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      Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential

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          Abstract

          The gastrointestinal tract harbors most of the microbiota associated with humans. In recent years, there has been a surge of interest in assessing the relationships between the gut microbiota and several gut alterations, including colorectal cancer. Changes in the gut microbiota in patients suffering colorectal cancer suggest a possible role of host-microbe interactions in the origin and development of this malignancy and, at the same time, open the door for novel ways of preventing, diagnosing, or treating this disease. In this review we survey current knowledge on the healthy microbiome of the gut and how it is altered in colorectal cancer and other related disease conditions. In describing past studies we will critically assess technical limitations of different approaches and point to existing challenges in microbiome research. We will have a special focus on host-microbiome interaction mechanisms that may be important to explain how dysbiosis can lead to chronic inflammation and drive processes that influence carcinogenesis and tumor progression in colon cancer. Finally, we will discuss the potential of recent developments of novel microbiota-based therapeutics and diagnostic tools for colorectal cancer.

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          Most cited references81

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          16S ribosomal DNA amplification for phylogenetic study.

          A set of oligonucleotide primers capable of initiating enzymatic amplification (polymerase chain reaction) on a phylogenetically and taxonomically wide range of bacteria is described along with methods for their use and examples. One pair of primers is capable of amplifying nearly full-length 16S ribosomal DNA (rDNA) from many bacterial genera; the additional primers are useful for various exceptional sequences. Methods for purification of amplified material, direct sequencing, cloning, sequencing, and transcription are outlined. An obligate intracellular parasite of bovine erythrocytes, Anaplasma marginale, is used as an example; its 16S rDNA was amplified, cloned, sequenced, and phylogenetically placed. Anaplasmas are related to the genera Rickettsia and Ehrlichia. In addition, 16S rDNAs from several species were readily amplified from material found in lyophilized ampoules from the American Type Culture Collection. By use of this method, the phylogenetic study of extremely fastidious or highly pathogenic bacterial species can be carried out without the need to culture them. In theory, any gene segment for which polymerase chain reaction primer design is possible can be derived from a readily obtainable lyophilized bacterial culture.
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            Enterotypes in the landscape of gut microbial community composition

            Population stratification is a useful approach towards a better understanding of complex biological problems in human health and well-being. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types, termed “enterotypes”, was met with both excitement and controversy. In view of accumulated data and re-analyses since the original work, we revisit the enterotype concept, discuss different methods of dividing up the landscape of possible microbiome configurations, and put these concepts into a functional, ecological and medical context. As enterotypes are of use in describing the gut microbial community landscape and may become relevant in clinical practice, we aim to reconcile differing views and encourage a balanced application of the concept.
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              Wild Mouse Gut Microbiota Promotes Host Fitness and Improves Disease Resistance

              Laboratory mice, while paramount for understanding basic biological phenomena, are limited in modeling complex diseases of humans and other free-living mammals. Because the microbiome is a major factor in mammalian physiology, we aimed to identify a naturally evolved reference microbiome to better recapitulate physiological phenomena relevant in the natural world outside the laboratory. Among 21 distinct mouse populations worldwide we identified a closely related wild relative to standard laboratory mouse strains. Its bacterial gut microbiome differed significantly from its laboratory mouse counterpart, and was transferred to and maintained in laboratory mice over several generations. Laboratory mice reconstituted with natural microbiota exhibited reduced inflammation and increased survival following influenza virus infection, and improved resistance against mutagen/inflammation-induced colorectal tumorigenesis. By demonstrating the host fitness-promoting traits of natural microbiota, our findings should enable the discovery of protective mechanisms relevant in the natural world and improve the modeling of complex diseases of free-living mammals. Characterization of a wild mice reference microbiome opens a window of opportunity to understand how the gut microbiota affects aspects of host physiology that are important in the natural world, outside the laboratory.
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                Author and article information

                Contributors
                Journal
                Mol Aspects Med
                Mol. Aspects Med
                Molecular Aspects of Medicine
                Elsevier Science
                0098-2997
                1872-9452
                1 October 2019
                October 2019
                : 69
                : 93-106
                Affiliations
                [a ]Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain
                [b ]Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain
                [c ]Oncology Service, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain
                [d ]ICREA, Pg. Lluís Companys 23, 08010, Barcelona, Spain
                Author notes
                []Corresponding author. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain. toni.gabaldon.bcn@ 123456gmail.com
                Article
                S0098-2997(19)30032-9
                10.1016/j.mam.2019.05.001
                6856719
                31082399
                763db44b-b73a-4cba-ae35-caba7fc2f0cf
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 7 March 2019
                : 8 May 2019
                Categories
                Article

                gut microbiome,colorectal cancer,colon,microbiota,t, tissue,f, feces,na, not available,scfa, short-chain fatty acids,16s, 16s ribosomal rna sequencing and/or pyrosequencing,wgs, whole-genome shotgun sequencing,qpcr, quantitative pcr

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