Neurodevelopmental pathologies,

neurodegenerative et neurotraumatic 

Axis 2

ENS and neurodegenerative pathologies

My research project in 1 image ...

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During development, the postnatal period represents a pivotal stage in the maturation of the digestive tract: consolidation of the intestinal epithelial barrier, establishment of motor activity, installation of the microbiota and maturation of the enteric nervous system (ENS). Our projects focus on studying the mechanisms involved in the maturation of ENS, and on dysfunctions associated with digestive neurodevelopmental pathologies, but also cerebral diseases such as autism.


  1. Mechanisms involved in the maturation of ENS

We study the role of semaphorins, several members of which have mutations associated with digestive (Hirschsprung) and cerebral (autism) developmental diseases. The role of semaphorins in gangliogenesis and the establishment of neuronal connectivity is studied on in vitro and in vivo models.


In vitro maturation of enteric neurons: formation of ganglia and neuronal connectivity



   2. ENS and Autism Spectrum Disorder (ASD)

There is a strong association between TSA and gastrointestinal disorders (gastrointestinal disorders, increased intestinal permeability, altered composition of the intestinal microbiota), suggesting a close relationship between behavioral and digestive disorders. We study the role of the microbiota from ASD patients on their ability to induce gastrointestinal disorders, ENS remodeling and behavioral alterations in animal models.





   3. ENS and post-operative digestive disorders in Hirschsprung's Disease

Patients with Hirschsprung's disease (lack of colonization of the gastrointestinal tract by ENS during the embryonic period, of genetic or environmental origin) present a significant risk of postoperative complications. These complications often last beyond the postnatal period. Nevertheless, the causes of these disorders, and in particular the ENS attacks, remain to be identified. On a cohort of Hirschsprung patients, we study the characterization of ENS lesions in order to identify 1) factors predicting post-operative gastrointestinal complications and 2) therapeutic targets to improve their management.



   4. Targeting digestive functions and ENS during the post-natal period: role of the gut microbiota.


The intestinal microbiota, and in particular its metabolites, are key players contributing to the postnatal development of digestive functions and their cellular constituents. In this context, our work aims to characterize the effects of bacterial strains or metabolites of interest (short chain fatty acids, ...) on the development of digestive functions and ENS during the postnatal period. These results are then used as a basis for the development of therapeutic approaches in patients (eg, Neotrans study).


Researchers / Clinicians

Hélène Boudin


+33 2 40 41 29 30


Maxime Mahé


+33 2 40 41 28 85

Sophie Talon


+33 2 40 41 29 30

Michel Neunlist


+33 2 40 41 28 44

ITA / Students

​Catherine Le Berre-Scoul


+33 2 40 41 29 50

Lisa Brossard.jpg

Lisa Brossard


+33 2 40 41 29 50

"Characterization of UNGE disorders in autism"

Jacques Gonzales


+33 2 40 41 29 74

Elise Loffet


+33 2 40 41 29 74

"Role of the enteric nervous system in the development and maturation of the intestinal mesenchyme in humans"

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Johanna Zoppi


+33 2 40 41 29 74

"Environmentally induced neurodevelopmental diseases: toward the characterization and modelling of the microbiome-gut-brain axis interactome"

Marine Mantel.jpg

"Involvement of the Enteric Nervous System in Autism Spectrum Disorders"

Marine Mantel


+33 2 40 41 29 30

Killian Hillion.jpg

"Development and characterization of human intestinal organoids for study host-bacteria interactions"

Killian Hillion


+33 2 40 41 28 85


Aubert P, Oleynikova E, Rizvi H, Ndjim M, Le Berre-Scoul C, Grohard PA, Chevalier J, Segain JP, Le Drean G, Neunlist M, Boudin H. Maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rat offspring. FASEB J. 2019 Jan;33(1):770-781. doi: 10.1096/fj.201800079R

Workman MJ, Mahe MM, Trisno S, Poling HM, Watson CL, Sundaram N, Chang CF, Schiesser J, Aubert P, Stanley EG, Elefanty AG, Miyaoka Y, Mandegar MA, Conklin BR, Neunlist M, Brugmann SA, Helmrath MA, Wells JM. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat Med. 2017 Jan;23(1):49-59.

Le Berre-Scoul C, Chevalier J, Oleynikova E, Cossais F, Talon S, Neunlist M, Boudin H. A novel enteric neuron-glia coculture system reveals the role of glia in neuronal development. J Physiol. 2017 Jan 15;595(2):583-598.

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