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Microbial markers in colorectal cancer detection and/or prognosis

World Journal of Gastroenterology 2018年第22期24卷 2327-2347页

作者： Romain Villéger Amélie Lopès julie veziant Johan Gagnière Nicolas Barnich Elisabeth Billard Delphine Boucher Mathilde Bonnet Université Clermont Auvergne Research Biologics Sanofi R&D Chirurgie digestive Centre Hospitalier Universitaire Université Clermont Auvergne Institut Universitaire de Technologie de Clermont-Ferrand

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.

关键词： Colorectal cancer microbiota F.nucleatum Colibactin-producing E.coli prognostic markers diagnostic markers dysbiosis

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Association of colorectal cancer with pathogenic Escherichia coli: Focus on mechanisms using optical imaging

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World Journal of Clinical Oncology 2016年第3期7卷 293-301页

作者： julie veziant Johan Gagnière Elodie Jouberton Virginie Bonnin Pierre Sauvanet Denis Pezet Nicolas Barnich Elisabeth Miot-Noirault Mathilde Bonnet UMR1071 Inserm/Université d’Auvergne and INRA USC2018 Clermont Université Service de Chirurgie Digestive Centre Hospitalier Universitaire UMR990 Inserm/Université d’Auvergne Clermont Université Service de Médecine Nucléaire Centre Jean Perrin

AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli(E. coli) using optical imaging.METHODS: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume(mm^3). Inflammation measuring myeloperoxidase(MPO) activity and reactive oxygen species production was monitored by a bioluminescent(BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay(ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells(HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitisCEABAC10 DSS models, which mimicked Crohn's disease. RESULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume(P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group(P < 0.005). ELISA confirmed that MPO levels were significantly higher(1556 ± 313.6 vs 234.6 ± 121.6 ng/m L P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model(CEABAC10/DSS).CONCLUSION: Using BLI and fluorescence optical imaging, we provided tools to better understand hostpathogen interac

关键词： Colorectal carcinoma Escherichia coli Colibactin Myeloperoxidase In vivo optical imaging

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Gut microbiota imbalance and colorectal cancer

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World Journal of Gastroenterology 2016年第2期22卷 501-518页

作者： Johan Gagnière Jennifer Raisch julie veziant Nicolas Barnich Richard Bonnet Emmanuel Buc Marie-Agnès Bringer Denis Pezet Mathilde Bonnet Clermont Université UMR 1071 Inserm/Universitéd’Auvergne63000 Clermont-FerrandFrance INRA USC-201863000 Clermont-FerrandFrance Chirurgie Digestive Centre Hospitalier Universitaire63000 Clermont-FerrandFrance Bactériologie Centre Hospitalier Universitaire63000 Clermont-FerrandFrance Laboratoire d’Immunologie Institut Armand FrappierLaval H7V 1B7Canada INRA UMR 1324 CNRS UMR 6265Universitéde BourgogneCentre des Sciences du Goût et de l’AlimentationEye Nutrition and Signalling Research Group21000 DijonFrance

The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes(e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies.

关键词： Colorectal cancer Gut microbiota Dysbiosis Cyclomodulin Oxidative stress

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