Gastrointestinal Injury Mechanisms in Infants

Gastrointestinal Injury in Infants Due to Formula Feeding:

A Mechanism for Asperger Spectrum Syndrome (Autism)?

We uncovered a mechanism for potential injury to intestine and other tissues of an infant due to formula feeding after digestion by lipase and generation of cytotoxic free fatty acids.

The idea is as follows: An infant needs to develop all its organs in-utero and continues to do that after birth. One organ that needs to develop is the intestine. During development, the intestine forms a (mucosal) barrier that prevents entry of digestive enzymes into the wall of the intestine and thus protects from autodigestion by its own digestive enzymes. Fresh mom's milk does not need digestive enzymes from the infant's pancreas and therefore the mucosal barrier does not need to be fully developed. But formula needs to be digested by the baby's pancreatic enzymes to be of nutritional value. If pancreatic digestive enzymes are released during a period of time when the intestine barrier is not yet fully developed, there is little protection against the digestive enzymes and the products they produce while digesting formula.

Mother's milk is ideal during the period of time when the intestinal barrier is not yet fully developed, since it does not require most digestive enzymes and it does not generate a cytotoxic mediator should it be exposed to digestive enzymes, like lipase.

In contrast, formula is different. It not only requires digestive enzymes, which may autodigest an intestine without a fully developed mucosal barrier, but formula generates cytotoxic mediators in the presence of lipase. We have identified unbound free fatty acid as a cytotoxic mediator produced by lipase in a variety of formulas. The free fatty acids are cytotoxic for every cell type, including epithelial cells, endothelial cells and leukocytes, and thus have the ability to cause damage to the intestine.

In premature infants the intestine and its barrier may not be developed while the pancreas is ready to secrete digestive enzymes. If formula is fed, digestive enzymes may cause generation of cytotoxic mediators that injure the intestine. This may be a major mechanism for necrotizing enterocolitis. It may also be a problem in infants with a delayed intestinal development, e.g. autism.

See further Discussion

Microscopic image of cells exposed for a short time to breast milk (top row) and infant formula (bottom row) after digestion with lipase. Cells are alive and healthy in the breast milk (top row) with only one cell showing bleb formation (B). In contrast, all cells are ruptured after exposure to the infant formula that was digested with lipase. Thus, infant formula (but not fresh breast milk) becomes cytotoxic in an intestine after exposure to lipase. See Penn et al.