Microbiome distinctions between the CRC carcinogenic pathways (original) (raw)

Towards the human colorectal cancer microbiome

2011

Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.

Linking Gut Microbiota to Colorectal Cancer

Journal of Cancer, 2017

Pre-clinical and clinical data produce mounting evidence that the microbiota is strongly associated with colorectal carcinogenesis. Dysbiosis may change the course of carcinogenesis as microbial actions seem to impact genetic and epigenetic alterations leading to dysplasia, clonal expansion and malignant transformation. Initiation and promotion of colorectal cancer may result from direct bacterial actions, bacterial metabolites and inflammatory pathways. Newer aspects of microbiota and colorectal cancer include quorum sensing, biofilm formation, sidedness and effects/countereffects of microbiota and probiotics on chemotherapy. In the future, targeting the microbiota will probably be a powerful weapon in the battle against CRC as gut microbiology, genomics and metabolomics promise to uncover important linkages between microbiota and intestinal health.

Role of colonic microbiota in colorectal carcinogenesis: A systematic review

Revista Española de Enfermedades Digestivas, 2015

Background and aim: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile). Recent findings lead to hypothesize that this unbalance may create a subclinical proinflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. Methods: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. Results: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales), while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema). Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. Conclusion: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.

Microbiome and Colorectal Carcinoma

The cancer journal, 2014

The mammalian microbiota plays a crucial role in the pathogenesis of many diseases. Thanks to recent advances in metagenomics, proteomics, and metabolomics, microbiome composition and metabolic activity can now be studied in detail. Results obtained by such fascinating and provocative studies would be meaningless without considering the perspective of the whole organism. Our work using gnotobiology as the major tool to unravel the mechanisms of host-microbe interaction has demonstrated the crucial role of microbiota in the initiation and progression of inflammation-associated colorectal neoplasia. Carcinogenesis in the gut is driven by the presence of potentially harmful microbes or by lack of protective ones, by the production of carcinogens generated by microbes, and by the induction of inflammation and modulation of the immune system. Here, we review these mechanisms with special emphasis on those where gnotobiology has yielded important insights.

Evidence for Contributions of Gut Microbiota to Colorectal Carcinogenesis

Current Nutrition Reports, 2012

The contributions of the commensal gut microbiota to the maintenance of human health have long been contemplated. Whereas earlier studies were limited by an inability to analyze microbiota in sufficient depth, recent advances in the application of high throughput sequencing have allowed for an in-depth microbiota analysis in large numbers of individuals. Multiple lines of evidence have been generated that are supportive of an active role of gut microbiota in colorectal carcinogenesis. Although no single microbe has yet been shown to be causally linked to CRC, contributions of the gut microbiota to colorectal carcinogenesis are evident. Further advances in the field, which should include prospective studies in high-risk cohorts, should generate the data needed to start translating findings into microbiota-based screening and prevention regimen that can help to reduce the burden of CRC.

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

2020

Background Long-term dysbiosis of the gut microbiome has a signi cant impact on the development, progression and the aggressiveness of colorectal cancer (CRC) and may explain part of the observed heterogeneity of the disease from phenotypic, prognostic and response to treatment perspectives. Although the shifts in gut microbiome in the normaladenoma-carcinoma sequence have been described, the landscape of microbiome within CRC and its associations with clinical variables remain under-explored. Results We performed 16S rRNA gene sequencing of paired tumour tissue, adjacent visually-normal mucosa and stool swabs of N=186 patients with stage 0-IV CRC to describe the tumour microbiome and its association with clinical variable and to derive tumour microbial subtypes. We identi ed new genera never previously associated with CRC tumour mucosa (Flavonifractor, Haemophilus, Howardella, Pseudomonas, Sutterella, Treponema 2) or CRC (Actinobacillus, Aggregatibacter, Bergeyella, Phocaeiola, De uviitaleaceae UCG-011, Massilia, Tyzzerella 4). The bacteria residing on tumour-mucosa were dominated by genera belonging to (potential) oral pathogens. Based on tumour microbial pro les, we strati ed CRC patients into three subtypes. The subtypes were signi cantly associated with prognostic factors such as tumor grade, primary tumour sidedness and TNM staging, with one subtype enriched in tumours with poor prognosis. Further, we inspected the associations of microbiome with clinical variables in a subtype-agnostic setting. The primary tumour-associated clinical variables predominantly correlated with tumour mucosal microbiome, while the presence of local and distant metastases was mostly associated with the stool microbiome. Conclusions Understanding the interactions of the bacteria residing on tumour mucosa within different CRC tumour microbiome subtypes will help to better understand the underlying biological background of the heterogeneity of this disease. Indeed, the tumour microbiome is a possible source of additional integrative markers of CRC patients' survival and prognosis. We found that CRC microbiome is strongly correlated with clinical variables, but these associations are dependent on the microbial environment (tumour mucosa, normal mucosa, stool). Our study thus identi es limitations of the usage of microbiome composition as marker of CRC progression, suggesting the need of combining several sampling sites (e.g. stool and tumour swabs).

Gut mucosal microbiome across stages of colorectal carcinogenesis

Nature communications, 2015

Gut microbial dysbiosis contributes to the development of colorectal cancer (CRC). Here we catalogue the microbial communities in human gut mucosae at different stages of colorectal tumorigenesis. We analyse the gut mucosal microbiome of 47 paired samples of adenoma and adenoma-adjacent mucosae, 52 paired samples of carcinoma and carcinoma-adjacent mucosae and 61 healthy controls. Probabilistic partitioning of relative abundance profiles reveals that a metacommunity predominated by members of the oral microbiome is primarily associated with CRC. Analysis of paired samples shows differences in community configurations between lesions and the adjacent mucosae. Correlations of bacterial taxa indicate early signs of dysbiosis in adenoma, and co-exclusive relationships are subsequently more common in cancer. We validate these alterations in CRC-associated microbiome by comparison with two previously published data sets. Our results suggest that a taxonomically defined microbial consortiu...

Shifts of Faecal Microbiota During Sporadic Colorectal Carcinogenesis

Scientific reports, 2018

Gut microbiota has been implicated in the etiopathogenesis of colorectal cancer. The development of colorectal cancer is a multistep process by which healthy epithelium slowly develops into preneoplastic lesions, which in turn progress into malignant carcinomas over time. In particular, sporadic colorectal cancers can arise from adenomas (about 85% of cases) or serrated polyps through the "adenoma-carcinoma" or the "serrated polyp-carcinoma" sequences, respectively. In this study, we performed 16 S rRNA gene sequencing of bacterial DNA extracted from faecal samples to compare the microbiota of healthy subjects and patients with different preneoplastic and neoplastic lesions. We identified putative microbial biomarkers associated with stage-specific progression of colorectal cancer. In particular, bacteria belonging to the Firmicutes and Actinobacteria phyla, as well as members of the Lachnospiraceae family, proved to be specific of the faecal microbiota of patien...

The oral microbiota in colorectal cancer is distinctive and predictive

Background and aims: Microbiota alterations are linked with colorectal cancer (CRC) and notably higher abundance of putative oral bacteria on colonic tumours. However, it is not known if colonic mucosa-associated taxa are indeed orally derived, if such cases are a distinct subset of patients or if the oral microbiome is generally suitable for screening for CRC. Methods: We profiled the microbiota in oral swabs, colonic mucosae and stool from individuals with CRC (99 subjects), colorectal polyps (32) or controls (103). Results: Several oral taxa were differentiallyabundant in CRC compared with controls, for example, Streptococcus and Prevotellas pp. A classification model of oral swab microbiota distinguished individuals with CRC or polyps from controls (sensitivity: 53% (CRC)/67% (polyps); specificity: 96%). Combining the data from faecal microbiota and oral swab microbiota increased the sensitivity of this model to 76% (CRC)/88% (polyps). We detected similar bacterial networks in colonic microbiota and oral microbiota datasets comprising putative oral biofilm forming bacteria. While these taxa were more abundant in CRC, core networks between pathogenic, CRC-associated oral bacteria such as Peptostreptococcus, Parvimonas and Fusobacterium were also detected in healthy controls. High abundance of Lachnospiraceae was negatively associated with the colonisation of colonic tissue with oral-like bacterial networks suggesting a protective role for certain microbiota types against CRC, possibly by conferring colonisation resistance to CRC-associated oral taxa and possibly mediated through habitual diet. Conclusion: The heterogeneity of CRC may relate to microbiota types that either predispose or provide resistance to the disease, and profiling the oral microbiome may offer an alternative screen for detecting CRC.