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      Capsulized Fecal Microbiota Transplantation Induces Remission in Patients with Ulcerative Colitis by Gut Microbial Colonization and Metabolite Regulation

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          ABSTRACT

          Fecal microbiota transplantation (FMT) can induce clinical remission in ulcerative colitis (UC) patients. Enemas, nasoduodenal tubes, and colonoscopies are the most common routes for FMT administration. However, there is a lack of definitive evidence regarding the effectiveness of capsulized FMT treatment in UC patients. In this study, we administered capsulized FMT to 22 patients with active UC to assess the efficiency of capsulized FMT and determine the specific bacteria and metabolite factors associated with the response to clinical remission. Our results showed that the use of capsulized FMT was successful in the treatment of UC patients. Capsulized FMT induced clinical remission and clinical response in 57.1% (12 of 21) and 76.2% (16 of 21) of UC patients, respectively. Gut bacterial richness was increased after FMT in patients who achieved remission. Patients in remission after FMT exhibited enrichment of Alistipes sp. and Odoribacter splanchnicus, along with increased levels of indolelactic acid. Patients who did not achieve remission exhibited enrichment of Escherichia coli and Klebsiella and increased levels of biosynthesis of 12,13-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid) and lipopolysaccharides. Furthermore, we identified a relationship between specific bacteria and metabolites and the induction of remission in patients. These findings may provide new insights into FMT in UC treatment and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects. (This study has been registered at ClinicalTrails.gov under registration no. NCT03426683).

          IMPORTANCE Fecal microbiota transplantation has been successfully used in patients. Recently, capsulized FMT was reported to induce a response in patients with UC. However, limited patients were enrolled in such studies, and the functional factors of capsulized FMT have not been reported in the remission of patients with UC. In this study, we prospectively recruited patients with UC to receive capsulized FMT. First, we found that capsulized FMT could induce clinical remission in 57.1% of patients and clinical response in 76.2% after 12 weeks, which was more acceptable. Second, we found a relationship between the decrease of opportunistic pathogen and lipopolysaccharide synthesis in patients in remission after capsulized FMT. We also identified an association between specific bacteria and metabolites and remission induction in patients after capsulized FMT. These findings put forward a possibility for patients to receive FMT at home and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects.

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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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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              UPARSE: highly accurate OTU sequences from microbial amplicon reads.

              Amplified marker-gene sequences can be used to understand microbial community structure, but they suffer from a high level of sequencing and amplification artifacts. The UPARSE pipeline reports operational taxonomic unit (OTU) sequences with ≤1% incorrect bases in artificial microbial community tests, compared with >3% incorrect bases commonly reported by other methods. The improved accuracy results in far fewer OTUs, consistently closer to the expected number of species in a community.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                Microbiol Spectr
                Microbiol Spectr
                spectrum
                Microbiology Spectrum
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2165-0497
                24 April 2023
                May-Jun 2023
                24 April 2023
                : 11
                : 3
                : e04152-22
                Affiliations
                [a ] Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
                [b ] Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
                [c ] Xiamen Key Laboratory of Intestinal Microbiome and Human Health, Zhongshan Hospital of Xiamen University, Xiamen, China
                [d ] Department of Digestive Disease, School of Medicine, Xiamen University, Xiamen, China
                Yangzhou University
                Author notes

                Qiongyun Chen, Yanyun Fan, and Bangzhou Zhang contributed equally to this work. The order of names was based on the contribution to this manuscript.

                The authors declare no conflict of interest.

                Author information
                https://orcid.org/0000-0002-2725-5359
                Article
                04152-22 spectrum.04152-22
                10.1128/spectrum.04152-22
                10269780
                37093057
                aa293582-fad7-48a2-a055-c47195d11072
                Copyright © 2023 Chen et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 13 October 2022
                : 30 March 2023
                Page count
                supplementary-material: 0, Figures: 6, Tables: 3, Equations: 0, References: 63, Pages: 20, Words: 11626
                Funding
                Funded by: National Natural Science Foundation of China (NSFC), FundRef https://doi.org/10.13039/501100001809;
                Award ID: 81770558
                Award ID: 81800517
                Award Recipient : Award Recipient :
                Funded by: Natural Science Foundation of Fujian Province (Fujian Provincial Natural Science Foundation), FundRef https://doi.org/10.13039/501100003392;
                Award ID: 2020J05286
                Award ID: 2021J011329
                Award Recipient : Award Recipient :
                Categories
                Research Article
                applied-and-industrial-microbiology, Applied and Industrial Microbiology
                Custom metadata
                May/June 2023

                fecal microbiota transplantation,ulcerative colitis,capsules,microbiome,gut microbiome,metabolism

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