Breast milk component induces expression of P-glycoprotein

Researchers at Children's Hospital Los Angeles have found that a component of breast milk induces expression of P-glycoprotein (Pgp), a protein that is protective against necrotizing enterocolitis (NEC)--a complex, lethal disease that affects up to 7 percent of babies admitted to the NICU. This laboratory finding could potentially lead to ways of treating or even preventing the disorder, researchers announced today at the 2011 Annual Clinical Congress of the American College of Surgeons.

The precise cause of NEC is unknown, but prematurity, gastrointestinal colonization with bacteria and formula feeding are known risk factors. The overwhelming inflammation that occurs in NEC can cause bowel necrosis, and once that happens, an operation is required to remove the dead tissue. But according to researchers, the antibacterial and immunity enhancing qualities of breast milk protect the infant.

"Currently, NEC is difficult to treat. We watch and wait, and in some cases we use surgical interventions," said Elizabeth Pontarelli, MD, a research fellow at Children's Hospital Los Angeles and lead researcher on the study. "Mortality for the most severe form of NEC approaches 100 percent."

In recent years, researchers at the laboratory of Dr. Henri R. Ford at Children's Hospital Los Angeles demonstrated that breast milk induces expression of the protein Pgp, which is known to be protective against gastrointestinal inflammation. Still, there remained an unanswered question: What component in breast milk is responsible for generating this protein? Building on this initial work, Dr. Pontarelli and her colleagues in the Ford lab set out to identify that individual factor.

The researchers began their quest by obtaining human breast milk from healthy volunteers. Using a strategy called purification, the researchers separated the milk into parts-- insoluble products, soluble products, and lipids. Then by adding salt at different concentrations and saturation levels to the solutions, they collected hundreds of proteins that precipitated within the soluble fraction of milk. Taking that sample and purifying it even further, the researchers were able to zero in on a smaller number of proteins with Pgp-producing activity. Using a technique called mass spectroscopy to analyze the proteins based upon their weight and electrical charge, as well as other strategies, the researchers are currently working to identify the individual Pgp-inducing protein.

The theory goes, Dr. Pontarelli explained, that if we find the one protein that induces Pgp, and we know that the presence of Pgp will help protect against NEC, then we can take this protein and supplement infant formula with it, possibly preventing NEC or decreasing the incidence of the disorder in high-risk neonates. There are still many things we need to determine, she added, such as the most effective way to deliver the protein intact into the small intestine, where it needs to do its work.

These early findings lay the groundwork for studies in animals, and eventually clinical trials. "It's exciting to be able to show this for the first time, because babies with NEC can develop short gut syndrome, and become totally dependent on parenteral nutrition," Dr. Pontarelli said. "It's not simply a bacterial infection, and it's not simply an inflammatory reaction. But it is a disease that doesn't have a treatment, so I think the best thing we can do is try to prevent it. Our research is trying to come up with a preventive strategy."