Tumour-associated and non-tumour-associated microbiota in colorectal cancer
Burkhardt Flemer,Denise B. Lynch,Jillian R.M. Brown,Ian B. Jeffery,Feargal J. Ryan,Marcus J. Claesson,M. G. O'riordain,Fergus Shanahan,Paul W. O'Toole +8 more
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TLDR
CRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles, which differ between distal and proximal cancers.Abstract:
Objective A signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study. Design We prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples (‘ON’ and ‘OFF’ the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR. Results The microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes. Conclusions CRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers.read more
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Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies
NaNa Keum,Edward Giovannucci +1 more
TL;DR: With increasing incidence of CRC at younger ages, there is an urgent need to better identify high-risk individuals younger than 50 years, the age when screening typically starts, and aspirin probably confers chemopreventive benefit against CRC.
Journal ArticleDOI
Gut microbiota in colorectal cancer: mechanisms of action and clinical applications
Sunny H. Wong,Jun Yu +1 more
TL;DR: The role of microorganisms in colorectal carcinogenesis, and the potential clinical translation of the gut microbiota as a biomarker for CRC diagnosis and prognosis are described, and as an approach for disease prevention and to improve therapy are described.
Journal ArticleDOI
Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer
Rona Yaeger,Walid K. Chatila,Marla Lipsyc,Jaclyn F. Hechtman,Andrea Cercek,Francisco Sanchez-Vega,Gowtham Jayakumaran,Sumit Middha,Ahmet Zehir,Mark T.A. Donoghue,Daoqi You,Agnes Viale,Nancy E. Kemeny,Neil H. Segal,Zsofia K. Stadler,Anna M. Varghese,Ritika Kundra,Jianjiong Gao,Aijazuddin Syed,David M. Hyman,Efsevia Vakiani,Neal Rosen,Barry S. Taylor,Marc Ladanyi,Michael F. Berger,David B. Solit,Jinru Shia,Leonard B. Saltz,Nikolaus Schultz +28 more
TL;DR: Right-sided primary site in microsatellite stable mCRC was associated with shorter survival, older age at diagnosis, increased mutations, and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43, and SMAD4 compared with left-sided primaries.
Journal ArticleDOI
The role of the microbiome in cancer development and therapy
TL;DR: The human body harbors enormous numbers of microbiota that influence cancer susceptibility, in part through their prodigious metabolic capacity and their profound influence on immune cell function as mentioned in this paper, which is supported by rigorously controlled preclinical studies using gnotobiotic mouse models colonized with one or more specific bacteria.
Journal ArticleDOI
The oral microbiota in colorectal cancer is distinctive and predictive.
Burkhardt Flemer,Ryan D. Warren,Maurice P. J. Barrett,Katryna Cisek,Anubhav Das,Ian B. Jeffery,Eimear Hurley,M. G. O'riordain,Fergus Shanahan,Paul W. O'Toole +9 more
TL;DR: 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.
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