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

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