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      Human Gut Microbiota and Gastrointestinal Cancer

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          Abstract

          Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.

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          Most cited references177

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            Fungal microbiota dysbiosis in IBD

            Objective The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Design Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. Results We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Conclusions Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis.
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              Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

              The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.
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                Author and article information

                Contributors
                Journal
                Genomics Proteomics Bioinformatics
                Genomics Proteomics Bioinformatics
                Genomics, Proteomics & Bioinformatics
                Elsevier
                1672-0229
                2210-3244
                21 February 2018
                February 2018
                21 February 2018
                : 16
                : 1
                : 33-49
                Affiliations
                [1 ]Institute for Systems Biology, Seattle, WA 98109, USA
                [2 ]Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
                [3 ]Swedish Cancer Institute, Seattle, WA 98104, USA
                [4 ]P4 Medicine Institute, Seattle, WA 98109, USA
                Author notes
                [* ]Corresponding author. Qiang.Tian@ 123456systemsbiology.org
                [a]

                ORCID: 0000-0002-9438-5719.

                [b]

                ORCID: 0000-0003-1333-9145.

                [c]

                ORCID: 0000-0002-2123-1014.

                [d]

                ORCID: 0000-0001-7158-3678.

                [e]

                ORCID: 0000-0002-1924-6217.

                Article
                S1672-0229(18)30003-2
                10.1016/j.gpb.2017.06.002
                6000254
                29474889
                02a1f386-5b75-4887-8d06-890e0be4f51b
                © 2018 Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China

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

                History
                : 8 June 2017
                : 4 July 2017
                Categories
                Review

                inflammation,immune regulation,microbial metabolites,carcinogenesis,traditional chinese medicine

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