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      The role of microbiota in the development of colorectal cancer

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          Abstract

          Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.

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          Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

          Charles Bevins, Nita Salzman (2011)
          Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.
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            Mechanisms and functions of DNA mismatch repair.

            Guo-Min Li (2008)
            DNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSalpha and MutLalpha, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.
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              Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity.

              Melanie Schirmer, Sanne Smeekens, Hera Vlamakis … (2016)
              Gut microbial dysbioses are linked to aberrant immune responses, which are often accompanied by abnormal production of inflammatory cytokines. As part of the Human Functional Genomics Project (HFGP), we investigate how differences in composition and function of gut microbial communities may contribute to inter-individual variation in cytokine responses to microbial stimulations in healthy humans. We observe microbiome-cytokine interaction patterns that are stimulus specific, cytokine specific, and cytokine and stimulus specific. Validation of two predicted host-microbial interactions reveal that TNFα and IFNγ production are associated with specific microbial metabolic pathways: palmitoleic acid metabolism and tryptophan degradation to tryptophol. Besides providing a resource of predicted microbially derived mediators that influence immune phenotypes in response to common microorganisms, these data can help to define principles for understanding disease susceptibility. The three HFGP studies presented in this issue lay the groundwork for further studies aimed at understanding the interplay between microbial, genetic, and environmental factors in the regulation of the immune response in humans. PAPERCLIP.
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                Author and article information

                Contributors
                Dong Tang:
                ORCID: https://orcid.org/0000-0002-4372-9972
                83392785@qq.com
                Daorong Wang: daorong666@sina.com
                Journal
                Journal ID (nlm-ta): Int J Cancer
                Journal ID (iso-abbrev): Int. J. Cancer
                Journal ID (doi): 10.1002/(ISSN)1097-0215
                Journal ID (publisher-id): IJC
                Title: International Journal of Cancer
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 0020-7136
                ISSN (Electronic): 1097-0215
                Publication date (Electronic): 15 January 2019
                Publication date (Print): 15 October 2019
                Volume: 145
                Issue: 8 ( doiID: 10.1002/ijc.v145.8 )
                Pages: 2032-2041
                Affiliations
                [ 1 ] Clinical Medical College Yangzhou University Yangzhou Jiangsu Province China
                [ 2 ] Department of General Surgery Institute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital Yangzhou China
                [ 3 ] Department of Gastroenterology Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital Yangzhou China
                Author notes
                [*] [* ] Correspondence to: Dong Tang, M.D., Ph.D., Department of General Surgery, Institute of General Surgery, Northern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, China, Tel.: +86‐18952783556, E‐mail: 83392785@ 123456qq.com ; or Daorong Wang, M.D., Ph.D., Department of General Surgery, Institute of General Surgery, Northern Jiangsu People’s Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, China, Tel.: +86‐13905252590, E‐mail: daorong666@ 123456sina.com

                Z.D., J.Z. and Q.W. contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-4372-9972
                Article
                Publisher ID: IJC32017
                DOI: 10.1002/ijc.32017
                PMC ID: 6899977
                PubMed ID: 30474116
                SO-VID: 60bc0bdc-46b6-4401-96dc-e2a65238e534
                Copyright © © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                Date received : 28 July 2018
                Date revision received : 25 October 2018
                Date accepted : 13 November 2018
                Page count
                Figures: 3, Tables: 0, Pages: 10, Words: 8798
                Funding
                Funded by: Standardized diagnosis and treatment of key diseases in Jiangsu Province: standardized diagnosis and treatment of rectal cancer and rectal cancer liver metastasis and its clinical application
                Award ID: BE2015664
                Funded by: training project of key talents of youth medicine in Jiangsu province, China
                Award ID: QNRC2016330
                Funded by: Yangzhou Science and Technology Bureau Social Development Project
                Award ID: YZ2018087
                Categories
                Subject: Mini Review
                Subject: Mini Reviews
                Custom metadata
                source-schema-version-number 2.0
                cover-date 15 October 2019
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.2 mode:remove_FC converted:05.12.2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: microbiota,inflammation,carcinogenesis,colorectal cancer
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: microbiota, inflammation, carcinogenesis, colorectal cancer

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