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      Microbial Engraftment and Efficacy of Fecal Microbiota Transplant for Clostridium Difficile in Patients With and Without Inflammatory Bowel Disease

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          Abstract

          Background

          Recurrent and severe Clostridium difficile infections (CDI) are treated with fecal microbiota transplant (FMT). Uncertainty exists regarding FMT effectiveness for CDI with underlying inflammatory bowel disease (IBD) and regarding its effects on disease activity and effectiveness in transferring the donor microbiota to patients with and without IBD.

          Methods

          Subjects with and without IBD who underwent FMT for recurrent or severe CDI between 2013 and 2016 at The Mount Sinai Hospital were followed for up to 6 months. The primary outcome was CDI recurrence 6 months after FMT. Secondary outcomes were (1) CDI recurrence 2 months after FMT; (2) frequency of IBD flare after FMT; (3) microbiota engraftment after FMT; (and 4) predictors of CDI recurrence.

          Results

          One hundred thirty-four patients, 46 with IBD, were treated with FMT. Follow-up was available in 83 and 118 patients at 6 and 2 months, respectively. There was no difference in recurrence in patients with and without IBD at 6 months (38.7% vs 36.5%; P > 0.99) and 2 months (22.5% vs 17.9%; P = 0.63). Proton pump inhibitor use, severe CDI, and comorbid conditions were predictors of recurrence. Pre-FMT microbiota was not predictive of CDI recurrence. Subjects with active disease requiring medication escalation had reduced engraftment, with no difference in engraftment based on CDI recurrence or IBD endoscopic severity at FMT.

          Conclusions

          Inflammatory bowel disease did not affect CDI recurrence rates 6 months after FMT. Pre-FMT microbiota was not predictive of recurrence, and microbial engraftment was impacted in those requiring IBD treatment escalation, though not by CDI recurrence or IBD disease severity.

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          Most cited references16

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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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            Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection

            Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (CDI). However, transferring undefined living bacteria entails uncontrollable risks for infectious and metabolic or malignant diseases, particularly in immunocompromised patients. We investigated whether sterile fecal filtrates (containing bacterial debris, proteins, antimicrobial compounds, metabolic products, and oligonucleotides/DNA), rather than intact microorganisms, are effective in patients with CDI.
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              Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients.

              Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients.
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                Author and article information

                Journal
                Inflamm Bowel Dis
                Inflamm. Bowel Dis
                ibd
                Inflammatory Bowel Diseases
                Oxford University Press (US )
                1078-0998
                1536-4844
                June 2019
                10 March 2019
                04 May 2020
                : 25
                : 6
                : 969-979
                Affiliations
                [1 ]The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                [2 ]Icahn Institute for Genomics & Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York NY, USA
                [3 ]Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                [4 ]Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York NY, USA
                Author notes
                Address correspondence to: Jose C. Clemente, 1470 Madison Avenue, New York NY, USA 10029. E-mail: jose.clemente@ 123456mssm.edu

                Robert P Hirten, Ari Grinspan, Shih-Chen Fu should be considered joint first authors.

                Article
                PMC6499938 PMC6499938 6499938 izy398
                10.1093/ibd/izy398
                6499938
                30852592
                92152a97-0108-4c0e-b6b5-f5717476084d
                © 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

                This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

                History
                : 27 August 2018
                Page count
                Pages: 11
                Funding
                Funded by: Crohn’s and Colitis Foundation of America 10.13039/100001063
                Award ID: #362048
                Funded by: George Waechter Memorial Foundation
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R01 DK114038
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases 10.13039/100000062
                Categories
                Leading Off

                microbiome,Clostridium difficile,fecal microbiota transplant,inflammatory bowel disease

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