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Moutsoglou D, Ramakrishnan P, Vaughn BP. Microbiota transplant therapy in inflammatory bowel disease: advances and mechanistic insights. Gut Microbes 2025; 17:2477255. [PMID: 40062406 PMCID: PMC11901402 DOI: 10.1080/19490976.2025.2477255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 01/27/2025] [Accepted: 03/04/2025] [Indexed: 03/14/2025] Open
Abstract
Microbiota transplant therapy is an emerging therapy for inflammatory bowel disease, but factors influencing its efficacy and mechanism remain poorly understood. In this narrative review, we outline key elements affecting therapeutic outcomes, including donor factors (such as age and patient relationship), recipient factors, control selection, and elements impacting engraftment and its correlation with clinical response. We also examine potential mechanisms through inflammatory bowel disease trials, focusing on the interplay between the microbiota, host, and immune system. Finally, we briefly explore potential future directions for microbiota transplant therapy and promising emerging treatments.
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Affiliation(s)
- Daphne Moutsoglou
- Gastroenterology Section, Minneapolis VA Health Care System, Minneapolis, MN, USA
- Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | | | - Byron P. Vaughn
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN, USA
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Liu HJ, Wu MC, Gau SY. Role of gut microbiota and mesenteric adipose tissue in the pathology of Crohn's disease: Potential therapeutic targets. World J Gastroenterol 2025; 31:102291. [PMID: 40248060 PMCID: PMC12001166 DOI: 10.3748/wjg.v31.i13.102291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 03/01/2025] [Accepted: 03/11/2025] [Indexed: 04/02/2025] Open
Abstract
This editorial comments on the article by Wu et al in the World Journal of Gastroenterology. The article explored the relationship between mesenteric adipose tissue, creeping fat, inflammation, and gut microbiota in Crohn's disease (CD). We discussed three key aspects of the interaction between gut microbiota and inflammatory bowel disease (IBD): The physiological functions of the gut microbiota, the potential role of probiotics in IBD treatment; and the effect of fecal microbiota transplantation (FMT) in combating IBD. IBD, comprising CD and ulcerative colitis (UC), is influenced by the gut microbiota. Changes in gut microbiota composition disrupt intestinal function and promote chronic inflammation, but the exact mechanisms remain unclear. Probiotics have demonstrated some efficacy in inducing remission in UC, though their effectiveness in CD is still debated. FMT shows promise in treating IBD, especially UC, by restoring gut microbiota diversity and inducing clinical remission. As for CD, FMT has potential, but more studies are needed to confirm its long-term effectiveness and safety. Dietary approaches may help manage IBD symptoms or disease activity, but patient adherence is crucial. Clinicians and researchers must recognize the importance of the gut microbiota and the need for personalized therapies targeting microbial imbalances.
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Affiliation(s)
- Han-Jung Liu
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Meng-Che Wu
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
- Division of Pediatric Gastroenterology, Children's Medical Center, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, Taiwan
| | - Shuo-Yan Gau
- Department and Graduate Institute of Business Administration, National Taiwan University, Taipei 106319, Taiwan
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Farah A, Paul P, Khan AS, Sarkar A, Laws S, Chaari A. Targeting gut microbiota dysbiosis in inflammatory bowel disease: a systematic review of current evidence. Front Med (Lausanne) 2025; 12:1435030. [PMID: 40041456 PMCID: PMC11876558 DOI: 10.3389/fmed.2025.1435030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 01/31/2025] [Indexed: 03/06/2025] Open
Abstract
Introduction The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies. Methods Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse. Results From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT. Conclusion Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.
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Affiliation(s)
| | | | | | | | | | - Ali Chaari
- Weill Cornell Medicine–Qatar, Qatar Foundation, Education City, Doha, Qatar
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4
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Laperrousaz B, Levast B, Fontaine M, Nancey S, Dechelotte P, Doré J, Lehert P. Safety comparison of single-donor and pooled fecal microbiota transfer product preparation in ulcerative colitis: systematic review and meta-analysis. BMC Gastroenterol 2024; 24:402. [PMID: 39528920 PMCID: PMC11552227 DOI: 10.1186/s12876-024-03487-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Multiple studies have evaluated fecal microbiota transfer (FMT) in patients with ulcerative colitis (UC) using single-donor (SDN) and multidonor (MDN) products. Systematic review and meta-analysis were performed to compare the safety of SDN and MDN products. METHODS Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence to identify studies that compared FMT products manufactured using SDN or MDN strategies against control treatment in patients with UC. Fifteen controlled studies were selected for meta-analysis (11 randomized controlled trials and 4 controlled cohort trials). Safety of each treatment type was assessed using the counts of adverse events and serious adverse events using fixed- and random-effects models. Significance of the indirect difference between FMT preparations was assessed using a network approach. Benefit-risk ratios were calculated by multiplicative utility model, incorporating geometric mean of risk ratios (RRs) of efficacy and safety. RESULTS Safety data was collected for a total of 587 patients (193 exposed to SDN products, 114 exposed to MDN products and 280 exposed to control treatment). The 12 studies showed similar overall safety event counts for MDN and SDN versus placebo (RRs: 0.90 and 1.09, respectively [P = 0.206 and P = 0.420, respectively]). Results indicated similar risk of safety events for MDN compared to SDN (RR: 0.83, P = 0.159). Positive benefit-risk ratios were demonstrated for MDN and SDN versus placebo (RRs: 1.70 and 1.16, respectively [P = 0.003 and P = 0.173, respectively]). MDN had a greater benefit-risk ratio compared to SDN (RR: 1.46, P = 0.072). CONCLUSION Similar safety profiles were observed for MDN and SDN strategies. Alongside previously described superior efficacy, treatment with MDN has greater benefit-risk ratio than SDN in patients with UC. Further development of MDN FMT treatment for UC should be considered.
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Affiliation(s)
| | | | | | - Stéphane Nancey
- Department of Gastroenterology, Lyon-Sud Hospital, CHU de Lyon, University Claude Bernard Lyon 1 and CIRI-INSERM U1111, Lyon, France
| | | | - Joël Doré
- Université Paris-Saclay, INRAE, MetaGenoPolis, AgroParis Tech, MICALIS, Jouy-en-Josas, 78350, France
| | - Philippe Lehert
- Faculty of Management, UCL, Louvain, Belgium
- Faculty of Medicine, University of Melbourne, Melbourne, Australia
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Prosty C, Katergi K, Papenburg J, Lawandi A, Lee TC, Shi H, Burnham P, Swem L, Routy B, Yansouni CP, Cheng MP. Causal role of the gut microbiome in certain human diseases: a narrative review. EGASTROENTEROLOGY 2024; 2:e100086. [PMID: 39944364 PMCID: PMC11770457 DOI: 10.1136/egastro-2024-100086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 08/16/2024] [Indexed: 03/19/2025]
Abstract
Composed of an elaborate ecosystem of bacteria, fungi, viruses and protozoa residing in the human digestive tract, the gut microbiome influences metabolism, immune modulation, bile acid homeostasis and host defence. Through observational and preclinical data, the gut microbiome has been implicated in the pathogenesis of a spectrum of chronic diseases ranging from psychiatric to gastrointestinal in nature. Until recently, the lack of unequivocal evidence supporting a causal link between gut microbiome and human health outcomes incited controversy regarding its significance. However, recent randomised controlled trial (RCT) evidence in conditions, such as Clostridioides difficile infection, cancer immunotherapy and ulcerative colitis, has supported a causal relationship and has underscored the potential of the microbiome as a therapeutic target. This review delineates the RCT evidence substantiating the potential for a causal relationship between the gut microbiome and human health outcomes, the seminal observational evidence that preceded these RCTs and the remaining knowledge gaps.
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Affiliation(s)
- Connor Prosty
- Faculty of Medicine, McGill University, Montreal, Quebec, Canada
| | - Khaled Katergi
- Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
| | - Jesse Papenburg
- Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada
| | - Alexander Lawandi
- Division of Infectious Diseases and Medical Microbiology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Todd C Lee
- Division of Infectious Diseases and Medical Microbiology, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Experimental Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Hao Shi
- Kanvas Biosciences, Princeton, New Jersey, USA
| | | | - Lee Swem
- Kanvas Biosciences, Princeton, New Jersey, USA
| | - Bertrand Routy
- Centre de recherche du Centre Hospitalier de l’Université de Montréal, Universite de Montreal, Montreal, Quebec, Canada
| | - Cedric P Yansouni
- Division of Infectious Diseases and Medical Microbiology, McGill University Health Centre, Montreal, Quebec, Canada
- JD MacLean Centre for Tropical Diseases, McGill University, Montreal, Quebec, Canada
| | - Matthew P Cheng
- Faculty of Medicine, McGill University, Montreal, Quebec, Canada
- Division of Infectious Diseases and Medical Microbiology, McGill University Health Centre, Montreal, Quebec, Canada
- Kanvas Biosciences, Princeton, New Jersey, USA
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Montrose JA, Kurada S, Fischer M. Current and future microbiome-based therapies in inflammatory bowel disease. Curr Opin Gastroenterol 2024; 40:258-267. [PMID: 38841848 DOI: 10.1097/mog.0000000000001027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/07/2024]
Abstract
PURPOSE OF REVIEW The role of the microbiome and dysbiosis is increasingly recognized in the pathogenesis of inflammatory bowel disease (IBD). Intestinal microbiota transplant (IMT), previously termed fecal microbiota transplant has demonstrated efficacy in restoring a healthy microbiome and promoting gut health in recurrent Clostridioides difficile infection. Several randomized trials (RCTs) highlighted IMT's potential in treating ulcerative colitis, while smaller studies reported on its application in managing Crohn's disease and pouchitis. RECENT FINDINGS This review delves into the current understanding of dysbiosis in IBD, highlighting the distinctions in the microbiota of patients with IBD compared to healthy controls. It explores the mechanisms by which IMT can restore a healthy microbiome and provides a focused analysis of recent RCTs using IMT for inducing and maintaining remission in IBD. Lastly, we discuss the current knowledge gaps that limit its widespread use. SUMMARY The body of evidence supporting the use of IMT in IBD is growing. The lack of a standardized protocol impedes its application beyond clinical trials. Further research is needed to identify patient profile and disease phenotypes that benefit from IMT, to delineate key donor characteristics, optimize the delivery route, dosage, and frequency.
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Affiliation(s)
| | - Satya Kurada
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Monika Fischer
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Mullish BH, Merrick B, Quraishi MN, Bak A, Green CA, Moore DJ, Porter RJ, Elumogo NT, Segal JP, Sharma N, Marsh B, Kontkowski G, Manzoor SE, Hart AL, Settle C, Keller JJ, Hawkey P, Iqbal TH, Goldenberg SD, Williams HRT. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut 2024; 73:1052-1075. [PMID: 38609165 DOI: 10.1136/gutjnl-2023-331550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 02/03/2024] [Indexed: 04/14/2024]
Abstract
The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.
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Affiliation(s)
- Benjamin H Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
- Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Blair Merrick
- Centre for Clinical Infection and Diagnostics Research, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK
| | - Mohammed Nabil Quraishi
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Microbiome Treatment Centre, University of Birmingham, Edgbaston, UK
- Institute of Cancer and Genomic Sciences, University of Birmingham, London, UK
| | - Aggie Bak
- Healthcare Infection Society, London, UK
| | - Christopher A Green
- Department of Infectious Diseases & Tropical Medicine, University Hospitals NHS Foundation Trust, Birmingham Heartlands Hospital, Birmingham, UK
- School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - David J Moore
- Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Robert J Porter
- Department of Microbiology, Royal Devon and Exeter Hospitals, Barrack Road, UK
| | - Ngozi T Elumogo
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
- Norfolk and Norwich University Hospital, Norwich, UK
| | - Jonathan P Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Naveen Sharma
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Microbiome Treatment Centre, University of Birmingham, Edgbaston, UK
- Institute of Cancer and Genomic Sciences, University of Birmingham, London, UK
| | - Belinda Marsh
- Lay representative for FMT Working Party, Healthcare Infection Society, London, UK
| | - Graziella Kontkowski
- Lay representative for FMT Working Party, Healthcare Infection Society, London, UK
- C.diff support, London, UK
| | - Susan E Manzoor
- Microbiome Treatment Centre, University of Birmingham, Edgbaston, UK
| | - Ailsa L Hart
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
- Department of Gastroenterology and Inflammatory Bowel Disease Unit, St Mark's Hospital and Academic Institute, Middlesex, UK
| | | | - Josbert J Keller
- Department of Gastroenterology, Haaglanden Medisch Centrum, The Hague, The Netherlands
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Peter Hawkey
- Microbiome Treatment Centre, University of Birmingham, Edgbaston, UK
- Public Health Laboratory, Faculty of Medicine, University of Birmingham, Birmingham, UK
| | - Tariq H Iqbal
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Microbiome Treatment Centre, University of Birmingham, Edgbaston, UK
- Institute of Cancer and Genomic Sciences, University of Birmingham, London, UK
| | - Simon D Goldenberg
- Centre for Clinical Infection and Diagnostics Research, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK
| | - Horace R T Williams
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
- Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
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Singh A, Midha V, Chauhan NS, Sood A. Current perspectives on fecal microbiota transplantation in inflammatory bowel disease. Indian J Gastroenterol 2024; 43:129-144. [PMID: 38334893 DOI: 10.1007/s12664-023-01516-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 12/26/2023] [Indexed: 02/10/2024]
Abstract
Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic modality within the domain of inflammatory bowel disease (IBD). While FMT has secured approval and demonstrated efficacy in addressing recurrent and refractory Clostridioides difficile infection, its application in IBD remains an area of active exploration and research. The current status of FMT in IBD reflects a nuanced landscape, with ongoing investigations delving into its effectiveness, safety and optimal implementation. Early-stage clinical trials and observational studies have provided insights into the potential of FMT to modulate the dysbiotic gut microbiota associated with IBD, aiming to mitigate inflammation and promote mucosal healing. However, considerable complexities persist, including variations in donor selection, treatment protocols and outcome assessments. Challenges in standardizing FMT protocols for IBD treatment are compounded by the dynamic nature of the gut microbiome and the heterogeneity of IBD itself. Despite these challenges, enthusiasm for FMT in IBD emanates from its capacity to address gut microbial dysbiosis, signifying a paradigm shift towards more comprehensive approaches in IBD management. As ongoing research progresses, an enhanced understanding of FMT's role in IBD therapy is anticipated. This article synthesizes the current status of FMT in IBD, elucidating the attendant challenges and aspiring towards the refinement of its application for improved patient outcomes.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Nar Singh Chauhan
- Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124 001, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India.
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Arora U, Kedia S, Ahuja V. The practice of fecal microbiota transplantation in inflammatory bowel disease. Intest Res 2024; 22:44-64. [PMID: 37981746 PMCID: PMC10850701 DOI: 10.5217/ir.2023.00085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/10/2023] [Accepted: 09/14/2023] [Indexed: 11/21/2023] Open
Abstract
Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.
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Affiliation(s)
- Umang Arora
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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10
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Newman KL, Allegretti JR. Emerging Noninfectious Indications for Live Biotherapeutic Products in Gastroenterology. Am J Gastroenterol 2024; 119:S30-S35. [PMID: 38153224 DOI: 10.14309/ajg.0000000000002584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 10/22/2023] [Indexed: 12/29/2023]
Affiliation(s)
- Kira L Newman
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Jessica R Allegretti
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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Tikunov AY, Fedorets VA, Shrainer EV, Morozov VV, Bystrova VI, Tikunova NV. Intestinal Microbiome Changes and Clinical Outcomes of Patients with Ulcerative Colitis after Fecal Microbiota Transplantation. J Clin Med 2023; 12:7702. [PMID: 38137770 PMCID: PMC10743744 DOI: 10.3390/jcm12247702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/06/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND AND AIMS Ulcerative colitis (UC) is a chronic inflammatory disease that affects many people. One of the possible ways to treat UC is fecal microbiota transplantation (FMT). In this study, changes in the intestinal microbiome and clinical outcomes of 20 patients with UC after FMT were estimated. METHODS FMT enemas were administrated ten times, once a day, and fecal microbiota from three donors was used for each enema. The clinical outcomes were assessed after eight weeks and then via a patient survey. The 16S rRNA profiles of the gut microbiota were compared between three samplings: samples from 20 patients with UC before and after FMT and samples from 18 healthy volunteers. RESULTS Clinical remission was achieved in 19 (95%) patients at week 8. Adverse events occurred in five patients, including one non-responder. A significant increase in average biodiversity was shown in samples after FMT compared to samples before FMT, as well as a decrease in the proportion of some potentially pathogenic bacteria. CONCLUSION The efficacy of FMT for UC treatment was confirmed; however, the duration of remission varied substantially, possibly due to different characteristics of the initial microbiota of patients. Targeted analysis of a patient's microbiome before FMT could increase the treatment efficacy.
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Affiliation(s)
- Artem Y. Tikunov
- Federal State Public Scientific Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (A.Y.T.); (V.A.F.); (E.V.S.); (V.V.M.); (V.I.B.)
| | - Valeria A. Fedorets
- Federal State Public Scientific Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (A.Y.T.); (V.A.F.); (E.V.S.); (V.V.M.); (V.I.B.)
| | - Evgenia V. Shrainer
- Federal State Public Scientific Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (A.Y.T.); (V.A.F.); (E.V.S.); (V.V.M.); (V.I.B.)
- Department of Obstetrics and Gynecology, V. Zelman Institute for Medicine and Psychology, Novosibirsk National Research State University, 630090 Novosibirsk, Russia
| | - Vitaliy V. Morozov
- Federal State Public Scientific Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (A.Y.T.); (V.A.F.); (E.V.S.); (V.V.M.); (V.I.B.)
| | - Valeria I. Bystrova
- Federal State Public Scientific Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (A.Y.T.); (V.A.F.); (E.V.S.); (V.V.M.); (V.I.B.)
- Department of Obstetrics and Gynecology, V. Zelman Institute for Medicine and Psychology, Novosibirsk National Research State University, 630090 Novosibirsk, Russia
| | - Nina V. Tikunova
- Federal State Public Scientific Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (A.Y.T.); (V.A.F.); (E.V.S.); (V.V.M.); (V.I.B.)
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12
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Liu H, Li J, Yuan J, Huang J, Xu Y. Fecal microbiota transplantation as a therapy for treating ulcerative colitis: an overview of systematic reviews. BMC Microbiol 2023; 23:371. [PMID: 38030980 PMCID: PMC10685500 DOI: 10.1186/s12866-023-03107-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Accepted: 11/03/2023] [Indexed: 12/01/2023] Open
Abstract
AIM The current overview on published systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically gather, evaluate, and synthesize solid evidence for using fecal microbiota transplantation (FMT) to treat ulcerative colitis (UC). METHODS Relevant articles published before January 2023 were collected from Web of Science, Embase, PubMed, and Cochrane Library. Two authors used Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, PRISMA checklists, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system were applied by two authors to independently evaluate the methodological quality, reporting quality, and evidence quality, respectively. Re-meta-analysis on the primary RCTs was conducted after excluding overlapping randomized controlled trials (RCTs). RESULTS Six SRs/MAs involving 12 primary RCTs and 544 participants were included. According to the AMSTAR-2 tool and PRISMA checklist, methodological quality and reporting quality of the included studies was overall satisfactory. The evidence quality of a great majority of outcomes was rated as moderate to high according to the GRADE system. Compared to placebo, the re-meta-analysis found a great advantage of use FMT in inducing combined clinical and endoscopic remission (OR 3.83 [2.31, 6.34]), clinical remission (3.31 [2.09, 5.25]), endoscopic remission (OR 3.75 [2.20, 6.39]), clinical response (OR 2.56 [1.64, 4.00]), and endoscopic response (OR 2.18 [1.12, 4.26]). Pooled data showed no significant difference in serious adverse events between patients receiving FMT and those receiving placebo (OR 1.53 [0.74, 3.19]). Evidence quality of the outcomes derived from re-meta-analysis was significantly higher after overcoming the limitations of previous SRs/MAs. CONCLUSION In conclusion, moderate- to high-quality evidence supported a promising use of FMT to safely induce remission in UC. However, further trials with larger sample size are still required to comprehensively analyze the delivery route, total dosage, frequency, and donor selection in FMT.
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Affiliation(s)
- Haixia Liu
- The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jing Li
- Guang'an Hospital of Traditional Chinese Medicine, Guang'an, China
| | - Jiaxin Yuan
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Jinke Huang
- Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Youqi Xu
- The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
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Marsool MDM, Vora N, Marsool ADM, Pati S, Narreddy M, Patel P, Gadam S, Prajjwal P. Ulcerative colitis: Addressing the manifestations, the role of fecal microbiota transplantation as a novel treatment option and other therapeutic updates. Dis Mon 2023; 69:101606. [PMID: 37357103 DOI: 10.1016/j.disamonth.2023.101606] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2023]
Abstract
The prevalence and incidence of Ulcerative Colitis (UC), a recurrent and remitting inflammatory condition, are rising. Any part of the colon may be affected, beginning with inflammation of the mucosa in the rectum and continuing proximally continuously. Bloody diarrhea, tenesmus, fecal urgency, and stomach pain are typical presenting symptoms. Many patients present with extraintestinal manifestations (EIMs) including musculoskeletal, ocular, renal, hepatobiliary, and dermatological presentation, among others. Most cases are treated with pharmacological therapy including mesalazine and glucocorticoids. Fecal microbiota transplantation (FMT) is a novel procedure that is increasingly being used to treat UC, however, its use yet remains controversial because of uncertain efficacy. FMT can lower gut permeability and consequently disease severity by boosting short-chain fatty acids production, helping in epithelial barrier integrity preservation. Upadacitinib (JAK Kinase inhibitor) is another newer treatment option, which is an FDA-approved drug that is being used to treat UC. This review article provides a comprehensive review of the EIMs of UC, the role of FMT along with various recent clinical trials pertaining to FMT as well as other diagnostic and therapeutic updates.
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Affiliation(s)
| | - Neel Vora
- B. J. Medical College, Ahmedabad, India
| | | | - Shefali Pati
- St George's University, School of Medicine, Grenada
| | | | - Parth Patel
- Pramukhswami Medical College, Karamsad, India
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Feng J, Chen Y, Liu Y, Lin L, Lin X, Gong W, Xia R, He J, Sheng J, Cai H, Xiao C. Efficacy and safety of fecal microbiota transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis. Sci Rep 2023; 13:14494. [PMID: 37661203 PMCID: PMC10475461 DOI: 10.1038/s41598-023-41182-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 08/23/2023] [Indexed: 09/05/2023] Open
Abstract
To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates.
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Affiliation(s)
- Jing Feng
- Department of Gastroenterology, Shanxi Provincial People's Hospital, The Fifth Hospital of Shanxi Medical University, Taiyuan, 030012, China
| | - Yexin Chen
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China
- Xiamen Treatgut Biotechnology Co., Ltd, Xiamen, 361101, China
| | - Yan Liu
- Department of Gastroenterology, Chongqing General Hospital, Chongqing, 401147, China
| | - Lin Lin
- Xiamen Treatgut Biotechnology Co., Ltd, Xiamen, 361101, China
| | - Xiujuan Lin
- Xiamen Treatgut Biotechnology Co., Ltd, Xiamen, 361101, China
| | - Wenxiu Gong
- Xiamen Treatgut Biotechnology Co., Ltd, Xiamen, 361101, China
| | - Rongmu Xia
- Xiamen Treatgut Biotechnology Co., Ltd, Xiamen, 361101, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, No.282, Wusi Road, Fuzhou, 350003, China
| | - Jianquan He
- Xiamen Treatgut Biotechnology Co., Ltd, Xiamen, 361101, China
- College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China
| | - Jianwen Sheng
- Department of Gastroenterology, Yichun People's Hospital, The Affiliated Hospital of Yichun University, No 1061, Jinxiu Road, Yichun, 336000, China.
| | - Huimei Cai
- Department of Gastroenterology, Fuzhou First Hospital Affiliated to Fujian Medical University, No. 190, Dadao Road, Fuzhou, 350009, China.
| | - Chuanxing Xiao
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
- Xiamen Treatgut Biotechnology Co., Ltd, Xiamen, 361101, China.
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15
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Lopetuso LR, Deleu S, Godny L, Petito V, Puca P, Facciotti F, Sokol H, Ianiro G, Masucci L, Abreu M, Dotan I, Costello SP, Hart A, Iqbal TH, Paramsothy S, Sanguinetti M, Danese S, Tilg H, Cominelli F, Pizarro TT, Armuzzi A, Cammarota G, Gasbarrini A, Vermeire S, Scaldaferri F. The first international Rome consensus conference on gut microbiota and faecal microbiota transplantation in inflammatory bowel disease. Gut 2023; 72:1642-1650. [PMID: 37339849 PMCID: PMC10423477 DOI: 10.1136/gutjnl-2023-329948] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/16/2023] [Indexed: 06/22/2023]
Abstract
BACKGROUND Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery, type of placebo and evaluated endpoints. Although the overall outcomes appear to be promising, they are highly dependent on both donor and recipient factors. OBJECTIVE To develop concensus-based statements and recommendations for the evaluation, management and potential treatment of IBD using FMT in order to move towards standardised practices. DESIGN An international panel of experts convened several times to generate evidence-based guidelines by performing a deep evaluation of currently available and/or published data. Twenty-five experts in IBD, immunology and microbiology collaborated in different working groups to provide statements on the following key issues related to FMT in IBD: (A) pathogenesis and rationale, (B) donor selection and biobanking, (C) FMT practices and (D) consideration of future studies and perspectives. Statements were evaluated and voted on by all members using an electronic Delphi process, culminating in a plenary consensus conference and generation of proposed guidelines. RESULTS AND CONCLUSIONS Our group has provided specific statements and recommendations, based on best available evidence, with the end goal of providing guidance and general criteria required to promote FMT as a recognised strategy for the treatment of IBD.
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Affiliation(s)
- Loris Riccardo Lopetuso
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Department of Medicine and Ageing Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy
- Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy
| | - Sara Deleu
- Department of Chronic Diseases & Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Lihi Godny
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Valentina Petito
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Pierluigi Puca
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Federica Facciotti
- Dipartimento di Biotecnologie e Bioscienze, University of Milan-Bicocca, Milano, Italy
| | - Harry Sokol
- INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, Sorbonne Universite, Paris, France
| | - Gianluca Ianiro
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Luca Masucci
- Department of Laboratory Sciences and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Maria Abreu
- Department of Medicine, Division of Gastroenterology, Crohn's and Colitis Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Samuel Paul Costello
- Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia
| | - Ailsa Hart
- IBD Unit, Saint Mark's Hospital, Harrow, UK
| | - Tariq H Iqbal
- Microbiome Treatment Center, University of Birmingham, Birmingham, UK
| | - Sudarshan Paramsothy
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Maurizio Sanguinetti
- Department of Laboratory Sciences and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria
| | - Fabio Cominelli
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Theresa T Pizarro
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Alessandro Armuzzi
- Deparment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
| | - Giovanni Cammarota
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Antonio Gasbarrini
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Séverine Vermeire
- Department of Chronic Diseases & Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Franco Scaldaferri
- IBD Unit, CEMAD Centro Malattie dell'Apparato Digerente, UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
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Rossier L, Matter C, Burri E, Galperine T, Hrúz P, Juillerat P, Schoepfer A, Vavricka SR, Zahnd N, Décosterd N, Seibold F. Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice. Swiss Med Wkly 2023; 153:40100. [PMID: 37769622 DOI: 10.57187/smw.2023.40100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023] Open
Abstract
INTRODUCTION Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT. METHODS A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre). RESULTS The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future.
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Affiliation(s)
- Laura Rossier
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| | - Christoph Matter
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| | - Emanuel Burri
- Department of Gastroenterology and Hepatology, University Medical Clinic, Baselland Canton Hospital, Liestal, Switzerland
| | - Tatiana Galperine
- Fecal microbiota transplantation center, Department of infectious disease, Lausanne University Hospital, Lausanne, Switzerland
| | - Petr Hrúz
- Clarunis, Department of Gastroenterology, St Clara hospital and University hospital Basel, Basel, Switzerland
| | - Pascal Juillerat
- GastroGeb - Gastroenterology practice and Crohn-colitis Center, Lausanne - Bulle, Switzerland
| | - Alain Schoepfer
- Department of Gastroenterology, Lausanne University Hospital, Lausanne, Switzerland
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | - Natalie Décosterd
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| | - Frank Seibold
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
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Kriger-Sharabi O, Malnick SDH, Fisher D. Manipulation of the intestinal microbiome-a slow journey to primetime. World J Clin Cases 2023; 11:4975-4988. [PMID: 37583860 PMCID: PMC10424025 DOI: 10.12998/wjcc.v11.i21.4975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/17/2023] [Accepted: 06/30/2023] [Indexed: 07/26/2023] Open
Abstract
The gut microbiota has important functions in the regulation of normal body functions. Alterations of the microbiota are being increasingly linked to various disease states. The microbiome has been manipulated via the administration of stool from animals or humans, for more than 1000 years. Currently, fecal microbiota transplantation can be performed via endoscopic administration of fecal matter to the duodenum or colon or via capsules of lyophilized stools. More recently fecal microbial transplantation has been shown to be very effective for recurrent Clostridoides difficile infection (CDI). In addition there is some evidence of efficacy in the metabolic syndrome and its hepatic manifestation, metabolic associated fatty liver disease (MAFLD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We review the current literature regarding the microbiome and the pathogenesis and treatment of CDI, MAFLD, IBS and IBD.
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Affiliation(s)
- Ofra Kriger-Sharabi
- Institute of Gastroenterology, Assuta Medical Center, Ashdod 7747629, Israel
| | - Stephen D H Malnick
- Department of Internal Medicine, Kaplan Medical Center, Rehovot 76100, Israel
| | - David Fisher
- Department of Endocrinology, Soroka Medical Center, Beer Sheva POB 151, Israel
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18
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Hasselblatt P, Reindl W, Gauss A, Neeff H, Fusco S, Klaus J. Questions to consider when caring for patients with ulcerative colitis. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:690-700. [PMID: 36257329 DOI: 10.1055/a-1890-6015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Although the management of patients with ulcerative colitis (UC) is well defined by national and international guidelines, there are many debates and open questions related to daily care of UC patients. Here, we aimed to review topics with high clinical relevance including therapy algorithms, potential biomarkers for disease prognosis and response to therapy, the role of interventions targeting the gut microbiota, insights from head-to-head trials, novel UC medications, exit strategies, the impact of COVID19 on UC, care of patients with acute severe disease, cancer screening, and the role of surgery.
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Affiliation(s)
- Peter Hasselblatt
- Department of Medicine II, University Hospital Freiburg, Freiburg, Germany
| | - Wolfgang Reindl
- Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Annika Gauss
- University Hospital Heidelberg, Heidelberg, Germany
| | - Hannes Neeff
- Dept. of General and Visceral Surgery, Medical Center - University of Freiburg, Freiburg, Germany
| | - Stefano Fusco
- Department of Gastroenterology, Eberhard-Karls-Universität Tübingen Medizinische Fakultät, Tübingen, Germany
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19
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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: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [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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Imdad A, Pandit NG, Zaman M, Minkoff NZ, Tanner-Smith EE, Gomez-Duarte OG, Acra S, Nicholson MR. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev 2023; 4:CD012774. [PMID: 37094824 PMCID: PMC10133790 DOI: 10.1002/14651858.cd012774.pub3] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT). OBJECTIVES To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022. SELECTION CRITERIA We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD. DATA COLLECTION AND ANALYSIS Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias. Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI -3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC. Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC. None of the included studies assessed use of FMT for induction of remission in people with CD. One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD. AUTHORS' CONCLUSIONS FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.
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Affiliation(s)
- Aamer Imdad
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Natasha G Pandit
- Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Muizz Zaman
- Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Nathan Zev Minkoff
- Pediatric Gastroenterology, Hepatology and Nutrition, Valley Children's Hospital, Madera, CA, USA
| | - Emily E Tanner-Smith
- Counseling Psychology and Human Services, University of Oregon, Eugene, Oregon, USA
| | - Oscar G Gomez-Duarte
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University at Buffalo, State University of New York, Buffalo, New York, USA
| | - Sari Acra
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Maribeth R Nicholson
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
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21
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Wei H, Yu C, Zhang C, Ren Y, Guo L, Wang T, Chen F, Li Y, Zhang X, Wang H, Liu J. Butyrate ameliorates chronic alcoholic central nervous damage by suppressing microglia-mediated neuroinflammation and modulating the microbiome-gut-brain axis. Biomed Pharmacother 2023; 160:114308. [PMID: 36709599 DOI: 10.1016/j.biopha.2023.114308] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/17/2023] [Accepted: 01/25/2023] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Alcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown. METHODS In this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated. RESULTS As indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1β, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions. CONCLUSION Dietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota-gut-brain axis.
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Affiliation(s)
- Huiling Wei
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Chunyang Yu
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Chun Zhang
- Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Yi Ren
- Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Li Guo
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Ting Wang
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Feifei Chen
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Yiwei Li
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Xiaoxia Zhang
- College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Hao Wang
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Juan Liu
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
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22
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Fuxman C, Sicilia B, Linares ME, García-López S, González Sueyro R, González-Lamac Y, Zabana Y, Hinojosa J, Barreiro-de Acosta M, Balderramo D, Balfour D, Bellicoso M, Daffra P, Morelli D, Orsi M, Rausch A, Ruffinengo O, Toro M, Sambuelli A, Novillo A, Gomollón F, De Paula JA. GADECCU 2022 Guideline for the treatment of Ulcerative Colitis. Adaptation and updating of the GETECCU 2020 Guideline. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46 Suppl 1:S1-S56. [PMID: 36731724 DOI: 10.1016/j.gastrohep.2023.01.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/04/2023] [Indexed: 02/01/2023]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory disease that compromises the colon, affecting the quality of life of individuals of any age. In practice, there is a wide spectrum of clinical situations. The advances made in the physio pathogenesis of UC have allowed the development of new, more effective and safer therapeutic agents. OBJECTIVES To update and expand the evaluation of the efficacy and safety of relevant treatments for remission induction and maintenance after a mild, moderate or severe flare of UC. RECIPIENTS Gastroenterologists, coloproctologists, general practitioners, family physicians and others health professionals, interested in the treatment of UC. METHODOLOGY GADECCU authorities obtained authorization from GETECCU to adapt and update the GETECCU 2020 Guide for the treatment of UC. Prepared with GRADE methodology. A team was formed that included authors, a panel of experts, a nurse and a patient, methodological experts, and external reviewers. GRADE methodology was used with the new information. RESULTS A 118-page document was prepared with the 44 GADECCU 2022 recommendations, for different clinical situations and therapeutic options, according to levels of evidence. A section was added with the new molecules that are about to be available. CONCLUSIONS This guideline has been made in order to facilitate decision-making regarding the treatment of UC, adapting and updating the guide prepared by GETECCU in the year 2020.
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Affiliation(s)
- Claudia Fuxman
- Servicio de Gastroenterología, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
| | - Beatriz Sicilia
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Burgos, Burgos, España
| | - María Eugenia Linares
- Servicio de Gastroenterología, Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Santiago García-López
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, España
| | - Ramiro González Sueyro
- Servicio de Gastroenterología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Yago González-Lamac
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Mútua Terrassa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España
| | - Joaquín Hinojosa
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital de Manise, Valencia, España
| | - Manuel Barreiro-de Acosta
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, España
| | - Domingo Balderramo
- Servicio de Gastroenterología, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Deborah Balfour
- Unidad de Enfermedades Inflamatorias, HIGEA Clínica de Gastroenterología, Mendoza, Argentina
| | - Maricel Bellicoso
- Área de Gastroenterología, Inmunología Buenos Aires, Buenos Aires, Argentina
| | - Pamela Daffra
- Servicio de Gastroenterología, Hospital Central de Mendoza, Mendoza, Argentina
| | - Daniela Morelli
- Departamento de Educación, Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina
| | - Marina Orsi
- Servicio de Gastroenterología Pediátrica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Astrid Rausch
- Servicio de Gastroenterología, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
| | - Orlando Ruffinengo
- Servicio de Gastroenterología, Hospital Provincial del Centenario, Rosario, Argentina
| | - Martín Toro
- Unidad de Enfermedades Inflamatorias, HIGEA Clínica de Gastroenterología, Mendoza, Argentina
| | - Alicia Sambuelli
- Sección de Enfermedades Inflamatorias Intestinales, Hospital Bonorino Udaondo, Buenos Aires, Argentina
| | - Abel Novillo
- Servicio de Gastroenterología, Sanatorio 9 de Julio, Tucumán, Argentina.
| | - Fernando Gomollón
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Instituto de Investigaciones Sanitarias de Aragón, Hospital Clínico Universitario Lozano Blesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestiva (CIBEREHD), Zaragoza, España
| | - Juan Andrés De Paula
- Servicio de Gastroenterología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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23
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Kempski J, Huber S. [Role of the gut microbiome in the pathogenesis and treatment of inflammatory bowel diseases]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2022; 63:1022-1027. [PMID: 36044059 DOI: 10.1007/s00108-022-01396-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/22/2022] [Indexed: 06/15/2023]
Abstract
Inflammatory bowel diseases (IBD) are systemic diseases that mainly manifest in the gastrointestinal tract. Due to chronically impaired intestinal homeostasis, they often require permanent and in some cases systemic therapy. The exact causes of IBD are largely unknown. It is postulated that these complex diseases arise in genetically susceptible individuals through a misdirected immune response, promoted by barrier defects, environmental toxins, and the gut microbiome. In this regard, the importance of the microbiome and its pathogenic changes (dysbiosis) in the pathogenesis of IBD is increasingly coming into focus. This review article presents the current state of research on the role of the microbiome in the development of IBD. Therapeutic approaches aimed at correcting intestinal dysbiosis are also discussed.
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Affiliation(s)
- Jan Kempski
- I. Medizinische Klinik und Poliklinik, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland
| | - Samuel Huber
- I. Medizinische Klinik und Poliklinik, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland.
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24
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Xu H, Cao C, Ren Y, Weng S, Liu L, Guo C, Wang L, Han X, Ren J, Liu Z. Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment. Front Immunol 2022; 13:949490. [PMID: 36177041 PMCID: PMC9513044 DOI: 10.3389/fimmu.2022.949490] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 08/04/2022] [Indexed: 11/20/2022] Open
Abstract
Fecal microbiome transplantation (FMT) from healthy donors is one of the techniques for restoration of the dysbiotic gut, which is increasingly being used to treat various diseases. Notably, mounting evidence in recent years revealed that FMT has made a breakthrough in the oncology treatment area, especially by improving immunotherapy efficacy to achieve antitumor effects. However, the mechanism of FMT in enhancing antitumor effects of immune checkpoint blockers (ICBs) has not yet been fully elucidated. This review systematically summarizes the role of microbes and their metabolites in the regulation of tumor immunity. We highlight the mechanism of action of FMT in the treatment of refractory tumors as well as in improving the efficacy of immunotherapy. Furthermore, we summarize ongoing clinical trials combining FMT with immunotherapy and further focus on refined protocols for the practice of FMT in cancer treatment, which could guide future directions and priorities of FMT scientific development.
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Affiliation(s)
- Hui Xu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Interventional Institute of Zhengzhou University, Zhengzhou, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, China
| | - Chenxi Cao
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuqing Ren
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Siyuan Weng
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Long Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chunguang Guo
- Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Libo Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Interventional Institute of Zhengzhou University, Zhengzhou, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, China
- *Correspondence: Xinwei Han, ; Jianzhuang Ren, ; Zaoqu Liu,
| | - Jianzhuang Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Xinwei Han, ; Jianzhuang Ren, ; Zaoqu Liu,
| | - Zaoqu Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Interventional Institute of Zhengzhou University, Zhengzhou, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, China
- *Correspondence: Xinwei Han, ; Jianzhuang Ren, ; Zaoqu Liu,
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25
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Feng B, Lin L, Li L, Long X, Liu C, Zhao Z, Li S, Li Y. Glucocorticoid induced group 2 innate lymphoid cell overactivation exacerbates experimental colitis. Front Immunol 2022; 13:863034. [PMID: 36032134 PMCID: PMC9411106 DOI: 10.3389/fimmu.2022.863034] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 07/14/2022] [Indexed: 11/24/2022] Open
Abstract
Abnormal activation of the innate and adaptive immune systems has been observed in inflammatory bowel disease (IBD) patients. Anxiety and depression increase the risk of IBD by activating the adaptive immune system. However, whether anxiety affects innate immunity and its impact on IBD severity remains elusive. This study investigated the mechanism by which anxiety contributes to IBD development in a murine model of acute wrap restraint stress (WRS). Here, we found that anxiety-induced overactivation of group 2 innate lymphoid cells (ILC2) aggravated colonic inflammation. Overactivation of the hypothalamic–pituitary–adrenal (HPA) axis is a hallmark of the physiological change of anxiety. Corticosterone (CORT), a stress hormone, is a marker of HPA axis activation and is mainly secreted by HPA activation. We hypothesized that the overproduction of CORT stimulated by anxiety exacerbated colonic inflammation due to the abnormally elevated function of ILC2. The results showed that ILC2 secreted more IL-5 and IL-13 in the WRS mice than in the control mice. Meanwhile, WRS mice experienced more body weight loss, shorter colon length, higher concentrations of IL-6 and TNF-α, more severely impaired barrier function, and more severe inflammatory cell infiltration. As expected, the serum corticosterone levels were elevated after restraint stress. Dexamethasone (DEX) was then injected to mimic HPA axis activation induced CORT secretion. DEX injection can also stimulate ILC2 to secrete more type II cytokines and exacerbate oxazolone (OXA) induced colitis. Blocking the IL-13/STAT6 signaling pathway alleviated colitis in WRS and DEX-injected mice. In conclusion, the overactivation of ILC2 induced by CORT contributed to the development of OXA-induced colitis in mice.
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Affiliation(s)
- Bingcheng Feng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lin Lin
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lixiang Li
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xin Long
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Chao Liu
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zixiao Zhao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Shiyang Li
- Advanced Medical Research Institute, Shandong University, Jinan, China
- *Correspondence: Shiyang Li, ; Yanqing Li,
| | - Yanqing Li
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Shiyang Li, ; Yanqing Li,
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26
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Gubatan J, Boye TL, Temby M, Sojwal RS, Holman DR, Sinha SR, Rogalla SR, Nielsen OH. Gut Microbiome in Inflammatory Bowel Disease: Role in Pathogenesis, Dietary Modulation, and Colitis-Associated Colon Cancer. Microorganisms 2022; 10:1371. [PMID: 35889090 PMCID: PMC9316834 DOI: 10.3390/microorganisms10071371] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/03/2022] [Accepted: 07/05/2022] [Indexed: 12/11/2022] Open
Abstract
The gut microbiome has increasingly been recognized as a critical and central factor in inflammatory bowel disease (IBD). Here, we review specific microorganisms that have been suggested to play a role in the pathogenesis of IBD and the current state of fecal microbial transplants as a therapeutic strategy in IBD. We discuss specific nutritional and dietary interventions in IBD and their effects on gut microbiota composition. Finally, we examine the role and mechanisms of the gut microbiome in mediating colitis-associated colon cancer.
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Affiliation(s)
- John Gubatan
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Theresa Louise Boye
- Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, DK-2730 Copenhagen, Denmark; (T.L.B.); or (O.H.N.)
| | - Michelle Temby
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Raoul S. Sojwal
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Derek R. Holman
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Sidhartha R. Sinha
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Stephan R. Rogalla
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; (M.T.); (R.S.S.); (D.R.H.); (S.R.S.); (S.R.R.)
| | - Ole Haagen Nielsen
- Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, DK-2730 Copenhagen, Denmark; (T.L.B.); or (O.H.N.)
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27
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Rees NP, Shaheen W, Quince C, Tselepis C, Horniblow RD, Sharma N, Beggs AD, Iqbal TH, Quraishi MN. Systematic review of donor and recipient predictive biomarkers of response to faecal microbiota transplantation in patients with ulcerative colitis. EBioMedicine 2022; 81:104088. [PMID: 35660786 PMCID: PMC9163485 DOI: 10.1016/j.ebiom.2022.104088] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/14/2022] [Accepted: 05/16/2022] [Indexed: 12/14/2022] Open
Affiliation(s)
- Nia Paddison Rees
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK
| | - Walaa Shaheen
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK
| | | | - Chris Tselepis
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Clinical Sciences, School of Biomedical Sciences, University of Birmingham, UK
| | - Richard D Horniblow
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Clinical Sciences, School of Biomedical Sciences, University of Birmingham, UK
| | - Naveen Sharma
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Andrew D Beggs
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Tariq H Iqbal
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Microbiology and Infection, University of Birmingham, UK
| | - Mohammed Nabil Quraishi
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
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The Role of Fecal Microbiota Transplantation in the Treatment of Inflammatory Bowel Disease. J Clin Med 2021; 10:jcm10184055. [PMID: 34575166 PMCID: PMC8465860 DOI: 10.3390/jcm10184055] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 12/12/2022] Open
Abstract
The exact pathogenesis of inflammatory bowel disease (IBD) is still not completely understood. It is hypothesized that a genetic predisposition leads to an exaggerated immune response to an environmental trigger, leading to uncontrolled inflammation. As there is no known causative treatment, current management strategies for inflammatory bowel disease focus on correcting the excessive immune response to environmental (including microbial) triggers. In recent years, there has been growing interest in new avenues of treatment, including targeting the microbial environment itself. Fecal microbiota transplantation (FMT) is a novel treatment modality showing promising results in early studies. The article discusses the rationale for the use of FMT in inflammatory bowel disease and the yet-unresolved questions surrounding its optimal use in practice.
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