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      Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening

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          Abstract

          Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washing-process. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.

          Electronic supplementary material

          The online version of this article (10.1007/s13238-019-00684-8) contains supplementary material, which is available to authorized users.

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          Most cited references54

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          Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.

          Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial.
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            Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.

            The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis.
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              European consensus conference on faecal microbiota transplantation in clinical practice

              Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.
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                Author and article information

                Contributors
                fzhang@njmu.edu.cn
                Journal
                Protein Cell
                Protein Cell
                Protein & Cell
                Higher Education Press (Beijing )
                1674-800X
                1674-8018
                9 January 2020
                9 January 2020
                April 2020
                : 11
                : 4
                : 251-266
                Affiliations
                [1 ]GRID grid.452511.6, Medical Center for Digestive Diseases, , The Second Affiliated Hospital of Nanjing Medical University, ; Nanjing, 210011 China
                [2 ]GRID grid.89957.3a, ISNI 0000 0000 9255 8984, Key Lab of Holistic Integrative Enterology, , Nanjing Medical University, ; Nanjing, 210011 China
                [3 ]Tianjin Key Laboratory of Optoelectronic Detection Technology and Systems, Tianjin, 300387 China
                [4 ]GRID grid.440785.a, ISNI 0000 0001 0743 511X, Department of Microbiology, School of Medicine, , Jiangsu University, ; Zhenjiang, 212013 China
                [5 ]GRID grid.464196.8, ISNI 0000 0004 1773 8394, Biogas Institute of Ministry of Agriculture and Rural Affairs, ; Chengdu, 610041 China
                [6 ]Center for Anaerobic Microbial Resources of Sichuan Province, Chengdu, 610041 China
                [7 ]GRID grid.89957.3a, ISNI 0000 0000 9255 8984, Division of Microbiotherapy, Sir Run Run Shaw Hospital, , Nanjing Medical University, ; Nanjing, 211166 China
                Author information
                http://orcid.org/0000-0003-4157-1144
                Article
                684
                10.1007/s13238-019-00684-8
                7093410
                31919742
                aeecd40f-0f6e-4ffa-85fe-adead4f229f1
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 8 November 2019
                : 3 December 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                fecal microbiota transplantation,washed microbiota transplantation,adverse event,safety,infection,virus,metabolomics,spectroscopy,transplant

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