Breast Milk: Probiotic Potpourri

19. February 2013
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More than 200 different short sugar chains are found in the secretion of the human female mammary glands. Aside from the probiotic effect, researchers have only in recent years also discovered a number of other functions – which are vital to the health of the child.

Only at first glance the two findings seem to contradict one another:

  • for the newborn, there is hardly healthier food than milk from the mother’s breast.
  • More than 700 different forms of bacteria may be present in breast milk, as Spanish researchers found last year.

The WHO recommends exclusive breast feeding up until 6 months of age, and after that as an addition up to the infant’s second year. Colostrum, the sticky early milk for the newborn, is the perfect food. “Mothers should begin breastfeeding in the very first hours after the birth”, the organisation writes in its advice for parents.

Several hundred sugar variants

Vital fats, proteins, growth factors in milk are the grounds for the WHO recommendation. At least as interesting, but so far little elucidated, are oligosaccharides, simple or branched complex sugars composed from five different building blocks that are not intended as an energy supply in our mini-consumers. The mammary glands produce not only just a few, but several hundred different such variants. Every mother has her own individual repertoire, which is made up from the elements lactose (glucose + galactose), fucose, N-acetylglucosamine and N-acetylneuraminic acid, their lengths being 2-32 units. In contrast to domestic animals such as sheep or cows, secretion from the human female breast contains from a hundred to a thousand times more of these special sugars.

Even if the modes of action of these bits of soluble cargo are not yet understood in detail, the researchers know at least some of its functions. In the intestine they prevent the spread of pathogenic germs, they make a positive impact on the developing immune system and are probably involved in the development of brain. They probably not only help the infant but also the mother.

Food for bifidobacteria and trap for pathogenic germs

Bifidobacteria play an important role in the initial colonisation of the uninoculated small intestine. With their growth they restrict supply of space and food for other unpleasant relatives. Whereas the human metabolism cannot get much done with complex sugars, some bifidobacteria have developed a whole battery of glycosidases by means of which they can cleave the sugar chains and even use them as a sole carbohydrate source. Sugar chains serve not only as a combustion material, but also as an anchor to the intestinal epithelium from which they project. Some Escherichia coli family members or even Helicobacter hang there freely and thus become sedentarily fixed. Glycans together with fucose remnants inhibit the attachment of for instance the diarrheal pathogen Campylobacter jejuni.

As with other bacteria, the milk sugars give the illusion of being an anchor, which then however moves on to the anus. In addition bacterial toxins based on lectin can bind to glycans where they are able to cause considerable damage. The oligosaccharides in the milk can capture them. Breastfed children also suffer to a lesser extent from respiratory or middle ear infections. The targeted actions of the sugar chains against Streptococcus pneumoniae, Pseudomonas aeroginosa or Haemophilus influenzae might be contributing to this, since milk even reaches these regions.

Against amoebic dysentery, noroviruses and HIV

However, it is not only bacteria whose lives depend on the carbohydrates in milk. Especially in developing countries parasites such as Entamoeba histolytica are accountable for often deadly diseases of the intestinal tract in young children. The sugars also prevent binding here between lectin and the intestinal epithelium. Similarly, viruses have a hard time with breast milk. This in particular relates to the diarrhea triggers norovirus and rotavirus. Findings from Africa showing that four out of five children are infected neither in the womb, nor later by the milk of HIV-infected mothers. Herein it appears that some of the sugars in the milk compete with receptors of dendritic cells (DC-SIGN, dendritic cell ICAM-3-grabbing non-integrin), to which glycoprotein 120 of the HIV virus would otherwise attach itself.

Necrotising enterocolitis – a case for oligosaccharides

In the interaction with the immune system lectins again play a large roll on the cell surface of leukocytes; the exact receptors are not yet known. With peanut allergy oligosaccharides reduce the production of interleukin-4 and are thus able to serve in allergy prevention. Selectins on the cell surface of endothelial cells react in the event of inflammation with the sugar chains on leukocytes, which are floating in the blood stream. They slow down the movement of the immune cells, bringing them to roll along the vessel wall and finally to a stop. From there, it’s not so far to exit the blood vessel into the tissue and migrate there to trigger inflammation. Platelets also possess such selectins and together with neutrophils are responsible for complex formation and subsequent phagocytosis. The sugars in milk can in turn intercept these reactions.

Although considerably more than 90 percent of maternal oligosaccharides leave the digestive tract unchanged, fine analysis can demonstrate the presence of one percent of these sugars in infant urine, a sure sign that a small part makes it into the bloodstream. Breastfed babies – especially premature babies – have a significantly lower risk of getting the often fatal necrotising enterocolitis, even though the reasons for this are not entirely clear. A key role is played nonetheless by di-sialyl-lacto-N-tetraose (DSLNT). In rats this sugar has reduced the intensity and the frequency of intestinal inflammation. Using a test for this sugar, five clinics in the U.S. want to test breast milk and thus reduce the risk for premature babies of this common disease. However since DSLNT is substantially longer than most of the other sugars, therapy would be expensive, regardless of whether the molecule is obtained synthetically or by extraction derived from milk.

Neuraminic acid supply to the brain

In the brain the growth of nerve cells is dependent on supply of neuraminic acid. It is an important building block for gangliosides and glycoproteins. The oligosaccharides in milk contain high concentrations of this substance. Thus they could be responsible for the fact that breastfed infants at school enrollment possess slightly higher IQs. Whether the fairly low concentration of milk-sugars in the circulation of the child is sufficient to be a direct supply source is however debatable. What could also be conceivably causal is the indirect effect on growth factors in the gastrointestinal tract.

The individual differences in milk’s sugar-chain biochemical armory are also dependent on the presence of fucosyl transferases. Because the “Lewis” blood group system is also based on the presence of the gene for this enzyme, the milk-sugar spectrum reflects the Lewis and secretor groups. In addition, content and composition varies with the duration of breastfeeding. The colostrum contains 20-25 grams per litre of complex sugars, after this the level decreases from 5 to 20 g /l. In the end, it is not only the very young who benefit from these essential ingredients. In all likelihood milk also protects the mother’s breast against infection from pathogens such as Staphylococci. Breast cancer is less common in nursing mothers, as is cervical cancer.

Milk substitutes – not always straight forward

With so many benefits gained from human milk, baby food producers naturally try to enhance their milk substitutes with at least some of these qualities. With the addition of galacto-oligosaccharides and a lactobacillus culture, HIPP is trying to upgrade its infant formula, competitor Nestlé (Alete, Beba) relies on using a bifidobacteria in its respective products. The problem, however, is the enormous cost of oligosaccheride additives. Often the relevant substances are derived from plants such as chicory. A diversity such as that present in the food source obtained from the mother’s breast is however hardly able to be achieved. In addition problematic side effects may occur. Fructo-oligosaccharides are often used to reduce the risk of allergies. Studies with rats however show that these sugars weaken the intestinal barrier and thus can promote the intrusion of unwanted visitors such as Salmonella. Most of these derivatives also do not contain the important fragments of neuraminic acid.

In Germany, around 70 percent of women are breast feeding about two months after giving birth, after half a year only half of them. In Norway after this time it is some 80 percent. Nevertheless, not all mothers can breastfeed and thus pass on the protective factors in the mammary gland to the child. With increased knowledge about the mechanisms of the sugar-defense system against infection and derailment of the immune system, “the dairy product substitutes are always getting better”, Mathilde Kersting from the Research Institute of Child Nutrition in Dortmund confirms. Finally, there are with mothers who breastfeed for longer than six months also indications of risks for anemia, allergies and celiac disease. Whether one is ultimately doing research and development a favour when forbidding advertising for milk substitutes and also prohibiting producers from having direct contact with mothers, as is done in the WHO Code from 1981, is another question.

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3 comments:

Dr Nadine De Ronne
Dr Nadine De Ronne

Remember the difference probiotics >< prebiotics!!!!

#3 |
  0
Dr Nadine De Ronne
Dr Nadine De Ronne

Remember the difference between probiotics and prebiotics!!!

#2 |
  2
Prof. Lovro Stanovnik
Prof. Lovro Stanovnik

Poglej si tole.

LpL

#1 |
  4
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