Digestive disorders: Therapeutic hope for premature children

August 13 2010

Premature children frequently present digestive disorders because of the immaturity of their digestive system, in particular the intestine. By studying the maturation of the enteric nervous system, a key player for intestinal function control, Michel Neunlist, and his team from the Inserm Unit 913 “Enteric nervous system neuropathies and digestive pathologies: the implication of enteric glial cells” of the Institut des Maladies de l’Appareil Digestif (Institute for Digestive System Pathologies) in Nantes, have brought a significant therapeutic target to light: the cholinergic neurones, which release acetylcholine. Their work is published in the August issue of the American journal of physiology.

Until the end of pregnancy, and in the months following birth, different organs in the child continue to mature and to develop. This is the case for the intestine where intestinal barrier motricity and activity (permeability, immunity, etc.) only become fully functional during the post-natal period; key moment of life. During the first months, prematurely-born children have an extremely immature intestine and present functional digestive disorders, such as slow intestinal transit and ballooning. Consequently, it is difficult to feed them and they are inclined to develop more serious pathologies. It is, therefore, indispensable to gain better understanding of the digestive system’s maturation mechanisms in order to try and cure disorders occurring in children.

The enteric nervous system: a key factor for intestinal function control

In this study, Michel Neunlist and his team concentrated their research on one of the most crucial intestinal function control factors: the enteric nervous system (ENS). The ENS, whose real implication and development throughout the post-natal period remain highly unknown, is made up of the mucosal plexus and the myenteric plexus. The latter controls more specifically intestinal motricity by releasing neuromediators (acetylcholine, nitrogen monoxide, etc.). This is referred to as the neuromuscular transmission phenomenon. These chemical substances, delivered by the neurones, induce coordinated intestinal muscle activity, which leads to alimentary bolus propagation.

During the first weeks of the young rat’s life, the change in neuron density of the Auerbach's plexus (green) and increase in proportion of cholinergic neurons (red) are correlated to the development of a motor activity in the colon.

During the first weeks of the young rat’s life, the change in neuron density of the Auerbach's plexus (green) and increase in proportion of cholinergic neurons (red) are correlated to the development of a motor activity in the colon.

Activité contractile => Contractile activity
Naissance => Birth
5 semaines => 5 weeks


The researchers carried out their studies on the colon of a newborn rat; highly-appropriate immature model for studying gastrointestinal malfunctioning in premature children. During the postnatal period, they observed modifications in the myenteric plexus neurone morphology and, more specifically, an increase in the percentage of cholinergic neurones that were synthesizing and releasing acetylcholine. The increase in the number of these neurones is linked to neuromuscular transmission development and to the establishment of in vivo and ex vivo colonic motor activity.

“Our study made it possible to identify the enteric nervous system’s cholinergic channels as a new key factor required for establishing post-natal intestinal motricity. This neuronal population appears as a new therapeutic target for caring for intestinal motricity disorders in newborn babies”, states Michel Neunlist.
This laboratory had recently demonstrated that butyrate, produced by the bacterial fermentation of alimentary fibres, accelerates the transit in adults by increasing the percentage of cholinergic neurones. These studies therefore establish the basis for using therapeutic approaches which use nutritional factors or their derivatives such as butyrate.


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Source
Postnatal development of myenteric neurochemical p 1 henotype and impact upon neuromuscular transmission in the rat colon
Am J Physiol Gastrointest Liver Physiol. 2010 Aug;299(2):G539-47. Epub 2010 Jun 3.

Contact chercheur
Michel Neunlist
Unité Inserm 913 "Neuropathies du système nerveux entérique et pathologies digestives : implication des cellules gliales entériques"
Tel : 02 40 08 75 15

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