Basic Study
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World J Gastroenterol. Aug 7, 2022; 28(29): 3903-3916
Published online Aug 7, 2022. doi: 10.3748/wjg.v28.i29.3903
Involvement of toll-like receptor 5 in mouse model of colonic hypersensitivity induced by neonatal maternal separation
Geoffroy Mallaret, Amandine Lashermes, Mathieu Meleine, Ludivine Boudieu, Julie Barbier, Youssef Aissouni, Agathe Gelot, Benoit Chassaing, Andrew T Gewirtz, Denis Ardid, Frederic Antonio Carvalho
Geoffroy Mallaret, Mathieu Meleine, Ludivine Boudieu, Julie Barbier, Youssef Aissouni, Agathe Gelot, Denis Ardid, Department of Pharmacology, UMR 1107 NeuroDol, University of Clermont Auvergne, Clermont-Ferrand 63000, France
Amandine Lashermes, Department of Microbiology, Université Paris-Saclay, National Research Institute for Agriculture, Food and the Environment, AgroParisTech, Micalis Institute, Jouy-en-Josas 78350, France
Benoit Chassaing, Team “Mucosal Microbiota in Chronic Inflammatory Diseases”, INSERM U1016, CNRS UMR 8104, Université Paris Cité, Paris 75014, France
Andrew T Gewirtz, Center for Inflammation, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA30033, United States
Frederic Antonio Carvalho, Department of Pharmacology, INSERM 1107 NeuroDOL/University of Clermont Auvergne, Clermont-Ferrand 63000, France
Author contributions: Mallaret G and Lashermes A contributed equally to this article; Study concept and design done by Mallaret G, Lashermes A, Ardid D and Carvalho FA; Acquisition of data done by Mallaret G, Lashermes A, Barbier J, Aissouni Y, Chassaing B; Analysis and interpretation of data done by Mallaret G, Lashermes A, Chassaing B, Gewirtz AT, Ardid D and Carvalho FA; Drafting of the manuscript done by Mallaret G, Lashermes A Meleine M, Boudieu L and Carvalho FA; Obtained funding done by Ardid D and Carvalho FA; Study supervision done by Gewirtz AT, Ardid D and Carvalho FA.
Supported by the Region Auvergne-Rhône-Alpes and FEDER, No. Thématiques émergentes and Pack Ambition Recherche; the French Government IDEX-ISITE Initiative, No. 16-IDEX-0001-CAP 20-25; the Ministère de la Recherche et de la Technologie, INSERM and University of Clermont Auvergne, No. UMR1071.
Institutional animal care and use committee statement: All experiments were performed according to the ethical guidelines set out by the International Association for the Study of Pain, complied with the European Union regulation and were approved by ethics committees: the local committees C2EA-02 of Clermont-Ferrand (approvals CE110-12 and CE111-12).
Conflict-of-interest statement: All authors have nothing to disclose.
Data sharing statement: All sequencing raw data have been deposited in European Nucleotide Archive (ENA) under accession number PRJEB50651.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Frederic Antonio Carvalho, PhD, Academic Research, Department of Pharmacology, INSERM 1107 NeuroDOL/University of Clermont Auvergne, 28 Place Henri Dunant, Clermont-Ferrand 63000, France. frederic.carvalho@inserm.fr
Received: March 15, 2022
Peer-review started: March 15, 2022
First decision: May 29, 2022
Revised: June 9, 2022
Accepted: July 5, 2022
Article in press: July 5, 2022
Published online: August 7, 2022
Core Tip

Core Tip: Neonatal maternal separation (NMS) model mimic deleterious events in childhood, which can induce a wide range of chronic disorders during adulthood. Herein, around 50% of NMS mice exhibited increased intestinal permeability and colonic hypersensitivity (CHS) associated with intestinal dysbiosis. Only toll-like receptor 5 (TLR5) mRNA expression was increased in colonocytes of NMS mice with CHS and acute intrarectal instillation of flagellin transiently increased intracolonic pressure variations, reflecting transient CHS appearance. Together, those findings suggest a pathophysiological continuum between intestinal permeability, intestinal dysbiosis and CHS, with a previously undescribed role for TLR5 in CHS.