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Hou S, Yu J, Li Y, Zhao D, Zhang Z. Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413197. [PMID: 40013938 PMCID: PMC11967859 DOI: 10.1002/advs.202413197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/22/2025] [Indexed: 02/28/2025]
Abstract
This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.
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Affiliation(s)
- Shuna Hou
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Jiachen Yu
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Yongshuang Li
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Duoyi Zhao
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Zhiyu Zhang
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
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Ko Y, Alaedin S, Fernando D, Zhou J, Ho V. A Review of Fecal Microbiota Transplantation in Children-Exploring Its Role in the Treatment of Inflammatory Bowel Diseases. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1899. [PMID: 39597084 PMCID: PMC11596230 DOI: 10.3390/medicina60111899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 10/23/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024]
Abstract
Background and Objectives: There is an increasing use of fecal matter transplantation (FMT) worldwide as research into the impact of the gut microbiome in various disease states is growing. FMT is the transfer of stool from a healthy human donor to a patient for the purpose of restoring intestinal dysbiosis. This review will assess the efficacy and safety of FMT in the treatment of pediatric inflammatory bowel diseases (IBDs) and explore the future directions of the use of FMT in children. Materials and Methods: A systematic review was performed where a literature search of publications published prior to 15 September 2023 was performed. Efficacy outcomes and safety data as well as microbiome analysis were reviewed from the studies where applicable. Results: Nine studies on UC and two studies on CD satisfied eligibility criteria and individually analysed. Most of the studies provided microbiome analyses. Conclusions: FMT is a safe treatment for paediatric IBD, and is shown to be effective in inducing clinical response by some studies. However the lack of randomized controlled trials limited the results of our study.
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Affiliation(s)
- Yanna Ko
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
- Canterbury Hospital, Sydney, NSW 2194, Australia
| | - Sara Alaedin
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
| | - Dewni Fernando
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
| | - Jerry Zhou
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
| | - Vincent Ho
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
- Camden and Campbelltown Hospitals, Sydney, NSW 2560, Australia
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Marsiglia R, Pane S, Del Chierico F, Russo A, Vernocchi P, Romani L, Cardile S, Diamanti A, Galli L, Tamborino A, Terlizzi V, De Angelis P, Angelino G, Putignani L. Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infections in a Cystic Fibrosis Child Previously Screen Positive, Inconclusive Diagnosis (CFSPID): A Case Report. Microorganisms 2024; 12:2059. [PMID: 39458368 PMCID: PMC11509880 DOI: 10.3390/microorganisms12102059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/10/2024] [Accepted: 10/11/2024] [Indexed: 10/28/2024] Open
Abstract
Clostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as "CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis" (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor-receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child's gut symptoms cleared, without CDI recurrence.
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Affiliation(s)
- Riccardo Marsiglia
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Research Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (R.M.); (F.D.C.); (P.V.)
| | - Stefania Pane
- Unit of Microbiomics, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (S.P.); (A.R.)
| | - Federica Del Chierico
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Research Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (R.M.); (F.D.C.); (P.V.)
| | - Alessandra Russo
- Unit of Microbiomics, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (S.P.); (A.R.)
| | - Pamela Vernocchi
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Research Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (R.M.); (F.D.C.); (P.V.)
| | - Lorenza Romani
- Infectious Diseases Unit, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy;
| | - Sabrina Cardile
- Unit of Gastroenterology and Nutrition, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (S.C.); (A.D.); (P.D.A.); (G.A.)
| | - Antonella Diamanti
- Unit of Gastroenterology and Nutrition, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (S.C.); (A.D.); (P.D.A.); (G.A.)
| | - Luisa Galli
- Department of Health Sciences, University of Florence, 50121 Florence, Italy;
- Infectious Disease Unit, Meyer Children’s Hospital IRCCS, 50121 Florence, Italy;
| | - Agnese Tamborino
- Infectious Disease Unit, Meyer Children’s Hospital IRCCS, 50121 Florence, Italy;
| | - Vito Terlizzi
- Department of Pediatric Medicine, Meyer Children’s Hospital IRCCS, Cystic Fibrosis Regional Reference Center, Viale Gaetano Pieraccini 24, 50139 Florence, Italy;
| | - Paola De Angelis
- Unit of Gastroenterology and Nutrition, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (S.C.); (A.D.); (P.D.A.); (G.A.)
| | - Giulia Angelino
- Unit of Gastroenterology and Nutrition, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (S.C.); (A.D.); (P.D.A.); (G.A.)
| | - Lorenza Putignani
- Unit of Microbiomics and Unit of Research of Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
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Bell J, Raidal S, Peters A, Hughes KJ. Storage of equine faecal microbiota transplantation solution has minimal impact on major bacterial communities and structure. Vet J 2024; 307:106220. [PMID: 39117173 DOI: 10.1016/j.tvjl.2024.106220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 07/15/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024]
Abstract
Management of diarrhoea in horses is usually non-specific and supportive. Faecal microbiota transplantations (FMT) are used to manage dysbiosis in horses with diarrhoea. There are few studies investigating the effects of storage on prepared FMT solutions. This study was an in vitro non-randomised controlled experiment that investigated the effects of FMT solution preparation and storage on the faecal microbiota. Fresh faeces were collected from five healthy adult horses and used for DNA extraction and preparation of FMT. From each FMT, seven aliquots were collected and DNA was extracted immediately after FMT preparation (0 hr), after storage at 4 °C for 24, 48 or 72 hours, and after storage at -20°C for 7 days, 14 days or 28 days. The extracted DNA was used for 16 S rRNA gene sequencing. The relative abundance, alpha diversity and beta diversity between fresh faeces and FMT 0 hr showed no differences (P ≥ 0.05). There were minimal changes in the microbiota of FMT stored at 4°C for up to 72 hours and -20°C for up to 28 days. The results of this study indicate that preparation of equine FMT solution has minimal effect on the microbiota in comparison to fresh faeces. FMT solution can be stored at 4°C for up to 3 days and -20°C for 28 days without major change in microbiota.
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Affiliation(s)
- J Bell
- Charles Sturt University School of Agricultural, Environmental and Veterinary Sciences, 132 Agriculture Avenue, Wagga Wagga, NSW 2650, Australia.
| | - S Raidal
- Charles Sturt University School of Agricultural, Environmental and Veterinary Sciences, 132 Agriculture Avenue, Wagga Wagga, NSW 2650, Australia
| | - A Peters
- Charles Sturt University School of Agricultural, Environmental and Veterinary Sciences, 132 Agriculture Avenue, Wagga Wagga, NSW 2650, Australia
| | - K J Hughes
- Charles Sturt University School of Agricultural, Environmental and Veterinary Sciences, 132 Agriculture Avenue, Wagga Wagga, NSW 2650, Australia
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Lauwers E, Sabino J, Hoffman I, van Hoeve K. Faecal microbiota transplantation in children: A systematic review. Acta Paediatr 2024; 113:1991-2002. [PMID: 38391047 DOI: 10.1111/apa.17167] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/25/2024] [Accepted: 02/13/2024] [Indexed: 02/24/2024]
Abstract
AIM Novel technologies offer insights into the potential role of the intestinal microbiota in human health and disease. Dysbiosis has been associated with several diseases, and it is thought to play a role in the pathogenesis of different gastrointestinal diseases. Faecal microbiota transplantation (FMT) is emerging as a method to modulate the gastrointestinal microbial ecosystem. While recurrent Clostridioides difficile infection is the recognised FMT indication, exploration of other therapeutic uses is ongoing. METHODS Following PRISMA guidelines, we conducted a systematic review, extracting 583 articles from Embase and PubMed (index date to October 2022). RESULTS The search yielded 58 studies for full review, with 50 included in the systematic review. Articles were categorised by FMT indication, study design, efficacy, adverse events, donor selection and administration route. FMT appears safe and effective for recurrent Clostridioides difficile infection, although severe adverse events are reported in children. However, there are currently insufficient data to support the use of FMT for other potential therapeutic indications (such as irritable or inflammatory bowel disease or obesity), beside the potential to decolonise multi-drug resistant organisms. CONCLUSION This underscores the need for randomised, controlled, prospective cohort studies in children to assess FMT effectiveness in diverse conditions and counteract publication bias.
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Affiliation(s)
- Ella Lauwers
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
| | - João Sabino
- TARGID, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
- Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Ilse Hoffman
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
| | - Karen van Hoeve
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
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Ottria R, Xynomilakis O, Casati S, Ciuffreda P. Pre- to Postbiotics: The Beneficial Roles of Pediatric Dysbiosis Associated with Inflammatory Bowel Diseases. Microorganisms 2024; 12:1582. [PMID: 39203424 PMCID: PMC11356122 DOI: 10.3390/microorganisms12081582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 09/03/2024] Open
Abstract
Probiotics are "live microorganisms which, when administered in adequate amount, confer health benefits on the host". They can be found in certain foods like yogurt and kefir and in dietary supplements. The introduction of bacterial derivatives has not only contributed to disease control but has also exhibited promising outcomes, such as improved survival rates, immune enhancement, and growth promotion effects. It is interesting to note that the efficacy of probiotics goes beyond the viability of the bacteria, giving rise to concepts like paraprobiotics, non-viable forms of probiotics, and postbiotics. Paraprobiotics offer various health benefits in children with intestinal dysbiosis, contributing to improved digestive health, immune function, and overall well-being. In this review, the potential of these therapeutic applications as alternatives to pharmacological agents for treating pediatric intestinal dysbiosis will be thoroughly evaluated. This includes an analysis of their efficacy, safety, long-term benefits, and their ability to restore gut microbiota balance, improve digestive health, enhance immune function, and reduce inflammation. The aim is to determine if these non-pharmacological interventions can effectively and safely manage intestinal dysbiosis in children, reducing the need for conventional medications and their side effects.
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Affiliation(s)
- Roberta Ottria
- Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, 20157 Milan, Italy; (O.X.); (S.C.); (P.C.)
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Arora U, Kedia S, Ahuja V. The practice of fecal microbiota transplantation in inflammatory bowel disease. Intest Res 2024; 22:44-64. [PMID: 37981746 PMCID: PMC10850701 DOI: 10.5217/ir.2023.00085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/10/2023] [Accepted: 09/14/2023] [Indexed: 11/21/2023] Open
Abstract
Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.
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Affiliation(s)
- Umang Arora
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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Pandey H, Jain D, Tang DWT, Wong SH, Lal D. Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease. Intest Res 2024; 22:15-43. [PMID: 37935653 PMCID: PMC10850697 DOI: 10.5217/ir.2023.00080] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/23/2023] [Accepted: 08/27/2023] [Indexed: 11/09/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.
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Affiliation(s)
| | | | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi, India
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Wang M, Shi J, Yu C, Zhang X, Xu G, Xu Z, Ma Y. Emerging strategy towards mucosal healing in inflammatory bowel disease: what the future holds? Front Immunol 2023; 14:1298186. [PMID: 38155971 PMCID: PMC10752988 DOI: 10.3389/fimmu.2023.1298186] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 11/30/2023] [Indexed: 12/30/2023] Open
Abstract
For decades, the therapeutic goal of conventional treatment among inflammatory bowel disease (IBD) patients is alleviating exacerbations in acute phase, maintaining remission, reducing recurrence, preventing complications, and increasing quality of life. However, the persistent mucosal/submucosal inflammation tends to cause irreversible changes in the intestinal structure, which can barely be redressed by conventional treatment. In the late 1990s, monoclonal biologics, mainly anti-TNF (tumor necrosis factor) drugs, were proven significantly helpful in inhibiting mucosal inflammation and improving prognosis in clinical trials. Meanwhile, mucosal healing (MH), as a key endoscopic and histological measurement closely associated with the severity of symptoms, has been proposed as primary outcome measures. With deeper comprehension of the mucosal microenvironment, stem cell niche, and underlying mucosal repair mechanisms, diverse potential strategies apart from monoclonal antibodies have been arising or undergoing clinical trials. Herein, we elucidate key steps or targets during the course of MH and review some promising treatment strategies capable of promoting MH in IBD.
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Affiliation(s)
- Min Wang
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jingyan Shi
- Medical School, Nanjing University, Nanjing, China
| | - Chao Yu
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xinyi Zhang
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Gaoxin Xu
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Ziyan Xu
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yong Ma
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Wu R, Xiong R, Li Y, Chen J, Yan R. Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation. J Autoimmun 2023; 141:103062. [PMID: 37246133 DOI: 10.1016/j.jaut.2023.103062] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 05/05/2023] [Accepted: 05/08/2023] [Indexed: 05/30/2023]
Abstract
Gut dysbiosis has been associated with inflammatory bowel disease (IBD), one of the most common gastrointestinal diseases. The microbial communities play essential roles in host physiology, with profound effects on immune homeostasis, directly or via their metabolites and/or components. There are increasing clinical trials applying fecal microbiota transplantation (FMT) with Crohn's disease (CD) and ulcerative colitis (UC). The restoration of dysbiotic gut microbiome is considered as one of the mechanisms of FMT therapy. In this work, latest advances in the alterations in gut microbiome and metabolome features in IBD patients and experimental mechanistic understanding on their contribution to the immune dysfunction were reviewed. Then, the therapeutic outcomes of FMT on IBD were summarized based on clinical remission, endoscopic remission and histological remission of 27 clinical trials retrieved from PubMed which have been registered on ClinicalTrials.gov with the results been published in the past 10 years. Although FMT is established as an effective therapy for both subtypes of IBD, the promising outcomes are not always achieved. Among the 27 studies, only 11 studies performed gut microbiome profiling, 5 reported immune response alterations and 3 carried out metabolome analysis. Generally, FMT partially restored typical changes in IBD, resulted in increased α-diversity and species richness in responders and similar but less pronounced shifts of patient microbial and metabolomics profiles toward donor profiles. Measurements of immune responses to FMT mainly focused on T cells and revealed divergent effects on pro-/anti-inflammatory functions. The very limited information and the extremely confounding factors in the designs of the FMT trials significantly hindered a reasonable conclusion on the mechanistic involvement of gut microbiota and metabolites in clinical outcomes and an analysis of the inconsistencies.
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Affiliation(s)
- Rongrong Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Rui Xiong
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Yan Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Junru Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Ru Yan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
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Vera Chamorro JF, Sánchez Franco C, Vargas Sandoval M, Mora Quintero DV, Riveros López JP, Sarmiento Quintero F, Ortiz-Piedrahita C, Calderón-Guerrero OG, Laignelet H, Losada Gómez CL, Sánchez DP, López Panqueva RDP, Aponte Barrios W, Triana Rodríguez GA, Osorno A, Becerra Granados LM, Ortega López MC, Correa Jiménez Ó, Maradei Anaya SJ, García Acero M, Acevedo Forero AM, Prada A, Ramírez Urrego LC, Salcedo Castilla LK, Enríquez A, Suárez Fuentes MA, González Leal N, Peña Hernández S, Sotaquirá Guáqueta L, Sosa F, Fierro F, Correa S, Martín de Carpi FJ. Consenso colombiano de la enfermedad inflamatoria intestinal pediátrica. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2023; 38:1-75. [DOI: 10.22516/25007440.943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Introducción: la colitis ulcerativa pediátrica (CUP), la enfermedad de Crohn pediátrica (ECP) y la enfermedad inflamatoria intestinal pediátrica no clasificable (EIIPNC) tienen particularidades clínicas y psicosociales que las diferencian de las del adulto y pueden condicionar enfoques terapéuticos distintos por las posibles repercusiones nutricionales, crecimiento y desarrollo, lo que representa un desafío para el pediatra y el gastroenterólogo. Objetivo: desarrollar recomendaciones basadas en la evidencia por consenso de expertos para el diagnóstico y el tratamiento oportunos y seguros de la enfermedad inflamatoria intestinal pediátrica (EIIP) en menores de 18 años, para los profesionales que atienden estos pacientes y los pagadores en salud. Metodología: a través de un panel de expertos del Colegio Colombiano de Gastroenterología, Hepatología y Nutrición Pediátrica (COLGAHNP) y un grupo multidisciplinario se formularon 35 preguntas en relación con el cuadro clínico, el diagnóstico y el tratamiento de la EIIP. A través de una revisión y un análisis crítico de la literatura, con especial énfasis en las principales guías de práctica clínica (GPC), estudios clínicos aleatorizados (ECA) y metaanálisis de los últimos 10 años, los expertos plantearon 77 recomendaciones que respondían a cada una de las preguntas de investigación con sus respectivos puntos prácticos. Posteriormente, cada una de las afirmaciones se sometieron a votación dentro del grupo desarrollador, incluyendo las afirmaciones que alcanzaron > 80 %. Resultados: todas las afirmaciones alcanzaron una votación > 80 %. La EIIP tiene mayor extensión, severidad y evolución hacia la estenosis, enfermedad perianal, manifestaciones extraintestinales y retraso en el crecimiento en comparación con los pacientes adultos, por lo que su manejo debe ser realizado por grupos multidisciplinarios liderados por gastroenterólogos pediatras y prepararlos para una transición a la edad adulta. Los criterios de Porto permiten una clasificación práctica de la EIIP. En la ECP, debemos usar la clasificación de París y debemos realizar ileocolonoscopia y esofagogastroduodenoscopia, ya que el 50 % tienen un compromiso superior, usando el SES-CD (UCEIS/Mayo en CUP) y tomando múltiples biopsias. Los laboratorios iniciales deben incluir marcadores de inflamación, calprotectina fecal y descartar infecciones intestinales. El tratamiento, la inducción y el mantenimiento de la EIIP deben ser individualizados y decididos según la estratificación de riesgo. En el seguimiento se debe usar el Pediatric Crohn Disease Activity Index (PCDAI) y Pediatric Ulcerative Colitis Activity Index (PUCAI) de las últimas 48 horas. Los pacientes con EIIP temprana e infantil, deben ser valorados por inmunólogos y genetistas. Conclusión: se proporciona una guía de consenso con recomendaciones basadas en la evidencia sobre el diagnóstico y los tratamientos oportunos y seguros en los pacientes con EIIP.
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Gu X, Chen ZH, Zhang SC. Fecal microbiota transplantation in childhood: past, present, and future. World J Pediatr 2023; 19:813-822. [PMID: 36484871 PMCID: PMC9734408 DOI: 10.1007/s12519-022-00655-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 11/13/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) has been well described in the treatment of pediatric diseases; however, the latest updates regarding its use in children are unclear and the concepts involved need to be revisited. DATA SOURCES We performed advanced searches in the MEDLINE, EMBASE, and Cochrane databases using the keywords "Fecal microbiota transplantation OR Fecal microbiota transfer" in the [Title/Abstract] to identify relevant articles published in English within the last five years. To identify additional studies, reference lists of review articles and included studies were manually searched. Retrieved manuscripts (case reports, reviews, and abstracts) were assessed by the authors. RESULTS Among the articles, studies were based on the mechanism (n = 28), sample preparation (n = 9), delivery approaches (n = 23), safety (n = 26), and indications (n = 67), including Clostridium difficile infection (CDI) and recurrent C. difficile infection (rCDI; n = 21), non-alcoholic fatty liver disease (NAFLD; n = 10), irritable bowel syndrome (IBS; n = 5), inflammatory bowel disease (IBD; n = 15), diabetes (n = 5), functional constipation (FC; n = 4), and autism spectrum disorder (ASD; n = 7). CONCLUSIONS Concepts of FMT in pediatric diseases have been updated with respect to underlying mechanisms, methodology, indications, and safety. Evidence-based clinical trials for the use of FMT in pediatric diseases should be introduced to resolve the challenges of dosage, duration, initiation, and the end point of treatment.
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Affiliation(s)
- Xu Gu
- Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang, 110004, China
| | - Zhao-Hong Chen
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shu-Cheng Zhang
- Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang, 110004, China.
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13
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Mamootil D. Pediatric Ulcerative Colitis in Siblings. Cureus 2023; 15:e40829. [PMID: 37489193 PMCID: PMC10363254 DOI: 10.7759/cureus.40829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/22/2023] [Indexed: 07/26/2023] Open
Abstract
This case report discusses a nine-year-old female that presented with abdominal pain, diarrhea, and weight loss, suggestive of inflammatory bowel disease (IBD). She had an older brother previously diagnosed with ulcerative colitis (UC), which raised suspicion that she may have the same condition. CT scan of the abdomen/pelvis showed signs of bowel thickening. Stool studies revealed elevated inflammatory markers including lactoferrin and calprotectin, as well as occult blood. She underwent a colonoscopy and rectal biopsy which further confirmed the diagnosis of ulcerative colitis. This article aims to discuss the clinical presentation, role of genetic factors, diagnostic workup, and therapeutic management of ulcerative colitis in the pediatric population.
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Affiliation(s)
- Divya Mamootil
- Internal Medicine, Ascension St. Agnes Hospital, Baltimore, USA
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14
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Boicean A, Bratu D, Bacila C, Tanasescu C, Fleacă RS, Mohor CI, Comaniciu A, Băluță T, Roman MD, Chicea R, Cristian AN, Hasegan A, Birsan S, Dura H, Mohor CI. Therapeutic Perspectives for Microbiota Transplantation in Digestive Diseases and Neoplasia-A Literature Review. Pathogens 2023; 12:766. [PMID: 37375456 PMCID: PMC10302701 DOI: 10.3390/pathogens12060766] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 05/23/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
In a mutually beneficial connection with its host, the gut microbiota affects the host's nutrition, immunity, and metabolism. An increasing number of studies have shown links between certain types of disease and gut dysbiosis or specific microorganisms. Fecal microbiota transplantation (FMT) is strongly advised for the treatment of recurrent or resistant Clostridium difficile infection (CDI) due to its outstanding clinical effectiveness against CDI. The therapeutic potential of FMT for other disorders, particularly inflammatory bowel diseases and malignancies, is currently gaining more and more attention. We summarized the most recent preclinical and clinical evidence to show the promise of FMT in the management of cancer as well as complications related to cancer treatment after reviewing the most recent research on the gut microbiota and its relationship to cancer.
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Affiliation(s)
- Adrian Boicean
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Dan Bratu
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Ciprian Bacila
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
| | - Ciprian Tanasescu
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Radu Sorin Fleacă
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Calin Ilie Mohor
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Andra Comaniciu
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
| | - Teodora Băluță
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
| | - Mihai Dan Roman
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Radu Chicea
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Adrian Nicolae Cristian
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Adrian Hasegan
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Sabrina Birsan
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Horațiu Dura
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Cosmin Ioan Mohor
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (C.B.); (C.T.); (R.S.F.); (C.I.M.); (A.C.); (T.B.); (M.D.R.); (R.C.); (A.N.C.); (A.H.); (S.B.); (H.D.); (C.I.M.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
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Hsu M, Tun KM, Batra K, Haque L, Vongsavath T, Hong AS. Safety and Efficacy of Fecal Microbiota Transplantation in Treatment of Inflammatory Bowel Disease in the Pediatric Population: A Systematic Review and Meta-Analysis. Microorganisms 2023; 11:1272. [PMID: 37317246 DOI: 10.3390/microorganisms11051272] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/04/2023] [Accepted: 05/05/2023] [Indexed: 06/16/2023] Open
Abstract
Background and Aims: Fecal microbiota transplantation (FMT) has been increasingly studied in the inflammatory bowel disease (IBD) population. However, most studies have focused on the adult population, and the safety and efficacy of FMT in a pediatric population is less well understood. This systematic review and meta-analysis investigates the safety and efficacy of FMT in a pediatric IBD population. Methods: A comprehensive literature search of publications published prior to 30 June 2022 was undertaken. Safety data, IBD-related outcomes, and microbiome analysis were obtained from these studies when accessible. Individual estimates of each study were pooled, and sensitivity analysis was conducted. Results: Eleven studies satisfied our eligibility criteria. The calculated pooled rate of adverse events was 29% (95% confidence interval [CI]: 15.0%, 44.0%; p < 0.001; I2 = 89.0%, Q = 94.53), and the calculated pooled rate of serious adverse events was 10% (95% confidence interval [CI]: 6.0%, 14.0%; p = 0.28; I2 = 18.0%, Q = 9.79). One month after FMT, clinical response was achieved in 20/34 (58.8%) pediatric IBD patients, clinical remission was achieved in 22/34 (64.7%), and both clinical response and remission were achieved in 15/34 (44.1%) pediatric IBD patients. Conclusions: FMT can be a safe and effective treatment in the pediatric IBD population and may demonstrate improved safety and efficacy in the pediatric population compared to the adult population. However, our results are limited by a lack of established protocol as well as long-term follow-up for FMT in a pediatric IBD population.
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Affiliation(s)
- Mark Hsu
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, University of Nevada, Las Vegas, NV 89102, USA
| | - Kyaw Min Tun
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, University of Nevada, Las Vegas, NV 89102, USA
| | - Kavita Batra
- Department of Medical Education, Kirk Kerkorian School of Medicine at UNLV, University of Nevada, Las Vegas, NV 89102, USA
- Office of Research, Kirk Kerkorian School of Medicine at UNLV, University of Nevada, Las Vegas, NV 89102, USA
| | - Lubaba Haque
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, University of Nevada, Las Vegas, NV 89102, USA
| | - Tahne Vongsavath
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, University of Nevada, Las Vegas, NV 89102, USA
| | - Annie S Hong
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, University of Nevada, Las Vegas, NV 89102, USA
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16
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Levast B, Fontaine M, Nancey S, Dechelotte P, Doré J, Lehert P. Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: A Systematic Review and Meta-analysis. Clin Transl Gastroenterol 2023; 14:e00568. [PMID: 37232579 PMCID: PMC10208705 DOI: 10.14309/ctg.0000000000000568] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 01/31/2023] [Indexed: 05/27/2023] Open
Abstract
INTRODUCTION Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis was performed to compare the efficacy of single-donor (SDN) and multidonor (MDN) strategies for product preparation. METHODS Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 nonrandomized). The treatment response was assessed by using fixed- and random-effects models, and the significance of the indirect difference between the interventions was assessed using a network approach. RESULTS Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios [RRs]: 4.41 and 1.57, respectively [P ≤ 0.001 for both]), and MDN was superior to SDN (RR: 2.81, P = 0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P = 0.042). Results were identical for both models. DISCUSSION There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation.JOURNAL/cltg/04.03/01720094-202305000-00002/2FFU1/v/2023-05-23T220055Z/r/image-tiff.
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Affiliation(s)
| | | | - Stéphane Nancey
- Department of Gastroenterology, CHU de Lyon, Lyon-Sud Hospital, University Claude Bernard Lyon 1 and CIRI-INSERM U1111, Lyon, France
| | | | - Joël Doré
- Université Paris-Saclay, INRAE, MetaGenoPolis, AgroParis Tech, MICALIS, 78350, Jouy-en-Josas, France
| | - Philippe Lehert
- Faculty of Management, UCL, Louvain, Belgium
- Faculty of Medicine, University of Melbourne, Australia
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17
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Imdad A, Pandit NG, Zaman M, Minkoff NZ, Tanner-Smith EE, Gomez-Duarte OG, Acra S, Nicholson MR. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev 2023; 4:CD012774. [PMID: 37094824 PMCID: PMC10133790 DOI: 10.1002/14651858.cd012774.pub3] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT). OBJECTIVES To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022. SELECTION CRITERIA We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD. DATA COLLECTION AND ANALYSIS Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias. Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI -3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC. Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC. None of the included studies assessed use of FMT for induction of remission in people with CD. One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD. AUTHORS' CONCLUSIONS FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.
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Affiliation(s)
- Aamer Imdad
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Natasha G Pandit
- Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Muizz Zaman
- Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Nathan Zev Minkoff
- Pediatric Gastroenterology, Hepatology and Nutrition, Valley Children's Hospital, Madera, CA, USA
| | - Emily E Tanner-Smith
- Counseling Psychology and Human Services, University of Oregon, Eugene, Oregon, USA
| | - Oscar G Gomez-Duarte
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University at Buffalo, State University of New York, Buffalo, New York, USA
| | - Sari Acra
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Maribeth R Nicholson
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
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18
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Piazzesi A, Putignani L. Impact of helminth-microbiome interactions on childhood health and development-A clinical perspective. Parasite Immunol 2023; 45:e12949. [PMID: 36063358 DOI: 10.1111/pim.12949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/26/2022] [Accepted: 09/01/2022] [Indexed: 12/01/2022]
Abstract
Humans have co-existed with parasites for virtually the entirety of our existence as a species. Today, nearly one third of the human population is infected with at least one helminthic species, most of which reside in the intestinal tract, where they have co-evolved alongside the human gut microbiota (GM). Appreciation for the interconnected relationship between helminths and GM has increased in recent years. Here, we review the evidence of how helminths and GM can influence various aspects of childhood development and the onset of paediatric diseases. We discuss the emerging evidence of how many of the changes that parasitic worms inflict on their host is enacted through gut microbes. In this light, we argue that helminth-induced microbiota modifications are of great importance in both facing the global challenge of overcoming parasitic infections, and in replicating helminthic protective effects against inflammatory diseases. We propose that deepening our knowledge of helminth-microbiota interactions will uncover novel, safer and more effective therapeutic strategies in combatting an array of childhood disorders.
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Affiliation(s)
- Antonia Piazzesi
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Lorenza Putignani
- Department of Diagnostic and Laboratory Medicine, Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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Boicean A, Birlutiu V, Ichim C, Anderco P, Birsan S. Fecal Microbiota Transplantation in Inflammatory Bowel Disease. Biomedicines 2023; 11:biomedicines11041016. [PMID: 37189634 DOI: 10.3390/biomedicines11041016] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/21/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT), FMT has shown its increasing effectiveness and safety in recent years for recurrent CDI; moreover, it showed real clinical benefits in treating SARS-CoV-2 and CDI co-infection. Crohn’s disease and ulcerative colitis are characterized by immune dysregulation, resulting in digestive tract damage caused by immune responses. Most current therapeutic strategies are associated with high costs and many adverse effects by directly targeting the immune response, so modifying the microbial environment by FMT offers an alternative approach that could indirectly influence the host’s immune system in a safe way. Studies outline the endoscopic and clinical improvements in UC and CD in FMT patients versus control groups. This review outlines the multiple benefits of FMT in the case of IBD by improving patients unbalanced gut, therefore improving endoscopic and clinical symptomatology. We aim to emphasize the clinical importance and benefits of FMT in order to prevent flares or complications of IBD and to highlight that further validation is needed for establishing a clinical protocol for FMT in IBD.
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20
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Green JE, McGuinness AJ, Berk M, Castle D, Athan E, Hair C, Strandwitz P, Loughman A, Nierenberg AA, Cryan JF, Mohebbi M, Jacka F. Safety and feasibility of faecal microbiota transplant for major depressive disorder: study protocol for a pilot randomised controlled trial. Pilot Feasibility Stud 2023; 9:5. [PMID: 36624505 PMCID: PMC9827014 DOI: 10.1186/s40814-023-01235-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 01/02/2023] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain-axis is now recognised as playing a role in mental and brain health, and promising preclinical and clinical data suggest Faecal Microbiota Transplants (FMT) may be efficacious for treating a range of mental illnesses. However, there are no existing published studies in humans evaluating the efficacy of FMT for MDD. METHODS AND DESIGN This protocol describes an 8-week, triple-blind, 2:1 parallel group, randomised controlled pilot trial (n = 15), of enema-delivered FMT treatment (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. There will be a further 26-week follow-up to monitor longer-term safety. Participants will receive four FMT or placebo enemas over four consecutive days. The primary aims of the study are to evaluate feasibility and safety of FMT as an adjunctive treatment for MDD in adults. Changes in gut microbiota will be assessed as a secondary outcome. Other data will be collected, including changes in depression and anxiety symptoms, and safety parameters. DISCUSSION Modification of the microbiota-gut-brain axis via FMT is a promising potential treatment for MDD, but there are no published rigorous clinical trials evaluating its use. If this study finds that our FMT strategy is safe and feasible, a larger fully powered RCT is planned. Further high-quality research in this field is urgently needed to address unmet need. TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry: ACTRN12621000932864.
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Affiliation(s)
- Jessica E. Green
- grid.414257.10000 0004 0540 0062Deakin University, Food & Mood Centre, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia ,grid.1002.30000 0004 1936 7857Monash Alfred Psychiatry Research Centre (MAPrc), Central Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, Australia ,grid.466993.70000 0004 0436 2893Department of Psychiatry, Peninsula Health, Frankston, Australia
| | - Amelia J. McGuinness
- grid.414257.10000 0004 0540 0062Deakin University, Food & Mood Centre, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
| | - Michael Berk
- grid.414257.10000 0004 0540 0062Deakin University, Food & Mood Centre, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia ,grid.1008.90000 0001 2179 088XDepartment of Psychiatry, University of Melbourne, Parkville, Australia ,grid.488596.e0000 0004 0408 1792Orygen Youth Health Research Centre and the Centre of Youth Mental Health, Melbourne, Australia ,grid.418025.a0000 0004 0606 5526The Florey Institute for Neuroscience and Mental Health, Parkville, Australia ,grid.414257.10000 0004 0540 0062Barwon Health, Geelong, Australia
| | - David Castle
- grid.17063.330000 0001 2157 2938Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Canada
| | - Eugene Athan
- grid.414257.10000 0004 0540 0062Deakin University, Food & Mood Centre, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia ,grid.414257.10000 0004 0540 0062Barwon Health, Geelong, Australia ,grid.1021.20000 0001 0526 7079School of Medicine, Deakin University, Geelong, Australia
| | - Christopher Hair
- grid.414257.10000 0004 0540 0062Barwon Health, Geelong, Australia
| | | | - Amy Loughman
- grid.414257.10000 0004 0540 0062Deakin University, Food & Mood Centre, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
| | - Andrew A. Nierenberg
- grid.32224.350000 0004 0386 9924Dauten Family Center for Bipolar Treatment Innovation, Department of Psychiatry, Massachusetts General Hospital, Boston, MA USA ,grid.38142.3c000000041936754XHarvard Medical School, Boston, MA USA
| | - John F. Cryan
- grid.7872.a0000000123318773Department of Anatomy and Neuroscience, University College Cork and APC Microbiome, Cork, Ireland
| | - Mohammadreza Mohebbi
- grid.414257.10000 0004 0540 0062Deakin University, Food & Mood Centre, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
| | - Felice Jacka
- grid.414257.10000 0004 0540 0062Deakin University, Food & Mood Centre, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia ,grid.416107.50000 0004 0614 0346Centre for Adolescent Health, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Australia ,grid.418393.40000 0001 0640 7766Black Dog Institute, Melbourne, Australia ,grid.1011.10000 0004 0474 1797James Cook University, Townsville, Australia
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Zhang X, Ishikawa D, Ohkusa T, Fukuda S, Nagahara A. Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease. Front Med (Lausanne) 2022; 9:1068567. [PMID: 36530877 PMCID: PMC9755187 DOI: 10.3389/fmed.2022.1068567] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 11/21/2022] [Indexed: 11/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic intestinal mucosal inflammatory disease with complex etiology. Traditional anti-inflammatory treatment regimens have yielded unsatisfactory results. As research continues to deepen, it has been found that the gut microbiota of patients with IBD is generally altered. The presence of microorganisms in the human gastrointestinal tract is inextricably linked to the regulation of health and disease. Disruption of the microbiotic balance of microbiota in the gastrointestinal tract is called dysbiosis, which leads to disease. Therefore, in recent years, the exploration of therapeutic methods to restore the homeostasis of the gut microbiota has attracted attention. Moreover, the use of the well-established fecal microbiota transplantation (FMT) regimen for the treatment of Clostridioides difficile infection has attracted the interest of IBD researchers. Therefore, there are an increasing number of clinical studies regarding FMT for IBD treatment. However, a series of questions regarding FMT in the treatment of IBD warrants further investigation and discussion. By reviewing published studies, this review explored hot topics such as the efficacy, safety, and administration protocol flow of FMT in the treatment of IBD. Different administration protocols have generally shown reassuring results with significant efficacy and safety. However, the FMT treatment regimen needs to be further optimized. We believe that in the future, individual customized or standard FMT implementation will further enhance the relevance of FMT in the treatment of IBD.
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Affiliation(s)
- Xiaochen Zhang
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Dai Ishikawa
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Toshifumi Ohkusa
- Department of Microbiota Research, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Department of Gastroenterology and Hepatology, The Jikei University Kashiwa Hospital, Chiba, Japan
| | - Shinji Fukuda
- Department of Regenerative Microbiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University School of Medicine, Tokyo, Japan
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22
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Wang JG, Liang Q, Dou HH, Ou Y. The global incidence of adverse events associated with fecal microbiota transplantation in children over the past 20 years: A systematic review and meta-analysis. J Gastroenterol Hepatol 2022; 37:2031-2038. [PMID: 36066910 DOI: 10.1111/jgh.15996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 08/25/2022] [Accepted: 09/03/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To understand the global incidence of the adverse events associated with fecal microbiota transplantation (FMT) in children over the past 20 years. METHODS We searched PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and Chongqing Weipu) for high-quality articles written over the past 20 years and made selections based on the quality standard score. The study characteristics and incidences of adverse events were extracted from each article, meta-analysis was performed using the R.3.6.3 software, and randomized-effect or fixed-effect meta-analyses were used to determine the incidence of adverse events. Subgroup analysis was performed to determine heterogeneity. RESULTS A total of 18 articles involving 681 children were included in the analysis. The total effective rate of FMT in children was 85.75% (95% CI: 76.23-93.15%), of which the overall efficacy of FMT for the treatment of Clostridium difficile infection was 91.22% (95% CI: 83.49-96.68%) and the overall adverse event rate was 28.86% (95% CI: 19.56-39.15%), with a mild to moderate adverse event rate of 27.72% (95% CI: 17.86-38.83%) and a severe adverse event rate of 0.90% (95% CI: 0.33-1.76%). The most common mild to moderate adverse events were as follows: bellyache, 14.02% (95% CI: 5.43-25.77%); diarrhea, 7.75% (95% CI: 2.69-15.11%); and bloating, 7.36% (95% CI: 1.79-16.28%). Other adverse events included fever, 2.34%; vomiting, 3.12%; nausea, 1.50%; hematochezia, 2.30%; anorexia, 1.94%; and fatigue, 0.03%. The only death reported was in a study from China, in which the patient died of sepsis and liver failure 4 weeks after FMT. The other serious adverse event was an immunodeficiency patient with severe hematochezia. Another study in the United States described seven serious adverse events including one death that was not considered to be related to FMT; however, they did not describe the events in detail. There was no difference in the incidence of adverse events between the upper and lower gastrointestinal tracts (OR = 0.61, 95% CI: 0.02-15.42, P = 0.76). CONCLUSION Adverse events related to FMT in children are mostly mild to moderate, of short duration, and self-limiting. Therefore, the use of FMT in children is safe and worthy of widespread promotion.
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Affiliation(s)
- Ji-Gan Wang
- Department of Pediatrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, China
| | - Qing Liang
- Department of Pediatrics, Ethnic Hospital of Guangxi Zhuang Autonomous Region, Affiliated Ethnic Hospital of Guangxi Medical University, Nanning, China
| | - Hui-Hong Dou
- Department of Pediatrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, China
| | - Yuan Ou
- Department of Pediatrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, China
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Ramos RJ, Zhu C, Joseph DF, Thaker S, Lacomb JF, Markarian K, Lee HJ, Petrov JC, Monzur F, Buscaglia JM, Chawla A, Small-Harary L, Gathungu G, Morganstern JA, Yang J, Li J, Pamer EG, Robertson CE, Frank DN, Cross JR, Li E. Metagenomic and bile acid metabolomic analysis of fecal microbiota transplantation for recurrent Clostridiodes difficile and/or inflammatory bowel diseases. MEDICAL RESEARCH ARCHIVES 2022; 10:10.18103/mra.v10i10.3318. [PMID: 36618438 PMCID: PMC9817289 DOI: 10.18103/mra.v10i10.3318] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infections (rCDI), but has more limited efficacy in treating either ulcerative colitis (UC) or Crohn's disease (CD), two major forms of inflammatory bowel diseases (IBD). We hypothesize that FMT recipients with rCDI and/or IBD have baseline fecal bile acid (BA) compositions that differ significantly from that of their healthy donors and that FMT will normalize the BA compositions. AIM To study the effect of single colonoscopic FMT on microbial composition and function in four recipient groups: 1.) rCDI patients without IBD (rCDI-IBD); 2.) rCDI with IBD (rCDI+IBD); 3.) UC patients without rCDI (UC-rCDI); 4.) CD patients without rCDI (CD-rCDI). METHODS We performed 16S rRNA gene sequence, shotgun DNA sequence and quantitative bile acid metabolomic analyses on stools collected from 55 pairs of subjects and donors enrolled in two prospective single arm FMT clinical trials (Clinical Trials.gov ID NCT03268213, 479696, UC no rCDI ≥ 2x IND 1564 and NCT03267238, IND 16795). Fitted linear mixed models were used to examine the effects of four recipient groups, FMT status (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on microbial diversity and composition, bile acid metabolites and bile acid metabolizing enzyme gene abundance. RESULTS The pre-FMT stools collected from rCDI ± IBD recipients had reduced α-diversity compared to the healthy donor stools and was restored post-FMT. The α-diversity in the pre-FMT stools collected from UC-rCDI or CD-rCDI recipients did not differ significantly from donor stools. FMT normalized some recipient/donor ratios of genus level taxa abundance in the four groups. Fecal secondary BA levels, including some of the secondary BA epimers that exhibit in vitro immunomodulatory activities, were lower in rCDI±IBD and CD-rCDI but not UC-rCDI recipients compared to donors. FMT restored secondary BA levels. Metagenomic baiE gene and some of the eight bile salt hydrolase (BSH) phylotype abundances were significantly correlated with fecal BA levels. CONCLUSION Restoration of multiple secondary BA levels, including BA epimers implicated in immunoregulation, are associated with restoration of fecal baiE gene counts, suggesting that the 7-α-dehydroxylation step is rate-limiting.
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Mazzawi T, Hausken T, Refsnes PF, Hatlebakk JG, Lied GA. The Effect of Anaerobically Cultivated Human Intestinal Microbiota Compared to Fecal Microbiota Transplantation on Gut Microbiota Profile and Symptoms of Irritable Bowel Syndrome, a Double-Blind Placebo-Controlled Study. Microorganisms 2022; 10:microorganisms10091819. [PMID: 36144420 PMCID: PMC9503104 DOI: 10.3390/microorganisms10091819] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/04/2022] [Accepted: 09/08/2022] [Indexed: 11/16/2022] Open
Abstract
Fecal microbiota transplantation (FMT) from healthy donors has been shown to improve the symptoms of irritable bowel syndrome (IBS) and changes the profile of the gut microbiota for the recipients. Alternatively, anaerobically cultivated human intestinal microbiota (ACHIM) can be used to manipulate the gut microbiota. The aim of the current study was to compare the efficacy and safety of ACHIM suspension with donor-FMT and placebo (patient's own feces) to treat IBS. Out of the 62 originally included eligible patients with diarrhea-predominant IBS and their respective donors, only 43 patients completed the study by answering the questionnaires and delivering fecal samples before transplantation and after 1, 4, 12 and 24 weeks. The patients were randomized into three subgroups for receiving ACHIM suspension (n = 17), donor-FMT (n = 11), or placebo (n = 15), and were followed up for 24 weeks. Fecal samples were analyzed by sequencing 16S rRNA gene using the GA-map Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). IBS symptom questionnaires improved in all three subgroups. Bacterial strain signals in IBS patients were more significant for Actinobacteria spp. and Bifidobacteria spp. after receiving donor-FMT compared to placebo and for Alistipes onderdonkii before and after treatment in the subgroups of ACHIM and donor-FMT vs. placebo. These signals change after treatment with ACHIM suspension and donor FMT towards those measured for healthy controls, but not after placebo. IBS symptom questionnaires improved in all three forms of transplantation. Some bacterial strain signals were significantly different between ACHIM and donor-FMT vs. placebo. However, the placebo subgroup failed to change the gut microbiota towards signals measured for healthy controls. The safety and efficacy of ACHIM and donor-FMT seems similar in the current study, but further larger studies are needed.
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Affiliation(s)
- Tarek Mazzawi
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
- Faculty of Medicine, Al-Balqa Applied University, 19117 Al-Salt, Jordan
- Correspondence:
| | - Trygve Hausken
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
| | - Per Førde Refsnes
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
| | - Jan Gunnar Hatlebakk
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
| | - Gülen Arslan Lied
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Norwegian Competence Center for Functional Gastrointestinal Disorders, Section of Gastroenterology, Haukeland University Hospital, 5021 Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
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Piazzesi A, Putignani L. Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention. Front Microbiol 2022; 13:958346. [PMID: 36071979 PMCID: PMC9441770 DOI: 10.3389/fmicb.2022.958346] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 07/25/2022] [Indexed: 11/15/2022] Open
Abstract
Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.
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Affiliation(s)
- Antonia Piazzesi
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Lorenza Putignani
- Department of Diagnostic and Laboratory Medicine, Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
- *Correspondence: Lorenza Putignani,
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Huang T, Xu J, Wang M, Pu K, Li L, Zhang H, Liang Y, Sun W, Wang Y. An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis. Medicine (Baltimore) 2022; 101:e29790. [PMID: 35905229 PMCID: PMC9333500 DOI: 10.1097/md.0000000000029790] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) as a promising therapy for ulcerative colitis (UC) remains controversial. We conducted a systematic review and meta-analysis to assess the efficiency and safety of FMT as a treatment for UC. METHODS The target studies were identified by searching PubMed, EMBASE, the Cochrane Library, Web of Science, and ClinicalTrials and by manual supplementary retrieval. We conducted a general review and quantitative synthesis of included studies. We used the RevMan and Stata programs in the meta-analysis. The outcomes were total remission, clinical remission, steroid-free remission, and serious adverse events. We also performed subgroup analyses based on different populations. RESULTS A total of 34 articles were included in the general review. Only 16 articles, including 4 randomized controlled trials, 2 controlled clinical trials, and 10 cohort studies, were selected for the meta-analysis. We found that donor FMT might be more effective than placebo for attaining total remission (risk ratio [RR]: 2.77, 95% confidence interval [CI]: 1.54-4.98; P = .0007), clinical remission (RR: 0.33, 95% CI: 0.24-0.41; P < .05), and steroid-free remission (RR: 3.63, 95% CI: 1.57-8.42; P = .003), but found no statistically significant difference in the incidence of serious adverse events (RR: 0.88, 95% CI: 0.34-2.31, P = .8). The subgroup analyses revealed significant differences between the pooled clinical remission rates for different regions, degrees of severity of the disease, and patients with steroid- or nonsteroid-dependent UC. CONCLUSIONS FMT can achieve clinical remission and clinical response in patients with UC.
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Affiliation(s)
- Taobi Huang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Jinlan Xu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Maoying Wang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Ke Pu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Longquan Li
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Huiyun Zhang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Yuan Liang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Weiming Sun
- Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, China
- *Correspondence: Yu Ping Wang, Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, No.1 West Donggang Road, Lanzhou, Gansu 730000, China (e-mail:
| | - Yuping Wang
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
- *Correspondence: Yu Ping Wang, Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, No.1 West Donggang Road, Lanzhou, Gansu 730000, China (e-mail:
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27
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Biazzo M, Deidda G. Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases. J Clin Med 2022; 11:jcm11144119. [PMID: 35887883 PMCID: PMC9320118 DOI: 10.3390/jcm11144119] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/08/2022] [Accepted: 07/12/2022] [Indexed: 02/01/2023] Open
Abstract
The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota dysbiosis, thereby suggesting that the reinstatement of physiological microflora balance and composition might ameliorate the clinical symptoms. Among possible microbiota-targeted interventions, pre/pro-biotics supplementations were shown to provide effective results, but the main limitation remains in the limited microbial species available as probiotics. Differently, fecal microbiota transplantation involves the transplantation of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition aiming to confer a health benefit. Firstly used in the 4th century in traditional Chinese medicine, nowadays, it has been exploited so far to treat recurrent Clostridioides difficile infections, but accumulating data coming from a number of clinical trials clearly indicate that fecal microbiota transplantation may also carry the therapeutic potential for a number of other conditions ranging from gastrointestinal to liver diseases, from cancer to inflammatory, infectious, autoimmune diseases and brain disorders, obesity, and metabolic syndrome. In this review, we will summarize the commonly used preparation and delivery methods, comprehensively review the evidence obtained in clinical trials in different human conditions and discuss the variability in the results and the pivotal importance of donor selection. The final aim is to stimulate discussion and open new therapeutic perspectives among experts in the use of fecal microbiota transplantation not only in Clostridioides difficile infection but as one of the first strategies to be used to ameliorate a number of human conditions.
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Affiliation(s)
- Manuele Biazzo
- The BioArte Limited, Life Sciences Park, Triq San Giljan, SGN 3000 San Gwann, Malta;
- SienabioACTIVE, University of Siena, Via Aldo Moro 1, 53100 Siena, Italy
| | - Gabriele Deidda
- Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy
- Correspondence: ; Tel.: +39-049-827-6125
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Liu Q, Zhang X, Li Z, Chen Y, Yin Y, Lu Z, Ouyang M, Chen L. Maternal diets have effects on intestinal mucosal flora and susceptibility to colitis of offspring mice during early life. Nutrition 2022; 99-100:111672. [PMID: 35594632 DOI: 10.1016/j.nut.2022.111672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 01/04/2022] [Accepted: 03/21/2022] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Intestinal flora is considered closely related to the occurrence of inflammatory bowel disease (IBD). This study aimed to discover whether diverse diet conditions during early life lead to different intestinal flora structure and impact different susceptibility to IBD. METHODS We performed a randomized, controlled trial to investigate the relationship between maternal diet, intestinal flora, and susceptibility of IBD in offspring mice. We treated the maternal mice with different dietary conditions (maternal high fat, high protein, or normal diet, and offspring continued maternal diets or changed to normal diet), and then extracted bacterial meta-genomic DNA from the intestinal mucosa of the offspring during the early life and adult stages. We amplified and sequenced the conserved gene v3-v4 of the bacterial 16 S ribosomal RNA. After dextran sulphate sodium intervention, we evaluated the susceptibility to intestinal inflammation with hematoxylin and eosin stains and disease activity index scores. RESULTS The number of species and alpha diversity of weaning mice (3 wk old) fed a maternal high-protein diet were significantly lower than those of the control diet group (P < 0.05). Among adult (8 wk old) offspring rats, the alpha diversity of mice that continued on a high-protein diet remained significantly decreased (P < 0.05). In addition, 12 kinds of weak bacteria were found in weaning mice fed a maternal high-protein diet compared with the control group. Offspring that continued in the maternal high-protein group had increased disease activity index and pathologic scores after weaning. CONCLUSIONS In general, our study shows that a maternal high-protein diet during early life can negatively regulate the intestinal flora diversity of offspring mice. A high-protein diet during early life led to higher susceptibility of IBD in offspring rats.
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Affiliation(s)
- Qian Liu
- Department of Gastroenterology, Xiangya Hospital Central South University, People's Republic of China
| | - Xiaomei Zhang
- Department of Gastroenterology, Xiangya Hospital Central South University, People's Republic of China
| | - Zichun Li
- Department of Gastroenterology, Xiangya Hospital Central South University, People's Republic of China
| | - Ying Chen
- Department of Gastroenterology, Xiangya Hospital Central South University, People's Republic of China
| | - Yani Yin
- Department of Gastroenterology, Xiangya Hospital Central South University, People's Republic of China
| | - Zhaoxia Lu
- Department of Gastroenterology, Xiangya Hospital Central South University, People's Republic of China
| | - Miao Ouyang
- Department of Gastroenterology, Xiangya Hospital Central South University, People's Republic of China
| | - Linlin Chen
- Fourth Department of the Digestive Disease Center, Suining Central Hospital, People's Republic of China.
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Nicholson MR, Alexander E, Ballal S, Davidovics Z, Docktor M, Dole M, Gisser JM, Goyal A, Hourigan SK, Jensen MK, Kaplan JL, Kellermayer R, Kelsen JR, Kennedy MA, Khanna S, Knackstedt ED, Lentine J, Lewis JD, Michail S, Mitchell PD, Oliva-Hemker M, Patton T, Queliza K, Sidhu S, Solomon AB, Suskind DL, Weatherly M, Werlin S, de Zoeten EF, Kahn SA. Efficacy and Outcomes of Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease. J Crohns Colitis 2022; 16:768-777. [PMID: 34788420 PMCID: PMC9228903 DOI: 10.1093/ecco-jcc/jjab202] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. METHODS We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. RESULTS A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. CONCLUSIONS Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.
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Affiliation(s)
- Maribeth R Nicholson
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Erin Alexander
- Department of Pediatrics, Mayo Clinic, Rochester, MN, USA
| | - Sonia Ballal
- Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
| | - Zev Davidovics
- Department of Pediatrics, Connecticut Children’s Medical Center, Hartford, CT, USA
| | - Michael Docktor
- Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
| | - Michael Dole
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jonathan M Gisser
- Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH, USA
| | - Alka Goyal
- Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO, USA
| | - Suchitra K Hourigan
- Department of Pediatrics, Pediatric Specialists of Virginia, Fairfax, VA, USA
| | - M Kyle Jensen
- Department of Pediatrics, University of Utah Department of Pediatrics, Salt Lake City, UT, USA
| | - Jess L Kaplan
- Department of Pediatrics, MassGeneral Hospital for Children, Boston, MA, USA
| | - Richard Kellermayer
- Baylor College of Medicine, Texas Children’s Hospital, USDA Children’s Nutrition and Research Center, Houston, TX, USA
| | - Judith R Kelsen
- Department of Pediatrics, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - Melissa A Kennedy
- Department of Pediatrics, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - Sahil Khanna
- Department of Pediatrics, Mayo Clinic, Rochester, MN, USA
| | - Elizabeth D Knackstedt
- Department of Pediatrics, University of Utah Department of Pediatrics, Salt Lake City, UT, USA
| | - Jennifer Lentine
- Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA
| | - Jeffery D Lewis
- Children’s Center for Digestive Healthcare at Children’s Healthcare of Atlanta, Atlanta, GA, USA
| | - Sonia Michail
- Department of Pediatrics, University of Southern California Children’s Hospital of Los Angeles, Los Angeles, CA, USA
| | - Paul D Mitchell
- Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
| | - Maria Oliva-Hemker
- Johns Hopkins University School of Medicine, Johns Hopkins Children’s Center, Baltimore, MD, USA
| | - Tiffany Patton
- Department of Pediatrics, University of Chicago, Comer Children’s Hospital, Chicago, IL, USA
| | - Karen Queliza
- Baylor College of Medicine, Texas Children’s Hospital, USDA Children’s Nutrition and Research Center, Houston, TX, USA
| | - Sarah Sidhu
- Johns Hopkins University School of Medicine, Johns Hopkins Children’s Center, Baltimore, MD, USA
| | - Aliza B Solomon
- Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA
| | - David L Suskind
- Department of Pediatrics, Seattle Children’s Hospital and the University of Washington, Seattle, WA, USA
| | - Madison Weatherly
- Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
| | - Steven Werlin
- Department of Pediatrics, Medical College of Wisconsin and Children’s Wisconsin, Milwaukee, WI, USA
| | - Edwin F de Zoeten
- Department of Pediatrics, Children’s Hospital Colorado, Aurora, CO, USA
| | - Stacy A Kahn
- Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
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Gupta K, Tappiti M, Nazir AM, Koganti B, Memon MS, Aslam Zahid MB, Shantha Kumar V, Mostafa JA. Fecal Microbiota Transplant in Recurrent Clostridium Difficile Infections: A Systematic Review. Cureus 2022; 14:e24754. [PMID: 35693372 PMCID: PMC9174020 DOI: 10.7759/cureus.24754] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 05/05/2022] [Indexed: 11/10/2022] Open
Abstract
Fecal Microbiota Transplantation (FMT) is the process of transferring the fecal microbiome from a healthy donor to an individual with repeated multiple episodes of Clostridium difficile infection. It is also known as stool transplant. Fecal microbiota transplant is effective and safe in various studies, the approval from the Food and Drug Administration (FDA) remains pending. The main objective of this systemic review is to evaluate the efficacy and safety of stool transplant in studies with only treatment groups (FMT) and studies with treatment (FMT) and antibiotic (AB) groups and previous studies. Online databases PubMed, PubMed Central, Science Direct, Google Scholar, and Embase were searched for relevant articles in the last five years (2016 to 2021) using automation tools. Following the removal of duplicates, screening of eligibility criteria, titles/abstracts, and quality appraisal were done by two authors independently. In total, seven observational studies are in this review article. Out of the seven observational studies, five are retrospective and two prospective. Two of the five retrospective and one of two prospective studies have a control group. In both the prospective studies and one retrospective study, FMT efficacy of (68% to 93%) was demonstrated in the elderly population despite high index comorbidities. In the younger individuals with inflammatory bowel disease, and efficacy of 90% or above was found. The most common side effects were minor such as fever, abdominal pain, bloating, and flatulence. In one study, two cases of aspiration events occurred attributed to the gastroscopy route of donor feces delivery. There was no statistical significance in the incidence of diseases such as (allergies, autoimmune diseases, cancer, inflammatory bowel diseases, and neurological diseases like dementia and migraine). Fecal microbiota transplantation has shown to be effective and safe in recurrent Clostridium difficile infections. Since very few pragmatic studies have demonstrated its efficacy and safety, their application is not well established. Robust studies, both observation and experiment, are required in the future to well-establish its effectiveness, safety in the treatment of recurrent Clostridium difficile infection.
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Rao A, Gokhale R. Ulcerative Colitis. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:401-421. [DOI: 10.1007/978-3-030-80068-0_30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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The role of enteric dysbacteriosis and modulation of gut microbiota in the treatment of inflammatory bowel disease. Microb Pathog 2021; 165:105381. [PMID: 34974123 DOI: 10.1016/j.micpath.2021.105381] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 12/27/2021] [Accepted: 12/28/2021] [Indexed: 12/12/2022]
Abstract
The incidence of inflammatory bowel disease (IBD) is globally increasing. This disorder seriously affects the quality of life in patients. Interestingly, studies have detected that the intestinal flora imbalance is a critical factor in the progression of IBD. One potential treatment strategy for IBD involves regulating the composition and function of the intestinal flora. To date, a multitude of experiments have confirmed the relationship between intestinal flora, immune regulation, and anti-inflammation. The intestinal flora can reduce intestinal inflammation by regulating immunity and increasing the secretion of metabolic short-chain fatty acids. In this review, we discuss the composition and function of the intestinal flora, the relationship between the intestinal flora and the host, the role of intestinal flora disorders in IBD, and the progress in IBD treatment. Combining the regulation of the intestinal flora with probiotics treatment is considered a promising strategy for substantially improving the treatment of IBD.
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Chen CC, Chiu CH. Current and future applications of fecal microbiota transplantation for children. Biomed J 2021; 45:11-18. [PMID: 34781002 PMCID: PMC9133305 DOI: 10.1016/j.bj.2021.11.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 10/23/2021] [Accepted: 11/07/2021] [Indexed: 12/18/2022] Open
Abstract
Fecal microbiota transplantation (FMT) is a new and adequate route to modify the microbial ecosystem in gastrointestinal tract of the hosts. Intestinal microbiota is highly associated with human health and disease. According to the reports of human clinical trials or case series, the application of FMT ranged from Clostridiodes difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome, refractory diarrhea, diabetes mellitus, metabolic syndrome, and even neurologic diseases, including Parkinson disease, and neuropsychiatric disorder (autism spectrum disorder, ASD). Although the current allowed indication of FMT is CDI in Taiwan, more application and development are expectable in the future. There is a relative rare data available for children in application of fecal microbiota transplantation. Thus, we review previous published research inspecting FMT in children, and address particular considerations when conducting FMT in pediatric patients.
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Affiliation(s)
- Chien-Chang Chen
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Cheng-Hsun Chiu
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
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Fitzgerald RS, Sanderson IR, Claesson MJ. Paediatric Inflammatory Bowel Disease and its Relationship with the Microbiome. MICROBIAL ECOLOGY 2021; 82:833-844. [PMID: 33666710 PMCID: PMC8551107 DOI: 10.1007/s00248-021-01697-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 01/19/2021] [Indexed: 05/07/2023]
Abstract
Paediatric inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract, comprising of Crohn's disease (CD), ulcerative colitis (UC), and, where classification is undetermined, inflammatory bowel disease unclassified (IBDU). Paediatric IBD incidence is increasing globally, with prevalence highest in the developed world. Though no specific causative agent has been identified for paediatric IBD, it is believed that a number of factors may contribute to the development of the disease, including genetics and the environment. Another potential component in the development of IBD is the microbiota in the digestive tract, particularly the gut. While the exact role that the microbiome plays in IBD is unclear, many studies acknowledge the complex relationship between the gut bacteria and pathogenesis of IBD. In this review, we look at the increasing number of studies investigating the role the microbiome and other biomes play in paediatric patients with IBD, particularly changes associated with IBD, varying disease states, and therapeutics. The paediatric IBD microbiome is significantly different to that of healthy children, with decreased diversity and differences in bacterial composition (such as a decrease in Firmicutes). Changes in the microbiome relating to various treatments of IBD and disease severity have also been observed in multiple studies. Changes in diversity and composition may also extend to other biomes in paediatric IBD, such as the virome and the mycobiome. Research into biome differences in IBD paediatric patients may help progress our understanding of the aetiology of the disease.
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Affiliation(s)
- Rachel S Fitzgerald
- School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Ian R Sanderson
- Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Marcus J Claesson
- School of Microbiology, University College Cork, Cork, Ireland.
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
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35
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Popov J, Caputi V, Nandeesha N, Rodriguez DA, Pai N. Microbiota-Immune Interactions in Ulcerative Colitis and Colitis Associated Cancer and Emerging Microbiota-Based Therapies. Int J Mol Sci 2021; 22:11365. [PMID: 34768795 PMCID: PMC8584103 DOI: 10.3390/ijms222111365] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/02/2021] [Accepted: 10/05/2021] [Indexed: 02/07/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn's disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.
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Affiliation(s)
- Jelena Popov
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, McMaster University, Hamilton, ON L8S 4L8, Canada;
- College of Medicine and Health, University College Cork, T12 XF62 Cork, Ireland
| | - Valentina Caputi
- Department of Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA;
| | - Nandini Nandeesha
- School of Medicine, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland;
| | | | - Nikhil Pai
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, McMaster University, Hamilton, ON L8S 4L8, Canada;
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada
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36
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Pai N, Popov J, Hill L, Hartung E, Grzywacz K, Moayyedi P. Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects. Gastroenterology 2021; 161:388-393.e3. [PMID: 33961887 DOI: 10.1053/j.gastro.2021.04.067] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 04/26/2021] [Accepted: 04/29/2021] [Indexed: 01/10/2023]
Affiliation(s)
- Nikhil Pai
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Division of Paediatric Gastroenterology & Nutrition, Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Jelena Popov
- Division of Paediatric Gastroenterology & Nutrition, Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Lee Hill
- Division of Paediatric Gastroenterology & Nutrition, Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada; Department of Exercise Science and Sports Medicine, University of Cape Town, Rondebosch, Cape Town, South Africa
| | - Emily Hartung
- Division of Paediatric Gastroenterology & Nutrition, Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Kelly Grzywacz
- Division de Gastroentérologie, Hépatologie & Nutrition, Département de Pédiatrie, Université de Montréal, Montreal, Quebec, Canada
| | - Paul Moayyedi
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
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Wu N, Mah C, Koentgen S, Zhang L, Grimm MC, El-Omar E, Hold GL. Inflammatory bowel disease and the gut microbiota. Proc Nutr Soc 2021; 80:1-11. [PMID: 34165053 DOI: 10.1017/s002966512100197x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Inflammatory bowel disease (IBD) is a group of immune-mediated disorders characterised by a chronic, relapsing-remitting inflammation predominantly affecting the gastrointestinal tract. IBD is incurable, affecting people in their most productive years. IBD is historically seen as a disease of Westernised nations although in recent times other countries have seen an exponential rise in cases. Although the exact pathogenesis remains unclear, evidence suggests that microbiota changes play a critical role in IBD pathogenesis. Over the past two decades, IBD has become one of the most studied human conditions linked to the gut microbiota. However, deciphering the intricate link between the gut microbiota and therapeutic efficacy remains elusive. This review will summarise the current evidence relating to the gut microbiota and its involvement in IBD pathogenesis as well as the impact of IBD treatments including pharmaceutical-, nutraceutical- and microbial-focused regimens on the gut microbiota.
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Affiliation(s)
- Nan Wu
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Cassandra Mah
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Sabrina Koentgen
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Leo Zhang
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Michael C Grimm
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Emad El-Omar
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Georgina L Hold
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
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Pavel FM, Vesa CM, Gheorghe G, Diaconu CC, Stoicescu M, Munteanu MA, Babes EE, Tit DM, Toma MM, Bungau S. Highlighting the Relevance of Gut Microbiota Manipulation in Inflammatory Bowel Disease. Diagnostics (Basel) 2021; 11:1090. [PMID: 34203609 PMCID: PMC8232187 DOI: 10.3390/diagnostics11061090] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/06/2021] [Accepted: 06/12/2021] [Indexed: 01/11/2023] Open
Abstract
Two different conditions are included in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), being distinguished by chronic recurrence of gut inflammation in persons that are genetically predisposed and subjected to environmental causative factors. The normal structure of the gut microbiome and its alterations in IBD were defined in several microbial studies. An important factor in the prolonged inflammatory process in IBD is the impaired microbiome or "dysbiosis". Thus, gut microbiome management is likely to be an objective in IBD treatment. In this review, we analyzed the existing data regarding the pathophysiological/therapeutic implications of intestinal microflora in the development and evolution of IBD. Furthermore, the main effects generated by the administration of probiotics, prebiotics, fecal transplantation, and phytochemicals supplementation were analyzed regarding their potential roles in improving the clinical and biochemical status of patients suffering from Crohn's disease (CD) and ulcerative colitis (UC), and are depicted in the sections/subsections of the present paper. Data from the literature give evidence in support of probiotic and prebiotic therapy, showing effects such as improving remission rate, improving macroscopic and microscopic aspects of IBD, reducing the pro-inflammatory cytokines and interleukins, and improving the disease activity index. Therefore, the additional benefits of these therapies should not be ignored as adjuvants to medical therapy.
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Affiliation(s)
- Flavia Maria Pavel
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (F.M.P.); (C.M.V.)
| | - Cosmin Mihai Vesa
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (F.M.P.); (C.M.V.)
| | - Gina Gheorghe
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (G.G.); (C.C.D.)
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Camelia C. Diaconu
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (G.G.); (C.C.D.)
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Manuela Stoicescu
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410041 Oradea, Romania; (M.S.); (M.A.M.); (E.E.B.)
| | - Mihai Alexandru Munteanu
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410041 Oradea, Romania; (M.S.); (M.A.M.); (E.E.B.)
| | - Elena Emilia Babes
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410041 Oradea, Romania; (M.S.); (M.A.M.); (E.E.B.)
| | - Delia Mirela Tit
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (D.M.T.); (M.M.T.)
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
| | - Mirela Marioara Toma
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (D.M.T.); (M.M.T.)
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (D.M.T.); (M.M.T.)
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
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Hmar EBL, Paul S, Boruah N, Sarkar P, Borah S, Sharma HK. Apprehending Ulcerative Colitis Management With Springing Up Therapeutic Approaches: Can Nanotechnology Play a Nascent Role? CURRENT PATHOBIOLOGY REPORTS 2021. [DOI: 10.1007/s40139-020-00218-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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40
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Marcella C, Cui B, Kelly CR, Ianiro G, Cammarota G, Zhang F. Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. Aliment Pharmacol Ther 2021; 53:33-42. [PMID: 33159374 DOI: 10.1111/apt.16148] [Citation(s) in RCA: 123] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 08/24/2020] [Accepted: 10/20/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) is an effective treatment in C. difficile infection (CDI) and is currently being investigated in other diseases. There is concern around the safety of FMT and that side effects or complications may be under-reported in the medical literature. AIM To evaluate the safety of FMT by summarising the overall reported Adverse Events (AEs) over a 20-year period METHODS: We searched EMBASE, MEDLINE, and Cochrane Library databases, and CNKI and Wanfang Data from January 2000 to April 2020. All original studies reporting FMT-related AEs were considered for inclusion. FMT-related AEs were further classified as delivery-related or microbiota-related. RESULTS Based on the inclusion criteria, 129 studies, which included 4241 patients (5688 FMT courses), were finally eligible. The most common indication for FMT was CDI. Overall, FMT-related AEs were observed in 19% of FMT procedures. The most frequently reported FMT-related AEs were diarrhoea (10%) and abdominal discomfort/pain/cramping (7%). FMT-related serious adverse events (SAEs), including infections and deaths, have been reported in 1.4% of patients who underwent FMT (0.99% microbiota-related SAEs). Four of five FMT-related deaths were reported in patients receiving FMT via the upper gastrointestinal route. Importantly, all reported FMT-related SAEs were in patients with mucosal barrier injury. CONCLUSION Most FMT-related AEs were mild or moderate and self-limiting. Although FMT appears to be highly safe, its methodology should be improved to reduce both delivery-related AEs and, microbiota-related AEs.
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Affiliation(s)
- Cicilia Marcella
- Medical Center of Digestive Disease, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Medical Center of Digestive Disease, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Colleen R Kelly
- Division of Gastroenterology, Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Gianluca Ianiro
- Digestive Diseases Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Digestive Diseases Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Faming Zhang
- Medical Center of Digestive Disease, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
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41
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Haifer C, Leong RW, Paramsothy S. The role of faecal microbiota transplantation in the treatment of inflammatory bowel disease. Curr Opin Pharmacol 2020; 55:8-16. [PMID: 33035780 PMCID: PMC7538387 DOI: 10.1016/j.coph.2020.08.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/19/2020] [Accepted: 08/20/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE OF THE REVIEW Faecal microbiota transplantation (FMT) has emerged as a potent form of therapeutic microbial manipulation. There is much interest in exploring its potential in conditions such as inflammatory bowel disease (IBD) where disturbances in the gastrointestinal microbiota play a crucial role in disease pathogenesis. RECENT FINDINGS There are 4 randomized controlled trials of FMT as induction therapy in ulcerative colitis, with meta-analyses suggesting significant benefit over placebo. Allied microbial studies have identified potential microbial and metabolic predictors of therapeutic efficacy and highlighted the importance of optimizing future donor and patient selection. Recent literature has evaluated the use of complementary microbial manipulation through pre-antibiotics to improve treatment efficacy. Studies have also assessed the durability of FMT response and its use in maintenance therapy of UC. While data on FMT are more limited in Crohn's disease and pouchitis, cohort and pilot randomized controlled data a now also emerging in these areas.
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Affiliation(s)
- Craig Haifer
- Concord Clinical School, The University of Sydney, New South Wales, Australia; Department of Gastroenterology, Concord Repatriation General Hospital, New South Wales, Australia
| | - Rupert W Leong
- Concord Clinical School, The University of Sydney, New South Wales, Australia; Department of Gastroenterology, Concord Repatriation General Hospital, New South Wales, Australia; Department of Gastroenterology, Macquarie University & Macquarie University Hospital, New South Wales, Australia
| | - Sudarshan Paramsothy
- Concord Clinical School, The University of Sydney, New South Wales, Australia; Department of Gastroenterology, Concord Repatriation General Hospital, New South Wales, Australia; Department of Gastroenterology, Macquarie University & Macquarie University Hospital, New South Wales, Australia.
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Ding X, Yang X, Wang H. Methodology, efficacy and safety of fecal microbiota transplantation in treating inflammatory bowel disease. MEDICINE IN MICROECOLOGY 2020. [DOI: 10.1016/j.medmic.2020.100028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Cheng YW, Fischer M. Fecal Microbiota Transplantation for Ulcerative Colitis. Are We Ready for Primetime? Gastroenterol Clin North Am 2020; 49:739-752. [PMID: 33121693 DOI: 10.1016/j.gtc.2020.08.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
"Patients with inflammatory bowel disease, including ulcerative colitis (UC) and Crohn disease, have altered gut microbiomes. The success of fecal microbiota transplantation (FMT) in the treatment of Clostridioides difficile infection, a disease that is also marked by dysbiosis, has spurred research in applying FMT to UC. So far, 3 randomized controlled trials have demonstrated benefit in mild to moderate UC disease course after FMT. However, important questions regarding optimal stool preparation, route, and frequency of administration, as well as characteristics of the stool donor and recipient still remain."
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Affiliation(s)
- Yao-Wen Cheng
- Division of Gastroenterology, Department of Medicine, University of California San Francisco, 513 Parnassus Avenue, Room S357, San Francisco, CA 94143, USA.
| | - Monika Fischer
- Division of Gastroenterology, Indiana University, 550 North University Boulevard, Suite 1634, Indianapolis, IN 46202, USA
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Dang XF, Qing-Xi Wang, Yin Z, Sun L, Yang WH. Recurrence of moderate to severe ulcerative colitis after fecal microbiota transplantation treatment and the efficacy of re-FMT: a case series. BMC Gastroenterol 2020; 20:401. [PMID: 33243141 PMCID: PMC7691068 DOI: 10.1186/s12876-020-01548-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 11/18/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), the pathogenesis of which is complicated, and it is difficult to treat. In recent years, the emerging fecal microbiota transplantation (FMT) has shown good effects in UC treatment and is therefore accepted by increasing numbers of patients. Our hospital has carried out FMT since 2017, and has achieved good results in UC treatment. We have found in our clinical work that the efficacy of re-FMT after recurrence decreased. This is difference from reported literatures. In order to attract clinical attention, here we selected typical cases for analysis. METHODS Among all UC patients who received FMT in our hospital, 12 patients with moderate to severe UC were selected. They all received multiple FMT and were followed up for 52 weeks. Besides, none of them had other underlying diseases. Colonoscopy images of patients were presentated, SCCAI and UCDAI were used assess the effect of FMT. RESULTS On the whole, FMT has a significant effect on moderate to severe UC. Of the 12 patients, 11 (91.7%) achieved a clinical response, 9 (75.0%) achieved clinical remission, and only one patient did not respond to FMT treatment. However, 6 patients relapsed within 52 weeks after remission, with a recurrence rate of 54.5%. Four of the six relapsed patients received FMT again, but the efficacy of FMT after relapse was significantly lower than that of the initial FMT. Fortunately, compared to before the initial FMT treatment, the severity of the disease after relapse was significantly reduced. CONCLUSION FMT has a good effect on the relief of moderate to severe UC. However, the effect of FMT treatment after relapse is reduced. For patients who relapse after remission, the efficacy of FMT reapplication requires more experiments to verify.
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Affiliation(s)
- Xiao-Fei Dang
- Department of Clinical Microbiology, Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong, China
| | - Qing-Xi Wang
- Department of Clinical Microbiology, Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong, China
| | - Zhao Yin
- Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, China
| | - Lin Sun
- Department of Clinical Microbiology, Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong, China
| | - Wei-Hua Yang
- Department of Clinical Microbiology, Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong, China.
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Chen M, Liu XL, Zhang YJ, Nie YZ, Wu KC, Shi YQ. Efficacy and safety of fecal microbiota transplantation by washed preparation in patients with moderate to severely active ulcerative colitis. J Dig Dis 2020; 21:621-628. [PMID: 32909356 PMCID: PMC7756426 DOI: 10.1111/1751-2980.12938] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 06/17/2020] [Accepted: 08/05/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE We aimed to evaluate the short-term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC. METHODS An open-label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end-point was a clinical response at week 2 post-FMT. The secondary end-points were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression. RESULTS Of the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti-tumor necrosis factor-α therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P > 0.05). Adverse events, all mild and self-limiting, were observed in 33.3% (3/9) of the patients. CONCLUSIONS FMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short-term follow-up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings.
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Affiliation(s)
- Min Chen
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Xiao Lei Liu
- Department of Medical InsuranceXijing Hospital, Air Force Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Yu Jie Zhang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Yong Zhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Kai Chun Wu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Yong Quan Shi
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
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Turner D, Bishai J, Reshef L, Abitbol G, Focht G, Marcus D, Ledder O, Lev-Tzion R, Orlanski-Meyer E, Yerushalmi B, Aloi M, Griffiths AM, Albenberg L, Kolho KL, Assa A, Cohen S, Gophna U, Vlamakis H, Lurz E, Levine A. Antibiotic Cocktail for Pediatric Acute Severe Colitis and the Microbiome: The PRASCO Randomized Controlled Trial. Inflamm Bowel Dis 2020; 26:1733-1742. [PMID: 31833543 DOI: 10.1093/ibd/izz298] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Indexed: 01/01/2023]
Abstract
BACKGROUND Alterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC). METHODS Hospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] ≥65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome. RESULTS Twenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 ± 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 ± 16.7 vs 40.4 ± 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm. CONCLUSION Patients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes (clinicaltrials.gov NCT02033408).
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Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | - Jason Bishai
- The Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Leah Reshef
- School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Tel Aviv, Israel
| | - Guila Abitbol
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | - Gili Focht
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | - Dana Marcus
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | - Oren Ledder
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | - Raffi Lev-Tzion
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | | | - Baruch Yerushalmi
- Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | | | | | - Lindsey Albenberg
- The Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, USA
| | - Kaija-Leena Kolho
- Hospital for Children and Adolescents, Children´s Hospital, Helsinki University, Helsinki, Finland
| | - Amit Assa
- Schneider Children's Medical Center, Petah Tikvah, Israel
| | - Shlomi Cohen
- Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Uri Gophna
- School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Tel Aviv, Israel
| | - Hera Vlamakis
- The Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | | | - Arie Levine
- Dr. von Hauner Children's Hospital, Ludwig Maximilians-University, Munich, Germany
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Zhang J, Rodríguez F, Navas MJ, Costa-Hurtado M, Almagro V, Bosch-Camós L, López E, Cuadrado R, Accensi F, Pina-Pedrero S, Martínez J, Correa-Fiz F. Fecal microbiota transplantation from warthog to pig confirms the influence of the gut microbiota on African swine fever susceptibility. Sci Rep 2020; 10:17605. [PMID: 33077775 PMCID: PMC7573625 DOI: 10.1038/s41598-020-74651-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 09/24/2020] [Indexed: 02/07/2023] Open
Abstract
African swine fever virus (ASFV) is the causative agent of a devastating hemorrhagic disease (ASF) that affects both domestic pigs and wild boars. Conversely, ASFV circulates in a subclinical manner in African wild pigs, including warthogs, the natural reservoir for ASFV. Together with genetic differences, other factors might be involved in the differential susceptibility to ASF observed among Eurasian suids (Sus scrofa) and African warthogs (Phacochoerus africanus). Preliminary evidence obtained in our laboratory and others, seems to confirm the effect that environmental factors might have on ASF infection. Thus, domestic pigs raised in specific pathogen-free (SPF) facilities were extremely susceptible to highly attenuated ASFV strains that were innocuous to genetically identical domestic pigs grown on conventional farms. Since gut microbiota plays important roles in maintaining intestinal homeostasis, regulating immune system maturation and the functionality of the innate/adaptive immune responses, we decided to examine whether warthog fecal microbiota transplantation (FMT) to domestic pigs affects host susceptibility to ASFV. The present work demonstrates that warthog FMT is not harmful for domestic weaned piglets, while it modifies their gut microbiota; and that FMT from warthogs to pigs confers partial protection against attenuated ASFV strains. Future work is needed to elucidate the protective mechanisms exerted by warthog FMT.
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Affiliation(s)
- Jinya Zhang
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain
| | - Fernando Rodríguez
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain. .,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain.
| | - Maria Jesus Navas
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain
| | - Mar Costa-Hurtado
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain
| | - Vanessa Almagro
- Veterinary Service Zoo Barcelona, Parc Ciudadella s/n 08003, Barcelona, Spain
| | - Laia Bosch-Camós
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain
| | - Elisabeth López
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain
| | - Raul Cuadrado
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain
| | - Francesc Accensi
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain.,Departament de Sanitat i Anatomia Animals, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain
| | - Sonia Pina-Pedrero
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain
| | - Jorge Martínez
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain.,Departament de Sanitat i Anatomia Animals, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain
| | - Florencia Correa-Fiz
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain. .,OIE Collaborating Centre for the Research and Control of Emerging and Re-emerging Swine Diseases in Europe (IRTA-CReSA), Bellaterra, Barcelona, Spain.
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Zhao HL, Chen SZ, Xu HM, Zhou YL, He J, Huang HL, Xu J, Nie YQ. Efficacy and safety of fecal microbiota transplantation for treating patients with ulcerative colitis: A systematic review and meta-analysis. J Dig Dis 2020; 21:534-548. [PMID: 33439534 DOI: 10.1111/1751-2980.12933] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 07/30/2020] [Accepted: 08/14/2020] [Indexed: 01/30/2023]
Abstract
OBJECTIVES To assess the effect of donor selection, stool procedures and pretreatment with antibiotics on the efficacy and safety of fecal microbiota transplantation (FMT)-treated ulcerative colitis (UC). METHODS A systematic review and meta-analysis was conducted including studies on UC treated with FMT as the primary therapeutic agent published up to June 30, 2020. Primary end-point data included clinical remission (CR) or CR combined with endoscopic remission. RESULTS A total of 37 studies (seven random controlled trials [RCTs], five controlled and 25 uncontrolled cohort studies) and 959 patients with UC were enrolled. In controlled cohort studies and RCTs, FMT had a significantly greater benefit than placebo (pooled odds ratio [P-OR] 3.392, 95% CI 2.196-5.240, P < 0.001), with no heterogeneity (I2 = 0%). Furthermore, administration of FMT via the lower gastrointestinal (GI) tract was more effective in achieving CR than via the upper GI tract (44.3% vs 31.7%). The remission rate was also higher when the total stool dosage was over 275 g compared with less than 275 g (51.9% vs 29.5%). Overall, the incidence of serious adverse events of FMT was 5.9%. There was no significant difference between single and multiple donors, fresh and frozen stool sample used, and whether or not antibiotic pretreatment was administered before FMT. CONCLUSION FMT administration via the lower GI tract and using higher dosage appear to be effective and safe in inducing remission of active UC.
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Affiliation(s)
- Hai Lan Zhao
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Shu Zhen Chen
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Hao Ming Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - You Lian Zhou
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Jie He
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Hong Li Huang
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Jing Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Yu Qiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
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Quagliariello A, Del Chierico F, Reddel S, Russo A, Onetti Muda A, D’Argenio P, Angelino G, Romeo EF, Dall’Oglio L, De Angelis P, Putignani L, all the other FMT OPBG Committee Collaborators. Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations. Microorganisms 2020; 8:microorganisms8101486. [PMID: 32992653 PMCID: PMC7599854 DOI: 10.3390/microorganisms8101486] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/11/2020] [Accepted: 09/23/2020] [Indexed: 01/10/2023] Open
Abstract
Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.
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Affiliation(s)
- Andrea Quagliariello
- Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.Q.); (S.R.)
| | - Federica Del Chierico
- Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.Q.); (S.R.)
- Correspondence: ; Tel.: +39-0668594061; Fax: +39-0668592904
| | - Sofia Reddel
- Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.Q.); (S.R.)
| | - Alessandra Russo
- Department of Laboratories, Unit of Parasitology, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Andrea Onetti Muda
- Department of Laboratories, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Patrizia D’Argenio
- Academic Department of Pediatrics, Unit of Immune and Infectious Diseases, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Giulia Angelino
- Digestive Surgery and Endoscopy Unit, Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy; (G.A.); (E.F.R.); (L.D.); (P.D.A.)
| | - Erminia Francesca Romeo
- Digestive Surgery and Endoscopy Unit, Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy; (G.A.); (E.F.R.); (L.D.); (P.D.A.)
| | - Luigi Dall’Oglio
- Digestive Surgery and Endoscopy Unit, Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy; (G.A.); (E.F.R.); (L.D.); (P.D.A.)
| | - Paola De Angelis
- Digestive Surgery and Endoscopy Unit, Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy; (G.A.); (E.F.R.); (L.D.); (P.D.A.)
| | - Lorenza Putignani
- Department of Laboratories, Unit of Parasitology and Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
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Caldeira LDF, Borba HH, Tonin FS, Wiens A, Fernandez-Llimos F, Pontarolo R. Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis. PLoS One 2020; 15:e0238910. [PMID: 32946509 PMCID: PMC7500646 DOI: 10.1371/journal.pone.0238910] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 08/25/2020] [Indexed: 02/07/2023] Open
Abstract
Objectives Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease. Methods Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted. Results Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn’s disease patients seemed to benefit more from the procedure. Conclusions The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn’s disease.
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Affiliation(s)
| | - Helena H. Borba
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Fernanda S. Tonin
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Astrid Wiens
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Fernando Fernandez-Llimos
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Roberto Pontarolo
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
- * E-mail:
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