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1
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Singh A, Midha V, Chauhan NS, Sood A. Current perspectives on fecal microbiota transplantation in inflammatory bowel disease. Indian J Gastroenterol 2024; 43:129-144. [PMID: 38334893 DOI: 10.1007/s12664-023-01516-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 12/26/2023] [Indexed: 02/10/2024]
Abstract
Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic modality within the domain of inflammatory bowel disease (IBD). While FMT has secured approval and demonstrated efficacy in addressing recurrent and refractory Clostridioides difficile infection, its application in IBD remains an area of active exploration and research. The current status of FMT in IBD reflects a nuanced landscape, with ongoing investigations delving into its effectiveness, safety and optimal implementation. Early-stage clinical trials and observational studies have provided insights into the potential of FMT to modulate the dysbiotic gut microbiota associated with IBD, aiming to mitigate inflammation and promote mucosal healing. However, considerable complexities persist, including variations in donor selection, treatment protocols and outcome assessments. Challenges in standardizing FMT protocols for IBD treatment are compounded by the dynamic nature of the gut microbiome and the heterogeneity of IBD itself. Despite these challenges, enthusiasm for FMT in IBD emanates from its capacity to address gut microbial dysbiosis, signifying a paradigm shift towards more comprehensive approaches in IBD management. As ongoing research progresses, an enhanced understanding of FMT's role in IBD therapy is anticipated. This article synthesizes the current status of FMT in IBD, elucidating the attendant challenges and aspiring towards the refinement of its application for improved patient outcomes.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Nar Singh Chauhan
- Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124 001, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India.
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2
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Levy B, Fliss Isakov N, Ziv-Baran T, Leshno M, Maharshak N, Werner L. Economic and Chronologic Optimization of Fecal Donors Screening Process. MDM Policy Pract 2024; 9:23814683241254809. [PMID: 38873648 PMCID: PMC11171430 DOI: 10.1177/23814683241254809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 04/01/2024] [Indexed: 06/15/2024] Open
Abstract
Background. Fecal microbial transplantation (FMT) is the delivery of fecal microbiome, isolated from healthy donors, into a patient's gastrointestinal tract. FMT is a safe and efficient treatment for recurrent Clostridioides difficile infection. Donors undergo strict screening to avoid disease transmission. This consists of several blood and stool tests, which are performed in a multistage, costly process. We performed a cost-minimizing analysis to find the optimal order in which the tests should be performed. Methods. An algorithm to optimize the order of tests in terms of cost was defined. Performance analysis for disqualifying a potential healthy donor was carried out on data sets based on either the published literature or our real-life data. For both data sets, we calculated the total cost to qualify a single donor according to the optimal order of tests, suggested by the algorithm. Results. Applying the algorithm to the published literature revealed potential savings of 94.2% of the cost of screening a potential donor and 7.05% of the cost to qualify a single donor. In our cohort of 87 volunteers, 53 were not eligible for donation. Of 34 potential donors, 10 were disqualified due to abnormal lab tests. Applying our algorithm to optimize the order of tests, the average cost for screening a potential donor resulted in potential savings of 49.9% and a 21.3% savings in the cost to qualify a single donor. Conclusions. Improving the order and timing of the screening tests of potential FMT stool donors can decrease the costs by about 50% per subject. Highlights What is known:Fecal microbial transplantation (FMT) is the transfer of microbiome from healthy donors to patients.Fecal donors undergo multiple strict screening tests to exclude any transmissible disease.Screening tests of potential fecal donors is expensive and time consuming.FMT is the most efficient treatment for recurrent C difficile infection.What is new here:An algorithm to optimize the order of donors' screening tests in terms of cost was defined.Optimizing the order tests can save nearly 50% in costs of screening a potential donor.
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Affiliation(s)
- Bar Levy
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Naomi Fliss Isakov
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
| | | | - Moshe Leshno
- Coller School of Management, Tel Aviv University, Tel Aviv, Israel
| | - Nitsan Maharshak
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Lael Werner
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
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3
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Jamal R, Messaoudene M, de Figuieredo M, Routy B. Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology. Semin Immunol 2023; 67:101754. [PMID: 37003055 DOI: 10.1016/j.smim.2023.101754] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 02/26/2023] [Accepted: 02/26/2023] [Indexed: 04/01/2023]
Abstract
The gut microbiota has rapidly emerged as one of the "hallmarks of cancers" and a key contributor to cancer immunotherapy. Metagenomics profiling has established the link between microbiota compositions and immune checkpoint inhibitors response and toxicity, while murine experiments demonstrating the synergistic benefits of microbiota modification with immune checkpoint inhibitors (ICIs) pave a clear path for translation. Fecal microbiota transplantation (FMT) is one of the most effective treatments for patients with Clostridioides difficile, but its utility in other disease contexts has been limited. Nonetheless, promising data from the first trials combining FMT with ICIs have provided strong clinical rationale to pursue this strategy as a novel therapeutic avenue. In addition to the safety considerations surrounding new and emerging pathogens potentially transmissible by FMT, several other challenges must be overcome in order to validate the use of FMT as a therapeutic option in oncology. In this review, we will explore how the lessons learned from FMT in other specialties will help shape the design and development of FMT in the immuno-oncology arena.
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Fortman D, Avellan MGP, Hurd D, Schwartz M, Dubner H, Hewitt C, Berton S, Ernst S, Rose A, Zarour HWH, Davar D. Screening costs associated with donor selection for fecal microbiota transplantation for treatment of PD-1 refractory melanoma patients. Melanoma Res 2023; 33:136-148. [PMID: 36806616 PMCID: PMC9949524 DOI: 10.1097/cmr.0000000000000871] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 11/14/2022] [Indexed: 02/23/2023]
Abstract
The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult. Therefore, we aimed to establish a novel donor-screening program to generate responder-derived FMT for use in PD-1 refractory melanoma. Candidate PD-1 responder donors and PD-1 refractory recipients were recruited via clinic-based encounters at the University of Pittsburgh Medical Center hospitals. Eligible donors and recipients underwent physician assessment and screening of serum, stool and nasopharynx for transmissible agents, which included SARS-CoV-2 modification. The cost of donor and recipient screening was calculated. Initially, 29 donors were screened with 14 eligible donors identified after exclusion; of the 14 donors, eight were utilized in clinical trials. The overall efficiency of screening was 48%. Seroprevalence rates for cytomegalovirus, Epstein-Barr virus, HSV-2, HHV-6, HTLV-1, HTLV-2, and syphilis were similar to published statistics from healthy blood donors in the USA. Donor stool studies indicated a 3.6% incidence of E. histolytica and norovirus, 3.7% incidence of giardia and 7.1% incidence of C. difficile. A single donor tested positive for SARS-CoV-2 in stool only. The cost for finding a single eligible donor was $2260.24 (pre-COVID) and $2,460.24 (post-COVID). The observed screening efficiency suggests that a well-resourced screening program can generate sufficient responder-derived donor material for clinical trial purposes. Eliminating testing for low-prevalence organisms may improve cost-effectiveness.
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Affiliation(s)
- Dylan Fortman
- Division of Internal Medicine, Department of Medicine
| | | | - Drew Hurd
- Department of Medicine, UPMC Hillman Cancer Center
| | - Marc Schwartz
- Division of Gastroenterology, Department of Medicine
| | - Howard Dubner
- Division of Gastroenterology, Department of Medicine
| | - Corey Hewitt
- Department of Medicine, UPMC Hillman Cancer Center
| | | | | | - Amy Rose
- Department of Medicine, UPMC Hillman Cancer Center
| | - Hong Wangd, Hassane Zarour
- Department of Medicine, UPMC Hillman Cancer Center
- Department of Biostatistics
- Department of Immunology and fDivision of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Diwakar Davar
- Department of Medicine, UPMC Hillman Cancer Center
- Department of Immunology and fDivision of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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5
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Bénard MV, de Bruijn CMA, Fenneman AC, Wortelboer K, Zeevenhoven J, Rethans B, Herrema HJ, van Gool T, Nieuwdorp M, Benninga MA, Ponsioen CY. Challenges and costs of donor screening for fecal microbiota transplantations. PLoS One 2022; 17:e0276323. [PMID: 36264933 PMCID: PMC9584411 DOI: 10.1371/journal.pone.0276323] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 10/03/2022] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND The increasing interest to perform and investigate the efficacy of fecal microbiota transplantation (FMT) has generated an urge for feasible donor screening. We report our experience with stool donor recruitment, screening, follow-up, and associated costs in the context of clinical FMT trials. METHODS Potential stool donors, aged between 18-65 years, underwent a stepwise screening process starting with an extensive questionnaire followed by feces and blood investigations. When eligible, donors were rescreened for MDROs and SARS-CoV-2 every 60-days, and full rescreening every 4-6 months. The costs to find and retain a stool donor were calculated. RESULTS From January 2018 to August 2021, 393 potential donors underwent prescreening, of which 202 (51.4%) did not proceed primarily due to loss to follow-up, medication use, or logistic reasons (e.g. COVID-19 measures). 191 potential donors filled in the questionnaire, of which 43 (22.5%) were excluded. The remaining 148 candidates underwent parasitology screening: 91 (61.5%) were excluded, mostly due to Dientamoeba fragilis and/or high amounts of Blastocystis spp. After additional feces investigations 18/57 (31.6%) potential donors were excluded (mainly for presence of Helicobacter Pylori and ESBL-producing organisms). One donor failed serum testing. Overall, 38 out of 393 (10%) potential donors were enrolled. The median participation time of active stool donors was 13 months. To recruit 38 stool donors, €64.112 was spent. CONCLUSION Recruitment of stool donors for FMT is challenging. In our Dutch cohort, failed eligibility of potential donors was often caused by the presence of the protozoa Dientamoeba fragilis and Blastocystis spp.. The exclusion of potential donors that carry these protozoa, especially Blastocystis spp., is questionable and deserves reconsideration. High-quality donor screening is associated with substantial costs.
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Affiliation(s)
- Mèlanie V. Bénard
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- * E-mail:
| | - Clara M. A. de Bruijn
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, The Netherlands
- Amsterdam Reproduction & Development Research Institute, Amsterdam UMC, Emma Children’s Hospital, Amsterdam, The Netherlands
| | - Aline C. Fenneman
- Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Clinical and Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Koen Wortelboer
- Department of Clinical and Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Judith Zeevenhoven
- Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, The Netherlands
| | - Bente Rethans
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Hilde J. Herrema
- Department of Clinical and Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Tom van Gool
- Section Clinical Parasitology, Department of Medical Microbiology, Amsterdam University Medical Centers, Amsterdam Medical Center, Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Department of Clinical and Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marc A. Benninga
- Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, The Netherlands
| | - Cyriel Y. Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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Xu H, Cao C, Ren Y, Weng S, Liu L, Guo C, Wang L, Han X, Ren J, Liu Z. Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment. Front Immunol 2022; 13:949490. [PMID: 36177041 PMCID: PMC9513044 DOI: 10.3389/fimmu.2022.949490] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 08/04/2022] [Indexed: 11/20/2022] Open
Abstract
Fecal microbiome transplantation (FMT) from healthy donors is one of the techniques for restoration of the dysbiotic gut, which is increasingly being used to treat various diseases. Notably, mounting evidence in recent years revealed that FMT has made a breakthrough in the oncology treatment area, especially by improving immunotherapy efficacy to achieve antitumor effects. However, the mechanism of FMT in enhancing antitumor effects of immune checkpoint blockers (ICBs) has not yet been fully elucidated. This review systematically summarizes the role of microbes and their metabolites in the regulation of tumor immunity. We highlight the mechanism of action of FMT in the treatment of refractory tumors as well as in improving the efficacy of immunotherapy. Furthermore, we summarize ongoing clinical trials combining FMT with immunotherapy and further focus on refined protocols for the practice of FMT in cancer treatment, which could guide future directions and priorities of FMT scientific development.
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Affiliation(s)
- Hui Xu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Interventional Institute of Zhengzhou University, Zhengzhou, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, China
| | - Chenxi Cao
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuqing Ren
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Siyuan Weng
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Long Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chunguang Guo
- Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Libo Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Interventional Institute of Zhengzhou University, Zhengzhou, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, China
- *Correspondence: Xinwei Han, ; Jianzhuang Ren, ; Zaoqu Liu,
| | - Jianzhuang Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Xinwei Han, ; Jianzhuang Ren, ; Zaoqu Liu,
| | - Zaoqu Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Interventional Institute of Zhengzhou University, Zhengzhou, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, China
- *Correspondence: Xinwei Han, ; Jianzhuang Ren, ; Zaoqu Liu,
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Parnell JM, Nicholson MR, Kellermayer R, Kahn SA. Pediatric Fecal Microbiota Transplantation in Recurrent Clostridioides Difficile. Pediatr Ann 2021; 50:e515-e521. [PMID: 34889135 DOI: 10.3928/19382359-20211111-01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
With the rising rates of Clostridioides (Clostridium) difficile infection (CDI) in children, recognizing the limitations of CDI-directed antibiotic therapy, especially in recurrent CDI (rCDI), is important. Fecal microbiota transplantation (FMT), which directly targets the underlying gut dysbiosis present in rCDI, is an important treatment option to consider in rCDI. This article will summarize indications, procedures, effectiveness, and the safety of FMT for rCDI in pediatric patients. [Pediatr Ann. 2021;50(12):e515-e521.].
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8
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Baunwall SMD, Dahlerup JF, Engberg JH, Erikstrup C, Helms M, Juel MA, Kjeldsen J, Nielsen HL, Nilsson AC, Rode AA, Vinter-Jensen L, Hvas CL. Danish national guideline for the treatment of Clostridioides difficile infection and use of faecal microbiota transplantation (FMT). Scand J Gastroenterol 2021; 56:1056-1077. [PMID: 34261379 DOI: 10.1080/00365521.2021.1922749] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Aim: This Danish national guideline describes the treatment of adult patients with Clostridioides (formerly Clostridium) difficile (CD) infection and the use of faecal microbiota transplantation (FMT). It suggests minimum standard for implementing an FMT service.Method: Four scientific societies appointed members for a working group which conducted a systematic literature review and agreed on the text and recommendations. All clinical recommendations were evalluated for evidence level and grade of recommendation.Results: In CD infection, the use of marketed and experimental antibiotics as well as microbiota-based therapies including FMT are described. An algorithm for evaluating treatment effect is suggested. The organisation of FMT, donor recruitment and screening, laboratory preparation, clinical application and follow-up are described.Conclusion: Updated evidence for the treatment of CD infection and the use of FMT is provided.
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Affiliation(s)
| | - Jens Frederik Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Morten Helms
- Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark
| | | | - Jens Kjeldsen
- Department of Gastroenterology, Odense University Hospital, Odense, Denmark
| | - Hans Linde Nielsen
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
| | | | - Anne Abildtrup Rode
- Department of Internal Medicine, Zealand University Hospital, Roskilde, Denmark
| | - Lars Vinter-Jensen
- Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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9
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Chen J, Zaman A, Ramakrishna B, Olesen SW. Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank. Front Cell Infect Microbiol 2021; 11:622949. [PMID: 33937092 PMCID: PMC8082449 DOI: 10.3389/fcimb.2021.622949] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 03/22/2021] [Indexed: 12/15/2022] Open
Abstract
Objectives Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of microbiota-mediated indications. Stool banks centralize FMT donor screening and FMT material preparation with the goal of expanding access to FMT material while simultaneously improving its safety, quality, and convenience. Although there are published consensuses on donor screening guidelines, there are few reports about the implementation of those guidelines in functioning stool banks. Methods To help inform consensus standards with data gathered from real-world settings and, in turn, to improve patient care, here we describe the general methodology used in 2018 by OpenBiome, a large stool bank, and its outputs in that year. Results In 2018, the stool bank received 7,536 stool donations from 210 donors, a daily average of 20.6 donations, and processed 4,271 of those donations into FMT preparations. The median time a screened and enrolled stool donor actively donated stool was 5.8 months. The median time between the manufacture of an FMT preparation and its shipment to a hospital or physician was 8.9 months. Half of the stool bank's partner hospitals and physicians ordered an average of 0.75 or fewer FMT preparations per month. Conclusions Further knowledge sharing should help inform refinements of stool banking guidelines and best practices.
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10
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Knežević D, Petković M. Faecal transplantation and Clostridioides difficile infection. SCRIPTA MEDICA 2021. [DOI: 10.5937/scriptamed52-32752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Faecal microbiota transplantation (FMT), known equally well as faecal transplantation or faecal bacteriotherapy, is the process of implanting the faecal suspension containing balanced microbiota from a healthy donor to the colon of a recipient patient. Excessive growth of Clostridioides difficile (C difficile) in the intestinal microbiota resulting from antibiotic consumption is currently a rising threat to public health. FMT is one of the most important, newer approaches to treating C difficile infections. Since C difficile is regarded as an opportunistic bacterium triggering disease in conditions of disturbed homeostasis of the intestinal microbiota, restoration of healthy intestinal microflora facilitates suppression of toxic strain of C difficile by anaerobic bacteria of normal intestinal microflora with concomitant cure. Nurses have important role in caring for patients after faecal transplantation.
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11
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Terra DADA, Vilela EG, Silva ROS, LeÃo LA, Lima KS, Passos RIFÂ, Diniz AN, Coelho LGV. STRUCTURING A FECAL MICROBIOTA TRANSPLANTATION CENTER IN A UNIVERSITY HOSPITAL IN BRAZIL. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:434-458. [PMID: 33331486 DOI: 10.1590/s0004-2803.202000000-79] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 06/30/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.
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Affiliation(s)
| | - Eduardo Garcia Vilela
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas / EBSERH, Universidade Federal de Mina Gerais, Belo Horizonte, MG, Brasil
| | | | - Laiane Alves LeÃo
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas / EBSERH, Universidade Federal de Mina Gerais, Belo Horizonte, MG, Brasil
| | - Karine Sampaio Lima
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas / EBSERH, Universidade Federal de Mina Gerais, Belo Horizonte, MG, Brasil
| | | | - Amanda Nádia Diniz
- Universidade Federal de Minas Gerais, Escola de Veterinária, Belo Horizonte, MG, Brasil
| | - Luiz Gonzaga Vaz Coelho
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas / EBSERH, Universidade Federal de Mina Gerais, Belo Horizonte, MG, Brasil
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12
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Kragsnaes MS, Nilsson AC, Kjeldsen J, Holt HM, Rasmussen KF, Georgsen J, Ellingsen T, Holm DK. How do I establish a stool bank for fecal microbiota transplantation within the blood- and tissue transplant service? Transfusion 2020; 60:1135-1141. [PMID: 32468608 DOI: 10.1111/trf.15816] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 03/11/2020] [Accepted: 03/15/2020] [Indexed: 12/13/2022]
Abstract
Worldwide, there is a rising demand for thoroughly screened, high-quality fecal microbiota transplantation (FMT) products that can be obtained at a reasonable cost. In the light of this evolving therapeutic area of the intestinal microbiota, both private and public stool banks have emerged. However, some of the larger difficulties when establishing stool banks are caused by the absence of or international disagreement on regulation and legislative formalities. In this context, the establishment of a stool bank within a nonprofit blood and tissue transplant service has several advantages. Especially, this setting can ensure that every step of the donation process, laboratory handling, and donor-traceability is in agreement with the current expert guidelines and meets the requirements of the European Union's regulative directives on human cells and tissues. Although safety and documentation are the top priority of the stool bank setup presented here, cost-effectiveness of the production is possible due to a high donor screening success rate and the knowhow, infrastructure, facilities, personnel, and laboratory- and quality-management systems that were already in place. Overall, our experience is that a centralized, nonprofit, blood and tissue transplant service is an ideal and safe facility to run a stool bank of high quality FMT products that are based on stool donations from volunteer, unpaid, healthy, blood donors.
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Affiliation(s)
- Maja Skov Kragsnaes
- The Rheumatology Research Unit, Department of Rheumatology, Odense University Hospital and University of Southern Denmark, Odense, Denmark
| | | | - Jens Kjeldsen
- Department of Gastroenterology, Odense University Hospital, Odense, Denmark
| | - Hanne Marie Holt
- Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
| | | | - Jørgen Georgsen
- Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
| | - Torkell Ellingsen
- The Rheumatology Research Unit, Department of Rheumatology, Odense University Hospital and University of Southern Denmark, Odense, Denmark
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13
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Kumar V, Fischer M. Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. Expert Opin Biol Ther 2020; 20:73-81. [PMID: 31690143 DOI: 10.1080/14712598.2020.1689952] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 11/04/2019] [Indexed: 02/07/2023]
Abstract
Introduction: Fecal microbiota transplantation (FMT) is a procedure involving transfer of stool from a healthy donor into the intestinal tract of a diseased recipient to restore intestinal microbial composition and functionality. FMT's tremendous success in recurrent and refractory Clostridioides difficile infection (CDI) catalyzed gut microbiota research and opened the door to microbiome-based therapy for various gastrointestinal and other disorders.Areas covered: We used PubMed search engine to identify significant publications in the field of CDI and FMT. Here we present an overview of the current literature on FMT's use for recurrent, non-severe, severe, and fulminant CDI and on promising future application.Expert opinion: FMT as the best tool for treatment of antibiotic-refractory CDI has gained immense popularity over the last decade. The future of gut microbiota-based therapy should include oral formulations that contain well-described ingredients in effective doses, clear mechanism of action, and excellent safety profile.
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Affiliation(s)
- Vinod Kumar
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Monika Fischer
- Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
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14
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Turse EP, Dailey FE, Ghouri YA, Tahan V. Fecal microbiota transplantation donation: the gift that keeps on giving. Curr Opin Pharmacol 2019; 49:24-28. [PMID: 31085417 DOI: 10.1016/j.coph.2019.04.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Accepted: 04/08/2019] [Indexed: 12/13/2022]
Abstract
Fecal microbiota transplantation (FMT) is being studied and utilized for various medical conditions including Clostridium difficile colitis, inflammatory bowel diseases (IBD), obesity, myasthenia gravis, and so on. Yet, FMT donation, whether from an individual or a stool bank, can be challenging given the numerous requirements and donor costs. Furthermore, data outcomes on recipients of FMT regarding donor's health co-morbidities, age, and weight are limited but emerging. The purpose of this review is to evaluate cost, safety, and accessibility in FMT donation.
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Affiliation(s)
- Erica P Turse
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, St. Joseph's Hospital and Medical Center/Creighton University, Phoenix, AZ, USA
| | - Francis E Dailey
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Missouri-Columbia, Missouri, USA
| | - Yezaz A Ghouri
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Missouri-Columbia, Missouri, USA
| | - Veysel Tahan
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Missouri-Columbia, Missouri, USA.
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15
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Jørgensen SMD, Hvas CL, Dahlerup JF, Mikkelsen S, Ehlers L, Hammeken LH, Licht TR, Bahl MI, Erikstrup C. Banking feces: a new frontier for public blood banks? Transfusion 2019; 59:2776-2782. [PMID: 31241182 PMCID: PMC6852397 DOI: 10.1111/trf.15422] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 05/27/2019] [Accepted: 05/27/2019] [Indexed: 12/15/2022]
Abstract
Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection and is potentially beneficial in other microbiota-related disorders. The provision of FMT in routine clinical practice requires an extensive infrastructure that is reliant on voluntary donors. Alongside an increasing demand for FMT, the logistic barriers of a large-scale donor-dependent operation and the difficulties among health authorities to regulate FMT limit the dissemination of sustainable FMT services. Blood centers are large organizations that handle a multitude of donor-dependent operations on a daily basis. Blood and feces share many of the same dependencies, and feces may present a new opportunity for the blood services to handle. In this paper, we describe how an FMT service may be established and embedded within the blood service infrastructure, and we explain the benefits of using blood donors as feces donors. We further explore the current indications of FMT, the challenges related to the lack of legislation, and the future perspectives for blood banks to meet a new and increasing demand.
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Affiliation(s)
| | | | | | - Susan Mikkelsen
- Department of Clinical ImmunologyAarhus University HospitalAarhusDenmark
| | - Lars Ehlers
- Department of Business and Management, Danish Centre for Healthcare ImprovementsAalborg UniversityAalborgDenmark
| | - Lianna Hede Hammeken
- Department of Business and Management, Danish Centre for Healthcare ImprovementsAalborg UniversityAalborgDenmark
| | - Tine Rask Licht
- National Food InstituteTechnical University of DenmarkKgs. LyngbyDenmark
| | - Martin Iain Bahl
- National Food InstituteTechnical University of DenmarkKgs. LyngbyDenmark
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16
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Dehlholm-Lambertsen E, Hall BK, Jørgensen SMD, Jørgensen CW, Jensen ME, Larsen S, Jensen JS, Ehlers L, Dahlerup JF, Hvas CL. Cost savings following faecal microbiota transplantation for recurrent Clostridium difficile infection. Therap Adv Gastroenterol 2019; 12:1756284819843002. [PMID: 31007720 PMCID: PMC6460887 DOI: 10.1177/1756284819843002] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 02/26/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Recurrent Clostridium difficile infection (rCDI) is becoming increasingly common. Faecal microbiota transplantation (FMT) is effective for rCDI, but the costs of an FMT and hospital cost savings related to FMT are unknown. The aim of this study was to calculate the cost of an FMT and the total hospital costs before and after FMT. METHODS This was an observational single-centre study, carried out in a public teaching hospital. We included all patients referred for rCDI from January 2014 through December 2015 and documented costs related to donor screening, laboratory processing, and clinical FMT application. We calculated patient-related hospital costs 1 year before FMT (pre-FMT) and 1 year after FMT (post-FMT). Sensitivity analyses were applied to assess the robustness of the results. RESULTS We included 50 consecutive adult patients who had a verified diagnosis of rCDI and were referred for FMT. The average cost of an outpatient FMT procedure if donor faeces were applied by colonoscopy was €3,326 per patient and €2,864 if donor faeces were applied using a nasojejunal tube. The total annual pre-FMT hospital costs per patient were €56,415 (95% confidence interval (CI) 41,133-71,697), and these costs dropped by 42% to €32,816 (22,618-42,014) post-FMT (p = 0.004). The main cost driver was hospital admissions. Sensitivity analyses demonstrated cost reductions in all scenarios. CONCLUSIONS In a public hospital with an implemented FMT service, the average cost of FMT applied by either colonoscopy or nasojejunal tube was €3,095. Total hospital costs dropped by 42% the first year after FMT. The reduction was mainly caused by reductions in the number of hospital admissions and in length of stay.
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Affiliation(s)
| | | | - Simon M. D. Jørgensen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Mia E. Jensen
- School of Medicine and Health (SMH), Aalborg University, Denmark
| | - Sara Larsen
- School of Medicine and Health (SMH), Aalborg University, Denmark
| | | | - Lars Ehlers
- Department of Business and Management, Danish Center for Healthcare Improvements, Aalborg University, Aalborg, Denmark
| | - Jens F. Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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17
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Kim KO, Gluck M. Fecal Microbiota Transplantation: An Update on Clinical Practice. Clin Endosc 2019; 52:137-143. [PMID: 30909689 PMCID: PMC6453848 DOI: 10.5946/ce.2019.009] [Citation(s) in RCA: 126] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Accepted: 03/06/2019] [Indexed: 12/17/2022] Open
Abstract
Fecal microbiota transplantation (FMT) is an infusion in the colon, or the delivery through the upper gastrointestinal tract, of stool from a healthy donor to a recipient with a disease believed to be related to an unhealthy gut microbiome. FMT has been successfully used to treat recurrent Clostridium difficile infection (rCDI). The short-term success of FMT in rCDI has led to investigations of its application to other gastrointestinal disorders and extra-intestinal diseases with presumed gut dysbiosis. Despite the promising results of FMT in these conditions, several barriers remain, including determining the characteristics of a healthy microbiome, ensuring the safety of the recipient with respect to long-term outcomes, adequate monitoring of the recipient of fecal material, achieving high-quality control, and maintaining reasonable costs. For these reasons, establishing uniform protocols for stool preparation, finding the best modes of FMT administration, maintaining large databases of donors and recipients, and assuring that oral ingestion is equivalent to the more widely accepted colonoscopic infusion are issues that need to be addressed.
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Affiliation(s)
- Kyeong Ok Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA
| | - Michael Gluck
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA
- Correspondence: Michael Gluck Digestive Disease Institute, Virginia Mason Medical Center, 1100 Ninth Ave, C3-GAS, Seattle, WA 98101, USA Tel: +1-206-223-2319, Fax: +1-206-341-1405, E-mail:
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18
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Sunkara T, Rawla P, Ofosu A, Gaduputi V. Fecal microbiota transplant - a new frontier in inflammatory bowel disease. J Inflamm Res 2018; 11:321-328. [PMID: 30214266 PMCID: PMC6124474 DOI: 10.2147/jir.s176190] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic multifactorial disease that affects the gastrointestinal tract and results from an aberrant immune response toward luminal antigens in genetically susceptible people. Most of the current therapies for IBD focus on the management of the inflammation by using corticosteroids, immune modulators, and more recently, monoclonal antibodies (biological therapy). Although these therapies provide benefit in most cases, there are still a significant number of patients who do not respond or become refractory over time, suggesting the need for alternative therapeutic options. In the last decade, it has been recognized that "dysbiosis," an imbalanced gut microbiota, is a key element in IBD suggesting microbiome-based therapies as an attractive approach. Recently, fecal microbiota transplant (FMT) has been successfully used for the treatment of Clostridium difficile infection, and it is now under investigation for the treatment of IBD. Clinical trials data are still poor but strongly support a future introduction of FMT in therapy to manage IBD microbiome. More studies are needed to assess the optimal route of administration and the frequency of FMT, the best matched donor for each patient as well as the risks associated with FMT in IBD.
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Affiliation(s)
- Tagore Sunkara
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Mount Sinai Health System, New York, NY, USA
| | - Prashanth Rawla
- Department of Internal Medicine, Sovah Health, Martinsville, VA, USA,
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Mount Sinai Health System, New York, NY, USA
| | - Vinaya Gaduputi
- Division of Gastroenterology, SBH Health System, Bronx, NY, USA
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19
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Hu J, Chen L, Tang Y, Xie C, Xu B, Shi M, Zheng W, Zhou S, Wang X, Liu L, Yan Y, Yang T, Niu Y, Hou Q, Xu X, Yan X. Standardized Preparation for Fecal Microbiota Transplantation in Pigs. Front Microbiol 2018; 9:1328. [PMID: 29971061 PMCID: PMC6018536 DOI: 10.3389/fmicb.2018.01328] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 05/30/2018] [Indexed: 12/26/2022] Open
Abstract
The intestine of pigs harbors a mass of microorganisms which are essential for intestinal homeostasis and host health. Intestinal microbial disorders induce enteric inflammation and metabolic dysfunction, thereby causing adverse effects on the growth and health of pigs. In the human medicine, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, has shown efficacy in intestinal microbiota restoration. In addition, it has been used widely in therapy for human gastrointestinal diseases, including Clostridium difficile infection, inflammatory bowel diseases, and irritable bowel syndrome. Given that pigs share many similarities with humans, in terms of anatomy, nutritional physiology, and intestinal microbial compositions, FMT may also be used to restore the normal intestinal microbiota of pigs. However, feasible procedures for performing FMT in pigs remains unclear. Here, we summarize a standardized preparation for FMT in pigs by combining the standard methodology for human FMT with pig production. The key issues include the donor selection, fecal material preparation, fecal material transfer, stool bank establishment, and the safety for porcine FMT. Optimal donors should be selected to ensure the efficacy of porcine FMT and reduce the risks of transmitting infectious diseases to recipients during FMT. Preparing for fresh fecal material is highly recommended. Alternatively, frozen fecal suspension can also be prepared as an optimal choice because it is convenient and has similar efficacy. Oral administration of fecal suspension could be an optimal method for porcine fecal material transfer. Furthermore, the dilution ratio of fecal materials and the frequency of fecal material transfer could be adjusted according to practical situations in the pig industry. To meet the potential large-scale requirement in the pig industry, it is important to establish a stool bank to make porcine FMT readily available. Future studies should also focus on providing more robust safety data on FMT to improve the safety and tolerability of the recipient pigs. This standardized preparation for porcine FMT can facilitate the development of microbial targeted therapies and improve the intestinal health of pigs.
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Affiliation(s)
- Jun Hu
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Lingli Chen
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Yimei Tang
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Chunlin Xie
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Baoyang Xu
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Min Shi
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Wenyong Zheng
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Shuyi Zhou
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Xinkai Wang
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Liu Liu
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Yiqin Yan
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Tao Yang
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Yaorong Niu
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Qiliang Hou
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Xiaofan Xu
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
| | - Xianghua Yan
- State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China.,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.,Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, China
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20
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Brumbaugh DE, De Zoeten EF, Pyo-Twist A, Fidanza S, Hughes S, Dolan SA, Child J, Dominguez SR. An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive. J Pediatr 2018; 194:123-127.e1. [PMID: 29198534 DOI: 10.1016/j.jpeds.2017.10.016] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 09/26/2017] [Accepted: 10/12/2017] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI). STUDY DESIGN Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube. RESULTS A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P = .04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative. CONCLUSION A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.
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Affiliation(s)
- David E Brumbaugh
- Section of Gastroenterology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO; Children's Hospital Colorado, Aurora, CO.
| | - Edwin F De Zoeten
- Section of Gastroenterology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO; Children's Hospital Colorado, Aurora, CO
| | - Amy Pyo-Twist
- Department of Nursing, Children's Hospital Colorado, Aurora, CO
| | - Sara Fidanza
- Department of Nursing, Children's Hospital Colorado, Aurora, CO
| | - Shannon Hughes
- Section of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO
| | - Susan A Dolan
- Department of Epidemiology, Children's Hospital Colorado, Aurora, CO
| | - Jason Child
- Department of Pharmacy, Children's Hospital Colorado, Aurora, CO
| | - Samuel R Dominguez
- Section of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO; Department of Epidemiology, Children's Hospital Colorado, Aurora, CO
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21
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Shen ZH, Zhu CX, Quan YS, Yang ZY, Wu S, Luo WW, Tan B, Wang XY. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol 2018; 24:5-14. [PMID: 29358877 PMCID: PMC5757125 DOI: 10.3748/wjg.v24.i1.5] [Citation(s) in RCA: 446] [Impact Index Per Article: 63.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Revised: 11/07/2017] [Accepted: 11/21/2017] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors contribute to the pathogenesis of UC. However, studies on the role of intestinal microbiota in the pathogenesis of UC have been inconclusive. Studies have shown that probiotics improve intestinal mucosa barrier function and immune system function and promote secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful bacteria in the intestine. Fecal microbiota transplantation (FMT) can reduce bowel permeability and thus the severity of disease by increasing the production of short-chain fatty acids, especially butyrate, which help maintain the integrity of the epithelial barrier. FMT can also restore immune dysbiosis by inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and production of inflammatory factors. Probiotics and FMT are being increasingly used to treat UC, but their use is controversial because of uncertain efficacy. Here, we briefly review the role of intestinal microbiota in the pathogenesis and treatment of UC.
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Affiliation(s)
- Zhao-Hua Shen
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
| | - Chang-Xin Zhu
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
| | - Yong-Sheng Quan
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
| | - Zhen-Yu Yang
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
| | - Shuai Wu
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
| | - Wei-Wei Luo
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
| | - Bei Tan
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
| | - Xiao-Yan Wang
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
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22
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Craven LJ, Nair Parvathy S, Tat-Ko J, Burton JP, Silverman MS. Extended Screening Costs Associated With Selecting Donors for Fecal Microbiota Transplantation for Treatment of Metabolic Syndrome-Associated Diseases. Open Forum Infect Dis 2017; 4:ofx243. [PMID: 29255739 PMCID: PMC5730934 DOI: 10.1093/ofid/ofx243] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Accepted: 11/02/2017] [Indexed: 11/22/2022] Open
Abstract
Background Knowledge of the impact of the gut microbiome on conditions other than Clostridium difficile infection has been rapidly increasing, and the potential usefulness of fecal microbiota transplantation (FMT) in these indications is being explored. The need to exclude donors with an increased risk of these diseases has left uncertainties regarding the cost and feasibility of donor screening. The aim of this study was to compare our experience to other donor-screening programs and report the costs associated with establishing a donor-screening program, for the treatment of metabolic syndrome-related conditions. Methods Forty-six potential donors (PDs) had their medical histories and physical examinations undertaken by a physician. Blood, stool, and urine were screened for 31 viral, bacterial, fungal, and protozoan agents in addition to biochemical characteristics. The price of advertising, doctor’s visits and diagnostic tests were calculated to determine the cost of finding a donor. Results Of the PDs screened, 5 of 46 passed the history, examination, blood, stool, and urine tests. The most common reasons for exclusion included a body mass index >25 or the detection of Blastocystis hominis, Dientamoeba fragilis, or Helicobacter pylori. Four of five eligible donors had subsequent travel or illness that contraindicated donation, so only 1 of 46 PDs was suitable. The total cost for finding a single suitable donor was $15190 US dollars. This screening was performed in Canada, and costs in the United States would be substantially higher. Conclusions New potential therapeutic uses for FMT have created a demand for stricter exclusion criteria for donors. This study illustrates that screening many individuals to find a donor and the subsequent associated costs may make central processing and shipment a more reasonable alternative.
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Affiliation(s)
- Laura J Craven
- Department of Microbiology and Immunology, London, Ontario, Canada.,Lawson Health Research Institute, London, Ontario, Canada
| | - Seema Nair Parvathy
- Department of Infectious Disease, St. Joseph's Health Care, London, Ontario, Canada
| | - Justin Tat-Ko
- Department of Microbiology and Immunology, London, Ontario, Canada
| | - Jeremy P Burton
- Department of Microbiology and Immunology, London, Ontario, Canada.,Division of Urology, Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.,Lawson Health Research Institute, London, Ontario, Canada
| | - Michael S Silverman
- Department of Microbiology and Immunology, London, Ontario, Canada.,Lawson Health Research Institute, London, Ontario, Canada.,Department of Infectious Disease, St. Joseph's Health Care, London, Ontario, Canada
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23
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Hampe CS, Roth CL. Probiotic strains and mechanistic insights for the treatment of type 2 diabetes. Endocrine 2017; 58:207-227. [PMID: 29052181 DOI: 10.1007/s12020-017-1433-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 09/20/2017] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The intestinal microbial composition appears to differ between healthy controls and individuals with Type 2 diabetes (T2D). This observation has led to the hypothesis that perturbations of the intestinal microbiota may contribute to the development of T2D. Manipulations of the intestinal microbiota may therefore provide a novel approach in the prevention and treatment of T2D. Indeed, fecal transplants have shown promising results in both animal models for obesity and T2D and in human clinical trials. To avoid possible complications associated with fecal transplants, probiotics are considered as a viable alternative therapy. An important, however often underappreciated, characteristic of probiotics is that individual strains may have different, even opposing, effects on the host. This strain specificity exists also within the same species. A comprehensive understanding of the underlying mechanisms at the strain level is therefore crucial for the selection of suitable probiotic strains. PURPOSE The aim of this review is to discuss the mechanisms employed by specific probiotic strains of the Lactobacillus and the Bifidobacterium genuses, which showed efficacy in the treatment of obesity and T2D. Some probiotic strains employ recurring beneficial effects, including the production of anti-microbial lactic acid, while other strains display highly unique features, such as hydrolysis of tannins. CONCLUSION A major obstacle in the evaluation of probiotic strains lays in the great number of strains, differences in detection methodology and measured outcome parameters. The understanding of further research should be directed towards the development of standardized evaluation methods to facilitate the comparison of different studies.
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Affiliation(s)
- Christiane S Hampe
- Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA, 98109, USA.
| | - Christian L Roth
- Center for Integrative Brain Research, Seattle Children's Hospital & Research Institute, Seattle, WA, 98101, USA
- Pediatric Endocrinology, Seattle Children's Hospital & Research Institute, Seattle, WA, 98101, USA
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24
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Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies. Clin Microbiol Rev 2017; 30:191-231. [PMID: 27856521 DOI: 10.1128/cmr.00049-16] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases.
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25
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Kelly BJ, Tebas P. Clinical Practice and Infrastructure Review of Fecal Microbiota Transplantation for Clostridium difficile Infection. Chest 2017; 153:266-277. [PMID: 28923757 DOI: 10.1016/j.chest.2017.09.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 08/31/2017] [Accepted: 09/05/2017] [Indexed: 12/14/2022] Open
Abstract
A substantial proportion of Clostridium difficile infection (CDI) cases recur after completion of antibiotic therapy, and antibiotic cure rates diminish with each recurrence of CDI. Fecal microbiota transplantation (FMT) is an effective therapy for recurrent FMT, which otherwise requires prolonged or indefinite antibiotic treatment. FMT is performed by introducing the fecal microbial community obtained from a healthy donor or pool of donors into the stomach, small intestine, or colon of a patient with CDI. Multiple clinical trials support the usefulness of FMT in treating recurrent CDI, and CDI treatment guidelines now include consideration of FMT at the third CDI recurrence. However, there remain challenges to incorporating FMT into clinical practice. First, methods of fecal bacterial community processing vary, as do methods of FMT administration. Second, the optimal dosing strategy and expected benefit of FMT for refractory CDI, particularly for severe and severe complicated cases, are uncertain. Third, the US Food and Drug Administration (FDA) considers FMT an investigational treatment. Fourth, insurance reimbursement for FMT usually falls short of FMT administration costs. In the setting of rising C difficile incidence and growing evidence for FMT efficacy, the demand for FMT has increased. However, uncertainty surrounding optimal FMT preparation and administration methods, FDA oversight, and insurance reimbursement presently limits the clinical practice of FMT.
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Affiliation(s)
- Brendan J Kelly
- Division of Infectious Diseases and Fecal Microbiota Transplantation Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
| | - Pablo Tebas
- Division of Infectious Diseases and Fecal Microbiota Transplantation Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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26
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Ma Y, Yang J, Cui B, Xu H, Xiao C, Zhang F. How Chinese clinicians face ethical and social challenges in fecal microbiota transplantation: a questionnaire study. BMC Med Ethics 2017; 18:39. [PMID: 28569156 PMCID: PMC5452366 DOI: 10.1186/s12910-017-0200-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 05/24/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is reportedly the most effective therapy for relapsing Clostridium Difficile infection (CDI) and a potential therapeutic option for many diseases. It also poses important ethical concerns. This study is an attempt to assess clinicians' perception and attitudes towards ethical and social challenges raised by fecal microbiota transplantation. METHODS A questionnaire was developed which consisted of 20 items: four items covered general aspects, nine were about ethical aspects such as informed consent and privacy issues, four concerned social and regulatory issues, and three were about an FMT bank. This was distributed to participants at the Second China gastroenterology and FMT conference in May 2015. Basic descriptive statistical analyses and simple comparative statistical tests were performed. RESULTS Nearly three quarters of the 100 respondents were gastro-enterologist physicians. 89% of all respondents believed FMT is a promising treatment modality for some diseases and 88% of whom chose clinical efficacy as the primary reason for recommending FMT. High expectation from patients and pressure on clinicians (33%) was reported as the most frequent reasons for not recommending FMT. The clinicians who had less familiarity with FMT reported significantly more worry related to the dignity and psychological impact of FMT compared to those who have high familiarity with FMT (51.6% vs 27.8%, p = 0.021).More than half of the respondents (56.1%) were concerned about the commercialization of FMT, although almost one in five respondents did not see this as a problem. CONCLUSIONS We found most respondents have positive attitudes towards FMT but low awareness of published evidence. Informed consent for vulnerable patients, privacy and protection of donors were perceived as the most challenging ethical aspects of FMT. This study identified areas of limited knowledge and ways of addressing ethical issues and indicates the need to devise the education and training for clinicians on FMT.
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Affiliation(s)
- Yonghui Ma
- Center for Bioethics, Medical College, Xiamen University, Xiamen, China
| | - Jinqiu Yang
- Department of Nursing, Medical College, Xiamen University, Xiamen, China
| | - Bota Cui
- Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hongzhi Xu
- Department of Gastroenterology, Xiamen Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China
| | - Chuanxing Xiao
- Department of Gastroenterology, Xiamen Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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27
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Terveer EM, van Beurden YH, Goorhuis A, Seegers JFML, Bauer MP, van Nood E, Dijkgraaf MGW, Mulder CJJ, Vandenbroucke-Grauls CMJE, Verspaget HW, Keller JJ, Kuijper EJ. How to: Establish and run a stool bank. Clin Microbiol Infect 2017; 23:924-930. [PMID: 28529025 DOI: 10.1016/j.cmi.2017.05.015] [Citation(s) in RCA: 114] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2017] [Revised: 05/12/2017] [Accepted: 05/13/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Since 2013, several stool banks have been developed following publications reporting on clinical success of 'faecal microbiota transplantation' (FMT) for recurrent Clostridium difficile infections (CDI). However, protocols for donor screening, faecal suspension preparation, and transfer of the faecal suspension differ between countries and institutions. Moreover, no European consensus exists regarding the legislative aspects of the faecal suspension product. Internationally standardized recommendations about the above mentioned aspects have not yet been established. OBJECTIVE In 2015, the Netherlands Donor Feces Bank (NDFB) was founded with the primary aim of providing a standardized product for the treatment of patients with recurrent CDI in the Netherlands. Standard operation procedures for donor recruitment, donor selection, donor screening, and production, storage, and distribution of frozen faecal suspensions for FMT were formulated. RESULTS AND DISCUSSION Our experience summarized in this review addresses current donor recruitment and screening, preparation of the faecal suspension, transfer of the faecal microbiota suspension, and the experiences and follow-up of the patients treated with donor faeces from the NDFB.
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Affiliation(s)
- E M Terveer
- Dept. of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
| | - Y H van Beurden
- Dept. of Medical Microbiology & Infection Control, VU University Medical Center, Amsterdam, The Netherlands; Dept. of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
| | - A Goorhuis
- Dept. of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - J F M L Seegers
- Dept. of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - M P Bauer
- Dept. of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - E van Nood
- Dept. of Internal Medicine, Havenziekenhuis, Rotterdam, The Netherlands
| | - M G W Dijkgraaf
- Clinical Research Unit, Academic Medical Center, Amsterdam, The Netherlands
| | - C J J Mulder
- Dept. of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
| | | | - H W Verspaget
- Dept. of Biobanking and Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands
| | - J J Keller
- Dept. of Gastroenterology, MC Haaglanden, The Hague, The Netherlands; Dept. of Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands.
| | - E J Kuijper
- Dept. of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
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28
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Chanyi RM, Craven L, Harvey B, Reid G, Silverman MJ, Burton JP. Faecal microbiota transplantation: Where did it start? What have studies taught us? Where is it going? SAGE Open Med 2017; 5:2050312117708712. [PMID: 28540051 PMCID: PMC5431603 DOI: 10.1177/2050312117708712] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 04/12/2017] [Indexed: 12/14/2022] Open
Abstract
The composition and activity of microorganisms in the gut, the microbiome, is emerging as an important factor to consider with regard to the treatment of many diseases. Dysbiosis of the normal community has been implicated in inflammatory bowel disease, Crohn’s disease, diabetes and, most notoriously, Clostridium difficile infection. In Canada, the leading treatment strategy for recalcitrant C. difficile infection is to receive faecal material which by nature is filled with microorganisms and their metabolites, from a healthy individual, known as a faecal microbiota transplantation. This influx of bacteria into the gut helps to restore the microbiota to a healthy state, preventing C. difficile from causing further disease. Much of what is known with respect to the microbiota and faecal microbiota transplantation comes from animal studies simulating the human disease. Although these models allow researchers to perform studies that would be difficult in humans, they do not always recapitulate the human microbiome. This makes the translation of these results to humans somewhat questionable. The purpose of this review is to analyse these animal models and discuss the advantages and the disadvantages of them in relation to human translation. By understanding some of the limitation of animal models, we will be better able to design and perform experiments of most relevance to human applications.
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Affiliation(s)
- Ryan M Chanyi
- Division of Urology, Department of Surgery, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.,Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.,Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, ON, Canada
| | - Laura Craven
- Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada
| | - Brandon Harvey
- Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada
| | - Gregor Reid
- Division of Urology, Department of Surgery, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.,Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.,Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, ON, Canada
| | - Michael J Silverman
- Division of Infectious Diseases, Department of Medicine, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada
| | - Jeremy P Burton
- Division of Urology, Department of Surgery, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.,Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.,Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, ON, Canada
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29
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Bokek-Cohen Y, Ravitsky V. Cultural and Personal Considerations in Informed Consent for Fecal Microbiota Transplantation. THE AMERICAN JOURNAL OF BIOETHICS : AJOB 2017; 17:55-57. [PMID: 28430060 DOI: 10.1080/15265161.2017.1299241] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
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30
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Ma Y, Liu J, Rhodes C, Nie Y, Zhang F. Ethical Issues in Fecal Microbiota Transplantation in Practice. THE AMERICAN JOURNAL OF BIOETHICS : AJOB 2017; 17:34-45. [PMID: 28430065 DOI: 10.1080/15265161.2017.1299240] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Fecal microbiota transplantation (FMT) has demonstrated efficacy and is increasingly being used in the treatment of patients with recurrent Clostridium difficile infection. Despite a lack of high-quality trials to provide more information on the long-term effects of FMT, there has been great enthusiasm about the potential for expanding its applications. However, FMT presents many serious ethical and social challenges that must be addressed as part of a successful regulatory policy response. In this article, we draw on a sample of the scientific and bioethics literatures to examine clusters of ethical and social issues arising in five main areas: (1) informed consent and the vulnerability of patients; (2) determining what a "suitable healthy donor" is; (3) safety and risk; (4) commercialization and potential exploitation of vulnerable patients; and (5) public health implications. We find that these issues are complex and worthy of careful consideration by health care professionals. Desperation of a patient should not be the basis for selecting treatment with FMT, and the patient's interests should always be of paramount concern. Authorities must prioritize development of appropriate and effective regulation of FMT to safeguard patients and donors, promote further research into safety and efficacy, and avoid abuse of the treatment.
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Affiliation(s)
| | | | | | | | - Faming Zhang
- e Second Affiliated Hospital of Nanjing Medical University
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31
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Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection. J Clin Microbiol 2017; 55:1002-1010. [PMID: 28077694 DOI: 10.1128/jcm.02327-16] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Fecal microbiota transplantation is an efficacious and inexpensive therapy for recurrent Clostridium difficile infection, yet its safety is thought to depend on appropriate fecal donor screening. FDA guidance for regulation of this procedure is in flux, but screening and manufacture of fecal material from asymptomatic donors present many challenges to clinical laboratories. This minireview summarizes FDA regulatory changes, principles of donor selection, and recommended laboratory screening practices for fecal microbiota transplantation.
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32
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Kazerouni A, Wein LM. Exploring the Efficacy of Pooled Stools in Fecal Microbiota Transplantation for Microbiota-Associated Chronic Diseases. PLoS One 2017; 12:e0163956. [PMID: 28068341 PMCID: PMC5221766 DOI: 10.1371/journal.pone.0163956] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 09/16/2016] [Indexed: 12/30/2022] Open
Abstract
Fecal microbiota transplantation is being assessed as a treatment for chronic microbiota-related diseases such as ulcerative colitis. Results from an initial randomized trial suggest that remission rates depend on unobservable features of the fecal donors and observable features of the patients. We use mathematical modeling to assess the efficacy of pooling stools from different donors during multiple rounds of treatment. In the model, there are two types of patients and two types of donors, where the patient type is observable and the donor type (effective or not effective) is not observable. In the model, clinical outcomes from earlier rounds of treatment are used to estimate the current likelihood that each donor is effective, and then each patient in each round is treated by a pool of donors that are currently deemed to be the most effective. Relative to the no-pooling case, pools of size two or three significantly increase the proportion of patients in remission during the first several rounds of treatment. Although based on data from a single randomized trial, our modeling suggests that pooling of stools – via daily cycling of encapsulated stool from several different donors – may be beneficial in fecal microbiota transplantation for chronic microbiota-related diseases.
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Affiliation(s)
- Abbas Kazerouni
- Department of Electrical Engineering, Stanford University, Stanford, California, Unites States of America
| | - Lawrence M. Wein
- Graduate School of Business, Stanford University, Stanford, California, Unites States of America
- * E-mail:
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33
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Pigneur B, Sokol H. Fecal microbiota transplantation in inflammatory bowel disease: the quest for the holy grail. Mucosal Immunol 2016; 9:1360-1365. [PMID: 27461176 DOI: 10.1038/mi.2016.67] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 06/22/2016] [Indexed: 02/04/2023]
Abstract
Inflammatory bowel disease (IBD) is due to an aberrant immune response toward luminal antigens, probably commensal bacteria, in genetically susceptible subjects and is also influenced by environmental factors. An imbalanced intestinal microbiota known as "dysbiosis," characterized by an increased proportion of pro-inflammatory microorganisms and a decreased proportion of anti-inflammatory microorganisms, has been repeatedly observed in IBD and is now recognized as a key factor in the gut inflammatory process. Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option in IBD. The goal of FMT in IBD is not only to correct the dysbiosis, but also to restore a normal dialog between the host immune system and the microbiota. Data are still scarce, but the results of the first studies suggest that FMT could be a promising therapy in IBD. More studies are needed to define the best indications, optimal timing, frequency, mode of delivery, and the optimal donor for each patient.
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Affiliation(s)
- B Pigneur
- Institut National de la Santé et de la Recherche Médicale INSERM UMR1163, Laboratory of Intestinal Immunity, Institut Imagine, Paris, France.,Department of Pediatric Gastroenterology, Hepatology and Nutrition, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes-Sorbonne Paris Cite, Paris, France.,French Group of Faecal Microbiota Transplantation (GFTF)
| | - H Sokol
- French Group of Faecal Microbiota Transplantation (GFTF).,Sorbonne University-UPMC Paris 06, INSERM ERL 1157, Avenir Team Gut Microbiota and Immunity, UMR 7203, Saint-Antoine Hospital, Paris, France.,INRA, UMR1319 Micalis and AgroParisTech, Jouy-en-Josas, France.,Department of Gastroenterology, Saint-Antoine Hospital, AP-HP, UPMC Univ Paris 06, Paris, France
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Carlucci C, Petrof EO, Allen-Vercoe E. Fecal Microbiota-based Therapeutics for Recurrent Clostridium difficile Infection, Ulcerative Colitis and Obesity. EBioMedicine 2016; 13:37-45. [PMID: 27720396 PMCID: PMC5264253 DOI: 10.1016/j.ebiom.2016.09.029] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 09/21/2016] [Accepted: 09/29/2016] [Indexed: 02/07/2023] Open
Abstract
The human gut microbiome is a complex ecosystem of fundamental importance to human health. Our increased understanding of gut microbial composition and functional interactions in health and disease states has spurred research efforts examining the gut microbiome as a valuable target for therapeutic intervention. This review provides updated insight into the state of the gut microbiome in recurrent Clostridium difficile infection (CDI), ulcerative colitis (UC), and obesity while addressing the rationale for the modulation of the gut microbiome using fecal microbiota transplant (FMT)-based therapies. Current microbiome-based therapeutics in pre-clinical or clinical development are discussed. We end by putting this within the context of the current regulatory framework surrounding FMT and related therapies.
There is an increased understanding of gut microbial composition and functional interactions in health and disease states. FMT is effective for rCDI and has led to the development of fecal microbiota-based therapeutics for other indications. For stool-substitute therapies to enter mainstream medicine, further mechanistic studies, RCTs and regulations are needed.
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Affiliation(s)
- Christian Carlucci
- Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
| | - Elaine O Petrof
- Division of Infectious Diseases/GI Diseases Research Unit Wing, Department of Medicine, Kingston General Hospital, Queen's University, 76 Stuart Street, Kingston, Ontario K7L 2V7, Canada.
| | - Emma Allen-Vercoe
- Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
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