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Kamath S, Bryant RV, Costello SP, Day AS, Forbes B, Haifer C, Hold G, Kelly CR, Li A, Pakuwal E, Stringer A, Tucker EC, Wardill HR, Joyce P. Translational strategies for oral delivery of faecal microbiota transplantation. Gut 2025:gutjnl-2025-335077. [PMID: 40301116 DOI: 10.1136/gutjnl-2025-335077] [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: 02/12/2025] [Accepted: 04/09/2025] [Indexed: 05/01/2025]
Abstract
Faecal microbiota transplantation (FMT) has emerged as a transformative therapy for Clostridioides difficile infections and shows promise for various GI and systemic diseases. However, the poor patient acceptability and accessibility of 'conventional' FMT, typically administered via colonoscopies or enemas, hinders its widespread clinical adoption, particularly for chronic conditions. Oral administration of FMT (OralFMT) overcomes these limitations, yet faces distinct challenges, including a significant capsule burden, palatability concerns and poor microbial viability during gastric transit. This review provides a comprehensive analysis of emerging strategies that aim to advance OralFMT by: (1) refining processing technologies (eg, lyophilisation) that enable manufacturing of low-volume FMT formulations for reducing capsule burden and (2) developing delivery technologies that improve organoleptic acceptability and safeguard the microbiota for targeted colonic release. These advancements present opportunities for OralFMT to expand its therapeutic scope, beyond C. difficile infections, towards chronic GI conditions requiring frequent dosing regimens. While this review primarily focuses on optimising OralFMT delivery, it is important to contextualise these advancements within the broader shift towards defined microbial consortia. Live biotherapeutic products (LBPs) offer an alternative approach, yet the interplay between OralFMT and LBPs in clinical practice remains unresolved. We postulate that continued innovation in OralFMT and LBPs via a multidisciplinary approach can further increase therapeutic efficacy and scalability by enabling disease site targeting, co-delivery of therapeutic compounds and overcoming colonisation resistance. Realising these goals positions OralFMT as a cornerstone of personalised care across a range of diseases rooted in microbiome health.
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Affiliation(s)
- Srinivas Kamath
- UniSA Clinical & Health Sciences, University of South Australia, Adelaide, South Australia, Australia
| | - Robert V Bryant
- Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
- Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia
| | - Samuel P Costello
- Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
- The University of Adelaide, Adelaide, South Australia, Australia
| | - Alice S Day
- Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia
- Gastroenterology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
| | | | - Craig Haifer
- Department of Gastroenterology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia
- School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Georgina Hold
- Microbiome Research Centre, University of New South Wales, Sydney, New South Wales, Australia
| | - Colleen R Kelly
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Anna Li
- Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia
| | - Evance Pakuwal
- Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia
| | - Andrea Stringer
- UniSA Clinical & Health Sciences, University of South Australia, Adelaide, South Australia, Australia
| | - Emily C Tucker
- Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia
- Infectious Diseases Unit, Central Adelaide Local Health Network, Adelaide, South Australia, Australia
| | - Hannah Rose Wardill
- Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia
- Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Paul Joyce
- University of South Australia, Adelaide, South Australia, Australia
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Rågård N, Baumwall SMD, Paaske SE, Hansen MM, Høyer KL, Mikkelsen S, Erikstrup C, Dahlerup JF, Hvas CL. Validation methods for encapsulated faecal microbiota transplantation: a scoping review. Therap Adv Gastroenterol 2025; 18:17562848251314820. [PMID: 39926318 PMCID: PMC11806493 DOI: 10.1177/17562848251314820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 01/03/2025] [Indexed: 02/11/2025] Open
Abstract
Faecal microbiota transplantation (FMT) is increasingly used for diseases associated with a disrupted intestinal microbiome, mainly Clostridioides difficile infection. Encapsulated FMT is a patient-friendly application method that improves accessibility and convenience. Capsule processing may be standardised, but validation protocols are warranted. This review aimed to describe published validation methods for encapsulated FMT. Original studies reporting using encapsulated faecal formulations were included, regardless of indication. Studies were excluded if they did not address processing and validation or used non-donor-derived content. We conducted a comprehensive scoping review, implementing a systematic search strategy in PubMed, Embase and Web of Science. Processing data and validation methods were registered during full-text analysis and combined to create an overview of approaches for assessing quality in encapsulated FMT processing. The searches identified 324 unique studies, of which 44 were included for data extraction and analysis. We identified eight validation covariables: donor selection, pre-processing, preservation, oxygen-sparing processing, microbial count, viability, engraftment and clinical effect outcomes, from which we constructed a model for quality assessment of encapsulated FMT that exhaustively categorised processing details and validation measures. Our model comprised three domains: (1) Processing (donor selection and processing protocol), (2) Content analysis (microbiota measures and dose measures) and (3) Clinical effect (engraftment and clinical outcomes). No studies presented a reproducible capsule protocol; their validation strategies were sparse and divergent. The validation of FMT capsules is heterogeneous, and processing requires relevant standardisation protocols, mainly focusing on capsule content. Future studies should report validation covariables to enable accurate comparative assessments of clinical effects.
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Affiliation(s)
- Nina Rågård
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Sara Ellegaard Paaske
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Mette Mejlby Hansen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Katrine Lundby Høyer
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Susan Mikkelsen
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Christian Erikstrup
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Jens Frederik Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 35, DK-8200 Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Mousa WK, Al Ali A. The Gut Microbiome Advances Precision Medicine and Diagnostics for Inflammatory Bowel Diseases. Int J Mol Sci 2024; 25:11259. [PMID: 39457040 PMCID: PMC11508888 DOI: 10.3390/ijms252011259] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/12/2024] [Accepted: 10/13/2024] [Indexed: 10/28/2024] Open
Abstract
The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.
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Affiliation(s)
- Walaa K. Mousa
- College of Pharmacy, Al Ain University of Science and Technology, Abu Dhabi 64141, United Arab Emirates;
- College of Pharmacy, Mansoura University, Mansoura 35516, Egypt
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 112612, United Arab Emirates
| | - Aya Al Ali
- College of Pharmacy, Al Ain University of Science and Technology, Abu Dhabi 64141, United Arab Emirates;
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 112612, United Arab Emirates
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Reygner J, Delannoy J, Barba-Goudiaby MT, Gasc C, Levast B, Gaschet E, Ferraris L, Paul S, Kapel N, Waligora-Dupriet AJ, Barbut F, Thomas M, Schwintner C, Laperrousaz B, Corvaïa N. Reduction of product composition variability using pooled microbiome ecosystem therapy and consequence in two infectious murine models. Appl Environ Microbiol 2024; 90:e0001624. [PMID: 38651930 PMCID: PMC11107171 DOI: 10.1128/aem.00016-24] [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: 01/04/2024] [Accepted: 03/27/2024] [Indexed: 04/25/2024] Open
Abstract
Growing evidence demonstrates the key role of the gut microbiota in human health and disease. The recent success of microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on its potential in conditions associated with gut dysbiosis, such as acute graft-versus-host disease, intestinal bowel diseases, neurodegenerative diseases, or even cancer. However, the difficulty in defining a "good" donor as well as the intrinsic variability of donor-derived products' taxonomic composition limits the translatability and reproducibility of these studies. Thus, the pooling of donors' feces has been proposed to homogenize product composition and achieve higher taxonomic richness and diversity. In this study, we compared the metagenomic profile of pooled products to corresponding single donor-derived products. We demonstrated that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria known to produce anti-inflammatory short chain fatty acids compared to single donor-derived products. We then evaluated pooled products' efficacy compared to corresponding single donor-derived products in Salmonella and C. difficile infectious mouse models. We were able to demonstrate that pooled products decreased pathogenicity by inducing a structural change in the intestinal microbiota composition. Single donor-derived product efficacy was variable, with some products failing to control disease progression. We further performed in vitro growth inhibition assays of two extremely drug-resistant bacteria, Enterococcus faecium vanA and Klebsiella pneumoniae oxa48, supporting the use of pooled microbiotherapies. Altogether, these results demonstrate that the heterogeneity of donor-derived products is corrected by pooled fecal microbiotherapies in several infectious preclinical models.IMPORTANCEGrowing evidence demonstrates the key role of the gut microbiota in human health and disease. Recent Food and Drug Administration approval of fecal microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on their potential to treat pathological conditions associated with gut dysbiosis. In this study, we combined metagenomic analysis with in vitro and in vivo studies to compare the efficacy of pooled microbiotherapy products to corresponding single donor-derived products. We demonstrate that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria compared to single donor-derived products. We further reveal that pooled products decreased Salmonella and Clostridioides difficile pathogenicity in mice, while single donor-derived product efficacy was variable, with some products failing to control disease progression. Altogether, these findings support the development of pooled microbiotherapies to overcome donor-dependent treatment efficacy.
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Affiliation(s)
| | | | | | | | | | | | | | - Stéphane Paul
- Team GIMAP, Centre International de Recherche en Infectiologie, Université Jean Monnet, Saint-Etienne, France
- Inserm, Université Claude Bernard Lyon, Lyon, France
- CIC 1408 Inserm Vaccinology, University Hospital of Saint-Etienne, Saint-Etienne, France
- Immunology Department, iBiothera Reference Center, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - Nathalie Kapel
- UMR-S 1139, INSERM, Université Paris Cite, Paris, France
- Service de Coprologie fonctionnelle, Hôpital de la Pitié-Salpêtrière-Charles Foix, AP-HP, Paris, France
| | | | - Frederic Barbut
- UMR-S 1139, INSERM, Université Paris Cite, Paris, France
- National Reference Laboratory for Clostridioides difficile, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
- The European Society of Clinical Microbiology and Infectious Diseases Study Group for Clostridioides difficile, Basel, Switzerland
| | - Muriel Thomas
- UMR1319, Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
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Hediyal TA, Vichitra C, Anand N, Bhaskaran M, Essa SM, Kumar P, Qoronfleh MW, Akbar M, Kaul-Ghanekar R, Mahalakshmi AM, Yang J, Song BJ, Monaghan TM, Sakharkar MK, Chidambaram SB. Protective effects of fecal microbiota transplantation against ischemic stroke and other neurological disorders: an update. Front Immunol 2024; 15:1324018. [PMID: 38449863 PMCID: PMC10915229 DOI: 10.3389/fimmu.2024.1324018] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 02/01/2024] [Indexed: 03/08/2024] Open
Abstract
The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-β accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer's disease. In Parkinson's disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature.
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Affiliation(s)
- Tousif Ahmed Hediyal
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, KA, India
- Centre for Experimental Pharmacology and Toxicology, JSS Academy of Higher Education & Research, Mysuru, KA, India
| | - C. Vichitra
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, KA, India
- Centre for Experimental Pharmacology and Toxicology, JSS Academy of Higher Education & Research, Mysuru, KA, India
| | - Nikhilesh Anand
- Department of Pharmacology, American University of Antigua, College of Medicine, Saint John’s, Antigua and Barbuda
| | - Mahendran Bhaskaran
- College of Pharmacy and Pharmaceutical Sciences, Frederic and Mary Wolf Centre University of Toledo, Health Science, Toledo, OH, United States
| | - Saeefh M. Essa
- Department of Computer Science, Northwest High School, Bethesda, MD, United States
| | - Pravir Kumar
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Delhi, India
| | - M. Walid Qoronfleh
- Q3CG Research Institute (QRI), Research and Policy Division, Ypsilanti, MI, United States
| | - Mohammed Akbar
- Division of Neuroscience and Behavior, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, United States
| | - Ruchika Kaul-Ghanekar
- Symbiosis Centre for Research and Innovation (SCRI), Cancer Research Lab, Symbiosis School of Biological Sciences (SSBS), Symbiosis International University (SIU), Pune, Maharashtra, India
| | - Arehally M. Mahalakshmi
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, KA, India
- Centre for Experimental Pharmacology and Toxicology, JSS Academy of Higher Education & Research, Mysuru, KA, India
| | - Jian Yang
- Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - Byoung-Joon Song
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Bio-physics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States
| | - Tanya M. Monaghan
- National Institute for Health Research Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | - Meena Kishore Sakharkar
- Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - Saravana Babu Chidambaram
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, KA, India
- Centre for Experimental Pharmacology and Toxicology, JSS Academy of Higher Education & Research, Mysuru, KA, India
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Al-Kuraishy HM, Al-Gareeb AI, Zaidalkiani AT, Alexiou A, Papadakis M, Bahaa MM, Al-Faraga A, Batiha GES. Calprotectin in Parkinsonian disease: Anticipation and dedication. Ageing Res Rev 2024; 93:102143. [PMID: 38008403 DOI: 10.1016/j.arr.2023.102143] [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: 10/10/2023] [Revised: 11/13/2023] [Accepted: 11/22/2023] [Indexed: 11/28/2023]
Abstract
Parkinson's disease (PD) is a neurodegenerative disease due to degeneration of dopaminergic neurons (DNs) in the substantia nigra pars compacta (SNpc). PD is characterized by motor and non-motor symptoms. Non-motor symptoms such as constipation and dysfunction of gastrointestinal tract (GIT) motility together with medications used in the management of PD affect gut microbiota. Alterations of gut microbiota with development of gut dyspiosis can induce momentous changes in gut barrier with subsequent systemic inflammation and induction of neuroinflammation. It has been shown that calprotectin which reflect intestinal inflammation and gut barrier injury are augmented in PD. Therefore, this review aims to elucidate the possible role of gut barrier injury and associated dysbiois in PD neuropathology, and how calprotectin reflects gut barrier injury in PD. Benefit of this review was to elucidate that high fecal calprotectin level in PD patients indicated gut dysbiosis and intestinal inflammation. Early increment of fecal calprotectin indicates the development of gut dysbiosis and/or gut-barrier injury which may precede motor symptoms by decades. Thus, fecal calprotectin could be a diagnostic and prognostic biomarker in PD. preclinical and clinical studies are warranted in this regard to emphasize the potential role of fecal calprotectin in PD neuropathology.
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Affiliation(s)
- Hayder M Al-Kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Ali I Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Ayah Talal Zaidalkiani
- Department of Nutrition, Faculty of Pharmacy and Medical Sciences, University of Petra, 11196 Amman, Jordan
| | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia; AFNP Med, 1030 Wien, Austria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283 Wuppertal, Germany
| | - Mostafa M Bahaa
- Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt.
| | - Ammar Al-Faraga
- Department of Biochemistry, College of Science University of Jeddah, Saudi Arabia
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira 22511, Egypt
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Chen Q, Fan Y, Zhang B, Yan C, Zhang Q, Ke Y, Chen Z, Wang L, Shi H, Hu Y, Huang Q, Su J, Xie C, Zhang X, Zhou L, Ren J, Xu H. Capsulized Fecal Microbiota Transplantation Induces Remission in Patients with Ulcerative Colitis by Gut Microbial Colonization and Metabolite Regulation. Microbiol Spectr 2023; 11:e0415222. [PMID: 37093057 PMCID: PMC10269780 DOI: 10.1128/spectrum.04152-22] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 03/30/2023] [Indexed: 04/25/2023] Open
Abstract
Fecal microbiota transplantation (FMT) can induce clinical remission in ulcerative colitis (UC) patients. Enemas, nasoduodenal tubes, and colonoscopies are the most common routes for FMT administration. However, there is a lack of definitive evidence regarding the effectiveness of capsulized FMT treatment in UC patients. In this study, we administered capsulized FMT to 22 patients with active UC to assess the efficiency of capsulized FMT and determine the specific bacteria and metabolite factors associated with the response to clinical remission. Our results showed that the use of capsulized FMT was successful in the treatment of UC patients. Capsulized FMT induced clinical remission and clinical response in 57.1% (12 of 21) and 76.2% (16 of 21) of UC patients, respectively. Gut bacterial richness was increased after FMT in patients who achieved remission. Patients in remission after FMT exhibited enrichment of Alistipes sp. and Odoribacter splanchnicus, along with increased levels of indolelactic acid. Patients who did not achieve remission exhibited enrichment of Escherichia coli and Klebsiella and increased levels of biosynthesis of 12,13-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid) and lipopolysaccharides. Furthermore, we identified a relationship between specific bacteria and metabolites and the induction of remission in patients. These findings may provide new insights into FMT in UC treatment and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects. (This study has been registered at ClinicalTrails.gov under registration no. NCT03426683). IMPORTANCE Fecal microbiota transplantation has been successfully used in patients. Recently, capsulized FMT was reported to induce a response in patients with UC. However, limited patients were enrolled in such studies, and the functional factors of capsulized FMT have not been reported in the remission of patients with UC. In this study, we prospectively recruited patients with UC to receive capsulized FMT. First, we found that capsulized FMT could induce clinical remission in 57.1% of patients and clinical response in 76.2% after 12 weeks, which was more acceptable. Second, we found a relationship between the decrease of opportunistic pathogen and lipopolysaccharide synthesis in patients in remission after capsulized FMT. We also identified an association between specific bacteria and metabolites and remission induction in patients after capsulized FMT. These findings put forward a possibility for patients to receive FMT at home and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects.
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Affiliation(s)
- Qiongyun Chen
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Yanyun Fan
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Bangzhou Zhang
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Changsheng Yan
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Qiang Zhang
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Yuhao Ke
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Zhangran Chen
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Lin Wang
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Huaxiu Shi
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Yiqun Hu
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Qingwen Huang
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Jingling Su
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Chenxi Xie
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Xu Zhang
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Lixiang Zhou
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Jianlin Ren
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Intestinal Microbiome and Human Health, Zhongshan Hospital of Xiamen University, Xiamen, China
- Department of Digestive Disease, School of Medicine, Xiamen University, Xiamen, China
| | - Hongzhi Xu
- Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
- Xiamen Key Laboratory of Intestinal Microbiome and Human Health, Zhongshan Hospital of Xiamen University, Xiamen, China
- Department of Digestive Disease, School of Medicine, Xiamen University, Xiamen, China
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8
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Porcari S, Benech N, Valles-Colomer M, Segata N, Gasbarrini A, Cammarota G, Sokol H, Ianiro G. Key determinants of success in fecal microbiota transplantation: From microbiome to clinic. Cell Host Microbe 2023; 31:712-733. [PMID: 37167953 DOI: 10.1016/j.chom.2023.03.020] [Citation(s) in RCA: 106] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Fecal microbiota transplantation (FMT) has achieved satisfactory results in preventing the recurrence of Clostridioides difficile infection, but these positive outcomes have only been partially replicated in other diseases. Several factors influence FMT success, including those related to donors and recipients (including diversity and specific composition of the gut microbiome, immune system, and host genetics) as well as to working protocols (fecal amount and number of infusions, route of delivery, and adjuvant treatments). Moreover, initial evidence suggests that the clinical success of FMT may be related to the degree of donor microbial engraftment. The application of cutting-edge technologies for microbiome assessment, along with changes in the current vision of fecal transplants, are expected to improve FMT protocols and outcomes. Here, we review the key determinants of FMT success and insights and strategies that will enable a close integration of lab-based and clinical approaches for increasing FMT success.
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Affiliation(s)
- Serena Porcari
- Department of Medical and Surgical Sciences, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Nicolas Benech
- Hospices Civils de Lyon, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Tumor Escape Resistance and Immunity Department, Cancer Research Center of Lyon (CRCL), Inserm U1052, CNRS UMR 5286, Lyon, France; French Fecal Transplant Group (GFTF), France
| | | | - Nicola Segata
- Department CIBIO, University of Trento, Trento, Italy; Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Department of Medical and Surgical Sciences, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Harry Sokol
- French Fecal Transplant Group (GFTF), France; Sorbonne University, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, Paris, France; Paris Centre for Microbiome Medicine FHU, Paris, France; INRA, UMR1319 Micalis & AgroParisTech, Jouy en Josas, France
| | - Gianluca Ianiro
- Department of Medical and Surgical Sciences, Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
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9
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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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10
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Zhang B, Yang L, Ning H, Cao M, Chen Z, Chen Q, Lian G, Tang H, Wang Q, Wang J, Lin Z, Wen J, Liu Y, Xuan J, Li X, Lin A, He J, Zhang L, Hou X, Zeng Q, Xiao C. A Matching Strategy To Guide Donor Selection for Ulcerative Colitis in Fecal Microbiota Transplantation: Meta-Analysis and Analytic Hierarchy Process. Microbiol Spectr 2023; 11:e0215921. [PMID: 36472435 PMCID: PMC9927247 DOI: 10.1128/spectrum.02159-21] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 11/07/2022] [Indexed: 12/12/2022] Open
Abstract
Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of ulcerative colitis (UC). However, preliminary trials showed that only a subset of patients responded to FMT, and the heterogeneity in donor gut microbiota probably played important roles in patients' responses, implying the significance of matching an appropriate donor to a specified patient. We developed a strategy to build a donor-recipient matching model to guide rational donor selection for UC in FMT. We collected and uniformly reanalyzed 656 fecal 16S rRNA gene sequencing samples (350 from UC patients and 306 from healthy subjects) from 9 studies. Significantly lower α-diversity indexes were observed in UC patients by random effects model. Thirty-four bacterial genera and 34 predicted pathways were identified with significant odds ratios and classification potentials for UC patients. Based on six bacterial indicators, including richness, overall distance, genera, and pathways (beneficial and harmful), the analytic hierarchy process-based donor-recipient matching model was set to rank and select appropriate donors for patients with UC. Finally, the model showed favorable classification powers (>70%) for FMT effectiveness in two previous clinical trials. This study revealed the dysbiosis of fecal bacterial diversity, composition, and predicted pathways of patients with UC by meta-analysis and hereby developed a donor-recipient matching strategy to guide donor selection for UC in FMT. This strategy can also be applied to other diseases associated with gut microbiota. IMPORTANCE Modulation of gut microbiota by FMT from donors has been applied to the treatment of UC and yielded variable effectiveness in clinical trials. One possibility is that this variable effectiveness was related to donor selection, as a patient's response to FMT may rely on the capability of the used donor's microbiota to restore the specific gut disturbances of the patient. However, the biggest issues on the practical level are what should be considered in the selection process and how to set up such a donor-recipient matching model. In this study, we presented a bacterial profile-based donor-recipient matching strategy to guide donor selection for UC in FMT by first meta-analysis of 656 fecal 16S rRNA gene sequencing samples from 9 studies to identify significant indicators and then setting up the model by an analytic hierarchy process. The applicability and accuracy of this model were verified in the data sets from two previous FMT clinical studies. Our data indicate that the donor-recipient matching model built in this study enables researchers to rationally select donors for UC patients in FMT clinical practice, although it needs more samples and prospective trials for validation. The strategy adopted in this study to leverage existing data sets to build donor-recipient matching models for precision FMT is feasible for other diseases associated with gut microbiota.
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Affiliation(s)
- Bangzhou Zhang
- School of Life Sciences, Xiamen University, Xiamen, China
- School of Medicine, Xiamen University, Xiamen, China
| | - Luxi Yang
- School of Life Sciences, Xiamen University, Xiamen, China
| | - Hanbing Ning
- Department of Digestive Diseases, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Man Cao
- Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Zhangran Chen
- School of Medicine, Xiamen University, Xiamen, China
| | - Qiongyun Chen
- School of Medicine, Xiamen University, Xiamen, China
| | - Guanghui Lian
- Department of Gastroenterology, Xiangya Hospital, Changsha, China
| | - Hailing Tang
- Department of Gastroenterology, Xi'an Central Hospital, Xi’an, China
| | - Qizhi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Junping Wang
- Department of Gastroenterology, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Zhihui Lin
- Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, China
| | - Jianbo Wen
- Department of Gastroenterology, Pingxiang People’s Hospital, Pingxiang, China
| | - Yuedong Liu
- Department of Gastroenterology, The Third Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Ji Xuan
- Department of Gastroenterology, Jinling Hospital, Nanjing, China
| | - Xuejun Li
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Aiqiang Lin
- Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Jianquan He
- School of Medicine, Xiamen University, Xiamen, China
| | - Lei Zhang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Technology and Science, Wuhan, China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Technology and Science, Wuhan, China
| | - Qiang Zeng
- Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Chuanxing Xiao
- Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
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11
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Mirsepasi-Lauridsen HC. Therapy Used to Promote Disease Remission Targeting Gut Dysbiosis, in UC Patients with Active Disease. J Clin Med 2022; 11:7472. [PMID: 36556089 PMCID: PMC9784819 DOI: 10.3390/jcm11247472] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/11/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
Ulcerative colitis (UC) is a relapsing non-transmural chronic inflammatory disease of the colon characterized by bloody diarrhea. The etiology of UC is unknown. The goal is to reduce the inflammation and induce disease remission in UC patients with active disease. The aim of this study is to investigate the innovative treatment method used to promote disease remission in UC patients with active disease targeting gut dysbiosis. Immunosuppressants such as TNF-α blocker are used to promote disease remission in UC, but it is expensive and with side effects. Probiotic, prebiotic and diet are shown to be effective in maintaining disease remission. Fecal microbiota transplantation (FMT) might be the future therapy option to promote disease remission in UC patients with active disease. However, correct manufacturing and administration of the FMT are essential to achieve successful outcome. A few cohorts with FMT capsules show promising results in UC patients with active disease. However, randomized controlled clinical trials with long-term treatment and follow-up periods are necessary to show FMT capsules' efficacy to promote disease remission in UC patients.
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12
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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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13
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Zhang J, Guo Y, Duan L. Features of Gut Microbiome Associated With Responses to Fecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review. Front Med (Lausanne) 2022; 9:773105. [PMID: 35721102 PMCID: PMC9198717 DOI: 10.3389/fmed.2022.773105] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 04/19/2022] [Indexed: 12/14/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has been seen as a novel treatment for inflammatory bowel disease (IBD). The results on microbial alterations and their relationship to treatment efficacy are varied among studies. We performed a systematic review to explore the association between microbial features and therapy outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to November 2020. Studies that investigated the efficacy of FMT and baseline microbial features or dynamic alteration of the microbiome during FMT were included. The methodological quality of the included cohort studies and randomized controlled trials (RCTs) was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane risk of bias tool, respectively. A total of 30 studies were included in the analysis. Compared to non-responders, the microbial structure of patients who responded to FMT had a higher similarity to that of their donors after FMT. Donors of responders (R-d) and non-responders (NR-d) had different microbial taxa, but the results were inconsistent. After FMT, several beneficial short-chain fatty acids- (SCFA-) producing taxa, such as Faecalibacterium, Eubacterium, Roseburia, and species belonging to them, were enriched in responders, while pathogenic bacteria (Escherichia coli and Escherichia-Shigella) belonging to the phylum Proteobacteria were decreased. Alterations of microbial functional genes and metabolites were also observed. In conclusion, the response to FMT was associated with the gut microbiota and their metabolites. The pre-FMT microbial features of recipients, the comparison of pre- and post-FMT microbiota, and the relationship between recipients and donors at baseline should be further investigated using uniform and standardized methods.
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Affiliation(s)
- Jindong Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yangyang Guo
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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14
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Smith BJ, Piceno Y, Zydek M, Zhang B, Syriani LA, Terdiman JP, Kassam Z, Ma A, Lynch SV, Pollard KS, El-Nachef N. Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis. Sci Rep 2022; 12:5517. [PMID: 35365713 PMCID: PMC8976058 DOI: 10.1038/s41598-022-09307-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 03/16/2022] [Indexed: 01/04/2023] Open
Abstract
Fecal microbiota transplant is a promising therapy for ulcerative colitis. Parameters maximizing effectiveness and tolerability are not yet clear, and it is not known how import the transmission of donor microbes to patients is. Here (clinicaltrails.gov: NCT03006809) we have tested the effects of antibiotic pretreatment and compared two modes of maintenance dose delivery, capsules versus enema, in a randomized, pilot, open-label, 2 × 2 factorial design with 22 patients analyzed with mild to moderate UC. Clinically, the treatment was well-tolerated with favorable safety profile. Of patients who received antibiotic pretreatment, 6 of 11 experienced remission after 6 weeks of treatment, versus 2 of 11 non-pretreated patients (log odds ratio: 1.69, 95% confidence interval: −0.25 to 3.62). No significant differences were found between maintenance dosing via capsules versus enema. In exploratory analyses, microbiome turnover at both the species and strain levels was extensive and significantly more pronounced in the pretreated patients. Associations were also revealed between taxonomic turnover and changes in the composition of primary and secondary bile acids. Together these findings suggest that antibiotic pretreatment contributes to microbiome engraftment and possibly clinical effectiveness, and validate longitudinal strain tracking as a powerful way to monitor the dynamics and impact of microbiota transfer.
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Affiliation(s)
- Byron J Smith
- Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.,Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | | | - Martin Zydek
- Division of Gastroenterology, University of California, San Francisco, CA, USA
| | - Bing Zhang
- Division of Gastroenterology, University of California, San Francisco, CA, USA.,Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Lara Aboud Syriani
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA
| | - Jonathan P Terdiman
- Division of Gastroenterology, University of California, San Francisco, CA, USA
| | | | - Averil Ma
- Department of Medicine, University of California, San Francisco, CA, USA
| | - Susan V Lynch
- Division of Gastroenterology, University of California, San Francisco, CA, USA.,Benioff Center for Microbiome Medicine, University of California, San Francisco, CA, USA
| | - Katherine S Pollard
- Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA. .,Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. .,Chan Zuckerberg Biohub, San Francisco, CA, USA.
| | - Najwa El-Nachef
- Division of Gastroenterology, University of California, San Francisco, CA, USA.
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15
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Long-Term Safety Following Faecal Microbiota Transplantation as a Treatment for Recurrent Clostridioides difficile Infection Compared with Patients Treated with a Fixed Bacterial Mixture: Results from a Retrospective Cohort Study. Cells 2022; 11:cells11030435. [PMID: 35159245 PMCID: PMC8834574 DOI: 10.3390/cells11030435] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/21/2022] [Accepted: 01/22/2022] [Indexed: 02/08/2023] Open
Abstract
Faecal microbiota transplantation (FMT) is the recommended treatment for recurrent C. difficile infection (rCDI) following a second recurrence. FMT is considered safe in the short term when procedures for the screening of donors and transferred material are followed. However, the long-term safety profile of FMT treatment is largely unknown. In a retrospective cohort study, we assessed the long-term safety of patients treated for rCDI with FMT or a fixed bacterial mixture, rectal bacteriotherapy (RBT). The overall survival, risk of hospital admission, onset of certain pre-specified diseases (cancer, diabetes mellitus, hypertension and inflammatory bowel disease) and risk of being diagnosed with a multidrug-resistant organism were assessed by undertaking a review of the treated patients’ medical records for up to five years following treatment. A total of 280 patients were treated for rCDI with FMT (n = 145) or RBT (n = 135) between 2016 and 2020. In the five years following treatment, there were no differences in survival (adjusted hazard ratio (aHR) 1.03; 95% CI 0.68–1.56), p = 0.89), risk of hospital admission ((aHR 0.92; 95% CI 0.72–1.18), p = 0.5) or onset of any of the analysed diseases. In conclusion, FMT was not associated with increased mortality, risk of hospital admission or onset of disease following treatment when compared with RBT.
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16
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Wortelboer K, Herrema H. Shedding light on dark matter - faecal microbiota transplantation in Europe. THE LANCET REGIONAL HEALTH. EUROPE 2021; 9:100187. [PMID: 34693389 PMCID: PMC8513115 DOI: 10.1016/j.lanepe.2021.100187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Affiliation(s)
- Koen Wortelboer
- Department of Experimental Vascular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, Netherlands
| | - Hilde Herrema
- Department of Experimental Vascular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, Netherlands
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17
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Cold F, Baunwall SMD, Dahlerup JF, Petersen AM, Hvas CL, Hansen LH. Systematic review with meta-analysis: encapsulated faecal microbiota transplantation - evidence for clinical efficacy. Therap Adv Gastroenterol 2021; 14:17562848211041004. [PMID: 34484424 PMCID: PMC8414624 DOI: 10.1177/17562848211041004] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/30/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infection (rCDI) and is being applied experimentally in other diseases. Encapsulated administration may be equivalent in efficacy to delivery through other routes. METHODS A systematic review was undertaken of studies using encapsulated FMT up to 26 October 2020. Data on indication, clinical outcomes, safety, treatment protocol and capsule preparation were collected and reported. Pooled rates of clinical efficacy in rCDI were calculated using random-effects meta-analysis. The impact of single variables on clinical efficacy was evaluated using univariate meta-regression. RESULTS A total of 35 studies reporting the treatment of 960 patients with encapsulated FMT for eight different indications met the inclusion criteria. Most studies (n = 18, 51%) and patients (n = 755, 79%) were from studies on rCDI. Cure rates after single and multiple courses of treatments with encapsulated FMT in rCDI were 85% (95% CI: 82%-88%) and 93% (95% CI: 88%-96%) respectively. The treatment outcome was not significantly affected by dose, number of delivered capsules, anaerobic/aerobic processing, single/multi-donor treatment, lyophilisation, or any other single factor in the production or delivery of encapsulated FMT. Promising but non-comparable results from the treatment of ulcerative colitis and multidrug-resistant organisms were reported. CONCLUSIONS Encapsulated FMT is an effective and safe treatment of rCDI, with cure rates comparable to FMT delivered through other routes. The treatment is effective despite variations in donor screening, preparation and treatment protocol. For other indications, the role of FMT capsules is still not sufficiently examined, although some studies show promising results. PLAIN LANGUAGE SUMMARY Transfer of faecal material through capsules in the treatment of various diseases. Evidence for clinical efficacy The bacteria and other microorganisms of the gut is different in patient with various diseases in comparison with healthy subjects.Therefore, ways to change the microorganisms of the gut in a beneficial direction has been the subject of various research projects within recent years.Faecal microbiota transplantation often referred as FMT is a method of transferring microorganisms from healthy donors to patients with various diseases and is seen as one way to change the microbial community of the gut in a beneficial direction.Faecal microbiota transplantation can be performed in different ways such as through endoscopy, enemas or capsules. The transfer through capsules is preferred by the patients and has advantages since it can be administered long-term and can be delivered to the patients in their home. In this paper, we evaluated all accessible research reporting treatment with encapsulated faecal microbiota transplantation in the treatment of various diseases. We report the following major findings:-Treatment with capsules is safe when guidelines for screening donors and testing faecal material is followed.-The treatment is highly effective in the treatment of recurrent C. difficile infection, a disease with high mortality often caused by repeated antibiotic treatments. The treatment was effective in 596 of 723 patients following one course of capsule treatment.-Faecal microbiota transplantation delivered through capsules is as effective as treatment delivered through other routes in the treatment of C. difficile infection.-The treatment is effective in the treatment of C. difficile infection across studies and countries, despite great differences in the ways the capsules were prepared and delivered.-Increasing the amount of faecal material used in the production did not affect the efficacy of the treatment.-There are promising results in the treatment of other diseases such as liver disease, inflammatory bowel disease and the treatment of multi-drug resistant bacteria.
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Affiliation(s)
| | | | - Jens Frederik Dahlerup
- Department of Hepatology and Gastroenterology,
Aarhus University Hospital, Aarhus, Denmark
| | - Andreas Munk Petersen
- Gastrounit, Medical Division, Copenhagen
University Hospital Hvidovre, Hvidovre, Denmark,Department of Clinical Microbiology, Copenhagen
University Hospital Hvidovre, Hvidovre, Denmark
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology,
Aarhus University Hospital, Aarhus, Denmark
| | - Lars Hestbjerg Hansen
- Department of Plant and Environmental Sciences,
Copenhagen University, Frederiksberg, Denmark
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18
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Crothers JW, Chu ND, Nguyen LTT, Phillips M, Collins C, Fortner K, Del Rio-Guerra R, Lavoie B, Callas P, Velez M, Cohn A, Elliott RJ, Wong WF, Vo E, Wilcox R, Smith M, Kassam Z, Budd R, Alm EJ, Mawe GM, Moses PL. Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study. BMC Gastroenterol 2021; 21:281. [PMID: 34238227 PMCID: PMC8268596 DOI: 10.1186/s12876-021-01856-9] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 06/23/2021] [Indexed: 02/22/2023] Open
Abstract
Background Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). Methods Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint. Results Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response. Conclusion These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-021-01856-9.
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Affiliation(s)
- Jessica W Crothers
- Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT, 05401, USA. .,Larner College of Medicine, The University of Vermont, 89 Beaumont Ave, Burlington, VT, 05401, USA.
| | - Nathaniel D Chu
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.,Center for Microbiome Informatics and Therapeutics, Broad Institute, Cambridge, MA, USA
| | - Le Thanh Tu Nguyen
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.,Center for Microbiome Informatics and Therapeutics, Broad Institute, Cambridge, MA, USA
| | - Magen Phillips
- Department of Medicine, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT, 05401, USA
| | - Cheryl Collins
- Department of Medicine, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT, 05401, USA
| | - Karen Fortner
- Department of Medicine, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT, 05401, USA
| | - Roxana Del Rio-Guerra
- Flow Cytometry and Cell Sorting Facility, Department of Surgery, Larner College of Medicine, University of Vermont, 89 Beaumont Ave, Burlington, VT, 05401, USA
| | - Brigitte Lavoie
- Department of Neurological Sciences, Larner College of Medicine, University of Vermont, 89 Beaumont Ave, Burlington, VT, 05401, USA
| | - Peter Callas
- Department of Medical Biostatistics, University of Vermont, 89 Beaumont Ave, Burlington, VT, 05401, USA
| | - Mario Velez
- Department of Medicine, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT, 05401, USA
| | - Aaron Cohn
- Department of Medicine, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT, 05401, USA
| | - Ryan J Elliott
- OpenBiome, 2067 Massachusetts Ave, Cambridge, MA, 02140, USA
| | - Wing Fei Wong
- OpenBiome, 2067 Massachusetts Ave, Cambridge, MA, 02140, USA
| | - Elaine Vo
- Finch Therapeutics, 200 Inner Belt Rd, Somerville, MA, 02143, USA
| | - Rebecca Wilcox
- Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT, 05401, USA.,Larner College of Medicine, The University of Vermont, 89 Beaumont Ave, Burlington, VT, 05401, USA
| | - Mark Smith
- Finch Therapeutics, 200 Inner Belt Rd, Somerville, MA, 02143, USA
| | - Zain Kassam
- Finch Therapeutics, 200 Inner Belt Rd, Somerville, MA, 02143, USA
| | - Ralph Budd
- Department of Medicine, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT, 05401, USA.,Larner College of Medicine, The University of Vermont, 89 Beaumont Ave, Burlington, VT, 05401, USA
| | - Eric J Alm
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.,Center for Microbiome Informatics and Therapeutics, Broad Institute, Cambridge, MA, USA
| | - Gary M Mawe
- Department of Neurological Sciences, Larner College of Medicine, University of Vermont, 89 Beaumont Ave, Burlington, VT, 05401, USA
| | - Peter L Moses
- Larner College of Medicine, The University of Vermont, 89 Beaumont Ave, Burlington, VT, 05401, USA.,Finch Therapeutics, 200 Inner Belt Rd, Somerville, MA, 02143, USA
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19
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Varga A, Kocsis B, Sipos D, Kása P, Vigvári S, Pál S, Dembrovszky F, Farkas K, Péterfi Z. How to Apply FMT More Effectively, Conveniently and Flexible - A Comparison of FMT Methods. Front Cell Infect Microbiol 2021; 11:657320. [PMID: 34150673 PMCID: PMC8213398 DOI: 10.3389/fcimb.2021.657320] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 05/18/2021] [Indexed: 01/02/2023] Open
Abstract
Purpose Metronidazol and vancomycin were long the two best options against Clostridioides (formerly Clostridium) difficile infections (CDI). Now, the cost of new drugs such as fidaxomicin directs us towards alternative treatment options, such as faecal microbiota transplant (FMT). Its effectiveness is similar to fidaxomicin. There are questions regarding its safety, but the biggest challenges are prejudice and inconvenience. Most protocols refer to FMT applied in the form of a solution. We investigated different modalities of FMT. Methods Instead of using nasoenteric tubes or colonoscopy, we place frozen or lyophilised stool in non-coated, size “00”, hard gelatine capsules or enterosolvent, size “0” capsules. Results We found that non-coated, size “00”, hard gelatine capsules are appropriate for conducting FMT. Capsules containing lyophilised supernatant with a low number of bacteria have been proven to be non-inferior to other FMT modalities. The primary cure rate in the supernatant group was 93.75%, and 66.67% in the sediment group. The overall cure rate was 82.14%. Depending on the protocol, 4–7 capsules are sufficient per patient. Capsules can be stored for up to one year at -20°C. Conclusions FMT is a feasible alternative to antibiotic treatments in CDI. Our method makes the process flexible and less inconvenient to patients. Long storage time allows a consistent supply of capsules, while small volume and formulation make the procedure tolerable.
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Affiliation(s)
- Adorján Varga
- Department of Medical Microbiology and Immunology, University of Pécs Clinical Centre, Pécs, Hungary
| | - Béla Kocsis
- Department of Medical Microbiology and Immunology, University of Pécs Clinical Centre, Pécs, Hungary
| | - Dávid Sipos
- 1stDepartment of Internal Medicine - Department of Infectology, University of Pécs Clinical Centre, Pécs, Hungary
| | - Péter Kása
- Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs Faculty of Pharmacy, Pécs, Hungary
| | - Szabolcs Vigvári
- 1stDepartment of Internal Medicine - Department of Infectology, University of Pécs Clinical Centre, Pécs, Hungary
| | - Szilárd Pál
- Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs Faculty of Pharmacy, Pécs, Hungary
| | - Fanni Dembrovszky
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Kornélia Farkas
- Institute of Bioanalysis, University of Pécs Medical School, Pécs, Hungary
| | - Zoltán Péterfi
- 1stDepartment of Internal Medicine - Department of Infectology, University of Pécs Clinical Centre, Pécs, Hungary
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20
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LeBlanc JF, Segal JP, de Campos Braz LM, Hart AL. The Microbiome as a Therapy in Pouchitis and Ulcerative Colitis. Nutrients 2021; 13:1780. [PMID: 34071065 PMCID: PMC8224581 DOI: 10.3390/nu13061780] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/18/2021] [Accepted: 05/18/2021] [Indexed: 12/22/2022] Open
Abstract
The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem's importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.
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Affiliation(s)
- Jean-Frédéric LeBlanc
- Inflammatory Bowel Disease Unit, St. Mark’s Hospital, Harrow HA1 3UJ, UK; (L.M.d.C.B.); (A.L.H.)
| | - Jonathan P. Segal
- Department of Gastroenterology, The Hillingdon Hospital, Uxbridge UB8 3NN, UK;
| | - Lucia Maria de Campos Braz
- Inflammatory Bowel Disease Unit, St. Mark’s Hospital, Harrow HA1 3UJ, UK; (L.M.d.C.B.); (A.L.H.)
- Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, London SW7 2AZ, UK
| | - Ailsa L. Hart
- Inflammatory Bowel Disease Unit, St. Mark’s Hospital, Harrow HA1 3UJ, UK; (L.M.d.C.B.); (A.L.H.)
- Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, London SW7 2AZ, UK
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21
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Mocanu V, Rajaruban S, Dang J, Kung JY, Deehan EC, Madsen KL. Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis. J Clin Med 2021; 10:959. [PMID: 33804464 PMCID: PMC7957789 DOI: 10.3390/jcm10050959] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/17/2021] [Accepted: 02/19/2021] [Indexed: 12/13/2022] Open
Abstract
The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies-antibiotic pre-treatment and repeated FMT dosing-on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.
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Affiliation(s)
- Valentin Mocanu
- Department of Surgery, University of Alberta Hospital, University of Alberta, 8440 112 Street NW, Edmonton, AB T6G 2B7, Canada;
| | - Sabitha Rajaruban
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada; (S.R.); (E.C.D.); (K.L.M.)
| | - Jerry Dang
- Department of Surgery, University of Alberta Hospital, University of Alberta, 8440 112 Street NW, Edmonton, AB T6G 2B7, Canada;
| | - Janice Y. Kung
- John W. Scott Health Sciences Library, University of Alberta, 2K3.28 Walter C. Mackenzie Health Sciences Centre, Edmonton, AB T6G 2R7, Canada;
| | - Edward C. Deehan
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada; (S.R.); (E.C.D.); (K.L.M.)
| | - Karen L. Madsen
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada; (S.R.); (E.C.D.); (K.L.M.)
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22
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Advances in the understanding of the intestinal micro-environment and inflammatory bowel disease. Chin Med J (Engl) 2021; 133:834-841. [PMID: 32106123 PMCID: PMC7147659 DOI: 10.1097/cm9.0000000000000718] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.
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23
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Fang H, Fu L, Li X, Lu C, Su Y, Xiong K, Zhang L. Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study. Microb Cell Fact 2021; 20:18. [PMID: 33468164 PMCID: PMC7816432 DOI: 10.1186/s12934-021-01513-6] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 01/07/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC). RESULTS Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6-38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26-131.7%) in both the FMT (range 6-38 months) and control groups (range 7-35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation. CONCLUSIONS Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.
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Affiliation(s)
- Haiming Fang
- Department of Gastroenterology and Hepatology, Second Hospital of Anhui Medical University, Hefei, China.
- Center for Gut Microbiota Research, Second Hospital of Anhui Medical University, Hefei, China.
| | - Lian Fu
- Department of Gastroenterology and Hepatology, Second Hospital of Anhui Medical University, Hefei, China
- Center for Gut Microbiota Research, Second Hospital of Anhui Medical University, Hefei, China
| | - Xuejun Li
- Department of Gastroenterology, Second Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Chunxia Lu
- Department of Gastroenterology and Hepatology, Second Hospital of Anhui Medical University, Hefei, China
- Center for Gut Microbiota Research, Second Hospital of Anhui Medical University, Hefei, China
| | - Yuan Su
- Department of Gastroenterology and Hepatology, Second Hospital of Anhui Medical University, Hefei, China
- Center for Gut Microbiota Research, Second Hospital of Anhui Medical University, Hefei, China
| | - Kangwei Xiong
- Department of Gastroenterology and Hepatology, Second Hospital of Anhui Medical University, Hefei, China
- Center for Gut Microbiota Research, Second Hospital of Anhui Medical University, Hefei, China
| | - Lijiu Zhang
- Department of Gastroenterology and Hepatology, Second Hospital of Anhui Medical University, Hefei, China
- Center for Gut Microbiota Research, Second Hospital of Anhui Medical University, Hefei, China
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24
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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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25
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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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26
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Cold F, Kousgaard SJ, Halkjaer SI, Petersen AM, Nielsen HL, Thorlacius-Ussing O, Hansen LH. Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review. Microorganisms 2020; 8:E1433. [PMID: 32962069 PMCID: PMC7565999 DOI: 10.3390/microorganisms8091433] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/09/2020] [Accepted: 09/16/2020] [Indexed: 12/13/2022] Open
Abstract
The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials Library from inception through April 2020. Human studies of all study types reporting results of FMT to treat chronic pouchitis were included. Nine studies, reporting FMT treatment of 69 patients with chronic pouchitis were found eligible for the review. Most studies were case series and cohort studies rated as having fair to poor quality due to high risk of bias and small sample size. Only one randomized controlled trial was included, finding no beneficial effect of FMT. In total clinical response after FMT was reported in 14 (31.8%) out of 44 evaluated patients at various timepoints after FMT, and clinical remission in ten (22.7%) patients. Only minor self-limiting adverse events were reported. FMT varied greatly regarding preparation, length of treatment, and route of delivery. The effects of FMT on symptoms of chronic pouchitis are not established, though some studies show promising results. Future controlled well-designed studies are warranted.
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Affiliation(s)
- Frederik Cold
- Department of Plant and Environmental Sciences, Section for Microbial Ecology and Biotechnology, Copenhagen University, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark;
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark; (S.I.H.); (A.M.P.)
| | - Sabrina Just Kousgaard
- Department of Gastrointestinal Surgery, Aalborg University Hospital, 9100 Aalborg, Denmark; (S.J.K.); (O.T.-U.)
- Department of Clinical Medicine, Aalborg University, 9100 Aalborg, Denmark;
| | - Sofie Ingdam Halkjaer
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark; (S.I.H.); (A.M.P.)
| | - Andreas Munk Petersen
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark; (S.I.H.); (A.M.P.)
- Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark
| | - Hans Linde Nielsen
- Department of Clinical Medicine, Aalborg University, 9100 Aalborg, Denmark;
- Department of Clinical Microbiology, Aalborg University Hospital, 9100 Aalborg, Denmark
| | - Ole Thorlacius-Ussing
- Department of Gastrointestinal Surgery, Aalborg University Hospital, 9100 Aalborg, Denmark; (S.J.K.); (O.T.-U.)
- Department of Clinical Medicine, Aalborg University, 9100 Aalborg, Denmark;
| | - Lars Hestbjerg Hansen
- Department of Plant and Environmental Sciences, Section for Microbial Ecology and Biotechnology, Copenhagen University, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark;
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27
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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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Zhong M, Sun Y, Wang HG, Marcella C, Cui BT, Miao YL, Zhang FM. Awareness and attitude of fecal microbiota transplantation through transendoscopic enteral tubing among inflammatory bowel disease patients. World J Clin Cases 2020; 8:3786-3796. [PMID: 32953854 PMCID: PMC7479546 DOI: 10.12998/wjcc.v8.i17.3786] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/28/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Transendoscopic enteral tubing (TET) has been used in China as a novel delivery route for fecal microbiota transplantation (FMT) into the whole colon with a high degree of patient satisfaction among adults. AIM To explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease (IBD). METHODS An anonymous questionnaire, evaluating their awareness and attitudes toward FMT and TET was distributed among IBD patients in two provinces of Eastern and Southwestern China. Question formats included single-choice questions, multiple-choice questions and sorting questions. Patients who had not undergone FMT were mainly investigated for their cognition and acceptance of FMT and TET. Patients who had experience of FMT, the way they underwent FMT and acceptance of TET were the main interest. Then all the patients were asked whether they would recommend FMT and TET. This study also analyzed the preference of FMT delivery in IBD patients and the patient-related factors associated with it. RESULTS A total of 620 eligible questionnaires were included in the analysis. The survey showed that 44.6% (228/511) of patients did not know that FMT is a therapeutic option in IBD, and 80.6% (412/511) of them did not know the concept of TET. More than half (63.2%, 323/511) of the participants stated that they would agree to undergo FMT through TET. Of the patients who underwent FMT via TET [62.4% (68/109)], the majority [95.6% (65/68)] of them were satisfied with TET. Patients who had undergone FMT and TET were more likely to recommend FMT than patients who had not (94.5% vs 86.3%, P = 0.018 and 98.5% vs 87.8%, P = 0.017). Patients' choice for the delivery way of FMT would be affected by the type of disease and whether the patient had the experience of FMT. When compared to patients without experience of FMT, Crohn's disease and ulcerative colitis patients who had experience of FMT preferred mid-gut TET (P < 0.001) and colonic TET (P < 0.001), respectively. CONCLUSION Patients' experience of FMT through TET lead them to maintain a positive attitude towards FMT. The present findings highlighted the significance of patient education on FMT and TET.
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Affiliation(s)
- Min Zhong
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Yang Sun
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming 650032, Yunnan, China
| | - Hong-Gang Wang
- Medical Center for Digestive Diseases, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian 223300, Jiangsu Province, China
| | - Cicilia Marcella
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Bo-Ta Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Ying-Lei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming 650032, Yunnan, China
| | - Fa-Ming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
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Abstract
PURPOSE OF REVIEW The purpose of this brief review is to investigate the current utility of fecal microbial transplantation (FMT) to ameliorate dysbiosis contributing to inflammatory bowel disease pathogenesis. RECENT FINDINGS Increasing data from randomized, controlled trials support a role for multiple FMT administrations in the induction of remission and even as a maintenance therapy in mild-to-moderate Ulcerative Colitis. Small series and one small randomized controlled trial among patients with Crohn's Disease and with pouchitis continue to produce conflicting clinical results and microbial profile data on the host and donor levels. It is not clear whether patients with Crohn's disease are more susceptible to disease flare after FMT. Novel FMT delivery systems, including oral, and early-intensity colonoscopic devices, are under investigation. SUMMARY The allure of minimizing the risks and cost of long-term immunosuppression via modulation of patient microbiota remains enticing, and the most recent randomized controlled data in ulcerative colitis reveals acceptable clinical remission rates. However, prior to wide adoption of FMT within the inflammatory bowel disease treatment armamentarium, large clinical trials identifying biomarkers of treatment success, ensuring safety across all indications, and cultivating optimized donor and host selection are needed.
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Affiliation(s)
| | - Najwa El-Nachef
- Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, California, USA
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The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study. Biomedicines 2020; 8:biomedicines8080268. [PMID: 32756350 PMCID: PMC7459721 DOI: 10.3390/biomedicines8080268] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 07/27/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove–Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients’ microbiota and resulted in the remission of patients with active UC.
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Chen HT, Huang HL, Xu HM, Luo QL, He J, Li YQ, Zhou YL, Nie YQ, Zhou YJ. Fecal microbiota transplantation ameliorates active ulcerative colitis. Exp Ther Med 2020; 19:2650-2660. [PMID: 32256746 PMCID: PMC7086197 DOI: 10.3892/etm.2020.8512] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 01/03/2020] [Indexed: 12/11/2022] Open
Abstract
Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.
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Affiliation(s)
- Hui-Ting Chen
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Hong-Li Huang
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Hao-Ming Xu
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Qing-Ling Luo
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Jie He
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yong-Qiang Li
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - You-Lian Zhou
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yu-Qiang Nie
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yong-Jian Zhou
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
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DuPont HL, Jiang ZD, DuPont AW, Utay NS. Abnormal Intestinal Microbiome in Medical Disorders and Potential Reversibility by Fecal Microbiota Transplantation. Dig Dis Sci 2020; 65:741-756. [PMID: 32008133 DOI: 10.1007/s10620-020-06102-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Reduction in diversity of the intestinal microbiome (dysbiosis) is being identified in many disease states, and studies are showing important biologic contributions of microbiome to health and disease. Fecal microbiota transplantation (FMT) is being evaluated as a way to reverse dysbiosis in diseases and disorders in an attempt to improve health. The published literature was reviewed to determine the value of FMT in the treatment of medical disorders for which clinical trials have recently been conducted. FMT is effective in treating recurrent C. difficile infection in one or two doses, with many healthy donors providing efficacious fecal-derived products. In inflammatory bowel disease (IBD), FMT may lead to remission in approximately one-third of moderate-to-severe illnesses with one study suggesting that more durable FMT responses may be seen when used once medical remissions have been achieved. Donor products differ in their efficacy in treatment of IBD. Combining donor products has been one way to increase the potential value of FMT in treating chronic disorders. FMT is being explored in a variety of clinical settings affecting different organ systems outside CDI, with positive preliminary signals, in treatment of functional constipation, immunotherapy-induced colitis, neurodegenerative disease, as well as prevention of cancer-related disorders like graft versus host disease and decolonization of patients with recurrent urinary tract infection due to antibiotic-resistant bacteria. Currently, intense research is underway to see how the microbiome products like FMT can be harnessed for health benefits.
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Affiliation(s)
- Herbert L DuPont
- Kelsey Research Foundation, Houston, TX, USA. .,University of Texas School of Public Health, 1200 Pressler St, Houston, TX, 77030, USA. .,University of Texas McGovern Medical School, Houston, USA. .,Baylor College of Medicine, Houston, USA. .,MD Anderson Cancer Center, Houston, USA.
| | - Zhi-Dong Jiang
- University of Texas School of Public Health, 1200 Pressler St, Houston, TX, 77030, USA
| | | | - Netanya S Utay
- Kelsey Research Foundation, Houston, TX, USA.,University of Texas McGovern Medical School, Houston, USA
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Lopetuso LR, Ianiro G, Allegretti JR, Bibbò S, Gasbarrini A, Scaldaferri F, Cammarota G. Fecal transplantation for ulcerative colitis: current evidence and future applications. Expert Opin Biol Ther 2020; 20:343-351. [PMID: 32083498 DOI: 10.1080/14712598.2020.1733964] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Established evidence suggests that gut microbiota plays a role in ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is clearly recognized as a highly effective treatment for patients with recurrent Clostridium difficile infection and has been investigated also in patients with UC, with promising results.Areas covered: Literature review was performed to select publications concerning current evidence on the role of gut microbiota in the pathogenesis of UC, and on the effectiveness of FMT in this disorder.Expert opinion: The randomized controlled trials published investigating the use of FMT suggested a potential role for FMT in the treatment of mild to moderate UC. However, given several unanswered questions regarding donor selection, dose, route of administration and duration of therapy, this is not yet recommended as a viable therapy option. FMT has allowed for more in depth investigation with regards to the role the gut microbiota may be playing in UC. This knowledge is critical to identifying where FMT may appropriately fit in the UC treatment paradigm. As our understanding of the role the microbiome plays in this chronic disease, FMT, and then eventually defined microbes, will hopefully serve in a complementary role to conventional IBD therapies.
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Affiliation(s)
- Loris R Lopetuso
- UOC MEDICINA INTERNA E GASTROENTEROLOGIA, Area Medicina Interna, Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.,Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Gianluca Ianiro
- UOC MEDICINA INTERNA E GASTROENTEROLOGIA, Area Medicina Interna, Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.,Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Stefano Bibbò
- UOC MEDICINA INTERNA E GASTROENTEROLOGIA, Area Medicina Interna, Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.,Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Antonio Gasbarrini
- UOC MEDICINA INTERNA E GASTROENTEROLOGIA, Area Medicina Interna, Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.,Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Franco Scaldaferri
- UOC MEDICINA INTERNA E GASTROENTEROLOGIA, Area Medicina Interna, Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.,Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Giovanni Cammarota
- UOC MEDICINA INTERNA E GASTROENTEROLOGIA, Area Medicina Interna, Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.,Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Roma, Italia
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