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      The gut microbiota in conventional and serrated precursors of colorectal cancer

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          Abstract

          Background

          Colorectal cancer is a heterogeneous disease arising from at least two precursors—the conventional adenoma (CA) and the serrated polyp. We and others have previously shown a relationship between the human gut microbiota and colorectal cancer; however, its relationship to the different early precursors of colorectal cancer is understudied. We tested, for the first time, the relationship of the gut microbiota to specific colorectal polyp types.

          Results

          Gut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples. Participants were categorized as CA cases ( n = 144), serrated polyp cases ( n = 73), or polyp-free controls ( n = 323). CA cases were further classified as proximal ( n = 87) or distal ( n = 55) and as non-advanced ( n = 121) or advanced ( n = 22). Serrated polyp cases were further classified as hyperplastic polyp (HP; n = 40) or sessile serrated adenoma (SSA; n = 33). We compared gut microbiota diversity, overall composition, and normalized taxon abundance among these groups.

          CA cases had lower species richness in stool than controls ( p = 0.03); in particular, this association was strongest for advanced CA cases ( p = 0.004). In relation to overall microbiota composition, only distal or advanced CA cases differed significantly from controls ( p = 0.02 and p = 0.002). In taxon-based analysis, stool of CA cases was depleted in a network of Clostridia operational taxonomic units from families Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and enriched in the classes Bacilli and Gammaproteobacteria, order Enterobacteriales, and genera Actinomyces and Streptococcus (all q < 0.10). SSA and HP cases did not differ in diversity or composition from controls, though sample size for these groups was small. Few taxa were differentially abundant between HP cases or SSA cases and controls; among them, class Erysipelotrichi was depleted in SSA cases.

          Conclusions

          Our results indicate that gut microbes may play a role in the early stages of colorectal carcinogenesis through the development of CAs. Findings may have implications for developing colorectal cancer prevention therapies targeting early microbial drivers of colorectal carcinogenesis.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s40168-016-0218-6) contains supplementary material, which is available to authorized users.

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          Most cited references 52

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            QIIME allows analysis of high-throughput community sequencing data.

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              Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.

              Estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. We review the sources and methods used in compiling the national cancer incidence and mortality estimates, and briefly describe the key results by cancer site and in 20 large "areas" of the world. Overall, there were 14.1 million new cases and 8.2 million deaths in 2012. The most commonly diagnosed cancers were lung (1.82 million), breast (1.67 million), and colorectal (1.36 million); the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000 deaths), and stomach cancer (723,000 deaths). © 2014 UICC.
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                Author and article information

                Contributors
                Jiyoung.Ahn@nyumc.org
                Journal
                Microbiome
                Microbiome
                Microbiome
                BioMed Central (London )
                2049-2618
                30 December 2016
                30 December 2016
                2016
                : 4
                Affiliations
                [1 ]Department of Population Health, New York University School of Medicine, New York, NY USA
                [2 ]Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA USA
                [3 ]Division of Environmental Health Sciences, School of Public Health, University of Minnesota, Minneapolis, MN USA
                [4 ]Department of Surgery, New York University School of Medicine, New York, NY USA
                [5 ]Department of Cell Biology, New York University School of Medicine, New York, NY USA
                [6 ]NYU Perlmutter Cancer Center, New York University School of Medicine, New York, NY USA
                [7 ]Kips Bay Endoscopy Center, New York, NY USA
                Article
                218
                10.1186/s40168-016-0218-6
                5203720
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000054, National Cancer Institute;
                Award ID: R03CA159414
                Award ID: R21CA183887
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/100000054, National Cancer Institute;
                Award ID: P30CA016087
                Funded by: FundRef http://dx.doi.org/10.13039/100000043, American Association for Cancer Research;
                Award ID: Career Development Award
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                serrated, microbiome, microbiota, adenoma, polyp, colorectal, cancer

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