Evolution of milk oligosaccharides and lactose: a hypothesis

Abstract

Mammalian milk or colostrum contains up to 10% of carbohydrate, of which free lactose usually constitutes more than 80%. Lactose is synthesized within lactating mammary glands from uridine diphosphate galactose (UDP-Gal) and glucose by a transgalactosylation catalysed by a complex of b4-galactosyltransferase and a-lactalbumin (a-LA). a-LA is believed to have evolved from C-type lysozyme. Mammalian milk or colostrum usually contains a variety of oligosaccharides in addition to free lactose. Each oligosaccharide has a lactose unit at its reducing end; this unit acts as a precursor that is essential for its biosynthesis. It is generally believed that milk oligosaccharides act as prebiotics and also as receptor analogues that act as anti-infection factors. We propose the following hypothesis. The proto-lacteal secretions of the primitive mammary glands of the common ancestor of mammals contained fat and protein including lysozyme, but no lactose or oligosaccharides because of the absence of a-LA. When a-LA first appeared as a result of its evolution from lysozyme, its content within the lactating mammary glands was low and lactose was therefore synthesized at a slow rate. Because of the presence of glycosyltransferases, almost all of the nascent lactose was utilized for the biosynthesis of oligosaccharides. The predominant saccharides in the proto-lacteal secretions or primitive milk produced by this common ancestor were therefore oligosaccharides rather than free lactose. Subsequent to this initial period, the oligosaccharides began to serve as anti-infection factors. They were then recruited as a significant energy source for the neonate, which was achieved by an increase in the synthesis of a-LA. This produced a concomitant increase in the concentration of lactose in the milk, and lactose therefore became an important energy source for most eutherians, whereas oligosaccharides continued to serve mainly as anti-microbial agents. Lactose, in addition, began to act as an osmoregulatory molecule, controlling the milk volume. Studies on the chemical structures of the milk oligosaccharides of a variety of mammalian species suggest that human milk or colostrum is unique in that oligosaccharides containing lacto-N-biose I (LNB) (Gal(b1 -3)GlcNAc, type I) predominate over those containing N-acetyllactosamine (Gal(b1 -4)GlcNAc, type II), whereas in other species only type II oligosaccharides are found or else they predominate over type I oligosaccharides. It can be hypothesized that this feature may have a selective advantage in that it may promote the growth of beneficial colonic bacteria, Bifidobacteria, in the human infant colon.Keywords: lactose, milk oligosaccharides, a-lactalbumin, lysozyme, lactation, prebiotics, bifidobacteria Implications Eutherian mammals' milk or colostrum usually contains small amounts of oligosaccharides and lactose, the dominant carbohydrate. Lactose acts as a main energy source for neonates, whereas milk oligosaccharides are believed to act as prebiotics that stimulate the growth of benefici...

Chemical characterization of acidic oligosaccharides in milk of the red kangaroo (Macropus rufus)

“…Tammar wallaby milk does not contain oligosaccharides whose core units are lacto-N-neotetraose (Gal(β1-4)GlcNAc(β1-3)Gal (β1-4)Glc) or lacto-N-neohexaose (Gal(β1-4)GlcNAc(β1-3)[Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc), unlike the milk of several eutherian species [2,3,16,17]. In addition, galactosyllactoses such as those found in tammar wallaby milk other than Gal(β1-3)Gal(β1-4)Glc, have never been found in any eutherian milk/colostrum [2,3,16,17]. However, lacto-N-novopentaose I has been found in the milk/ colostrum of both the tammar wallaby and a few eutherian species including cow [18][19][20], camel [11], pig [21], horse [22] and capuchin monkey [23].…”

A unique gene cluster for the utilization of the mucosal and human milk‐associated glycans galacto‐N‐biose and lacto‐N‐biose in Lactobacillus casei

“…Although L. casei can be cultured on LNB as the only carbon source, the simultaneous presence of GNB and LNB in environments such as the gastrointestinal tract of breast-fed infants would possibly enhance the efficiency of LNB utilization. GNB and LNB form part of a great variety of bioactive molecules, such as HMO, glycosphingolipids, mucin glycoproteins and glycolipids (Hakomori, 2008;Thurl et al, 2010;Moran et al, 2011;Urashima et al, 2012;Liu and Newburg, 2013). In order to be used by L. casei, they must be previously released from those glycocomplexes by the action of other microbial glycosidases.…”

“…GNB is also a crucial structure in functional sugar chains like the T-antigen disaccharide and it is also an essential part of the carbohydrate moieties of complex glycosphingolipids (Lloyd et al, 1996;Moran et al, 2011;Liu and Newburg, 2013). Another important disaccharide present in human secretions is lacto-N-biose (LNB; Galβ1-3GlcNAc), which is the major core structure of human milk oligosaccharides (HMO) (Thurl et al, 2010;Urashima et al, 2012). HMO are classified into type-1 and type-2, containing LNB and N-acetyllactosamine, respectively, as disaccharide building blocks.…”

Monotreme Lactation Protein Is Highly Expressed in Monotreme Milk and Provides Antimicrobial Protection

“…It has been proposed that monotreme lactation originally evolved to prevent desiccation of the eggs or for protection against microbes, and subsequently evolved a nutritional role (Warren et al 2008; Oftedal 2012, 2002b; Urashima et al 2012). Several studies have shown that a variety of antimicrobial proteins are expressed in either mammary glands or milk in marsupials, humans, cow and mouse, and these factors are believed to contribute to a lower incidence of infections (Aniansson et al 1990; Strömqvist et al 1995; Murakami et al 2005; Hettinga et al 2011; Nicholas et al 2012; Dallas et al 2013).…”