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      Featured Gut Microbiomes Associated With the Progression of Chronic Hepatitis B Disease

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          Abstract

          Dysbiosis of gut microbiota during the progression of HBV-related liver disease is not well understood, as there are very few reports that discuss the featured bacterial taxa in different stages. The aim of this study was to reveal the featured bacterial species whose abundances are directly associated with HBV disease progression, that is, progression from healthy subjects to, chronic HBV infection, chronic hepatitis B to liver cirrhosis. Approximately 400 fecal samples were collected, and 97 samples were subjected to 16S rRNA gene sequencing after age and BMI matching. Compared with the healthy individuals, significant gut microbiota alterations were associated with the progression of liver disease. LEfSe results showed that the HBV infected patients had higher Fusobacteria, Veillonella, and Haemophilus abundance while the healthy individuals had higher levels of Prevotella and Phascolarctobacterium. Indicator analysis revealed that 57 OTUs changed as the disease progressed, and their combination produced an AUC value of 90% (95% CI: 86–94%) between the LC and non-LC groups. In addition, the abundances of OTU51 ( Dialister succinatiphilus) and OTU50 ( Alistipes onderdonkii) decreased as the disease progressed, and these results were further verified by qPCR. The LC patients had the higher bacterial network complexity, which was accompanied with a lower abundance of potential beneficial bacterial taxa, such as Dialister and Alistipes, while they had a higher abundance of pathogenic species within Actinobacteria. The compositional and network changes in the gut microbiota in varied CHB stages, suggest the potential contributions of gut microbiota in CHB disease progression.

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          Most cited references42

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          FLASH: fast length adjustment of short reads to improve genome assemblies.

          Next-generation sequencing technologies generate very large numbers of short reads. Even with very deep genome coverage, short read lengths cause problems in de novo assemblies. The use of paired-end libraries with a fragment size shorter than twice the read length provides an opportunity to generate much longer reads by overlapping and merging read pairs before assembling a genome. We present FLASH, a fast computational tool to extend the length of short reads by overlapping paired-end reads from fragment libraries that are sufficiently short. We tested the correctness of the tool on one million simulated read pairs, and we then applied it as a pre-processor for genome assemblies of Illumina reads from the bacterium Staphylococcus aureus and human chromosome 14. FLASH correctly extended and merged reads >99% of the time on simulated reads with an error rate of <1%. With adequately set parameters, FLASH correctly merged reads over 90% of the time even when the reads contained up to 5% errors. When FLASH was used to extend reads prior to assembly, the resulting assemblies had substantially greater N50 lengths for both contigs and scaffolds. The FLASH system is implemented in C and is freely available as open-source code at http://www.cbcb.umd.edu/software/flash. t.magoc@gmail.com.
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            Gut microbiota profiling of pediatric NAFLD and obese patients unveiled by an integrated meta-omics based approach.

            There is evidence that non-alcoholic fatty liver disease (NAFLD) is affected by gut microbiota. Therefore, we investigated its modifications in paediatric NAFLD patients using targeted-metagenomics (MG) and metabolomics (MB). Stools were collected from 61 consecutive patients diagnosed with NAFL, NASH, or obesity and 54 healthy subjects (CTRLs), matched in a case-control fashion. Operational taxonomic units were pyrosequenced targeting 16S ribosomal RNA and volatile organic compounds (VOCs) determined by solid-phase micro-extraction GC-MS. The α-diversity was highest in CTRLs followed by obese, NASH, NAFL patients and β-diversity distinguished between patients and CTRLs, but not NAFL and NASH. Compared to CTRLs, in NAFLD patients Actinobacteria were significantly increased and Bacteroidetes reduced. There were no significant differences amongst NAFL, NASH, and obese groups. Overall NAFLD patients had increased levels of Bradyrhizobium, Anaerococcus, Peptoniphilus, Propionibacterium acnes, Dorea, Ruminococcus and reduced proportions of Oscillospira and Rikenellaceae compared to CTRLs. After reducing MG and MB data dimensionality, multivariate analyses indicated Oscillospira decrease in NAFL and NASH groups, and Ruminococcus, Blautia, and Dorea increase in NASH patients compared to CTRLs. Of the 292 VOCs, 26 were up- and 2 down-regulated in NAFLD patients. Multivariate analyses found that combination of Oscillospira, Rickenellaceae, Parabacteroides, Bacteroides fragilis, Sutterella, Lachnospiraceae, 4-methyl-2-pentanone, 1-butanol, and 2-butanone could discriminate NAFLD patients from CTRLs. Univariate analyses found significantly lower levels of Oscillospira and higher levels of 1-pentanol and 2-butanone in NAFL compared to CTRLs. In NASH, lower levels of Oscillospira were associated with higher abundance of Dorea, Ruminococcus and higher levels of 2-butanone, 4-methyl-2-pentanone compared to CTRLs.
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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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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                20 March 2020
                2020
                : 11
                : 383
                Affiliations
                [1] 1Department of Gastroenterology, Zhongshan Hospital Xiamen University , Xiamen, China
                [2] 2Institute for Microbial Ecology, School of Medicine, Xiamen University , Xiamen, China
                [3] 3College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, China
                [4] 4School of Life Sciences, Xiamen University , Xiamen, China
                [5] 5Fisheries College, Jimei University , Xiamen, China
                [6] 6Civil and Environmental Engineering, Michigan State University , East Lansing, MI, United States
                Author notes

                Edited by: Thomas Dandekar, Julius Maximilian University of Würzburg, Germany

                Reviewed by: Oskar Karlsson Lindsjö, Swedish University of Agricultural Sciences, Sweden; Gianni Panagiotou, Leibniz Institute for Natural Product Research and Infection Biology, Germany

                These authors have contributed equally to this work

                This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2020.00383
                7098974
                32265857
                8761db0e-fbeb-4acd-800e-37daf445e598
                Copyright © 2020 Chen, Xie, Zhou, Zhang, Wu, Yang, Xu, Stedtfeld, Chen, Liu, Zhang, Xu and Ren.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 March 2019
                : 20 February 2020
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 68, Pages: 15, Words: 0
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                hepatitis b virus,gut dysbiosis,cooccurrence network,liver cirrhosis,random forest

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