Human Milk Oligosaccharides


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About Human Milk Oligosaccharides

At the beginning of the 20th century, pediatricians discovered that human mothers’ milk contained hitherto unknown complex sugars, now known as human milk oligosaccharides. Scientists were led to the discovery by the significantly lower mortality rate of breastfed children. In the early 1900s, an average of 15–20 children from every 100 born would die within their first year. At that time, the infant mortality rate for non-breastfed children was seven times higher than for breastfed infants.

Even then it was recognized that these specific human milk oligosaccharides were of paramount importance for the health and development of infants. Since then, scientists have identified more than 150 different human milk oligosaccharide structures and have investigated the properties of these sugars. Human milk oligosaccharides are unique in terms of quantity and complexity compared to oligosaccarides from other mammals.

Extensive scientific studies showing  diverse positive properties of human milk oligosaccharides have been published, particularly in recent decades. These suggest that the prebiotic properties of human milk oligosaccharides may contribute to the establishment of a protective gut microbiota. In addition, it was shown that these sugars have an antimicrobial effect since they prevent adhesion of pathogens to epithelial cells. Human milk oligosaccharides (in particular sialylated sugars) have been shown to provide the developing brain with the essential nutrient sialic acid and support neuronal functions.

Despite ground-breaking insights into the unique functions of human milk oligosaccharides, these special sugars have not, until recently, been available in large quantities, reflecting their highly complex structure and limited occurrence in Nature. For this reason, it has not been possible in the past to use these unique oligosaccharides as food ingredient.

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Natural Occurrence and Concentration

Human milk is unique with regard to its high content of complex oligosaccharides. The structural diversity and high concentration of complex oligosaccharides in human milk is specific to humans, and is not found in milk of dairy animals.

After lactose and proteins, human milk oligosaccharides represent the third largest fraction in human mothers’ milk. The natural concentration ranges from approximately 10 to 15 grams per liter. In contrast to bovine milk, human milk has a much higher concentration of carbohydrates / sugars and a significantly lower concentration of proteins.

More than 150 different human milk oligosaccharides have been identified in human milk, ranging from trisaccharides up to very complex structures made of more than 12 sugar residues. The most abundant human milk oligosaccharide is 2’-Fucosyllactose, which can be found in approximately 80% of human milk at concentrations of up to 2.5 grams per liter. Other abundant human milk oligosaccharides are 3-Fucosyllactose, Lacto-N-tetraose, Lacto-N-neotetraose, Lacto-N-fucopentaose and the sialic acid containing HMOs 3’-Sialyllactose and 6’-Sialyllactose.

These diverse structures are presumed to reflect the range of different functions of human milk oligosaccharides.  Scientific studies have shown that some of these sugars may conduct antimicrobial effects on specific pathogens, and affect the composition of the gut microbiota by promoting the growth of specific beneficial bacteria.

human milk oligosaccharides infection risks comparison

Reduction of Infection Risks

Studies have shown that breastfeeding reduces the risk of infectious diseases in children by up to 50 percent. Additional studies suggest that human milk oligosaccharides contribute significantly to reducing this risk.

The simple but highly effective mechanism of action used by human milk oligosaccharides is very well understood. Human milk oligosaccharides intervene directly in the ability of pathogens to recognize the human body as a host and thereby trigger an infection.

Pathogens mostly initiate an infection by binding to specific structures present on the surface of human cells. These surface-bound structures are vital to certain body functions, such as the immune system, cell to cell communication, or the specification of blood groups. Pathogens, including bacteria and viruses, use these surface-bound structures as receptors to identify their host as human and to gain entry into the cell and thereby trigger an infection. It is believed that over 70% off all human pathogens use cell standing oligosaccharide structures as receptor or co-receptor for their infection.

Human milk oligosaccharides dissolved in food imitate these surface-bound structures and therefore act as decoys. Pathogens cannot distinguish between human milk oligosaccharides and genuine surface-bound structures on the cell membrane. Pathogens entering the body therefore bind to the human milk oligosaccharides, and this irreversible process makes it impossible for the pathogen to subsequently bind to cells because the structures that interact with the receptors are already blocked. The pathogens are therefore excreted together with the indigestible human milk oligosaccharides and the risk of infection is reduced.

Most pathogens enter the body through the digestive tract or the respiratory system. Because human milk oligosaccharides are ingested with food, the sugars are present in high concentrations in the digestive tract. However, human milk oligosaccharides can also be absorbed in the gut so they pass into the blood stream and circulate around the body. This means the sugars can exert their healthy effect all over the body, which is known as a systemic effect, and may explain how they can protect against infections in areas of the body far away from the gut such as the lungs, the brain, and the auditory canal.

human milk oligosaccharides brain development comparison

Nutrient for Optimal Brain Development

The presence of salylated human milk oligosaccharides in human milk is one potential explanation for the better early neurodevelopment of breastfed infants. Premature babies nourished through their first months of life with mothers’ milk show significantly higher developmental scores and a better verbal behavior at the age of seven to eight years.

Sialic acid is an important building block for gangliosides in the brain, which are complex molecules displayed on the surface of neurons with a key role in brain development. According to current findings, these rare sugars play an essential role in the transmission of nerve impulses along neurons, in the formation of memories, and in cell-to-cell communication.

Sialic acid is highly concentrated in human milk in the form of sialylated human milk oligosaccharides. Scientific studies assume that the consumption of these sialylated sugars may contribute to neural development and brain cognition.

It has already been shown that consuming sialic acid sustainably improves learning ability. Sialylated human milk oligosaccharides may therefore provide an important nutrient for the development of the nervous system in children.

Gut Flora Prebiotic Effect Comparison

Prebiotic Effect for a Healthy Gut Flora

Prebiotics are non-digestible food components that create an environment favoring the growth of beneficial bacteria like bifidobacteria in the gut. Recent scientific studies have shown that improved growth and activity of these bacteria have an antimicrobial and immunomodulatory effect.

The prebiotic properties of human milk oligosaccharides are very well established and were first described by pediatricians at the beginning of the 20th century. Even before then, the gut flora of breastfed and non-breastfed children was known to be different. One week after birth, 95 percent of the total population (concentration) of bacteria in the gut of breastfed infants are bifidobacteria, which influences the acid content of the intestine, and thus reduces the growth opportunities for other – undesirable – bacteria.

Human milk oligosaccharides have a prebiotic or bifidogenic effect. Beneficial microorganisms such as bifidobacteria can, unlike human cells or pathogens, use human milk oligosaccharides as an energy source to support their growth and activity.

Human milk oligosaccharides also have an additional positive effect on intestinal flora, by binding certain undesirable bacteria and preventing them from attaching to receptors on the surface of cells, thus reducing their ability to colonize the body. The unique potpourri of human milk oligosaccharides in breast milk influences the composition of the intestinal microbiome. On the one hand, the mixture  may stimulate the growth and activity of desirable intestinal bacteria, whilst on the other, it is suggested to inhibit the growth of undesirable bacteria which helps to eliminate them from the body.

Current research suggests that about 5 percent of consumed human milk oligosaccharides are used for bacterial metabolism in the human digestive tract. The oligosaccharides thus contribute significantly to the improved growth and activity of these bacteria. The vast majority of human milk oligosaccharides pass through the human body via the digestive system and blood stream and are then excreted.

The microbiome is part of the human metabolic system and exerts a considerable influence on human vitality and wellbeing.