Infant Milk Allergy, Colic and Sialic Acid

Speculation on the cause of infant reactions to cow’s milk in formula or transmitted into mother’s milk.  Are mother’s priming their newborns in utero with antibodies to react to non-human sugars (Neu5Gc)?

Sialic Acids Mark the Surface of Human Cells

Human cells are covered with a forest of long and short carbohydrates, polysaccharides and oligosaccharides resp., which control the interaction of the cells with the outside world.  The sugars exposed on the ends of these sugar chains are sialic acids.  It is not surprising that pathogenic viruses and bacteria target sialic acids as the first step in attacking human cells and that policing immune cells avoid attacking their own cells by recognizing the sialic acids.  The surprise is that essentially all other mammals have the same two sialic acids, Neu5Ac and Neu5Gc, but humans have only Neu5Ac.  Meat and cow’s milk have both.  Babies and mother’s milk should have only Neu5Ac.

Evolution to Lose Neu5Gc to Avoid Pathogens

Surviving defective remnants of genes needed to make Neu5Gc suggest that loss of Neu5Gc was an adaptation to avoid general mammalian pathogens and to facilitate brain development.  One of the limitations of using other mammals as models of human diseases is the differences in sialic acids that are commonly used for initial docking of pathogens on human cells.  Other mammals have different forms of malaria than humans and we are well aware that influenza adapted to birds and pigs does not infect humans without adjusting to the lack of Neu5Gc.

Antibodies Against Neu5Gc

Humans make antibodies to Neu5Gc when injected with blood products from other mammals.  A sudden change from a long term vegan diet to a meat diet can also lead to the production of anti-Neu5Gc antibodies.  These types of antibodies may contribute to some types of non-lactose milk intolerance/allergies.

Neu5Gc from Cow’s Milk Gangliosides to Mother’s Milk

A significant problem in infant health is the reaction of the infant with abdominal distress after eating cow’s milk-based formula or in some cases from breastfeeding after the mother has eaten milk or other dairy products.  Milk oligosaccharides, proteins and lipids have Neu5Gc.  It is unlikely that cow’s milk proteins or oligosaccharides can move from the mother’s intestines to her breast milk, but it is possible that Neu5Gc attached to fatty acids in the form of gangliosides may be transferred to breast milk.

Mother’s Anti-Neu5Gc in Infants Gut Reacts with Cow Neu5Gc

If cow’s milk gangliosides are the source of Neu5Gc in breastmilk, then how do the infants develop antibodies to these relatively rare antigens?  Babies receive all of their antibodies from their mother until their immune systems start to develop at about six months of age.  The answer is hinted at by the observation of a mother whose exclusively breastfed infant developed sensitivity to breast milk after the mother ate dairy products.  The mother reported that she shifted from a long term vegan diet to a meat diet to improve her nutrition during her pregnancy.  It is also likely that she produced IgE antibodies to Neu5Gc, which were then transferred to her baby across the placenta during gestation.

Anti-Neu5Gc Antibodies May Explain Infant Milk Intolerance and Colic

Infants with anti-Neu5Gc antibodies obtained from their mother during gestation in utero, will have mast cells in the lining of their gut that are primed to react to Neu5Gc in cow’s milk present as components in formula or in trace amounts transferred into breast milk.  Infants may respond to these immunological reactions with a variety of symptoms, including those observed as rejection of formula or breast milk after the mother has eaten dairy products or as colic.

reference:

Varki A. 2010 Colloquium paper: uniquely human evolution of sialic acid genetics and biology.  Proc Natl Acad Sci U S A. 107 Suppl 2:8939-46.