The Immature Intestine in Infants – A Risk for Autodigestion

A mechanism for potential injury to the intestine and other organs in an infant due to premature formula feeding.

Asperger's Spectrum Disorders, like Autism, are accompanied by high prevalence of gastrointestinal complications. The source of these complications is presently unknown. Our research on autodigestion shows that a permeable intestine with digestive enzymes is potentially a source for severe peripheral organ injury.

The problem is as follows: An infant is born with organs still under development. One organ to mature after birth is the intestine. During development, the intestine forms an important epithelial barrier that prevents entry of digestive enzymes into the wall of the intestine and protects against autodigestion by its own digestive enzymes. Mother's milk (a liquid tissue of stem and immune cells, hundreds of proteins, membrane covered lipid droplets, etc.) needs no digestion and is optimal during the period when the epithelial barrier in the intestine of a new born baby is not yet fully developed.

In contrast, formula (i.e. pasteurized milk in which cellular and molecular structures are largely degraded by heating) needs to be digested by the baby's pancreatic enzymes to be of nutritional value, just like in an adult intestine. If pancreatic digestive enzymes are released from the baby's pancreas during a period when the intestinal barrier is not yet fully developed, there is no protection of the baby against its own digestive enzymes.

Formula feeding not only requires digestive enzymes, but also generates cytotoxic mediators in the presence of pancreatic digestive enzymes in formula. We identified unbound free fatty acids as cytotoxic mediators produced by pancreatic digestive lipase in formula. They are cytotoxic for every cell type, and can damage intestinal epithelium (1, 2).

Therefore, formula feeding, at a time when the intestinal barrier in an infant is not fully developed, may be a mechanism for organ injuries in a baby, such as necrotizing enterocolitis (1).

Besides the intestine, other structures and organs may be affected, including the brain, since digestive enzymes may be transported throughout the circulation into different tissues.

Epidemiology suggests that the longer an infant is purely breast-fed, the lower the incidence of gastrointestinal complications (3). Even partial supplementation of breast feeding with formula still requires the action of the baby's digestive enzymes in order to gain a nutritional value from the formula.

In premature infants the practice of feeding formula - instead of mom's milk - is being stopped in many medical centers and has reduced the incidence of necrotizing enterocolitis, a potentially lethal condition with similarities to autodigestion.

Future Directions

  • There is a need for bioengineering designs to provide families with the ability to reliably evaluate the intestine of a baby and determine whether it has an intestinal barrier that minimizes leakage of digestive enzymes at the time of formula feeding.
  • Families need to be advised of the risk associated with digestive enzymes.
  • Prolonged storage of human milk leads to release of unbound free fatty acids (2). There is a need for a new technology to minimize milk degradation during storage.


(1) Penn A. H., Altshuler, A.E., Small, J.W., Taylor, S.F., Dobkins, K.R., Schmid-Schönbein, G.W.: Digested formula but not digested fresh human breast milk causes death of intestinal cells in vitro: implications for necrotizing enterocolitis. Pediatric Research, 72(6):560-567, 2012

(2) Penn, A. H., Altshuler, A.E., Small, J.W., Taylor, S.F., Dobkins, K.R., Schmid-Schönbein, G.W.: Effect of digestion and storage of human milk on free fatty acid concentration and cytotoxicity. J. Pediatric Gastroenterology & Nutrition. 59(3):365-373, 2014

(3) Penn, A.P, Carver, L.J., Herbert, C.A., Lai, T.S., McIntire, M.J., Taylor, S.F., Schmid-Schönbein, G.W., Dobkins, K.R.: Breast milk protects against gastrointestinal symptoms in infants at high risk for autism during early development. J. Pediatric Gastroenterology & Nutrition, 62(2):317-27, 2016

Microscopic image of cells exposed for a short time to breast milk (top row) and infant formula (bottom row) after digestion with lipase, just like inside the small intestine. Note: 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 (R) after exposure to the infant formula that was digested with lipase. Thus, infant formula (but less so fresh breast milk) becomes cytotoxic in an intestine after exposure to lipase.

Image Credit: Dr. Alexander Penn, Department of Bioengineering, UC San Diego Jacobs School of Engineering.

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