About This Project

Necrotizing enterocolitis is a severe inflammatory gastrointestinal disease and is the leading cause of morbidity and mortality (30-50%) in preterm neonates. An altered newborn's gut microbiota plays a major role in this condition. We hypothesize that secreted factors from one probiotic, Bifidobacterium infantis, could exert anti-inflammatory effects in the newborn's intestine. These observations might lead to ways to prevent excessive intestinal inflammation causing necrotizing enterocolitis.

Ask the Scientists

What is the context of this research?

Necrotizing Enterocolitis (NEC) is a severe inflammatory gastrointestinal disease that occurs during the neonatal period and leads to an early death of the premature neonate. The pathogenesis of NEC is not well characterized. However, intestinal inflammation in premature neonates is likely caused by a combination of intestinal cells immaturity and gut microbiota imbalance. The gut microbiota is the complex community of microorganisms, including bacteria, that live in the digestive tracts of humans and which influence our health.

It has been shown, in clinical trials outside the US, that a major probiotic, Bifidobacterium infantis, could protect premature infants against NEC. Bifidobacterium infantis is a common commensal bacteria found in the healthy newborn intestine.

What is the significance of this project?

Necrotizing enterocolitis (NEC) is a medical condition which typically occurs in newborns that are premature. About 5% of those that are born premature develop NEC. Among those affected, about 30-50% die. Hence, new medical treatments to prevent this disease are urgently needed.

In that way, a growing body of experimental and clinical evidence, from outside the US, supports the concept that probiotics may have a preventative application in NEC. However, the FDA (Food and Drug Administration) does not allow the use of live probiotics in neonates yet. Hence, this laboratory is looking for the use of secreted factors from Bifidobacterium infantis, without the use of the live bacteria, to protect neonates against NEC though anti-inflammatory mechanisms on immature intestinal cells.

What are the goals of the project?

We hypothesize that the anti-inflammatory effect of Bifidobacterium infantis secreted factor on immature human intestinal cells may be mediated by the aryl hydrocarbon receptor (AhR), a nuclear receptor expressed in immune cells.

The first step, starting February the 4th, will be to test if immature human intestinal cells (a model representing the premature newborn's intestine) express AhR. The second step will be to confirm if Bifidobacterium infantis secreted factor exerts anti-inflammatory effect on these cells. Then, we will analyze if this anti-inflammatory effect is mediated by the aryl hydrocarbon receptor (AhR) and evaluate the precise mechanism of its action.

This project will last 5 months without involvement of any human subjects.