New understanding of nervous system gives insight into common gut problem in newborn babies

Medical Research Council (MRC) researchers have unlocked the mysteries of the nervous system responsible for proper formation and function of the gut. This new understanding has implications for treating Hirschsprung’s disease, a common disorder in newborns that requires corrective surgery in order for food to pass through the bowel and the colon.

The study shows that two important molecular switches work together to regulate the movement of crucially important cells, that will eventually become ‘enteric neurons.’ During early embryonic development these cells move from the brain to the gut, to create the ‘enteric’ nervous system. This specialised branch of the nervous system works independently of the brain and is responsible for ‘peristalsis’ of the gut – the wave-like contraction of the gut that allows the contents to be propelled through the bowel.

Failure of these migrating cells to populate the entire length of the gut causes Hirschprung’s disease, a common disorder that affects approximately one in every 4500 children. The affected portion does not expand and the contents of the bowel accumulate in the upper colon, causing swelling, abdominal pain and severe constipation, which could have serious consequences if left untreated.

The team, led by Professor Vassilis Pachnis at the MRC National Institute for Medical Research, found that some of the key molecules* that are individually important for development of the enteric nervous system, work together to act as master regulators to allow normal colonisation of the gut by the enteric neurons.

The researchers also found that the balance of both these key molecules is critical to correct development and function of the gut.

Professor Pachnis said: “The work we’ve been doing is very basic and doesn’t offer an immediate alternative to surgery, which is used successfully at the moment to alleviate the immediate effects of obstruction. However, frequently, and despite successful surgery Hirschsprung’s patients continue to have associated problems throughout life.

“By modifying defective versions of these molecules, so the enteric neurons can establish themselves appropriately along the full length of the gut, it might be possible to prevent this common problem and remove the need for surgery in future. We’re already looking at how stem-cell technology could help us in this approach.”