"The Enteric Nervous System in gut and brain disorders"
Assessment of ENS lipidomic remodeling in IBD and consequent therapeutic uses
Graphical Abstract
Project display
BD pathogenesis involves aberrant immune responses associated with changes in microbiota composition as well as alterations of the intestinal epithelial barrier (Xavier and Podolsky, 2007). IEB increased permeability has been described as an early feature of IBD, has been observed in non-inflamed segments of the gut and precedes the onset and relapses of CD (Arnott et al., 2000; Irvine and Marshall, 2000). Our previous research contributed to identify the ENS as a key contributor to IEB dysfunctions in IBD. Indeed, we showed that neurons as well as enteric glial cells (EGC) are altered in CD patients (Pochard et al., 2018; Prigent et al., 2020; Prigent et al., 2019). In particular, we showed that EGC produce lower concentrations of various n-6 polyunsaturated fatty acid (PUFA) derivatives (11PGF2, PGE2 or the PGI2)(Coquenlorge et al., 2016; Pochard et al., 2016) leading to a loss of control of IEB permeability and healing through AMPK dependent pathways (Coquenlorge et al., 2016; Pochard et al., 2016). Furthermore, we showed that in vivo supplementation with PGI2 can prevent colitis and improve IEB permeability (Pochard et al, in revision). Interestingly, it has recently been described that certain proteo- and cyanobacteria can modulate the metabolism of n-6 PUFA in the host by (i) by secreting enzymes involved in the metabolism of PUFA (eg lipoxygenases) or (ii) modulating the host lipid metabolism of the IEB (Morello et al., 2019). Therefore, our aim is to 1) to assess whether CD ENS remodelling affecting the production of n-6 PUFA derivatives is involved in IEB dysfunctions and colitis and 2) to develop new therapeutic strategies to strengthen the IEB.
Researchers / Clinicians
Malvyne Rolli-Derkinderen
+33 2 40 41 29 74
Malvyne.Derkinderen@univ-nantes.fr
Arnaud Bourreille
+33 2 40 08 31 52
arnaud.bourreille@chu-nantes.fr
Mathurin Flamant
+33 2 40 08 31 52
mathurin.flamant@chu-nantes.fr
Guillaume Meurette
guillaume.meurette@univ-nantes.fr
ITA
Tony Durand
+33 2 40 41 29 50
tony.durand@univ-nantes.fr
Students
Marine Mantel
+33 2 40 41 11 07
marine.mantel@etu.univ-nantes.fr
Farouk Drissi
+33 2 40 41 11 07
farouk.drissi@univ-nantes.fr
Collaborators
B. Viollet, Cochin, Fr
N. Cenac, Inserm 1220 Fr
M. Bodinier, Inrae BIA, Fr
J. Gwenal, Inrae STLO, Fr
M. Metzger, Ger
Funding
Publications
Mantel M, Durand T, Bessard A, Pernet S, Beaudeau J, Guimaraes-Laguna J, Maillard MB, Guédon E, Neunlist M, Le Loir Y, Jan G, Rolli-Derkinderen M. Am J Physiol Gastrointest Liver Physiol. 2024 Feb 1;326(2):G163-G175. doi: 10.1152/ajpgi.00198.2023. Epub 2023 Nov 21.
Enteric glia at center stage of inflammatory bowel disease.
Le Berre C, Naveilhan P, Rolli-Derkinderen M. Neurosci Lett. 2023 Jul 13;809:137315. doi: 10.1016/j.neulet.2023.137315. Epub 2023 May 29.
Crosstalk between omega-6 oxylipins and the enteric nervous system: Implications for gut disorders?
Mantel M, Derkinderen P, Bach-Ngohou K, Neunlist M, Rolli-Derkinderen M. Front Med (Lausanne)2023 Mar 28:10:1083351. doi: 10.3389/fmed.2023.1083351. eCollection 2023.
Maternal prebiotic supplementation impacts colitis development in offspring mice.
Lê A, Selle A, Aubert P, Durand T, Brosseau C, Bordron P, Delage E, Chaffron S, Petitfils C, Cenac N, Neunlist M, Bodinier M, Rolli-Derkinderen M. Front Nutr. 2023 Jan 5;9:988529. doi: 10.3389/fnut.2022.988529. eCollection 2022. PMID: 36687706 Free PMC article.
Dairy starters and fermented dairy products modulate gut mucosal immunity.
Illikoud N, Mantel M, Rolli-Derkinderen M, Gagnaire V, Jan G. Immunol Lett. 2022 Dec;251-252:91-102. doi: 10.1016/j.imlet.2022.11.002. Epub 2022 Nov 2. PMID: 36334759 Free article. Review.
Lê A, Mantel M, Marchix J, Bodinier M, Jan G, Rolli-Derkinderen M. Am J Physiol Gastrointest Liver Physiol. 2022 Dec 1;323(6):G523-G553. doi: 10.1152/ajpgi.00002.2022. Epub 2022 Sep 27. PMID: 36165557 Review.
Olivier S, Diounou H, Pochard C, Frechin L, Durieu E, Foretz M, Neunlist M, Rolli-Derkinderen M, Viollet B. Cells. 2022 Feb 9;11(4):590. doi: 10.3390/cells11040590. PMID: 35203241 Free PMC article.
[AMPK activity is a gatekeeper of the intestinal epithelial barrier].
Olivier S, Diounou H, Foretz M, Guilmeau S, Daniel N, Marette A, Rolli-Derkinderen M, Viollet B. Med Sci (Paris). 2022 Feb;38(2):136-138. doi: 10.1051/medsci/2021251. Epub 2022 Feb 18. PMID: 35179465 Free article. French. No abstract available.
Mild Chronic Colitis Triggers Parkinsonism in LRRK2 Mutant Mice through Activating TNF-α Pathway.
Derkinderen P, de Guilhem de Lataillade A, Neunlist M, Rolli-Derkinderen M. Mov Disord. 2022 Mar;37(3):664-665. doi: 10.1002/mds.28948. Epub 2022 Jan 31. PMID: 35100471 Free article. No abstract available.