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      Dysbiosis of gut microbiota in promoting the development of colorectal cancer

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          Abstract

          Gastrointestinal microbiome, containing at least 100 trillion bacteria, resides in the mucosal surface of human intestine. Recent studies show that perturbations in the microbiota may influence physiology and link to a number of diseases, including colon tumorigenesis. Colorectal cancer (CRC), the third most common cancer, is the disease resulting from multi-genes and multi-factors, but the mechanistic details between gut microenvironment and CRC remain poorly characterized. Thanks to new technologies such as metagenome sequencing, progress in large-scale analysis of the genetic and metabolic profile of gut microbial has been possible, which has facilitated studies about microbiota composition, taxonomic alterations and host interactions. Different bacterial species and their metabolites play critical roles in the development of CRC. Also, microbiota is important in the inflammatory response and immune processes deregulation during the development and progression of CRC. This review summarizes current studies regarding the association between gastrointestinal microbiota and the development of CRC, which provides insights into the therapeutic strategy of CRC.

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          Most cited references95

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          Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella.

          The gut microbiota plays an important role in human health by interacting with host diet, but there is substantial inter-individual variation in the response to diet. Here we compared the gut microbiota composition of healthy subjects who exhibited improved glucose metabolism following 3-day consumption of barley kernel-based bread (BKB) with those who responded least to this dietary intervention. The Prevotella/Bacteroides ratio was higher in responders than non-responders after BKB. Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had increased potential to ferment complex polysaccharides after BKB. Finally, germ-free mice transplanted with microbiota from responder human donors exhibited improved glucose metabolism and increased abundance of Prevotella and liver glycogen content compared with germ-free mice that received non-responder microbiota. Our findings indicate that Prevotella plays a role in the BKB-induced improvement in glucose metabolism observed in certain individuals, potentially by promoting increased glycogen storage.
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            The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota.

            Mucosal surfaces constantly encounter microbes. Toll-like receptors (TLRs) mediate recognition of microbial patterns to eliminate pathogens. By contrast, we demonstrate that the prominent gut commensal Bacteroides fragilis activates the TLR pathway to establish host-microbial symbiosis. TLR2 on CD4(+) T cells is required for B. fragilis colonization of a unique mucosal niche in mice during homeostasis. A symbiosis factor (PSA, polysaccharide A) of B. fragilis signals through TLR2 directly on Foxp3(+) regulatory T cells to promote immunologic tolerance. B. fragilis lacking PSA is unable to restrain T helper 17 cell responses and is defective in niche-specific mucosal colonization. Therefore, commensal bacteria exploit the TLR pathway to actively suppress immunity. We propose that the immune system can discriminate between pathogens and the microbiota through recognition of symbiotic bacterial molecules in a process that engenders commensal colonization.
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              A catalog of the mouse gut metagenome.

              We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies.
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                Author and article information

                Journal
                Gastroenterol Rep (Oxf)
                Gastroenterol Rep (Oxf)
                gastro
                Gastroenterology Report
                Oxford University Press
                2052-0034
                February 2018
                11 October 2017
                11 October 2017
                : 6
                : 1
                : 1-12
                Affiliations
                [1 ]Research Institute of Gastroenterology, Sun Yat-sen University, Guangzhou 510020, China
                [2 ]Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510020, China
                Author notes
                Corresponding author. Research Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, 26 Yuanchun Er Heng Road, Guangzhou, Guangdong 510020, China. Tel: +86-13802833476; Email: limh33@ 123456mail.sysu.edu.cn

                Shaomin Zou and Lekun Fang authors who contributed equally to the article.

                Article
                gox031
                10.1093/gastro/gox031
                5806407
                29479437
                9d05a62f-ea89-4964-b788-56fb15959561
                © The Author(s) 2017. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 21 July 2017
                : 21 July 2017
                Page count
                Pages: 12
                Categories
                Review Articles

                gut microbiota,microbiome dysbiosis,colorectal cancer,tumorigenesis

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