and function

Keita Nishiyama / Takao Mukai

last updated 2022/04/01 (Glycoforum. 2022 Vol.25 (2), A3)  

Sialic acid was first isolated from bovine submaxillary gland mucin by Blix in 1936, and more than 50 types of sialic acid have been identified to date. Sialic acid is a general term for neuraminic acid derivatives of negatively charged carboxyl group-containing nine-carbon acidic amino saccharides, which can be classified according to the carbon-5 position into three types: N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc), and deaminoneuraminic acid. Sialic acid is closely related to various biological phenomena and is essential for maintaining the development of the human brain and nervous system and regulating the immune system. Sialic acid is also associated with colonization by symbiotic microorganisms, including bacteria, viruses, and fungi. Therefore, sialic acid is extremely important for understanding the host-microorganism symbiotic relationship. In this study, we review sialic acid metabolism by the gut microbiome and its effects on the physiological state of the host. ...and more

Diverse strategies for utilizing fucosylated human milk oligosaccharides found in bifidobacteria

Mikiyasu Sakanaka

last updated 2022/02/01 (Glycoforum. 2022 Vol.25 (1), A1)  

Human milk oligosaccharides (HMOs), which are abundant in human breastmilk, have a prebiotic effect that selectively promotes the growth of bifidobacteria. As a result, breastfed infants often have a bifidobacteria-rich gut microbiota, with bifidobacteria accounting for over 50 % of the total bacterial community. Given this, the application of HMOs to infant formula has begun to make progress in recent years. 2ʹ-Fucosyllactose (2ʹ-FL), a representative species of HMOs decorated with fucose (fucosylated HMOs; FHMOs), was the first HMO species approved for use in infant formula and has attracted attention worldwide. In this chapter, I will describe the diverse FHMO utilization strategies found in bifidobacteria, focusing on their glycosidases and transporters, and discuss the significance of FHMOs applied to fortify infant formula in terms of promoting the formation of a bifidobacteria-rich microbiota. ...and more

Human Milk Oligosaccharides and Intestinal Bacteria: Current and Past Perspectives

Motomitsu Kitaoka / Takane Katayama

last updated 2021/12/01 (Glycoforum. 2021 Vol.24 (6), A16)  

In general, a bifidobacteria-predominant microbiota is established in breastfed infant guts, and such microbiota formation is believed to be beneficial to host health. Since the isolation of Bifidobacterium sp. in 1899, research has been conducted to elucidate how bifidobacteria proliferate in the infant gut and which components, if present, in breastmilk promote their growth. In the 1950s, human milk oligosaccharides (HMOs) were reported to act as a growth factor for bifidobacteria. However, until relatively recently, the structural complexity of HMOs has hampered the elucidation of the molecular mechanism underlying HMOs-mediated selective growth of bifidobacteria. In the early 21st century, systematic understanding of the HMO utilization mechanism of bifidobacteria rapidly advanced. In this chapter, we describe the historical aspects and recent progress of the research on HMOs and bifidobacteria. ...and more

The galectin-lattice: a decoder of bio-equivalent glycans

Tadasu Urashima

last updated 2021/10/01 (Glycoforum. 2021 Vol.24 (5), A14)  

Human milk contains 7% of carbohydrate, 80% of which consists of lactose (Galβ1-4Glc), while 20% consists of oligosaccharides. The concentrations of milk oligosaccharides are 12 ~ 13 g/L in mature milk and 22 ~ 24 g/L in colostrum; these are the third largest solid component after lactose and lipid. Their concentrations are surprisingly high. Most of the human milk oligosaccharides (HMOs), with few exceptions, contain a lactose unit at their reducing ends, to which monosaccharides residues including N-acetylglucosamine (GlcNAc), galactose (Gal), fucose (Fuc), and N-acetylneuraminic acid (Neu5Ac) are attached. To date about 250 HMOs have been separated, of which about 170 structures have been characterized. When breast-fed infants consume their mothers’ milk, the lactose is hydrolyzed to Glc and Gal by small intestinal lactase, to be absorbed, whereas most HMOs remain intact within the small intestine and thus reach the colon, where they have significant physiological functions other than nutritional effects. Based on the experimental evidence, the following functions have been proposed: stimulation of the growth of beneficial colonic bacteria such as bifidobacterium, anti-infection against pathogenic bacteria and viruses, immune modulation including anti-inflammation, prevention of necrotizing enterocolitis and reinforcement of the colonic barrier function, and activation of brain-nerve functions. In this series of Glycoforum, some of the exciting discoveries will be described, focusing on the metabolic pathways of HMOs by bifidobacteria, the functions of HMOs relating to the cross talk between colonic bacteria and host epithelial cells, and the industrial production of HMOs. In this series the history of studies in this field, with future aspects, will be dynamically expanded by first-class researchers. In the beginning of this series, international studies clarifying the biological functions of HMOs will be introduced. ...and more