Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2024; 30(21): 2817-2826
Published online Jun 7, 2024. doi: 10.3748/wjg.v30.i21.2817
Preclinical and clinical evidence of the association of colibactin-producing Escherichia coli with anxiety and depression in colon cancer
Fabien Rondepierre, Maëva Meynier, Johan Gagniere, Vincent Deneuvy, Anissa Deneuvy, Gwenaelle Roche, Elodie Baudu, Bruno Pereira, Richard Bonnet, Nicolas Barnich, Frédéric Antonio Carvalho, Denis Pezet, Mathilde Bonnet, Isabelle Jalenques
Fabien Rondepierre, Vincent Deneuvy, Isabelle Jalenques, Service de Psychiatrie de l’Adulte A et Psychologie Médicale, CHU Clermont-Ferrand, Clermont-Ferrand 63000, France
Maëva Meynier, Johan Gagniere, Gwenaelle Roche, Elodie Baudu, Richard Bonnet, Nicolas Barnich, Denis Pezet, Mathilde Bonnet, M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, Clermont-Ferrand 63001, France
Maëva Meynier, Elodie Baudu, Frédéric Antonio Carvalho, NeuroDol, UMR 1107, INSERM, University of Clermont Auvergne, Clermont-Ferrand 63001, France
Johan Gagniere, Anissa Deneuvy, Denis Pezet, Department of Digestive Surgery, CHU de Clermont-Ferrand, Clermont-Ferrand 63001, France
Bruno Pereira, Biostatistics Unit, Department of Clinical Research and Innovation, CHU Clermont-Ferrand, Clermont-Ferrand 63000, France
Richard Bonnet, Department of Bacteriology, CHU de Clermont-Ferrand, Clermont-Ferrand 63001, France
Isabelle Jalenques, Université Clermont Auvergne, INP, CNRS, Clermont Auvergne Institut Pascal, Clermont-Ferrand 63000, France
Co-first authors: Fabien Rondepierre and Maëva Meynier.
Co-corresponding authors: Mathilde Bonnet and Isabelle Jalenques.
Author contributions: Rondepierre F, Gagniere J, Bonnet M and Jalenques I designed and coordinated the study; Deneuvy A included the patients and Deneuvy V assessed the psychiatric evaluation; Rondepierre F, Pereira B and Jalenques I analyzed and interpreted the patient data; Meynier M, Roche G and Baudu E performed the experiments, acquired and analyzed the data; Meynier M, Carvalho FA and Bonnet M interpreted the animal data; Rondepierre F, Meynier M, Bonnet M and Jalenques I wrote the manuscript; Gagniere J, Bonnet R, Barnich N, Carvalho FA and Pezet D revised the manuscript; all authors approved the final version of the article. Rondepierre F and Meynier M contributed equally to this multidisciplinary work with both clinical part (Rondepierre F) and preclinical experiments (Meynier M); Jalenques I and Bonnet M designed, financed and coordinated altogether the study and then contributed equally to manage this work as co-corresponding authors.
Supported by the French patient’s association against cancer (ligue contre le cancer), No. 00001005238; the French government IDEX-ISITE initiative, No. 16-IDEX-0001-CAP 20-25; CPER (Nex-N-Mob); the Auvergne-Rhône-Alpes region (“Thématiques émergentes”), No. AV0004111; the Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, INSERM, University of Clermont Auvergne [UMR1071, UMR1107], INRAE [USC-1382].
Institutional review board statement: The clinical study “MicrobioPsy” received approval from an Institutional Review Board (Comité de Protection des Personnes Sud-Est VI, reference 2016-A01233-48/AU1290) and was registered at ClinicalTrials.gov (NCT 02970513).
Institutional animal care and use committee statement: All experiments were approved by the local ethical committee (No. CE-2912) and the French Ethical Animal Use Committee.
Conflict-of-interest statement: Pr. Bonnet has nothing to disclose.
Data sharing statement: The data that support the findings of this study are openly available in Mendeley Data, “MicrobioPsy dataset”, V1, https://data.mendeley.com/drafts/bvryp9v4fj; doi: 10.17632/bvryp9v4fj.1.
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: Mathilde Bonnet, PhD, Professor, M2iSH, UMR 1071, INSERM, University of Clermont Auvergne, INRAE USC 1382, 28 Place Henri Dunant, Clermont-Ferrand 63001, France. mathilde.bonnet@uca.fr
Received: February 29, 2024
Revised: April 17, 2024
Accepted: April 23, 2024
Published online: June 7, 2024
Processing time: 94 Days and 16.5 Hours
Core Tip

Core Tip: Colibactin-producing Escherichia coli (CoPEC) have been associated to colorectal carcinogenesis. We demonstrated that all colorectal cancer patients colonized by CoPEC had psychiatric disorders that occurred several years before colorectal cancer diagnosis. Mice chronically infected with a CoPEC strain exhibited a significant increase of anxiety-/depressive-like behaviors in several tests. These first results suggest that CoPEC infection could induce microbiota-gut-brain axis disturbances in addition to their pro-carcinogenic properties.