The Multifaceted Role of the Intestinal Microbiota in Colon Cancer

Irrazábal, Thergiory; Belcheva, A.; Girardin, Stephen E.; Martín, Alberto; Philpott, Dana J.

doi:10.1016/j.molcel.2014.03.039

Cited by 270 publications

(203 citation statements)

References 123 publications

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“…Many Asian countries including China have experienced a 2-to 4-fold increase in colorectal cancer incidence during the past decade (1). Abnormality in the composition of the gut microbiota has been implicated as a potentially important etiologic factor in the initiation and progression of colorectal cancer (2). With the widespread application of metagenome sequencing and pyrosequencing in the investigation of intestinal microbiota, an increasing number of bacteria have been identified to be positively associated with the incidence of colorectal cancer (3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

Liang

Chiu

Chen

et al. 2017

Clinical Cancer Research

239

242

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Purpose: Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.Experimental Design: Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.Results: Candidates identified by metagenome sequencing, including Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), and one undefined species (labeled as m7), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (r ¼ 0.801-0.934, all P < 0.0001). Fn was significantly more abundant in colorectal cancer than controls (P < 0.0001), with AUROC of 0.868 (P < 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity, Fn discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (Fn þ Ch þ m7-Bc) showed an improved diagnostic ability compared with Fn alone (AUROC ¼ 0.886, P < 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of Fn alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.Conclusions: Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

Liang

Chiu

Chen

et al. 2017

Clinical Cancer Research

239

242

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“…2,3 In addition to these factors, gut microbiota dysbiosis has been reported in CRC patients. [4][5][6][7][8][9] Recent pyrosequencing analysis of CRC-associated bacterial microbiota has revealed dysbiosis with, in particular, overrepresentation of Fusobacterium and Bacteroides. [10][11][12][13][14] In addition, our group and others have shown that colonic adenomas, carcinomas, and the mucosa of CRC patients are abnormally colonized by Escherichia coli belonging to the B2 phylogroup, with a high prevalence of E. coli producing a genotoxin, termed colibactin, encoded by the pks genomic island.…”

mentioning

confidence: 99%

Intracellular colon cancer-associated Escherichia coli promote protumoral activities of human macrophages by inducing sustained COX-2 expression

Raisch

Rolhion

Dubois

et al. 2015

Laboratory Investigation

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Intestinal dysbiosis has been reported in patients with colorectal cancer, and there is a high prevalence of Escherichia coli belonging to B2 phylogroup and producing a genotoxin, termed colibactin. Macrophages are one of the predominant tumor-infiltrating immune cells supporting key processes in tumor progression by producing protumoral factors such as cyclooxygenase-2 (COX-2). Here, we investigated whether B2 E. coli colonizing colon tumors could influence protumoral activities of macrophages. In contrast to commensal or nonpathogenic E. coli strains that were efficiently and rapidly degraded by macrophages at 24 h after infection, colon cancer-associated E. coli were able to resist killing by human THP-1 macrophages, to replicate intracellularly, and to persist inside host cells until at least 72 h after infection. Significant increases in COX-2 expression were observed in macrophages infected with colon cancer E. coli compared with macrophages infected with commensal and nonpathogenic E. coli strains or uninfected cells at 72 h after infection. Induction of COX-2 expression required live bacteria and was not due to colibactin production, as similar COX-2 levels were observed in macrophages infected with the wild-type colon cancer-associated E. coli 11G5 strain or a clbQ mutant unable to produce colibactin. Treatment of macrophages with ofloxacin, an antibiotic with intracellular tropism, efficiently decreased the number of intracellular bacteria and suppressed bacteria-induced COX-2 expression. This study provides new insights into the understanding of how tumor-infiltrating bacteria could influence cancer progression through their interaction with immune cells. Manipulation of microbes associated with tumors could have a deep influence on the secretion of protumoral molecules by infiltrating macrophages. Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide, making it the fourth most common cause of cancer deaths throughout the world. 1 CRC is a heterogeneous disease, including at least three major forms: hereditary, sporadic, and colitis-associated CRC. A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle deeply affect CRC onset. 2,3 In addition to these factors, gut microbiota dysbiosis has been reported in CRC patients. [4][5][6][7][8][9] Recent pyrosequencing analysis of CRC-associated bacterial microbiota has revealed dysbiosis with, in particular, overrepresentation of Fusobacterium and Bacteroides. [10][11][12][13][14] In addition, our group and others have shown that colonic adenomas, carcinomas, and the mucosa of CRC patients are abnormally colonized by Escherichia coli belonging to the B2 phylogroup, with a high prevalence of E. coli producing a genotoxin, termed colibactin, encoded by the pks genomic island. [15][16][17][18][19][20] It has been recently demonstrated that cells that survive infection with colibactin-producing E. coli display hallmarks of cellular senescence accompanied with productio...

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“…However, these studies neither answer the cause or consequence question of dysbiosis in CRC, nor do they provide mechanistic insights by which the intestinal microbiota influences the development of CRC [4]. Also, several studies found that gut microbiota have a strong impact on regulation and development of immune system which could in turn initiate regulation of immune cells within the lamina propria of the intestine as well as mediating the inflammatory process [5].…”

Section: Introductionmentioning

confidence: 99%

Interplay between Gut Microbiota and T Lymphocytes in Colorectal Cancer

Hetta¹,

Elkady²,

Mekky³

et al. 2017

Colorec Cancer

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Colorectal cancer is one of the third leading causes of cancer mortality worldwide. There is increasing evidences about the involvement of gut microbiota in colorectal carcinogenesis. Several recent studies have shed light on the cross talk between gut microbiota and mucosal T cell subsets, specifically intraepithelial lymphocytes and lamina propria CD4 + T cells including T-helper cells and Tregulatory (Treg) cells which may be responsible for development of colorectal cancer through creating imbalance between proinflammatory and antiinflammatory immune cells and their cytokines. In this review, we will focus on the influence gut microbiota on the development of mucosal T cells and their role in promoting colorectal cancer.

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The Multifaceted Role of the Intestinal Microbiota in Colon Cancer

Cited by 270 publications

References 123 publications

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

Intracellular colon cancer-associated Escherichia coli promote protumoral activities of human macrophages by inducing sustained COX-2 expression

Interplay between Gut Microbiota and T Lymphocytes in Colorectal Cancer

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