Preclinical and clinical evidence of the association of colibactinproducing Escherichia coli with anxiety and depression in colon cancer

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 wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple 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.

Microbial markers in colorectal cancer detection and/or prognosis

Colorectal cancer(CRC) is the second leading cause of cancer worldwide. CRC is still associated with a poor prognosis among patients with advanced disease. On the contrary, due to its slow progression from detectable precancerous lesions, the prognosis for patients with early stages of CRC is encouraging. While most robust methods are invasive and costly, actual patient-friendly screening methods for CRC suffer of lack of sensitivity and specificity. Therefore, the development of sensitive, non-invasive and cost-effective methods for CRC detection and prognosis are necessary for increasing the chances of a cure. Beyond its beneficial functions for the host, increasing evidence suggests that the intestinal microbiota is a key factor associated with carcinogenesis. Many clinical studies have reported a disruption in the gut microbiota balance and an alteration in the faecal metabolome of CRC patients, suggesting the potential use of a microbialbased test as a non-invasive diagnostic and/or prognostic tool for CRC screening. This review aims to discuss the microbial signatures associated with CRC known to date, including dysbiosis and faecal metabolome alterations, andthe potential use of microbial variation markers for noninvasive early diagnosis and/or prognostic assessment of CRC and advanced adenomas. We will finally discuss the possible use of these markers as predicators for treatment response and their limitations.