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      Towards the Human Colorectal Cancer Microbiome

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          Abstract

          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.

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          Commensal host-bacterial relationships in the gut.

          One potential outcome of the adaptive coevolution of humans and bacteria is the development of commensal relationships, where neither partner is harmed, or symbiotic relationships, where unique metabolic traits or other benefits are provided. Our gastrointestinal tract is colonized by a vast community of symbionts and commensals that have important effects on immune function, nutrient processing, and a broad range of other host activities. The current genomic revolution offers an unprecedented opportunity to identify the molecular foundations of these relationships so that we can understand how they contribute to our normal physiology and how they can be exploited to develop new therapeutic strategies.
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            Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry.

            Most cancer cells predominantly produce energy by glycolysis rather than oxidative phosphorylation via the tricarboxylic acid (TCA) cycle, even in the presence of an adequate oxygen supply (Warburg effect). However, little has been reported regarding the direct measurements of global metabolites in clinical tumor tissues. Here, we applied capillary electrophoresis time-of-flight mass spectrometry, which enables comprehensive and quantitative analysis of charged metabolites, to simultaneously measure their levels in tumor and grossly normal tissues obtained from 16 colon and 12 stomach cancer patients. Quantification of 94 metabolites in colon and 95 metabolites in stomach involved in glycolysis, the pentose phosphate pathway, the TCA and urea cycles, and amino acid and nucleotide metabolisms resulted in the identification of several cancer-specific metabolic traits. Extremely low glucose and high lactate and glycolytic intermediate concentrations were found in both colon and stomach tumor tissues, which indicated enhanced glycolysis and thus confirmed the Warburg effect. Significant accumulation of all amino acids except glutamine in the tumors implied autophagic degradation of proteins and active glutamine breakdown for energy production, i.e., glutaminolysis. In addition, significant organ-specific differences were found in the levels of TCA cycle intermediates, which reflected the dependency of each tissue on aerobic respiration according to oxygen availability. The results uncovered unexpectedly poor nutritional conditions in the actual tumor microenvironment and showed that capillary electrophoresis coupled to mass spectrometry-based metabolomics, which is capable of quantifying the levels of energy metabolites in tissues, could be a powerful tool for the development of novel anticancer agents that target cancer-specific metabolism.
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              Nucleic Acid Techniques in Bacterial Systematics

              A comprehensive laboratory manual written by specialists who have made significant contributions to developments of these techniques. Considers all of the major nucleic acid based techniques that are revolutionizing bacterial classification and identification. Also provides a comparison of methods for converting molecular data to phylogenetic trees.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                24 May 2011
                : 6
                : 5
                : e20447
                Affiliations
                [1 ]School of Biosciences, Cardiff University, Cardiff, United Kingdom
                [2 ]Centre for Molecular and Biomolecular Informatics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
                [3 ]Departments of Computer Science and Biology, San Diego State University, San Diego, California, United States of America
                [4 ]Centre for Genomic Research, School of Biological Sciences, University of Liverpool, Liverpool, United Kingdom
                [5 ]Department of Gastroenterology, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Radboud University Centre for Oncology (RUCO) of the Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
                [6 ]Department of Laboratory Medicine, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Radboud University Centre for Oncology (RUCO) of the Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
                University of Hyderabad, India
                Author notes

                Conceived and designed the experiments: JRM HT AB. Performed the experiments: JRM RR. Analyzed the data: JRM BED HT. Contributed reagents/materials/analysis tools: NH WHMP. Wrote the paper: JRM BED AB HT.

                Article
                PONE-D-11-03579
                10.1371/journal.pone.0020447
                3101260
                21647227
                c35a3b88-4274-41fe-9cac-d37ad8ee382b
                Marchesi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 18 February 2011
                : 22 April 2011
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Microbiology
                Bacterial Pathogens
                Escherichia Coli
                Gram Positive
                Gram Negative
                Salmonella
                Streptococci
                Emerging Infectious Diseases
                Host-Pathogen Interaction
                Microbial Ecology
                Microbial Growth and Development
                Microbial Metabolism
                Microbial Pathogens
                Pathogenesis
                Medicine
                Gastroenterology and Hepatology
                Colon
                Gastrointestinal Cancers
                Gastrointestinal Infections

                Uncategorized
                Uncategorized

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