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      Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate


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          The gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation.


          C57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis. Blood and pancreas were collected for bacteriology and immune analysis. The cecum microbiota composition of mice was analysed using 16S rRNA gene amplicon sequencing and cecal content metabolites were analysed by targeted (ie, butyrate) and untargeted metabolomics. Prevention of necrotising pancreatitis in this model was compared between faecal microbiota transplantation (FMT) from healthy mice, antibiotic decontamination against Gram-negative bacteria and oral or systemic butyrate administration. Additionally, the faecal microbiota of patients with pancreatitis and healthy subjects were analysed.


          Mortality, systemic inflammation and bacterial dissemination were increased in mice fed Western diet and their gut microbiota were characterised by a loss of diversity, a bloom of Escherichia coli and an altered metabolic profile with butyrate depletion. While antibiotic decontamination decreased mortality, Gram-positive dissemination was increased. Both oral and systemic butyrate supplementation decreased mortality, bacterial dissemination, and reversed the microbiota alterations. Paradoxically, mortality and bacterial dissemination were increased with FMT administration. Finally, patients with acute pancreatitis demonstrated an increase in Proteobacteria and a decrease of butyrate producers compared with healthy subjects.


          Butyrate depletion and its repletion appear to play a central role in disease progression towards necrotising pancreatitis.

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          Most cited references 55

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            The SILVA ribosomal RNA gene database project: improved data processing and web-based tools

            SILVA (from Latin silva, forest, http://www.arb-silva.de) is a comprehensive web resource for up to date, quality-controlled databases of aligned ribosomal RNA (rRNA) gene sequences from the Bacteria, Archaea and Eukaryota domains and supplementary online services. The referred database release 111 (July 2012) contains 3 194 778 small subunit and 288 717 large subunit rRNA gene sequences. Since the initial description of the project, substantial new features have been introduced, including advanced quality control procedures, an improved rRNA gene aligner, online tools for probe and primer evaluation and optimized browsing, searching and downloading on the website. Furthermore, the extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches.
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              Search and clustering orders of magnitude faster than BLAST.

               Robert Edgar (2010)
              Biological sequence data is accumulating rapidly, motivating the development of improved high-throughput methods for sequence classification. UBLAST and USEARCH are new algorithms enabling sensitive local and global search of large sequence databases at exceptionally high speeds. They are often orders of magnitude faster than BLAST in practical applications, though sensitivity to distant protein relationships is lower. UCLUST is a new clustering method that exploits USEARCH to assign sequences to clusters. UCLUST offers several advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved sensitivity, clustering at lower identities and classification of much larger datasets. Binaries are available at no charge for non-commercial use at http://www.drive5.com/usearch.

                Author and article information

                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                May 2021
                1 September 2020
                : 70
                : 5
                : 915-927
                [1 ] departmentDepartment of Surgery , Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism , Amsterdam, The Netherlands
                [2 ] departmentDepartment of Surgery , Radboudumc , Nijmegen, The Netherlands
                [3 ] departmentDepartment of Surgery , University of Chicago, Pritzker School of Medicine , Chicago, Illinois, USA
                [4 ] departmentDepartment of Surgery , Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center , Utrecht, The Netherlands
                [5 ] departmentDepartment of Surgery , Sint Antonius Hospital , Nieuwegein, The Netherlands
                [6 ] departmentCenter for Experimental and Molecular Medicine, Department of Medicine , Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands
                Author notes
                [Correspondence to ] Fons F van den Berg, Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands; f.f.vandenberg@ 123456amsterdamumc.nl
                © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01-GM062344-18
                Funded by: AMC Executive Board;
                Award ID: AMC PhD Scholarship 2018
                Original research
                Custom metadata

                Gastroenterology & Hepatology

                acute pancreatitis, bacterial infection, diet, butyrate, antibiotics


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