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      Alteration in gut microbiota associated with hepatitis B and non-hepatitis virus related hepatocellular carcinoma

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          Abstract

          Background

          The onset of hepatocellular carcinoma (HCC) ranked fifth malignancies all over the world. Increasing evidences showed that the distribution of HCC was related to the incidence of chronic hepatitis B virus (HBV) infection and other factors, such as alcoholism, aflatoxin B1 ingestion and obesity. Recent studies demonstrated that gut dysbiosis plays an important role in liver diseases. However, the researches on gut microbiota of HBV and non-HBV non-HCV related HCC have not been reported. In this study, we investigated the differences between the gut microbiota of HBV related HCC (B-HCC) and non-HBV non-HCV related HCC (NBNC-HCC), finally found some potential bacteria, linking different pathological mechanism of both types of HCCs.

          Results

          We carried out 16S rRNA analyses in a cohort of 33 healthy controls, 35 individuals with HBV related HCC (B-HCC) and 22 individuals with non-HBV non-HCV (NBNC) related HCC (NBNC-HCC). We found that the species richness of fecal microbiota of B-HCC patients was much higher than other two groups. Interestingly, the feces of NBNC-HCC patients harbored more potential pro-inflammatory bacteria ( Escherichia- Shigella, Enterococcus) and reduced levels of Faecalibacterium, Ruminococcus, Ruminoclostridium which results in decrease potential of anti-inflammatory short-chain fatty acids. The feces of NBNC-HCC patients had relatively fewer abundance of multiple biological pathways related to amino acid and glucose metabolism, but high level of transport and secretion in some types. However, the B-HCC patients had opposite results of bacterial composition and associated multiple biological pathways versus NBNC-HCC patients. Meanwhile, we found that aberrant network of gut microbiota occurred differently in B-HCC and NBNC-HCC patients.

          Conclusions

          Our study indicated that B-HCC and NBNC-HCC patients showed differential abundance of bacteria involved in different functions or biological pathways. We suggested the modification of specific gut microbiota may provide the therapeutic benefit for B-HCC and NBNC-HCC.

          Electronic supplementary material

          The online version of this article (10.1186/s13099-018-0281-6) contains supplementary material, which is available to authorized users.

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          Most cited references24

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          Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease

          Non-alcoholic fatty liver disease (NAFLD) has recently been considered to be under the influence of the gut microbiota, which might exert toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. In this study, the composition of the gut microbiota in NAFLD patients and healthy subjects was determined via 16S ribosomal RNA Illumina next-generation sequencing. Among those taxa displaying greater than 0.1% average abundance in all samples, five genera, including Alistipes and Prevotella, were significantly more abundant in the gut microbiota of healthy subjects compared to NAFLD patients. Alternatively, Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in the gut microbiota of NAFLD patients compared to healthy subjects. In addition, decreased numbers of CD4+ and CD8+ T lymphocytes and increased levels of TNF-α, IL-6 and IFN-γ were detected in the NAFLD group compared to the healthy group. Furthermore, irregularly arranged microvilli and widened tight junctions were observed in the gut mucosa of the NAFLD patients via transmission electron microscopy. We postulate that aside from dysbiosis of the gut microbiota, gut microbiota-mediated inflammation of the intestinal mucosa and the related impairment in mucosal immune function play an important role in the pathogenesis of NAFLD.
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            The gut microbiome and liver cancer: mechanisms and clinical translation

            Increasing evidence suggests that the gut microbiota are important modulators of chronic liver disease progression and the development of hepatocellular carcinoma. In this Review, Yu and Schwabe discuss the mechanisms by which the gut microbiota promote hepatocarcinogenesis, and explore therapeutic interventions with clinical potential.
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              Immune system stimulation by probiotic microorganisms.

              Probiotic organisms are claimed to offer several functional properties including stimulation of immune system. This review is presented to provide detailed informations about how probiotics stimulate our immune system. Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, Bifidobacterium animalis Bb-12, Lactobacillus johnsonii La1, Bifidobacterium lactis DR10, and Saccharomyces cerevisiae boulardii are the most investigated probiotic cultures for their immunomodulation properties. Probiotics can enhance nonspecific cellular immune response characterized by activation of macrophages, natural killer (NK) cells, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in strain-specific and dose-dependent manner. Mixture and type (gram-positive and gram-negative) of probiotic organisms may induce different cytokine responses. Supplementation of probiotic organisms in infancy could help prevent immune-mediated diseases in childhood, whereas their intervention in pregnancy could affect fetal immune parameters, such as cord blood interferon (IFN)-γ levels, transforming growth factor (TGF)-β1 levels, and breast milk immunoglobulin (Ig)A. Probiotics that can be delivered via fermented milk or yogurt could improve the gut mucosal immune system by increasing the number of IgA(+) cells and cytokine-producing cells in the effector site of the intestine.
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                Author and article information

                Contributors
                zhangyewei@seu.edu.cn
                xingyinliu@njmu.edu.cn
                Journal
                Gut Pathog
                Gut Pathog
                Gut Pathogens
                BioMed Central (London )
                1757-4749
                18 January 2019
                18 January 2019
                2019
                : 11
                : 1
                Affiliations
                [1 ]ISNI 0000 0000 9255 8984, GRID grid.89957.3a, Department of Microbiology, Key Laboratory of Pathogen of Jiangsu Province, , Nanjing Medical University, ; Nanjing, China
                [2 ]ISNI 0000 0000 9255 8984, GRID grid.89957.3a, Key Laboratory of Human Functional Genomics of Jiangsu Province, , Nanjing Medical University, ; Nanjing, China
                [3 ]GRID grid.452511.6, Key Laboratory of Holistic Integrative Enterology, , Second Affiliated Hospital of Nanjing Medical University, ; Nanjing, China
                [4 ]ISNI 0000 0004 1764 4566, GRID grid.452509.f, Department of Hepatobiliary and Pancreatic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, , Nanjing Medical University Affiliated Cancer Hospital, ; Nanjing, China
                [5 ]GRID grid.452511.6, Department of General Surgery, , Second Affiliated Hospital of Nanjing Medical University, ; Nanjing, China
                [6 ]Department of Clinical Laboratory, Affiliated Yixing Hospital of Jiangsu University, Yixing, China
                [7 ]ISNI 0000 0004 1761 0489, GRID grid.263826.b, Department of Hepatobiliary and Pancreatic Surgery, Zhongda Hospital, Medical School, , Southeast University, ; Nanjing, China
                Article
                281
                10.1186/s13099-018-0281-6
                6337822
                30675188
                58ca357e-c17b-4b4a-b71e-ed48df1f5b83
                © The Author(s) 2019

                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.

                History
                : 3 September 2018
                : 31 December 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004608, Natural Science Foundation of Jiangsu Province;
                Award ID: BK20161025
                Award ID: BK20161572
                Award Recipient :
                Funded by: Nanjing Medical University (CN)
                Award ID: 2015NJMUZD014
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81671983
                Award Recipient :
                Funded by: 33 Program for High Level Talents of Jiangsu Province
                Award ID: BRA2016508
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100010014, Six Talent Peaks Project in Jiangsu Province;
                Award ID: WSW041
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100005066, Key Medical Subjects of Jiangsu Province;
                Award ID: 2016KJQWZDRC-03
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Gastroenterology & Hepatology
                gut microbiome,dysbiosis,liver cancer,hepatocellular carcinoma,hbv
                Gastroenterology & Hepatology
                gut microbiome, dysbiosis, liver cancer, hepatocellular carcinoma, hbv

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