Preclinical and clinical evidence of the association of colibactin-producing Escherichia coli with anxiety and depression in colon cancer

doi:10.3748/wjg.v30.i21.2817

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 30, Issue 21

This Article

Peer-Review Report of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Supplementary Materials of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (6658)

All Articles published online

The chart showing PDF series, HTML series, Figures (1-5) series, Tables (1-1) series.

Item

Count

PDF

177

HTML

3254

Figures (1-5)

441

Tables (1-1)

459

Sum=4331

Featured Article

The chart showing Browse series, Download series.

Item

Count

Browse

293

Download

1048

Sum=1341

Publishing Process of This Article

Item

Count

Browse

110

Download

659

Sum=769

Jun 7, 2024 (publication date) through Feb 26, 2026

Times Cited of This Article

Times Cited (9)

Journal Information of This Article

Publication Name

World Journal of Gastroenterology

ISSN

1007-9327

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

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.

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

Abstract

BACKGROUND

The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent. The gut microbiota contributes to colorectal carcinogenesis (CRC), as demonstrated with colibactin-producing Escherichia coli (CoPEC).

AIM

To evaluate the association between CoPEC prevalence and anxiety- and depressive-like behaviors with both preclinical and clinical approaches.

METHODS

Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview. Results were compared according to the CoPEC colonization. In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain. Their behavior was assessed using the Elevated Plus Maze test, the Forced Swimming Test and the Behavior recognition system PhenoTyper^®.

RESULTS

In a limited cohort, all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis, whereas only one patient (17%) without CoPEC did. This result was confirmed in C57BL6/J wild-type mice and in a CRC susceptibility mouse model (adenomatous polyposis coli^{multiple intestinal neoplasia/+}). Mice exhibited a significant increase in anxiety- and depressive-like behaviors after chronic infection with a CoPEC strain.

CONCLUSION

This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.

Keywords: Colorectal cancer; Colibactin; Escherichia coli; Colibactin-producing Escherichia coli; Inflammation; Anxiety; Depression; Behavior

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.