"The Enteric Nervous System in gut and brain disorders"
Project display
During development, the postnatal period is a key developmental window for maturation of the digestive tract: strengthening of the intestinal epithelial barrier, establishment of gut motility, microbiota colonization and maturation of the enteric nervous system (ENS). Our research projects focus on (1) the mechanisms involved in ENS maturation, (2) ENS dysfunctions in neurodevelopmental disorders and (3) microbiota-derived approaches for gut disorders.
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Mechanisms involved in ENS maturation
We study the role of semaphorines (Sema), a class of developmental molecules for which several members harbour mutations associated with Hirschsprung disease and Autisme Spectrum Disorder (ASD).
Neurodeveloppmental diseases
The maturation of the enteric nervous system and neurodeveloppemental disorders
Maturation of the enteric neuronal network: neuronal cell bodies progressively aggregate in ganglia (red) and the axons group together as interganglionic fibers (green).
The maturation of the neuronal connectivity is revealed by the presence of synapses.
The role of sema3A and 5A on neuronal connectivity is studied on and models. We found that Sema3A reduces axonal extensions and the size of synapses.
2. Role of microbiota on gut, ENS and brain functions in Autism Spectrum Disorder (ASD)
There is a strong association between ASD symptoms and gut disorders (gastro-intestinal symptoms, modifications of the intestinal permeability, changes in gut microbiota composition), suggesting that common mechanisms could underlie behavioral and digestive symptoms. We study the ability of gut microbiota from humans to transfer in mice gastrointestinal disorders, ENS remodeling and behavioral symptoms. The transfer of human gut microbiota on ENS culture models provides insights into the involved mechanisms.
3. Targeting the gut and ENS during the postnatal period : role of the gut microbiota.
The gut microbiota is a key actor in gut development and function. We study the role of specific bacterial strain and microbiota-derived metabolites/compounds on the development of gut functions during the postnatal period. These data are then translated to the clinic to treat patients. (e.g. Neotrans Study).
Researchers / Clinicians
Hélène Boudin
+33 2 40 41 29 30
hélène.boudin@univ-nantes.fr
Sophie Talon
+33 2 40 41 90 80
sophie.talon@univ-nantes.fr
Michel Neunlist
+33 2 40 41 28 44
michel.neunlist@univ-nantes.fr
ITA
Catherine Leberre Scoul
+33 2 40 41 29 50
catherine.scoul@univ-nantes.fr
Students
Morgane Le Dréan
+33 2 40 41 11 07
morgane.ledrean@univ-nantes.fr
Baptiste Ganachaud
baptiste.ganachaud@univ-nantes.fr
Funding
Publications
Caillaud M, Le Dréan ME, De-Guilhem-de-Lataillade A, Le Berre-Scoul C, Montnach J, Nedellec S, Loussouarn G, Paillé V, Neunlist M, Boudin H. A functional network of highly pure enteric neurons in a dish. Front Neurosci. 2023 Jan 6;16:1062253. doi: 10.3389/fnins.2022.1062253. Link
Gonzales J, Marchix J, Aymeric L, Le Berre-Scoul C, Zoppi J, Bordron P, Burel M, Davidovic L, Richard JR, Gaman A, Lejuste F , Brouillet JZ,Le Vacon F, Samuel Chaffron S, Leboyer M, Boudin H*, and Neunlist M*. (2021) Fecal Supernatant from Adult with Autism Spectrum Disorder Alters Digestive Functions, Intestinal Epithelial Barrier, and Enteric Nervous System. Microorganisms 9, 1723. Link
Dariel A, Grynberg L, Auger M, Lefèvre C, Durand T, Aubert P, Le Berre-Scoul C, Venara A, Suply E, Leclair MD, de Vries P, Levard G, Parmentier B, Podevin G, Schmitt F, Couvrat V, Irtan S, Hervieux E, Villemagne T, Lardy H, Capito C, Muller C, Sarnacki S, Mosnier JF, Galmiche L, Derkinderen P, Boudin H, Brochard C, Neunlist M. (2020) Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung's disease. Sci Rep. 10(1):21725. Link
Gonzales J, Le Berre-Scoul C, Dariel A, Bréhéret P, Neunlist M, Boudin H. (2020) Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease. Sci Rep. Sep 15;10(1):15119. Link
Rincel M, Aubert P, Chevalier J, Grohard PA, Basso L, Monchaux de Oliveira C, Helbling JC, Lévy É, Chevalier G, Leboyer M, Eberl G, Layé S, Capuron L, Vergnolle N, Neunlist M, Boudin H, Lepage P, Darnaudéry M. (2019) Multi-hit early life adversity affects gut microbiota, brain and behavior in a sex-dependent manner. Brain Behav Immun. (80):179-192 Link
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. (2019) Maternal protein restriction induces gastrointestinal dysfunctions and enteric nervous system remodeling in rat offspring. FASEB J, 33(1):770-781 Link
Duchalais E, Guilluy C, Nedellec S, Touvron M, Bessard A, Touchefeu Y, Bossard C, Boudin H, Louarn G, Neunlist M, Van Landeghem L. (2017) Colorectal Cancer Cells Adhere to and Migrate Along the Neurons of the Enteric Nervous System. Cell Mol Gastroenterol Hepatol. 5(1):31-49. Link
Vanhaecke T, Aubert P, Grohard PA, Durand T, Hulin P, Paul-Gilloteaux P, Fournier A, Docagne F, Ligneul A, Fressange-Mazda C, Naveilhan P, Boudin H, Le Ruyet P, Neunlist M. (2017) L. fermentum CECT 5716 prevents stress-induced intestinal barrier dysfunction in newborn rats. Neurogastroenterol Motil, 29(8). Link
Ward M, Chen R, Taubes A, Huang HY, Boudin H, Minami S, Reichert M, Albrecht P, Gelfand J, Cruz Herranz A, Alavi M, Leslie S, Li Y, Seeley B, Miller B, Bigio E, Mackenzie I, Staropoli JF, Cotman SL, Huang EJ, Gan L, Green A. (2017) Clinicopathological features of NCL occur in humans with progranulin haploinsufficiency. , 9:385.
Le Berre-Scoul C, Chevalier J, Oleynikova E, Cossais F, Talon S, Neunlist M and Boudin H. (2017) A novel enteric neuron-glia coculture system reveals the role of glia in neuronal development. J Physiol, 595(2):583-598. Link
Noraz N, Jaaoini I, Charoy C, Watrin C, Chounlamountri N, Benon A, Malleval C, Boudin H, Honnorat J, Castellani V, Pellier-Monnin V. (2016) Syk kinases are required for spinal commissural axon repulsion at the midline via the ephrin/Eph pathway. Development 143(12):2183-93. Link
Cisternas P, Louveau A, Bueno S, Kalergis A, Boudin H*, Riedel C*. (2016) Gestational hypothyroxinemia affects glutamatergic synaptic protein distribution and neuronal plasticity through neuron-astrocyte interplay. Molecular Neurobiology 53(10):7158-7169 *co-corresponding author Link
Le Loupp AG, Bach-Ngohou K, Bourreille A, Boudin H, Rolli-Derkinderen M, Denis MG, Neunlist M, Masson D. (2015) Activation of the prostaglandin D2 metabolic pathway in Crohn's disease: involvement of the enteric nervous system. BMC Gastroenterol 15:112. Link
Louveau A, Nerrière-Daguin V, Vanhove B, Naveilhan P, Neunlist M, Nicot A and Boudin H. (2015) Targeting the CD80/CD86 costimulatory pathway with CTLA4-Ig directs microglia towards a repair phenotype and promotes axonal outgrowth . Glia, 63(12):2298-2312. Link
Dothel, G.*, Barbaro, M. R.*, Boudin, H., Vasina, V., Cremon, C., Gargano, L., Bellacosa, L., De Giorgio, R., Le Berre-Scoul, C., Aubert, P., Neunlist, M., De Ponti, F., Stanghellini, V., and Barbara, G. (2015) Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology 148, 1002-1011 e1004. *co-first author Link
Louveau A, Angibaud J, Haspot F, Opazo MC, Thinard R, Thepenier V, Baudouin SJ, Lescaudron L, Hulin P, Riedel CA, Boudin H. (2013) Impaired Spatial Memory in Mice Lacking CD3ζ Is Associated with Altered NMDA and AMPA Receptors Signaling Independent of T-Cell Deficiency. J Neurosci. 33(47):18672-85. Link
Angibaud J, Baudouin SJ, Louveau A, Nerrière-Daguin V, Bonnamain V, Csaba Z, Dournaud P, Naveilhan P, Noraz N, Pellier-Monnin V, and Boudin H. (2012) Ectopic expression of the immune adaptor protein CD3zeta in neural stem/progenitor cells disrupts cell-fate specification. J Mol Neurosci., 46(2):431-41. Link
Angibaud J*, Louveau A*, Baudouin SJ, Nerrière-Daguin V, Evain S, Bonnamain V, Hulin P, Csaba Z, Dournaud P, Thinard R, Naveilhan P, Noraz N, Pellier-Monnin V, and Boudin H (2011) The immune molecule CD3zeta and its downstream effectors ZAP-70/Syk mediate ephrin signaling in neurons to regulate early neuritogenesis. J. Neurochem. 119(4):708-22. Link
Hatterer E, Benon A, Chounlamountri N, Watrin C, Angibaud J, Jouanneau E, Boudin H, Honnorat J, Pellier-Monnin V, Noraz N (2011) Syk kinase is phosphorylated in specific areas of the developing nervous system. Neurosci Res. 70(2):172-82 Link
Choveau, F., N. Rodriguez, F. Abderemane Ali, A. J. Labro, T. Rose, S. Dahimene, H. Boudin, C. Le Henaff, D. Escande, D. J. Snyders, F. Charpentier, J. Merot, I. Baro, and G. Loussouarn (2011) KCNQ1 channels voltage dependency through a voltage-dependent binding of the S4-S5 linker to the pore domain. J Biol Chem. 286(1):707-16. Link
Reviews
Le Dréan ME, Marchix J, Neunlist M and Boudin H. (2021) Sept minutes pour comprendre le microbiote intestinal et son impact sur la santé. Hepato-gastro et oncologie digestive. 28 (5) : 555-560.
Boudin H, Gonzales J, Derkinderen P et Neunlist M. (2018) Le microbiote, l’intestin et le cerveau. Phytothérapie, 16(6): 315 - 319
Vanhaecke T., Gonzales J.A., Neunlist M., Boudin H. (2017) Coévolution de l’axe microbiote-intestin-cerveau: fonctions et conséquences physiopathologiques. La Lettre des neurosciences N°52 ISSN 2117-5635
Opazo MC, Ortega-Rocha EM, Coronado-Arrázola I, Bonifaz LC, Boudin H, Neunlist M, Bueno SM, Kalergis AM, Riedel CA. Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases. Front Microbiol. 2018 Mar 12;9:432. Link
Opazo MC, Haensgen H, Bohmwald K, Venegas LF, Boudin H, Elorza AA, Simon F, Fardella C, Bueno SM, Kalergis AM, Riedel CA. (2017) Imprinting of maternal thyroid hormones in the offspring. Int Rev Immunol. 36(4):240-255. Link
Book chapters
Marchix J, Aymeric L, Berthelot L, Boudin H et Neunlist M (2021) "Microbiote intestinal et régulation de l'axe intestin-cerveau" dans l'ouvrage MICROBIOTE INTESTINAL ET SANTE HUMAINE. Edition Elsevier Masson.
Boudin H and Louveau A (2015) Role of fundamental pathways of innate and adaptive immunity in neural differentiation: focus on Toll-like receptors, complement system and T-cell related signaling in Neural Surface Antigens: From Basic Biology Towards Biomedical Applications (Ed. Elsevier).