Breast milk ingredient could prevent necrotizing enterocolitis—deadly intestinal problem in preemies

May 6, 2013

An ingredient that naturally occurs in breast milk might be used to prevent premature babies from developing a deadly intestinal condition that currently is largely incurable, according to researchers at the University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh of UPMC in this week's online early edition of the Proceedings of the National Academy of Sciences.

The story begins with a baby who is born too early, meaning before 36 weeks gestation, said senior author David Hackam, M.D., Ph.D., Watson Family Professor of Surgery, Pitt School of Medicine, and co-director of the Fetal Diagnosis and Treatment Center at Children's Hospital. Once stable, typically the baby is fed with formula because often breast milk is not readily available to .

"Within about 10 days of birth, the baby starts to vomit and a few hours later, the belly becomes distended and discolored," Dr. Hackam said. "It becomes clear that the child has developed a major problem in his or her tummy, and an X-Ray will usually confirm the diagnosis of , or NEC, in which the is dying. We have no choice but to remove the dead parts of the intestine, but despite surgery, half of these preemie babies still die from the condition."

Dr. Hackam and his team noted NEC occurs when the intestines start getting colonized with bacteria, a process that occurs normally after birth. They focused on toll-like receptor 4 (TLR4), an immune protein that is involved in recognizing microbes and which they recently discovered plays a role in gut development. In the current work, Hackam and colleagues found that TLR4 is present in higher amounts in the blood vessel lining in preemies than in full-term babies.

The study shows that unlike normal mice, those bred to lack TLR4 in their blood vessels did not develop NEC in a model designed to induce the condition. The findings indicate that bacteria in the blood activate TLR4 leading to a reduction in , which in turn narrows blood vessels and decreases blood flow, Dr. Hackam said.

"This pathway can be dangerous when the preemie's immature gut becomes inflamed from exposure to the bacteria normally present in the intestine," he said. "Abundant TLR4 triggers a shutdown of the blood supply to the intestine, leading to tissue death or necrosis."

who are nursed rather than formula-fed are more likely to survive NEC, so co-author and nitric oxide expert Mark Gladwin, M.D., chief, Division of Pulmonary Allergy and Critical Care Medicine, Pitt School of Medicine, and director of Pitt's Vascular Medicine Institute, and the team took a closer look at the components of breast milk.

They found that contains high levels of sodium nitrate, which is converted to nitrite by gut bacteria. Nitrite can be directly converted to the vasodilator nitric oxide, which can both protect the intestinal lining and improve blood flow.

"The additional nitrite appears to overcome the effects of TLR4 activation and corrects the blood flow problem," Dr. Gladwin said. "When we gave formula supplemented with a sodium nitrate and nitrite analog to the premature mice, we saw improved in the intestine, and NEC did not develop."

Drs. Hackam and Gladwin are testing the compound, which is FDA approved for other uses, in other models of NEC with the hope that it could be routinely added to formula fed to premature infants to prevent NEC.

"This condition is frightening for parents and frustrating for doctors because currently there is little we can do to treat it," said Dr. Hackam, a pediatric surgeon. "I look forward to one day putting myself out of business and having a therapy that truly saves these children."

Explore further: Formula-fed preemies at higher risk for dangerous GI condition than babies who get donor milk

More information: Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling: www.pnas.org/cgi/doi/10.1073/pnas.1219997110

Related Stories

Formula-fed preemies at higher risk for dangerous GI condition than babies who get donor milk

May 1, 2011
Extremely premature babies fed human donor milk are less likely to develop the dangerous intestinal condition necrotizing enterocolitis (NEC) than babies fed a standard premature infant formula derived from cow's milk, according ...

Urine test identifies babies at most risk of necrotizing enterocolitis

April 15, 2013
Abnormal gut bacteria in premature babies can be found days before the onset of necrotizing enterocolitis (NEC) finds new research in BioMed Central's open access journal Microbiome. Babies who later went on to develop NEC ...

Life-threatening condition in preemies linked to blood type

November 21, 2011
Many premature infants suffer a life-threatening destruction of intestinal tissue called necrotizing enterocolitis (NEC).

Immune system implicated in prematurity complication

March 19, 2012
Despite advances in neonatal care, necrotizing enterocolitis (NEC) – the most common gastrointestinal emergency in premature infants – continues to be a deadly disease.

Recommended for you

Finish your antibiotics course? Maybe not, experts say

July 27, 2017
British disease experts on Thursday suggested doing away with the "incorrect" advice to always finish a course of antibiotics, saying the approach was fuelling the spread of drug resistance.

Co-infection with two common gut pathogens worsens malnutrition in mice

July 27, 2017
Two gut pathogens commonly found in malnourished children combine to worsen malnutrition and impair growth in laboratory mice, according to new research published in PLOS Pathogens.

Phase 3 trial confirms superiority of tocilizumab to steroids for giant cell arteritis

July 26, 2017
A phase 3 clinical trial has confirmed that regular treatment with tocilizumab, an inhibitor of interleukin-6, successfully reduced both symptoms of and the need for high-dose steroid treatment for giant cell arteritis, the ...

A large-scale 'germ trap' solution for hospitals

July 26, 2017
When an infectious airborne illness strikes, some hospitals use negative pressure rooms to isolate and treat patients. These rooms use ventilation controls to keep germ-filled air contained rather than letting it circulate ...

Researchers report new system to study chronic hepatitis B

July 25, 2017
Scientists from Princeton University's Department of Molecular Biology have successfully tested a cell-culture system that will allow researchers to perform laboratory-based studies of long-term hepatitis B virus (HBV) infections. ...

Male hepatitis B patients suffer worse liver ailments, regardless of lifestyle

July 25, 2017
Why men with hepatitis B remain more than twice as likely to develop severe liver disease than women remains a mystery, even after a study led by a recent Drexel University graduate took lifestyle choices and environments ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

eachus
1 / 5 (1) May 06, 2013
Amazing! So if you have a child suffering from NEC administer BACON immediately.

(For the humor impaired, yes, I'm joking. It's just that diet fascists have talked about the caused by sodium nitrite--and sodium nitrite--in bacon. As in all things dietary, the right answer is moderation.)
Tom_Hennessy
not rated yet May 07, 2013
"Abundant TLR4 triggers a shutdown of the blood supply to the intestine, leading to tissue death or necrosis."

This is precisely why polycythemia is found in NEC. Polycythemia causes hyperviscous blood , thicker blood , which cannot nourish the gut , leading to lack of 'blood supply to the intestine, leading to tissue death or necrosis'.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.