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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] [Download PDF] [Figures] [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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Nagayama M, Gogokhia L, Longman RS. Precision microbiota therapy for IBD: premise and promise. Gut Microbes 2025; 17:2489067. [PMID: 40190259 PMCID: PMC11980506 DOI: 10.1080/19490976.2025.2489067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 12/19/2024] [Accepted: 03/28/2025] [Indexed: 04/11/2025] Open
Abstract
Inflammatory Bowel Disease (IBD) is a spectrum of chronic inflammatory diseases of the intestine that includes subtypes of ulcerative colitis (UC) and Crohn's Disease (CD) and currently has no cure. While IBD results from a complex interplay between genetic, environmental, and immunological factors, sequencing advances over the last 10-15 years revealed signature changes in gut microbiota that contribute to the pathogenesis of IBD. These findings highlight IBD as a disease target for microbiome-based therapies, with the potential to treat the underlying microbial pathogenesis and provide adjuvant therapy to the emerging spectrum of advanced therapies for IBD. Building on the success of fecal microbiota transplantation (FMT) for Clostridioides difficile infection, therapies targeting gut microbiota have emerged as promising approaches for treating IBD; however, unique aspects of IBD pathogenesis highlight the need for more precision in the approach to microbiome therapeutics that leverage aspects of recipient and donor selection, diet and xenobiotics, and strain-specific interactions to enhance the efficacy and safety of IBD therapy. This review focuses on both pre-clinical and clinical studies that support the premise for microbial therapeutics for IBD and aims to provide a framework for the development of precision microbiome therapeutics to optimize clinical outcomes for patients with IBD.
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Affiliation(s)
- Manabu Nagayama
- Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA
- Jill Roberts Center for Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Lasha Gogokhia
- Jill Roberts Center for Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Randy S. Longman
- Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA
- Jill Roberts Center for Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
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3
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Faith JJ. Assessing live microbial therapeutic transmission. Gut Microbes 2025; 17:2447836. [PMID: 39746875 DOI: 10.1080/19490976.2024.2447836] [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: 09/23/2024] [Revised: 12/09/2024] [Accepted: 12/23/2024] [Indexed: 01/04/2025] Open
Abstract
The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent Clostridioides difficile infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology. Broad and correct usage of strain detection methods is essential to this advancement. This article describes strain detection approaches, where they are best applied, what data they require, and clinical trial designs that are best suited to their application.
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Affiliation(s)
- Jeremiah J Faith
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Jansen D, Deleu S, Caenepeel C, Marcelis T, Simsek C, Falony G, Machiels K, Sabino J, Raes J, Vermeire S, Matthijnssens J. Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses. Gut Microbes 2025; 17:2499575. [PMID: 40371968 PMCID: PMC12087655 DOI: 10.1080/19490976.2025.2499575] [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: 01/21/2025] [Revised: 04/02/2025] [Accepted: 04/24/2025] [Indexed: 05/16/2025] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplantation (FMT), which transfers healthy donor microbiota to patients. The role of viruses in this process, however, remains underexplored. To address this, we analyzed the gut virome using metagenomic sequencing of enriched viral particles from 320 longitudinal fecal samples of 44 patients enrolled in the RESTORE-UC FMT trial. Patients were treated with FMTs from healthy donors (allogenic, treatment) or themselves (autologous, control). We found that colonic inflammation, both its presence and location, had a greater impact on the gut virome than FMT itself. In autologous FMT patients, the virome was unstable and showed rapid divergence over time, a phenomenon we termed virome drift. In allogenic FMT patients, the virome temporarily shifted toward the healthy donor, lasting up to 5 weeks and primarily driven by microviruses. Notably, two distinct virome configurations were identified and linked to either healthy donors or patients. In conclusion, inflammation strongly affects the gut virome in UC patients, which may lead to instability and obstruct the engraftment of allogeneic FMT.
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Affiliation(s)
- Daan Jansen
- Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, Belgium
| | - Sara Deleu
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Clara Caenepeel
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Tine Marcelis
- Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, Belgium
| | - Ceren Simsek
- Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, Belgium
| | - Gwen Falony
- Department of Microbiology Immunology and Transplantation, Rega Institute, Laboratory of Molecular Bacteriology, KU Leuven, Leuven, Belgium
- Center for Microbiology, VIB, Leuven, Belgium
- Institute of Medical Microbiology and Hygiene and Research Centre for Immunotherapy (FZI), University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Kathleen Machiels
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - João Sabino
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Jeroen Raes
- Department of Microbiology Immunology and Transplantation, Rega Institute, Laboratory of Molecular Bacteriology, KU Leuven, Leuven, Belgium
- Center for Microbiology, VIB, Leuven, Belgium
| | - Séverine Vermeire
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Jelle Matthijnssens
- Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, Belgium
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Magier SJ, Morley TS, Kelly CR. Optimizing Therapeutic Potential of Fecal Transplant in Inflammatory Bowel Disease. Gastroenterol Clin North Am 2025; 54:277-293. [PMID: 40348488 DOI: 10.1016/j.gtc.2024.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract influenced by genetic, environmental, immune, and microbial factors. Reduced gut microbial diversity and elevated proinflammatory bacteria levels in IBD disrupt mucosal immunity, barrier function, and inflammatory pathways. Fecal microbiota transplantation (FMT) is a potential therapy to restore microbial balance. Studies suggest that FMT may induce remission in mild-to-moderate ulcerative colitis but show limited efficacy in Crohn's disease and pouchitis. Donor microbiota colonization correlates with remission, but varied study designs challenge findings. Further research is required to standardize FMT protocols, optimize donor selection, and ensure long-term safety.
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Affiliation(s)
- Samantha J Magier
- Department of Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Thomas S Morley
- Department of Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Colleen R Kelly
- Department of Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
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Sartor RB. Beyond Random Fecal Microbial Transplants: Next Generation Personalized Approaches to Normalize Dysbiotic Microbiota for Treating IBD. Gastroenterol Clin North Am 2025; 54:333-350. [PMID: 40348491 DOI: 10.1016/j.gtc.2024.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
This review and commentary outline the strong rationale for normalizing the abnormal microbiota of patients with ulcerative colitis, Crohn's disease, and pouchitis and focus on strategies to improve current variable outcomes of fecal microbial transplant (FMT) in ulcerative colitis. Applying lessons from successful FMT therapy of recurrent Clostridioides difficile and insights from basic scientific understanding of host/microbial interactions provide strategies to enhance clinical outcomes in IBD. We outline promising approaches to develop novel-defined consortia of live biotherapeutic products and combination treatments to improve current results and to optimize and personalize treatment approaches in individual patients and disease subsets.
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Affiliation(s)
- R Balfour Sartor
- Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina - Chapel Hill, Chapel Hill, NC 27517, USA; Department of Microbiology & Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina - Chapel Hill, Chapel Hill, NC 27517, USA.
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Karimianghadim R, Satokari R, Yeo S, Arkkila P, Kao D, Pakpour S. Prolonged effect of antibiotic therapy on the gut microbiota composition, functionality, and antibiotic resistance genes' profiles in healthy stool donors. Front Microbiol 2025; 16:1589704. [PMID: 40415928 PMCID: PMC12098650 DOI: 10.3389/fmicb.2025.1589704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Accepted: 04/22/2025] [Indexed: 05/27/2025] Open
Abstract
Introduction Fecal microbiota transplantation (FMT) is highly effective in preventing Clostridioides difficile recurrence by restoring gut microbiota composition and function. However, the impact of recent antibiotic use, a key exclusion criterion for stool donors, on gut microbiota recovery is poorly understood. Methods We investigated microbial recovery dynamics following antibiotic use in three long-term stool donors from Canada and Finland. Using longitudinal stool sampling, metagenomic sequencing, and qPCR, we assessed changes in bacterial diversity, community composition, microbial functions, the gut phageome, and the risk of transmitting antibiotic-resistant genes (ARGs). Results Antibiotics caused lasting disruption to bacterial communities, significantly reducing important taxa like Bifidobacterium bifidum, Blautia wexlerae, Akkermansia muciniphila, Eubacterium sp. CAG 180, and Eubacterium hallii, with effects persisting for months. Functional analyses revealed alterations in housekeeping genes critical for energy production and biosynthesis, with no direct links to key health-related pathways. Antibiotics also disrupted viral populations, decreasing diversity and increasing crAssphage abundance, reflecting disrupted host-bacteriophage dynamics. No significant increase in clinically important ARGs was detected. Discussion These findings highlight the unpredictable and complex recovery of gut microbiota post-antibiotics. Individualized suspension periods in donor programs, guided by metagenomic analyses, are recommended to optimize FMT outcomes in various indications by considering antibiotic spectrum, duration, and host-specific factors.
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Affiliation(s)
| | - Reetta Satokari
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Sam Yeo
- School of Engineering, University of British Columbia, Kelowna, BC, Canada
| | - Perttu Arkkila
- Department of Gastroenterology, Helsinki University Hospital and Helsinki University, Helsinki, Finland
| | - Dina Kao
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Sepideh Pakpour
- School of Engineering, University of British Columbia, Kelowna, BC, Canada
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Zaiou M, Joubert O. Racial and Ethnic Disparities in NAFLD: Harnessing Epigenetic and Gut Microbiota Pathways for Targeted Therapeutic Approaches. Biomolecules 2025; 15:669. [PMID: 40427561 PMCID: PMC12109303 DOI: 10.3390/biom15050669] [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] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 04/28/2025] [Accepted: 04/29/2025] [Indexed: 05/29/2025] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern, impacting approximately 32.4% of the worldwide population. As a disease linked to metabolic dysfunction, NAFLD continues to rise alongside global increases in obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. There is considerable evidence indicating that NAFLD disproportionately affects racial, ethnic, and minority groups, although the exact reasons for these disparities remain elusive. Contributing factors to this disease may include socioeconomic status, cultural influences, stress, genetic factors, and lifestyle choices. Emerging evidence suggests that these causal factors could influence epigenetic mechanisms, particularly DNA methylation and histone modifications, as well as the composition and diversity of gut microbiota. Nevertheless, there is a scarcity of research that comprehensively examines the interplay between epigenetic changes and gut microbiome variations in relation to NAFLD disparities across different racial and ethnic populations globally. This paper intends to (i) explore the connections between NAFLD, ethnic disparities, gut microbiota composition, and epigenetic alterations, while reviewing pertinent studies that illustrate how these factors contribute to health inequities among various ethnic groups impacted by this disease; (ii) explore potential therapeutic targets and biomarkers to advance the management of NAFLD; and (iii) provide insights to enhance our understanding of the mechanisms associated with this disease, thereby promoting further research in this field. Advancements in this area are anticipated to enhance our understanding of disease susceptibilities in at-risk groups and to provide new therapeutic options for NAFLD and its associated complications.
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Affiliation(s)
- Mohamed Zaiou
- Université de Lorraine, CNRS, IJL, F-54000 Nancy, France;
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Tay SW, Low AHL. Is faecal microbiota transplantation ready for prime time in systemic sclerosis? THE LANCET. RHEUMATOLOGY 2025; 7:e305-e307. [PMID: 39900090 DOI: 10.1016/s2665-9913(24)00376-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 11/28/2024] [Indexed: 02/05/2025]
Affiliation(s)
- Shu Wen Tay
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Andrea Hsiu Ling Low
- Department of Rheumatology and Immunology, Singapore General Hospital, Singapore 169608; Duke-National University of Singapore Medical School, Singapore.
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Sutanto H, Elisa E, Rachma B, Fetarayani D. Gut Microbiome Modulation in Allergy Treatment: The Role of Fecal Microbiota Transplantation. Am J Med 2025; 138:769-777.e3. [PMID: 39855612 DOI: 10.1016/j.amjmed.2025.01.005] [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: 12/05/2024] [Revised: 01/10/2025] [Accepted: 01/14/2025] [Indexed: 01/27/2025]
Abstract
The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.
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Affiliation(s)
- Henry Sutanto
- Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Elisa Elisa
- Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Betty Rachma
- Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Deasy Fetarayani
- Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia; Division of Allergy and Clinical Immunology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
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Karmisholt Grosen A, Mikkelsen S, Aas Hindhede L, Ellegaard Paaske S, Dahl Baunwall SM, Mejlby Hansen M, Frederik Dahlerup J, Steen Mortensen M, Rask Licht T, Kjærgaard Boldsen J, Tornvig Erikstrup L, Lodberg Hvas C, Erikstrup C. Effects of clinical donor characteristics on the success of faecal microbiota transplantation for patients in Denmark with Clostridioides difficile infection: a single-centre, prospective cohort study. THE LANCET. MICROBE 2025; 6:101034. [PMID: 40024260 DOI: 10.1016/j.lanmic.2024.101034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 10/20/2024] [Accepted: 10/24/2024] [Indexed: 03/04/2025]
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) is an effective treatment for patients with recurrent Clostridioides difficile infection, but donor selection can influence its clinical success. We aimed to investigate the effect of clinical donor characteristics on FMT outcomes in patients with C difficile infection. METHODS In this single-centre, prospective cohort study, we included all donors who fulfilled the national criteria for faeces donation and delivered donations to the Centre for Faecal Microbiota Transplantation, Aarhus University Hospital, Denmark, between May 2, 2016, and Oct 31, 2023, and corresponding recipients treated with one-dose FMT for primary or recurrent C difficile infection. In mixed-effects models, we evaluated the effect of donor sex, age, BMI, smoking status, donation stool consistency, total donation weight, antibiotic use, Helicobacter pylori carriage, birth mode, donor-recipient sex concordance, and the alpha diversity of faeces donations on FMT outcomes in recipients. The primary outcome was the resolution of diarrhoea associated with C difficile infection in patients 8 weeks after FMT. FINDINGS Among 145 blood donors who also donated faeces, 115 (79·3%) were men and 30 (20·7%) were women. 90 (62·1%) provided faeces for 1351 evaluable FMTs in 952 patients with C difficile infection. 1037 (76·8%) FMTs were administered through oral capsules, 151 (11·2%) via colonoscopy, and 163 FMTs (12·1%) via nasojejunal tube. Antibiotic use 3-12 months before donation decreased the effectiveness of FMT (odds ratio 0·55 [95% CI 0·33-0·91]; p=0·019). Compared with donations with a Bristol Stool Form Scale (BSFS) score of 3, donations with a score of 4 (odds ratio 1·38 [95% CI 1·04-1·83]; p=0·024) and 5 or above (2·89 [1·33-6·26]; p=0·0072) showed improved FMT effectiveness. Donor sex, BMI, smoking status, H pylori carriage, birth mode, total donation weight, and donor-recipient sex concordance did not affect FMT outcomes. INTERPRETATION Expanding current donor selection criteria to avoid antibiotic use in the 12 months preceding donation and including donations with a BSFS score of 5 might improve FMT outcomes for patients with C difficile infection. Our findings call for the revision of current clinical donor screening practices, and future studies could further optimise the criteria for selecting optimal faeces donors. FUNDING Innovation Fund Denmark.
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Affiliation(s)
- Anne Karmisholt Grosen
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Susan Mikkelsen
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Lotte Aas Hindhede
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Sara Ellegaard Paaske
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Mette Mejlby Hansen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Jens Frederik Dahlerup
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Tine Rask Licht
- National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Jens Kjærgaard Boldsen
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark; Danish Big Data Centre for Environment and Health, Aarhus University, Aarhus, Denmark
| | | | - Christian Lodberg Hvas
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Turpin W, Lee SH, Croitoru K. Gut Microbiome Signature in Predisease Phase of Inflammatory Bowel Disease: Prediction to Pathogenesis to Prevention. Gastroenterology 2025; 168:902-913. [PMID: 39914464 DOI: 10.1053/j.gastro.2025.01.004] [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: 07/05/2024] [Revised: 01/02/2025] [Accepted: 01/08/2025] [Indexed: 03/23/2025]
Abstract
Advances in understanding the pathogenesis of inflammatory bowel disease (IBD) point toward a key role of the gut microbiome. We review the data describing the changes in the gut microbiome from IBD case-control studies and compare these findings with emerging data from studies of the preclinical phase of IBD. What is apparent is that assessing changes in the composition and function of the gut microbiome during the preclinical phase helps address confounding factors, such as disease activity and drug therapy, which can directly influence the gut microbiome. Understanding these changes in the predisease phase provides a means of predicting IBD in high-risk populations and offers insights into possible mechanisms involved in disease pathogenesis. Finally, we discuss strategies to use this information to design interventions aimed at modulating the microbiome as a means of preventing or delaying the onset of IBD.
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Affiliation(s)
- Williams Turpin
- Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Sun-Ho Lee
- Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Kenneth Croitoru
- Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
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13
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Malik S, Naqvi SAA, Shadali AH, Khan H, Christof M, Niu C, Schwartz DA, Adler DG. Fecal Microbiota Transplantation (FMT) and Clinical Outcomes Among Inflammatory Bowel Disease (IBD) Patients: An Umbrella Review. Dig Dis Sci 2025; 70:1873-1896. [PMID: 40038211 DOI: 10.1007/s10620-025-08946-8] [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: 07/17/2024] [Accepted: 02/19/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND AND AIMS Recent systematic reviews and meta-analyses (SRMAs) have shown inconsistent effectiveness of FMT among patients with IBD. This study aimed to appraise the evidence for clinically relevant outcomes with FMT in patients with IBD using published SRMAs. METHODS We searched major databases from inception through Nov 2023 to identify SRMAs assessing the effectiveness of FMT in patients with IBD. Primary outcomes included clinical remission, clinical response, endoscopic remission/response, a composite endpoint, and adverse effects. We included SRMAs investigating FMT's effect in patients with IBD using RCTs and observational studies data. Methodological quality and evidence certainty were assessed using AMSTAR 2 and GRADE. RESULTS Out of 106 citations, 16 SRMAs were included with varying study sizes (2 to 60 primary studies) and participants (112 to 1169 per SRMA). Five SRMAs assessed FMT in IBD, while 11 focused on Ulcerative Colitis (UC). Seven SRMAs included RCTs only, and nine included both RCTs and observational studies. Methodological quality was critically low in 9 SRMAs (56%) and low in 7 studies (44%). FMT showed clinical remission benefit in all 16 SRMAs, with varying certainty: 3 high, 4 moderate, 4 low, and 5 very low. Endoscopic remission/response was reported in 5 meta-analyses on UC, with 1 high, 3 moderate, and 1 very low certainty. Combined clinical remission and endoscopic response were reported in 3 SRMAs on UC, with 1 low and 2 moderate certainty. Adverse events were reported in 6 SRMAs, with 1 high, 3 moderate, 1 low, and 1 very low certainty. CONCLUSION Current evidence shows potential benefits of FMT in IBD, particularly UC, supported by significant associations in 16 meta-analyses. However, poor methodological quality and variability in evidence certainty call for high-quality RCTs to strengthen the evidence.
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Affiliation(s)
- Sheza Malik
- Internal Medicine, Rochester General Hospital, Rochester, NY, USA
| | | | | | - Hajra Khan
- Rawalpindi Medical College, Rawalpindi, Pakistan
| | | | - Chengu Niu
- Internal Medicine, Rochester General Hospital, Rochester, NY, USA
| | - David A Schwartz
- Gastroenterology and Hepatology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Douglas G Adler
- Gastroenterology and Hepatology, Porter Adventist Hospital in Denver, Denver, CO, USA.
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Cui X, Li C, Zhong J, Liu Y, Xiao P, Liu C, Zhao M, Yang W. Gut microbiota - bidirectional modulator: role in inflammatory bowel disease and colorectal cancer. Front Immunol 2025; 16:1523584. [PMID: 40370465 PMCID: PMC12075242 DOI: 10.3389/fimmu.2025.1523584] [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] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 04/08/2025] [Indexed: 05/16/2025] Open
Abstract
The gut microbiota is a diverse ecosystem that significantly impacts human health and disease. This article focuses on how the gut microbiota interacts with inflammatory bowel diseases and colorectal tumors, especially through immune regulation. The gut microbiota plays a role in immune system development and regulation, while the body's immune status can also affect the composition of the microbiota. These microorganisms exert pathogenic effects or correct disease states in gastrointestinal diseases through the actions of toxins and secretions, inhibition of immune responses, DNA damage, regulation of gene expression, and protein synthesis. The microbiota and its metabolites are essential in the development and progression of inflammatory bowel diseases and colorectal tumors. The complexity and bidirectionality of this connection with tumors and inflammation might render it a new therapeutic target. Hence, we explore therapeutic strategies for the gut microbiota, highlighting the potential of probiotics and fecal microbiota transplantation to restore or adjust the microbial community. Additionally, we address the challenges and future research directions in this area concerning inflammatory bowel diseases and colorectal tumors.
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Affiliation(s)
- Xilun Cui
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Changfeng Li
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jing Zhong
- Department of Medical Imaging, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China
| | - Yuanda Liu
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Pengtuo Xiao
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Chang Liu
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Mengwei Zhao
- Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Wei Yang
- Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China
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15
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Hansen SH, Maseng MG, Grännö O, Vestergaard MV, Bang C, Olsen BC, Lund C, Olbjørn C, Løvlund EE, Vikskjold FB, Huppertz-Hauss G, Perminow G, Yassin H, Valeur J, Aass Holten KI, Henriksen M, Bengtson MB, Ricanek P, Opheim R, Boyar R, Torp R, Frigstad SO, Aabrekk TB, Detlie TE, Kristensen VA, Strande V, Hovde Ø, Asak Ø, Jess T, Franke A, Halfvarsson J, Høivik ML, Hov JR. Fecal Microbiome Reflects Disease State and Prognosis in Inflammatory Bowel Disease in an Adult Population-Based Inception Cohort. Inflamm Bowel Dis 2025:izaf060. [PMID: 40285477 DOI: 10.1093/ibd/izaf060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Indexed: 04/29/2025]
Abstract
INTRODUCTION We aimed to determine the diagnostic and prognostic potential of baseline microbiome profiling in inflammatory bowel disease (IBD). METHODS Participants with ulcerative colitis (UC), Crohn's disease (CD), suspected IBD, and non-IBD symptomatic controls were included in the prospective population-based cohort Inflammatory Bowel Disease in South-Eastern Norway III (third iteration) based on suspicion of IBD. The participants donated fecal samples that were analyzed with 16S rRNA sequencing. Disease course severity was evaluated at the 1-year follow-up. A stringent statistical consensus approach for differential abundance analysis with 3 different tools was applied, together with machine learning modeling. RESULTS A total of 1404 individuals were included, where n = 1229 samples from adults were used in the main analyses (n = 658 UC, n = 324 CD, n = 36 IBD-U, n = 67 suspected IBD, and n = 144 non-IBD symptomatic controls). Microbiome profiles were compared with biochemical markers in machine learning models to differentiate IBD from non-IBD symptomatic controls (area under the receiver operating curve [AUC] 0.75-0.79). For UC vs controls, integrating microbiome data with biochemical markers like fecal calprotectin mildly improved classification (AUC 0.83 to 0.86, P < .0001). Extensive differences in microbiome composition between UC and CD were identified, which could be quantified as an index of differentially abundant genera. This index was validated across published datasets from 3 continents. The UC-CD index discriminated between ileal and colonic CD (linear regression, P = .008) and between colonic CD and UC (P = .005), suggesting a location-dependent gradient. Microbiome profiles outperformed biochemical markers in predicting a severe disease course in UC (AUC 0.72 vs 0.65, P < .0001), even in those with a mild disease at baseline (AUC 0.66 vs 0.59, P < .0001). CONCLUSIONS Fecal microbiome profiling at baseline held limited potential to diagnose IBD from non-IBD compared with standard-of-care. However, microbiome shows promise for predicting future disease courses in UC.
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Affiliation(s)
- Simen Hyll Hansen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
| | - Maria Gjerstad Maseng
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
- Bio-Me, Oslo, Norway
| | - Olle Grännö
- School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Marie V Vestergaard
- Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Corinna Bang
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Bjørn C Olsen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Telemark Hospital, Skien, Norway
| | - Charlotte Lund
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Christine Olbjørn
- Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway
| | - Emma E Løvlund
- Department of Pediatric and Adolescent Medicine, Østfold Hospital Trust, Kalnes, Norway
| | - Florin B Vikskjold
- Department of Pediatric and Adolescent Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
| | | | - Gøri Perminow
- Department of Pediatrics, Oslo University Hospital, Oslo, Norway
| | - Hussain Yassin
- Department of Pediatrics, Telemark Hospital Kjørbekk, Skien, Norway
| | - Jørgen Valeur
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Kristina I Aass Holten
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Østfold Hospital Trust, Grålum, Norway
| | - Magne Henriksen
- Department of Gastroenterology, Østfold Hospital Trust, Grålum, Norway
| | - May-Bente Bengtson
- Department of Gastroenterology, Vestfold Hospital Trust, Tonsberg, Norway
| | - Petr Ricanek
- Department of Gastroenterology, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Randi Opheim
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
- Department of Nursing Science, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Raziye Boyar
- Department of Medicine, Diakonhjemmet Hospital, Oslo, Norway
| | - Roald Torp
- Medical Department, Innlandet Hospital Trust, Hamar, Norway
| | - Svein O Frigstad
- Department of Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway
| | - Tone Bergene Aabrekk
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Vestfold Hospital Trust, Tonsberg, Norway
| | - Trond Espen Detlie
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Vendel A Kristensen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Vibeke Strande
- Department of Gastroenterology, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Øistein Hovde
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Medicine, Innlandet Hospital Trust, Gjøvik, Norway
| | - Øyvind Asak
- Department of Gastroenterology, Innlandet Hospital Trust, Lillehammer, Norway
| | - Tine Jess
- Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Jonas Halfvarsson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Marte L Høivik
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Johannes R Hov
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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16
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Fehily SR, Wright EK, Basnayake C, Wilson-O'Brien AL, Stanley A, Marks EP, Russell EE, Hamilton AL, Bryant RV, Costello SP, Kamm MA. Faecal microbiota transplantation in Crohn's disease: an Australian randomised placebo-controlled trial protocol. BMJ Open 2025; 15:e094714. [PMID: 40254304 PMCID: PMC12010309 DOI: 10.1136/bmjopen-2024-094714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 03/24/2025] [Indexed: 04/22/2025] Open
Abstract
INTRODUCTION The enteric microbiota drives inflammation in Crohn's disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn's disease. The Microbial Restoration (MIRO) study aims to establish this evidence. METHODS AND ANALYSIS At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn's Disease Activity Index (CDAI) reduction ≥100 points or to <150 points) is the primary outcome measure. Non-responders to placebo and partial responders to FMT (CDAI decrease <100 but >70) receive FMT for weeks 8-16.Patients achieving clinical response from FMT after 8 or 16 weeks will be randomised in a 1:1 ratio to either a 44-week maintenance phase of FMT or placebo. Patients will receive FMT from one donor throughout the study.The MIRO study will establish whether FMT is an effective and safe therapy to induce and maintain remission in patients with active Crohn's disease. ETHICS AND DISSEMINATION Ethical approval has been received by the St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC-A 084/21). The results will be disseminated in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER ClinicalTrials.gov: NCT04970446; Registered on 20 July 2021.
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Affiliation(s)
- Sasha R Fehily
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Chamara Basnayake
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Amy L Wilson-O'Brien
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Annalise Stanley
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Elise P Marks
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Erin E Russell
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Amy L Hamilton
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Robert V Bryant
- Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
| | - Sam P Costello
- Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
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17
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Gefen R, Dourado J, Emile SH, Wignakumar A, Rogers P, Aeschbacher P, Garoufalia Z, Horesh N, Wexner SD. Fecal microbiota transplantation for patients with ulcerative colitis: a systematic review and meta-analysis of randomized control trials. Tech Coloproctol 2025; 29:103. [PMID: 40246750 PMCID: PMC12006273 DOI: 10.1007/s10151-025-03113-7] [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: 08/19/2024] [Accepted: 01/30/2025] [Indexed: 04/19/2025]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) has been shown to restore gut microbiome composition with an acceptable safety profile. FMT in inflammatory bowel disease, specifically ulcerative colitis (UC), has been investigated. We aimed to assess the efficacy of FMT in inducing UC remission. METHODS PubMed, Scopus, Google Scholar, and clinicaltrials.gov were searched for randomized control trials that assessed FMT in inducing UC remission. The primary outcome was combined clinical and endoscopic remission. Secondary outcomes were clinical remission, endoscopic remission, post-treatment overall adverse events, and colitis. Sensitivity analyses, meta-regression, bias assessment, and grading of certainty of evidence were performed. RESULTS A total of 14 studies including 600 patients (55.8% male; median age 40.7 years) were assessed. FMT was used in 299 patients and associated with significantly higher odds of combined clinical and endoscopic remission (OR 2.25, 95% CI 1.54, 3.3; p < 0.0001), clinical remission (OR 2.02, 95% CI 1.4, 2.93; p = 0.0002), and endoscopic remission (OR 1.95, 95% CI 1.17, 3.28; p = 0.011). The odds of post-treatment overall adverse events (OR 1.24, 95% CI 0.79, 1.95; p = 0.34) and colitis (OR 0.85, 95% CI 0.52, 1.93; p = 0.512) were similar between groups. Compared with baseline, FMT was more effective when biologics (OR 2.71), steroids (OR 2.27), or methotrexate (OR 3.07) were used as pre-FMT treatment. Oral delivery of FMT (OR 3.15) and pooled donors (OR 3.32) led to higher odds of remission. On meta-regression, pooled donors and methotrexate pre-treatment were associated with an increased likelihood of remission. CONCLUSIONS FMT is promising in inducing UC remission. Administration of medical treatments before FMT may help achieve higher remission rates. Current evidence shows that oral delivery of FMT and multidonor FMT may confer better results.
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Affiliation(s)
- R Gefen
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
- Department of General Surgery Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - J Dourado
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
| | - S H Emile
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
- Colorectal Surgery Unit, Mansoura University Hospital, Mansoura University, Mansoura, Egypt
| | - A Wignakumar
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
| | - P Rogers
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
| | - P Aeschbacher
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Z Garoufalia
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
| | - N Horesh
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
- Department of Surgery and Transplantations, Sheba Medical Center, Ramat Gan, Israel
| | - S D Wexner
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA.
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18
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Hand E, Hood-Pishchany I, Darville T, O'Connell CM. Influence of cervicovaginal microbiota on Chlamydia trachomatis infection dynamics. MICROBIAL CELL (GRAZ, AUSTRIA) 2025; 12:93-108. [PMID: 40309355 PMCID: PMC12042374 DOI: 10.15698/mic2025.04.848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 02/25/2025] [Accepted: 03/01/2025] [Indexed: 05/02/2025]
Abstract
The cervicovaginal microbiome (CVM) is increasingly being considered as an important aspect of women's health, particularly in relation to the risk and progression of sexually transmitted infections (STIs). CVM composition varies significantly between individuals and is shaped by factors including diet, age, environmental exposures, and lifestyle. Understanding these influences may shed light on how microbial imbalances contribute to infection susceptibility and the development of reproductive health disorders. Five distinct community state types (CSTs) classify common CVM compositions. Most CSTs (I, II, III, V) are characterized by a dominant Lactobacillus species and are associated with better or neutral reproductive health, including reduced coincident detection of STIs such as Chlamydia trachomatis. In contrast, CST IV is composed of diverse, predominantly anaerobic, microbial species and is associated with CVM dysbiosis, bacterial vaginosis, and a heightened risk of STI acquisition. This review examines the complex interplay between the CVM, C. trachomatis infection, and host immune responses, highlighting the role of metabolites such as short-chain and long-chain fatty acids, indole, and iron in modulating pathogen survival and host defenses. Additionally, the impacts of CVM composition on C. trachomatis persistence, ascension, and clearance are discussed, alongside co-infection dynamics with pathogens like Neisseria gonorrhoeae and Mycoplasma genitalium.
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Affiliation(s)
- Emily Hand
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill
| | - Indriati Hood-Pishchany
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill
- Department of Pediatrics, University of North Carolina at Chapel Hill
| | - Toni Darville
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill
- Department of Pediatrics, University of North Carolina at Chapel Hill
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Shekarriz S, Szamosi JC, Whelan FJ, Lau JT, Libertucci J, Rossi L, Fontes ME, Wolfe M, Lee CH, Moayyedi P, Surette MG. Detecting microbial engraftment after FMT using placebo sequencing and culture enriched metagenomics to sort signals from noise. Nat Commun 2025; 16:3469. [PMID: 40216789 PMCID: PMC11992129 DOI: 10.1038/s41467-025-58673-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
Fecal microbiota transplantation (FMT) has shown efficacy for the treatment of ulcerative colitis but with variable response between patients and trials. The mechanisms underlying FMT's therapeutic effects remains poorly understood but is generally assumed to involve engraftment of donor microbiota into the recipient's microbiome. Reports of microbial engraftment following FMT have been inconsistent between studies. Here, we investigate microbial engraftment in a previous randomized controlled trial (NCT01545908), in which FMT was sourced from a single donor, using amplicon-based profiling, shotgun metagenomics, and culture-enriched metagenomics. Placebo samples were included to estimate engraftment noise, and a significant level of false-positive engraftment was observed which confounds the prediction of true engraftment. We show that analyzing engraftment across multiple patients from a single donor enhances the accuracy of detection. We identified a unique set of genes engrafted in responders to FMT which supports strain displacement as the primary mechanism of engraftment in our cohort.
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Affiliation(s)
- Shahrokh Shekarriz
- Department of Medicine, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research, Institute McMaster University, Hamilton, ON, Canada
| | - Jake C Szamosi
- Department of Medicine, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research, Institute McMaster University, Hamilton, ON, Canada
| | - Fiona J Whelan
- School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK
| | - Jennifer T Lau
- Farncombe Family Digestive Health Research, Institute McMaster University, Hamilton, ON, Canada
| | - Josie Libertucci
- Farncombe Family Digestive Health Research, Institute McMaster University, Hamilton, ON, Canada
| | - Laura Rossi
- Department of Medicine, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research, Institute McMaster University, Hamilton, ON, Canada
| | - Michelle E Fontes
- Department of Medicine, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research, Institute McMaster University, Hamilton, ON, Canada
| | - Melanie Wolfe
- Department of Medicine, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research, Institute McMaster University, Hamilton, ON, Canada
| | - Christine H Lee
- Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada
| | - Paul Moayyedi
- Department of Medicine, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research, Institute McMaster University, Hamilton, ON, Canada
| | - Michael G Surette
- Department of Medicine, McMaster University, Hamilton, ON, Canada.
- Farncombe Family Digestive Health Research, Institute McMaster University, Hamilton, ON, Canada.
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
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20
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Chen C, Wang X, Han X, Peng L, Zhang Z. Gut microbiota and gastrointestinal tumors: insights from a bibliometric analysis. Front Microbiol 2025; 16:1558490. [PMID: 40264971 PMCID: PMC12012581 DOI: 10.3389/fmicb.2025.1558490] [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: 01/10/2025] [Accepted: 03/24/2025] [Indexed: 04/24/2025] Open
Abstract
Introduction Despite the growing number of studies on the role of gut microbiota in treating gastrointestinal tumors, the overall research trends in this field remain inadequately characterized. Methods A bibliometric analysis was conducted using publications retrieved from the Web of Science Core Collection (up to September 30, 2024). Analytical tools including VOSviewer, CiteSpace, and an online bibliometric platform were employed to evaluate trends and hotspots. Results Analysis of 1,421 publications revealed significant geographical disparities in research output, with China and the United States leading contributions. Institutionally, the University of Adelaide, Zhejiang University, and Shanghai Jiao Tong University were prominent contributors. Authorship analysis identified Hannah R. Wardill as the most prolific author, while the International Journal of Molecular Sciences emerged as a leading journal. Rapidly growing frontiers include "proliferation," "inhibition," "immunotherapy," "drug delivery," and "tumorigenesis." Discussion This study provides a comprehensive overview of research trends and highlights emerging directions, aiming to advance scientific and clinical applications of gut microbiota in gastrointestinal tumor therapy.
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Affiliation(s)
- Chaofan Chen
- Department of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Xiaolan Wang
- Department of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Xu Han
- Department of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Lifan Peng
- Department of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Zhiyun Zhang
- Department of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, China
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21
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Ishikawa D, Watanabe H, Nomura K, Zhang X, Maruyama T, Odakura R, Koma M, Shibuya T, Osada T, Fukuda S, Nakahara T, Terauchi J, Nagahara A, Yamada T. Patient-donor similarity and donor-derived species contribute to the outcome of fecal microbiota transplantation for ulcerative colitis. J Crohns Colitis 2025; 19:jjaf054. [PMID: 40168084 DOI: 10.1093/ecco-jcc/jjaf054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Indexed: 04/03/2025]
Abstract
BACKGROUND AND AIMS Clinical applications of fecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. However, whether the beneficial effects of FMT are due to the transfer and colonization of donor-derived species in patients remains unclear. Here, we investigated the factors affecting the efficacy of the administration of triple antibiotics (A-FMT) and the criteria for appropriate donor and patient-donor matching. METHODS Ninety-seven patients with active UC who were enrolled between March 2014 and October 2019 underwent FMT. The clinical features were assessed based on a reduction in Lichtiger's clinical activity index 4 weeks after A-FMT, with long-term responders (LTR) defined as those with no increase or intensification within 12 months after A-FMT. Microbiome analysis was performed on 147 fecal samples (pre-A-FMT, post-A-FMT, and donor) from 49 patient-donor combinations that were assigned using the one-patient-to-one-donor strategy. RESULTS Of the 97 patients, 61 achieved a clinical response, and of those, 35 were classified as having clinical remission. The efficacy of A-FMT was affected by UC severity and previous administration of steroids (P = .027), immunosuppressants (P = .049), and biologics (P = .029). Effective donors were rich in taxa such as Bacteroidota, which are lost in UC, and the abundances of "patient-origin" and "new-amplicon sequence variant" taxa were significantly lower in Responders compared to Nonresponders (Remission; P = .03, LTR; P = .05). "Donor-derived" amplicon sequence variant sequences, Oscillospiraceae UCG-002 and Alistipes, were significantly enriched in Responders (P < .05). Our results showed that the taxonomic composition of patients and the similarity of Bacteroides and butyric-acid-producing bacteria in the patient-donor microbiota significantly influenced A-FMT efficacy (P < .05). CONCLUSIONS This study provides important insights for developing patient-tailored FMT-based therapies for UC.
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Affiliation(s)
- Dai Ishikawa
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Metagen Therapeutics, Inc., Yamagata, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Hikaru Watanabe
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Metagen Therapeutics, Inc., Yamagata, Japan
| | - Kei Nomura
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Xiaochen Zhang
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Takafumi Maruyama
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Rina Odakura
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Masao Koma
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Taro Osada
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Shinji Fukuda
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Metagen Therapeutics, Inc., Yamagata, Japan
- Institute for Advanced Biosciences, Keio University, Yamagata, Japan
- Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kanagawa, Japan
- Transborder Medical Research Center, University of Tsukuba, Ibaraki, Japan
| | | | | | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Juntendo University Graduate School of Medicine Innovative Microbiome Therapy Research Center, Tokyo, Japan
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El Jaddaoui I, Sehli S, Al Idrissi N, Bakri Y, Belyamani L, Ghazal H. The Gut Mycobiome for Precision Medicine. J Fungi (Basel) 2025; 11:279. [PMID: 40278100 PMCID: PMC12028274 DOI: 10.3390/jof11040279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2025] [Revised: 03/29/2025] [Accepted: 03/31/2025] [Indexed: 04/26/2025] Open
Abstract
The human gastrointestinal tract harbors a vast array of microorganisms, which play essential roles in maintaining metabolic balance and immune function. While bacteria dominate the gut microbiome, fungi represent a much smaller, often overlooked fraction. Despite their relatively low abundance, fungi may significantly influence both health and disease. Advances in next-generation sequencing, metagenomics, metatranscriptomics, metaproteomics, metabolomics, and computational biology have provided novel opportunities to study the gut mycobiome, shedding light on its composition, functional genes, and metabolite interactions. Emerging evidence links fungal dysbiosis to various diseases, including inflammatory bowel disease, colorectal cancer, metabolic disorders, and neurological conditions. The gut mycobiome also presents a promising avenue for precision medicine, particularly in biomarker discovery, disease diagnostics, and targeted therapeutics. Nonetheless, significant challenges remain in effectively integrating gut mycobiome knowledge into clinical practice. This review examines gut fungal microbiota, highlighting analytical methods, associations with human diseases, and its potential role in precision medicine. It also discusses pathways for clinical translation, particularly in diagnosis and treatment, while addressing key barriers to implementation.
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Affiliation(s)
- Islam El Jaddaoui
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, University Mohammed V, Rabat 10000, Morocco; (I.E.J.); (Y.B.)
- Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat 10000, Morocco
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
| | - Sofia Sehli
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
| | - Najib Al Idrissi
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
| | - Youssef Bakri
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, University Mohammed V, Rabat 10000, Morocco; (I.E.J.); (Y.B.)
- Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat 10000, Morocco
| | - Lahcen Belyamani
- School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco;
| | - Hassan Ghazal
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
- Laboratory of Sports Sciences and Performance Optimization, Royal Institute of Executive Management, Salé 10102, Morocco
- National Center for Scientific and Technical Research, Rabat 10102, Morocco
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Bonazzi E, De Barba C, Lorenzon G, Maniero D, Bertin L, Barberio B, Facciotti F, Caprioli F, Scaldaferri F, Zingone F, Savarino EV. Recent developments in managing luminal microbial ecology in patients with inflammatory bowel disease: from evidence to microbiome-based diagnostic and personalized therapy. Expert Rev Gastroenterol Hepatol 2025; 19:563-576. [PMID: 40247656 DOI: 10.1080/17474124.2025.2495087] [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: 11/08/2024] [Revised: 03/21/2025] [Accepted: 04/15/2025] [Indexed: 04/19/2025]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic condition characterized by abnormal immune responses and intestinal inflammation. Emerging evidence highlights the vital role of gut microbiota in IBD's onset and progression. Recent advances have shaped diagnostic and therapeutic strategies, increasingly focusing on microbiome-based personalized care. Methodology: this review covers studies from 2004 to 2024, reflecting the surge in research on luminal microbial ecology in IBD. Human studies were prioritized, with select animal studies included for mechanistic insights. Only English-language, peer-reviewed articles - clinical trials, systematic reviews, and meta-analyses - were considered. Studies without clinical validation were excluded unless offering essential insights. Searches were conducted using PubMed, Scopus, and Web of Science. AREAS COVERED we explore mechanisms for managing IBD-related microbiota, including microbial markers for diagnosis and novel therapies such as fecal microbiota transplantation, metabolite-based treatments, and precision microbiome modulation. Additionally, we review technologies and diagnostic tools used to analyze gut microbiota composition and function in clinical settings. Emerging data supporting personalized therapeutic strategies based on individual microbial profiles are discussed. EXPERT OPINION Standardized microbiome research integration into clinical practice will enhance precision in IBD care, signaling a shift toward microbiota-based personalized medicine.
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Affiliation(s)
- Erica Bonazzi
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Caterina De Barba
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Greta Lorenzon
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Daria Maniero
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Luisa Bertin
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale-Università Padova, Padua, Italy
| | - Brigida Barberio
- Gastroenterology Unit, Azienda Ospedale-Università Padova, Padua, Italy
| | - Federica Facciotti
- INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy
- Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
- Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy
| | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Franco Scaldaferri
- Department of Gastroenterological Area, "A. Gemelli" Hospital, Catholic University of the Sacred Heart, Rome, Italy
| | - Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale-Università Padova, Padua, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale-Università Padova, Padua, Italy
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Hou S, Yu J, Li Y, Zhao D, Zhang Z. Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413197. [PMID: 40013938 PMCID: PMC11967859 DOI: 10.1002/advs.202413197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/22/2025] [Indexed: 02/28/2025]
Abstract
This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.
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Affiliation(s)
- Shuna Hou
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Jiachen Yu
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Yongshuang Li
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Duoyi Zhao
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Zhiyu Zhang
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
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Kaden T, Alonso‐Román R, Stallhofer J, Gresnigt MS, Hube B, Mosig AS. Leveraging Organ-on-Chip Models to Investigate Host-Microbiota Dynamics and Targeted Therapies for Inflammatory Bowel Disease. Adv Healthc Mater 2025; 14:e2402756. [PMID: 39491534 PMCID: PMC12004439 DOI: 10.1002/adhm.202402756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 09/29/2024] [Indexed: 11/05/2024]
Abstract
Inflammatory bowel disease (IBD) is an idiopathic gastrointestinal disease with drastically increasing incidence rates. Due to its multifactorial etiology, a precise investigation of the pathogenesis is extremely difficult. Although reductionist cell culture models and more complex disease models in animals have clarified the understanding of individual disease mechanisms and contributing factors of IBD in the past, it remains challenging to bridge research and clinical practice. Conventional 2D cell culture models cannot replicate complex host-microbiota interactions and stable long-term microbial culture. Further, extrapolating data from animal models to patients remains challenging due to genetic and environmental diversity leading to differences in immune responses. Human intestine organ-on-chip (OoC) models have emerged as an alternative in vitro model approach to investigate IBD. OoC models not only recapitulate the human intestinal microenvironment more accurately than 2D cultures yet may also be advantageous for the identification of important disease-driving factors and pharmacological interventions targets due to the possibility of emulating different complexities. The predispositions and biological hallmarks of IBD focusing on host-microbiota interactions at the intestinal mucosal barrier are elucidated here. Additionally, the potential of OoCs to explore microbiota-related therapies and personalized medicine for IBD treatment is discussed.
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Affiliation(s)
- Tim Kaden
- Dynamic42 GmbH07745JenaGermany
- Institute of Biochemistry IICenter for Sepsis Control and CareJena University Hospital07747JenaGermany
| | - Raquel Alonso‐Román
- Department of Microbial Pathogenicity MechanismsLeibniz Institute for Natural Product Research and Infection Biology – Hans‐Knöll‐Institute07745JenaGermany
- Cluster of Excellence Balance of the MicroverseFriedrich Schiller University Jena07745JenaGermany
- Junior Research Group Adaptive Pathogenicity StrategiesLeibniz Institute for Natural Product Research and Infection Biology – Hans‐Knöll‐Institute07745JenaGermany
| | | | - Mark S. Gresnigt
- Cluster of Excellence Balance of the MicroverseFriedrich Schiller University Jena07745JenaGermany
- Junior Research Group Adaptive Pathogenicity StrategiesLeibniz Institute for Natural Product Research and Infection Biology – Hans‐Knöll‐Institute07745JenaGermany
| | - Bernhard Hube
- Department of Microbial Pathogenicity MechanismsLeibniz Institute for Natural Product Research and Infection Biology – Hans‐Knöll‐Institute07745JenaGermany
- Cluster of Excellence Balance of the MicroverseFriedrich Schiller University Jena07745JenaGermany
- Institute of MicrobiologyFaculty of Biological SciencesFriedrich Schiller University07743JenaGermany
| | - Alexander S. Mosig
- Institute of Biochemistry IICenter for Sepsis Control and CareJena University Hospital07747JenaGermany
- Cluster of Excellence Balance of the MicroverseFriedrich Schiller University Jena07745JenaGermany
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26
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Roujansky A, Diop S, Pasqueron J, Aparicio M, Cook F, Kallel H, Mounier R. Pathophysiology and Prevention of Ventriculostomy-Related Infections: A Review. Neurosurgery 2025; 96:744-750. [PMID: 39264162 DOI: 10.1227/neu.0000000000003181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 08/07/2024] [Indexed: 09/13/2024] Open
Abstract
This qualitative review aims to summarize current knowledge on ventriculostomy-related infection (VRI) pathophysiology and its prevention. VRI generally occurs at day 10, mainly because of Gram-positive cocci , after a cerebrospinal fluid leak. Skin microbiota and biofilm seem to play a major role in VRI pathogenesis. Colonization of external ventricular drain by biofilm is universal and occurs quickly after catheter insertion. However, pathogens from the skin are more often associated with VRI than commensal bacteria. A review of proposed preventive measures shows that none has proven to be fully efficient. Periprocedural and prolonged systemic prophylactic antimicrobials have not shown to prevent VRIs and may promote the emergence of more resistant or pathogenic strains. Antimicrobial and silver-impregnated external ventricular drains, although promising, have not demonstrated preventive effects and may modify bacterial ecology. These results are consistent with the proposed pathophysiology. Finally, we will present a few propositions for future research that may help in improving our knowledge and thus better prevent VRIs. Until then, given the available data, limiting the duration of ventricular drainage may be the most attainable option to prevent VRIs.
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Affiliation(s)
- Ariane Roujansky
- Réanimation polyvalente, Centre Hospitalier de Cayenne, Cayenne , French Guiana
- Tropical Biome et immunopathologie CNRS UMR-9017, Inserm U 1019, Université de Guyane, Cayenne , French Guiana
| | - Sylvain Diop
- Département d'Anesthésie et réanimation, Hôpital Marie Lannelongue, Le Plessis-Robinson , France
| | - Jean Pasqueron
- Service d'anesthésie-réanimation chirurgicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil , France
| | - Maxime Aparicio
- Department of Anaesthesiology and Critical Care, Georges Pompidou European Hospital, Paris , France
| | - Fabrice Cook
- Service d'anesthésie-réanimation, Centre Hospitalier du Sud Francilien, Corbeil-Essonnes , France
| | - Hatem Kallel
- Réanimation polyvalente, Centre Hospitalier de Cayenne, Cayenne , French Guiana
- Tropical Biome et immunopathologie CNRS UMR-9017, Inserm U 1019, Université de Guyane, Cayenne , French Guiana
| | - Roman Mounier
- Department of Anaesthesiology and Critical Care, Georges Pompidou European Hospital, Paris , France
- Université Paris Cité, Paris , France
- INSERM U955, équipe 15, institut Mondor de la recherche biomédicale, Université Paris-Est-Créteil, Créteil , France
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Rabinowitz LG, Gade A, Feuerstein JD. Medical management of acute severe ulcerative colitis in the hospitalized patient. Expert Rev Gastroenterol Hepatol 2025; 19:467-480. [PMID: 40187895 DOI: 10.1080/17474124.2025.2488884] [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: 11/25/2024] [Accepted: 04/01/2025] [Indexed: 04/07/2025]
Abstract
INTRODUCTION Approximately one in every four patients with ulcerative colitis will develop acute severe ulcerative colitis (ASUC). Historically, this was managed with intravenous steroids and surgery when steroids failed. The use of rescue therapy. AREAS COVERED This review summarizes the latest research in the management of hospitalized patients with ASUC. Covering the historical data and success of rescue therapy with cyclosporine and then with infliximab changed outcomes and reduced the risk of colectomy during the hospitalization and at 1 year. More recently, more biologics and small molecules have been approved and more patients present to the hospital with ASUC already failing anti-tumor necrosis factor antagonists. More recent studies have shown some efficacy of rescue therapy with other classes of biologics (e.g. interleukins and anti-integrins). The more recently approved small molecules (i.e. tofacitinib and Upadacitinib) have shown a rapid onset in therapeutic efficacy in as little as 1 day with sustained response at 1 year in reducing the risk of colectomy following ASUC. EXPERT OPINION In the expert opinion, we discuss the challenges in the treatment of patients with ASUC. We summarize the data of current biologics and new small molecules and their emerging roles in the management of ASUC.
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Affiliation(s)
- Loren G Rabinowitz
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Ajay Gade
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Murgiano M, Bartocci B, Puca P, di Vincenzo F, Del Gaudio A, Papa A, Cammarota G, Gasbarrini A, Scaldaferri F, Lopetuso LR. Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools. Int J Mol Sci 2025; 26:3059. [PMID: 40243712 PMCID: PMC11988433 DOI: 10.3390/ijms26073059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 03/18/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders primarily comprising two main conditions: ulcerative colitis and Crohn's disease. The gut microbiota's role in driving inflammation in IBD has garnered significant attention, yet the precise mechanisms through which the microbiota influences IBD pathogenesis remain largely unclear. Given the limited therapeutic options for IBD, alternative microbiota-targeted therapies-including prebiotics, probiotics, postbiotics, and symbiotics-have been proposed. While these approaches have shown promising results, microbiota modulation is still mainly considered an adjunct therapy to conventional treatments, with a demonstrated impact on patients' quality of life. Fecal microbiota transplantation (FMT), already approved for treating Clostridioides difficile infection, represents the first in a series of innovative microbiota-based therapies under investigation. Microbial biotherapeutics are emerging as personalized and cutting-edge tools for IBD management, encompassing next-generation probiotics, bacterial consortia, bacteriophages, engineered probiotics, direct metabolic pathway modulation, and nanotherapeutics. This review explores microbial modulation as a therapeutic strategy for IBDs, highlighting current approaches and examining promising tools under development to better understand their potential clinical applications in managing intestinal inflammatory disorders.
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Affiliation(s)
- Marco Murgiano
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
| | - Bianca Bartocci
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
| | - Pierluigi Puca
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Federica di Vincenzo
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
| | - Angelo Del Gaudio
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
| | - Alfredo Papa
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Giovanni Cammarota
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Franco Scaldaferri
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Loris Riccardo Lopetuso
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (B.B.); (P.P.); (F.d.V.); (A.D.G.); (A.P.); (G.C.); (A.G.); (F.S.)
- Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie, Università degli Studi Link, 00165 Rome, Italy
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Liu Y, Li X, Chen Y, Yao Q, Zhou J, Wang X, Meng Q, Ji J, Yu Z, Chen X. Fecal microbiota transplantation: application scenarios, efficacy prediction, and factors impacting donor-recipient interplay. Front Microbiol 2025; 16:1556827. [PMID: 40201444 PMCID: PMC11975908 DOI: 10.3389/fmicb.2025.1556827] [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: 01/07/2025] [Accepted: 03/07/2025] [Indexed: 04/10/2025] Open
Abstract
Fecal microbiota transplantation (FMT) represents a therapeutic approach that directly regulates the gut microbiota of recipients, normalizes its composition and reaping therapeutic rewards. Currently, in addition to its general application in treating Clostridium difficile (C. difficile) infection (CDI), FMT treatment has also been extended to the fields of other gastrointestinal diseases, infections, gut-liver or gut-brain axis disorders, metabolic diseases and cancer, etc. Prior to FMT, rigorous donor screening is essential to reduce the occurrence of adverse events. In addition, it is imperative to evaluate whether the recipient can safely and effectively undergo FMT treatment. However, the efficacy of FMT is influenced by the complex interactions between the gut microbiota of donor and recipient, the degree of donor microbiota engraftment is not necessarily positively related with the success rate of FMT. Furthermore, an increasing number of novel factors affecting FMT outcomes are being identified in recent clinical trials and animal experiments, broadening our understanding of FMT treatment. This article provides a comprehensive review of the application scenarios of FMT, the factors influencing the safety and efficacy of FMT from the aspects of both the donors and the recipients, and summarizes how these emerging novel regulatory factors can be combined to predict the clinical outcomes of patients undergoing FMT.
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Affiliation(s)
- Yaxin Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xinru Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Yuchao Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Qinyan Yao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Jinjie Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiaoxuan Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Qingguo Meng
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Jiaxuan Ji
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Zihan Yu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
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Rahman R, Fouhse JM, Ju T, Fan Y, Bhardwaj T, Brook RK, Nosach R, Harding J, Willing BP. The impact of wild-boar-derived microbiota transplantation on piglet microbiota, metabolite profile, and gut proinflammatory cytokine production differs from sow-derived microbiota. Appl Environ Microbiol 2025; 91:e0226524. [PMID: 39902926 PMCID: PMC11921332 DOI: 10.1128/aem.02265-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 12/19/2024] [Indexed: 02/06/2025] Open
Abstract
Colonization of co-evolved, species-specific microbes in early life plays a crucial role in gastrointestinal development and immune function. This study hypothesized that modern pig production practices have resulted in the loss of co-evolved species and critical symbiotic host-microbe interactions. To test this, we reintroduced microbes from wild boars (WB) into conventional piglets to explore their colonization dynamics and effects on gut microbial communities, metabolite profiles, and immune responses. At postnatal day (PND) 21, 48 piglets were assigned to four treatment groups: (i) WB-derived mixed microbial community (MMC), (ii) sow-derived MMC, (iii) a combination of WB and sow MMC (Mix), or (iv) Control (PBS). Post-transplantation analyses at PND 48 revealed distinct microbial communities in WB-inoculated piglets compared with Controls, with trends toward differentiation from Sow but not Mix groups. WB-derived microbes were more successful in colonizing piglets, particularly in the Mix group, where they competed with Sow-derived microbes. WB group cecal digesta enriched with Lactobacillus helveticus, Lactobacillus mucosae, and Lactobacillus pontis. Cecal metabolite analysis showed that WB piglets were enriched in histamine, acetyl-ornithine, ornithine, citrulline, and other metabolites, with higher histamine levels linked to Lactobacillus abundance. WB piglets exhibited lower cecal IL-1β and IL-6 levels compared with Control and Sow groups, whereas the Mix group showed reduced IFN-γ, IL-2, and IL-6 compared with the Sow group. No differences in weight gain, fecal scores, or plasma cytokines were observed, indicating no adverse effects. These findings support that missing WB microbes effectively colonize domestic piglets and may positively impact metabolite production and immune responses.IMPORTANCEThis study addresses the growing concern over losing co-evolved, species-specific microbes in modern agricultural practices, particularly in pig production. The implementation of strict biosecurity measures and widespread antibiotic use in conventional farming systems may disrupt crucial host-microbe interactions that are essential for gastrointestinal development and immune function. Our research demonstrates that by reintroducing wild boar-derived microbes into domestic piglets, these microbes can successfully colonize the gut, influence microbial community composition, and alter metabolite profiles and immune responses without causing adverse effects. These findings also suggest that these native microbes can fill an intestinal niche, positively impacting immune activation. This research lays the groundwork for future strategies to enhance livestock health and performance by restoring natural microbial populations that produce immune-modulating metabolites.
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Affiliation(s)
- Rajibur Rahman
- Department of Agricultural Food & Nutritional Science, Faculty of Agricultural, Life & Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Janelle M. Fouhse
- Department of Agricultural Food & Nutritional Science, Faculty of Agricultural, Life & Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Tingting Ju
- Department of Agricultural Food & Nutritional Science, Faculty of Agricultural, Life & Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA
| | - Yi Fan
- Department of Agricultural Food & Nutritional Science, Faculty of Agricultural, Life & Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Tulika Bhardwaj
- Department of Agricultural Food & Nutritional Science, Faculty of Agricultural, Life & Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
- University of Calgary, Calgary, Alberta, Canada
| | - Ryan K. Brook
- College of Agriculture and Bioresources, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Roman Nosach
- Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - John Harding
- Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Benjamin P. Willing
- Department of Agricultural Food & Nutritional Science, Faculty of Agricultural, Life & Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
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Wang Y, Xie Z, Du L, Wang Q, Zhang L, Wu Y, Han J. Heat-killed Lacticaseibacillus paracasei 6235 is more effective than live on DSS-induced colitis via modulation of intestinal microbiota and MAPK/NF-κB signaling pathways. Food Funct 2025; 16:2247-2261. [PMID: 39569739 DOI: 10.1039/d4fo04873c] [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: 11/22/2024]
Abstract
This study compared the protective effects of both live Lacticaseibacillus paracasei 6235 (LLP 6235) and heat-killed Lacticaseibacillus paracasei 6235 (HK-LP 6235) on ulcerative colitis. Using a dextran sulfate sodium (DSS)-induced colitis mouse model, we evaluated physiological state, colon tissue integrity, inflammatory factors, tight junction (TJ) proteins, and intestinal microbiota variations. The findings demonstrated that both LLP 6235 and HK-LP 6235 have the capacity to mitigate colitis damage, enhance TJ protein levels, and restore colon morphology. In addition, these interventions modulated the intestinal inflammatory response by inhibiting pro-inflammatory factors and upregulating anti-inflammatory factors through the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Moreover, treatment with LLP 6235 and HK-LP 6235 significantly altered intestinal microbiota diversity, increased the relative abundance of beneficial bacteria, and regulated the short-chain fatty acid (SCFA) levels. Spearman correlation analysis revealed a strong association between TJ proteins, SCFAs, intestinal microbiota, and inflammatory response, suggesting that LLP 6235 and HK-LP 6235 may provide an effective approach to colitis prevention. In conclusion, LLP 6235 and HK-LP 6235 have similar abilities; furthermore, HK-LP 6235 modulated the intestinal microbiota through lipid metabolic pathways, resulting in a greater improvement. Moreover, considering the high stability and safety of prebiotics and their wide applicability, HK-LP 6235 is recommended for use as a modulator of intestinal inflammatory diseases.
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Affiliation(s)
- Yucong Wang
- College of Food Science, Northeast Agricultural University, Harbin, 150030, China
| | - Zhixin Xie
- College of Food Science, Northeast Agricultural University, Harbin, 150030, China
| | - Lei Du
- College of Food Science, Northeast Agricultural University, Harbin, 150030, China
| | - Qi Wang
- LS CORPORATION CO., LTD, Tokyo, 0611374, Japan
| | - Lili Zhang
- College of Food Science, Northeast Agricultural University, Harbin, 150030, China
| | - Yunzhou Wu
- College of Life Science, Northeast Agricultural University, Harbin, 150030, China
| | - Jianchun Han
- College of Food Science, Northeast Agricultural University, Harbin, 150030, China
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Fan J, Wu Y, Wang X, Ullah H, Ling Z, Liu P, Wang Y, Feng P, Ji J, Li X. The probiotic enhances donor microbiota stability and improves the efficacy of fecal microbiota transplantation for treating colitis. J Adv Res 2025:S2090-1232(25)00177-8. [PMID: 40089059 DOI: 10.1016/j.jare.2025.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 03/04/2025] [Accepted: 03/10/2025] [Indexed: 03/17/2025] Open
Abstract
INTRODUCTION The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored. OBJECTIVES This study investigated whether pretreatment of donor microbiota with L. plantarum GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions. METHODS Donor mice received L. plantarum GR-4 for 3 weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms. RESULTS GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, p < 0.0001) enriched butyrogenic Butyricicoccus (73 % butyrate increase, p < 0.05) and improved stress resistance to bile acids/gastric conditions (1.25 × survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3 % of tryptophan (vs. 10.3 % for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and β-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83 % remission rate (vs. 50 % for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25 × and enriched success-associated taxa (Sporobacter, Butyricimonas), while suppressing pathogens (Clostridium papyrosolvens). CONCLUSIONS L. plantarum GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.
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Affiliation(s)
- Jingjing Fan
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, PR China
| | - Ying Wu
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, PR China
| | - Xing Wang
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, PR China
| | - Habib Ullah
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, PR China
| | - Zhenmin Ling
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, PR China
| | - Pu Liu
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, PR China
| | - Yu Wang
- Nutrition and Health Research Center, Lanzhou University, Lanzhou, Gansu 730000, PR China
| | - Pengya Feng
- Department of Children Rehabilitation Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China
| | - Jing Ji
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, PR China.
| | - Xiangkai Li
- Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, PR China.
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Iliev ID, Ananthakrishnan AN, Guo CJ. Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities. Nat Rev Microbiol 2025:10.1038/s41579-025-01163-0. [PMID: 40065181 DOI: 10.1038/s41579-025-01163-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2025] [Indexed: 03/26/2025]
Abstract
Perturbations in the intestinal microbiome are strongly linked to the pathogenesis of inflammatory bowel disease (IBD). Bacteria, fungi and viruses all make up part of a complex multi-kingdom community colonizing the gastrointestinal tract, often referred to as the gut microbiome. They can exert various effects on the host that can contribute to an inflammatory state. Advances in screening, multiomics and experimental approaches have revealed insights into host-microbiota interactions in IBD and have identified numerous mechanisms through which the microbiota and its metabolites can exert a major influence on the gastrointestinal tract. Looking into the future, the microbiome and microbiota-associated processes will be likely to provide unparalleled opportunities for novel diagnostic, therapeutic and diet-inspired solutions for the management of IBD through harnessing rationally designed microbial communities, powerful bacterial and fungal metabolites, individually or in combination, to foster intestinal health. In this Review, we examine the current understanding of the cross-kingdom gut microbiome in IBD, focusing on bacterial and fungal components and metabolites. We examine therapeutic and diagnostic opportunities, the microbial metabolism, immunity, neuroimmunology and microbiome-inspired interventions to link mechanisms of disease and identify novel research and therapeutic opportunities for IBD.
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Affiliation(s)
- Iliyan D Iliev
- Joan and Sanford I. Weill Department of Medicine, Gastroenterology and Hepatology Division, Weill Cornell Medicine, New York, NY, USA.
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.
- Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Chun-Jun Guo
- Joan and Sanford I. Weill Department of Medicine, Gastroenterology and Hepatology Division, Weill Cornell Medicine, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA
- Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA
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Caenepeel C, Deleu S, Vazquez Castellanos JF, Arnauts K, Braekeleire S, Machiels K, Baert F, Mana F, Pouillon L, Hindryckx P, Lobaton T, Louis E, Franchimont D, Verstockt B, Ferrante M, Sabino J, Vieira-Silva S, Falony G, Raes J, Vermeire S. Rigorous Donor Selection for Fecal Microbiota Transplantation in Active Ulcerative Colitis: Key Lessons From a Randomized Controlled Trial Halted for Futility. Clin Gastroenterol Hepatol 2025; 23:621-631.e7. [PMID: 38788915 DOI: 10.1016/j.cgh.2024.05.017] [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: 02/09/2024] [Revised: 04/03/2024] [Accepted: 05/02/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND & AIMS Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated fecal microbiota transplantation (FMT) administration were hypothesized to improve FMT induction of remission in ulcerative colitis (UC). METHODS The RESTORE-UC trial was a multi-centric, double-blind, sham-controlled, randomized trial. Patients with moderate to severe UC (defined by total Mayo 4-10) were randomly allocated to receive 4 anaerobic-prepared allogenic or autologous donor FMTs. Allogenic donor material was selected after a rigorous screening based on microbial cell count, enterotype, and the abundance of specific genera. The primary endpoint was steroid-free clinical remission (total Mayo ≤2, no sub-score >1) at week 8. A pre-planned futility analysis was performed after 66% (n = 72) of intended inclusions (n = 108). Quantitative microbiome profiling (n = 44) was performed at weeks 0 and 8. RESULTS In total, 72 patients were included, of which 66 received at least 1 FMT (allogenic FMT, n = 30 and autologous FMT, n = 36). At week 8, respectively, 3 and 5 patients reached the primary endpoint of steroid-free clinical remission (P = .72), indicating no treatment difference of at least 5% in favor of allogenic FMT. Hence, the study was stopped due to futility. Microbiome analysis showed numerically more enterotype transitions upon allogenic FMT compared with autologous FMT, and more transitions were observed when patients were treated with a different enterotype than their own at baseline (P = .01). Primary response was associated with lower total Mayo scores, lower bacterial cell counts, and higher Bacteroides 2 prevalence at baseline. CONCLUSION The RESTORE-UC trial did not meet its primary endpoint of increased steroid-free clinical remission at week 8. Further research should additionally consider patient selection, sterilized sham-control, increased frequency, density, and viability of FMT prior to administration. CLINICALTRIALS gov, Number: NCT03110289.
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Affiliation(s)
- Clara Caenepeel
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium
| | - Sara Deleu
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Jorge Francisco Vazquez Castellanos
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium
| | - Kaline Arnauts
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Sara Braekeleire
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Kathleen Machiels
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Filip Baert
- AZ Delta Roeselare, Department of Gastroenterology and Hepatology, Roeselare, Belgium
| | - Fazia Mana
- University Hospitals Brussels, Department of Gastroenterology and Hepatology, Brussels, Belgium
| | - Lieven Pouillon
- Imelda Hospital Bonheiden, Department of Gastroenterology and Hepatology, Bonheiden, Belgium
| | - Pieter Hindryckx
- Ghent University Hospital, Department of Gastroenterology, Ghent, Belgium
| | - Triana Lobaton
- Ghent University Hospital, Department of Gastroenterology, Ghent, Belgium; Department of Internal Medicine and Paediatrics, Ghent University, Gent, Belgium
| | - Edouard Louis
- Liège University Hospital, CHU Liège, Department of Gastroenterology and Hepatology, Liège, Belgium
| | - Denis Franchimont
- Erasmus Hospital Brussels, Department of Gastroenterology and Hepatology, Brussels, Belgium
| | - Bram Verstockt
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium
| | - Marc Ferrante
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium
| | - João Sabino
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium
| | - Sara Vieira-Silva
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Institute of Molecular Biology (IMB), Mainz, Germany
| | - Gwen Falony
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Jeroen Raes
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium
| | - Séverine Vermeire
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.
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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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Morshedbak M, Rahimi K, Tabandeh MR. Effect of fecal microbiota transplantation on ulcerative colitis model in rats: The gut-brain axis. Heliyon 2025; 11:e42430. [PMID: 39995913 PMCID: PMC11848074 DOI: 10.1016/j.heliyon.2025.e42430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 01/27/2025] [Accepted: 01/31/2025] [Indexed: 02/26/2025] Open
Abstract
Study objectives The impact of fecal microbiota transplantation (FMT) on the TLR4/MYD88/NF-kB signaling pathway in the colon in the ulcerative colitis model, as well as the incidence of anxiety behaviors caused by the colitis model was investigated. Methods Twenthy four ats were induced with ulcerative colitis using a 4 % acetic acid solution administered intrarectally and were subsequently treated with prednisolone and FMT. The study examined several indicators, such as TLR4, MYD88, and NF-κB mRNA expression, along with oxidative stress factors. Additionally, it examined the relationship between anxiety-related behaviors and colitis and assessed the pro-inflammatory cytokines in the hippocampus. Results FMT led to lower disease score index and improved colon tissue pathology findings. This was associated with reduced mRNA expression of TLR4, MYD88, and NF-κB, as well as lower levels of TOS, and higher levels of TAC, GSH, and GSSG in colon tissues. FMT was found to reduce anxiety in both the open field and elevated plus maze tests. Additionally, levels of IL-6 and TNF-a were decreased in the hippocampus. Conclusions FMT suppressed acetic acid-induced colitis by inhibiting the TLR4/MYD88/NF-kB signaling pathway. FMT reduced anxiety in open field and plus maze tests, and resulted in decreased levels of IL-6 and TNF-a in the hippocampus.
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Affiliation(s)
- Mahdis Morshedbak
- Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Kaveh Rahimi
- Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Mohammad Reza Tabandeh
- Department of Basic Sciences, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran Univeristy of Ahvaz, Ahvaz, Iran
- Stem Cells and Transgenic Technology Research Center, Shahid Chamran University of Ahvaz, Ahvaz, Iran
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Hu DX, Lu CM, Si XY, Wu QT, Wu LH, Zhong HJ, He XX. Effects of gastrointestinal symptoms on the efficacy of washed microbiota transplantation in patients with autism. Front Pediatr 2025; 13:1528167. [PMID: 40017709 PMCID: PMC11865235 DOI: 10.3389/fped.2025.1528167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 01/24/2025] [Indexed: 03/01/2025] Open
Abstract
Objective Washed microbiota transplantation (WMT) has emerged as a promising therapeutic strategy for autism spectrum disorder (ASD), though the factors that influence its efficacy remain poorly understood. This study explores the impact of gastrointestinal (GI) symptoms on the effectiveness of WMT in ASD. Methods Clinical data encompassing ASD symptoms, GI disturbances, and sleep disorders were collected from patients with ASD undergoing WMT. The therapeutic impact of WMT and the contributing factors to its efficacy were assessed. Results WMT significantly reduced scores on the Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Sleep Disturbance Scale for Children (SDSC), alongside a significant reduction in the incidence of constipation, abnormal stool forms, and diarrhea (all p < 0.05). After six courses of WMT, substantial reductions were observed in ABC, CARS, and SDSC scores, with increased treatment courses correlating with greater improvement (p < 0.05). Multiple linear regression analysis revealed that WMT efficacy was enhanced in patients with pre-existing GI symptoms (diarrhea: β = 0.119, p < 0.001; abnormal stool form: β = 0.201, p < 0.001) and those receiving a higher number of treatment courses (β = 0.116, p < 0.001). Additionally, the analysis indicated that treatment outcomes were more favorable in patients who had not undergone adjunct interventions (β = -0.041, p = 0.002), had a longer disease duration (β = 0.168, p = 0.007), and exhibited more severe disease symptoms (β = 0.125, p < 0.001). Conclusion WMT significantly alleviates both ASD and GI symptoms, along with sleep disturbances, in affected individuals. Six treatment courses resulted in notable improvement, with increased course numbers further improving therapeutic outcomes. Furthermore, pre-treatment GI symptoms, such as diarrhea and abnormal stool forms, may influence the effectiveness of WMT. Notably, patients who did not receive additional interventions, had a prolonged disease duration, and presented with more severe symptoms experienced markedly improved treatment responses.
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Affiliation(s)
- Dong-Xia Hu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Cai-Mei Lu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Xin-Yu Si
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Qing-Ting Wu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Li-Hao Wu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Hao-Jie Zhong
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, China
| | - Xing-Xiang He
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, China
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Lopetuso LR, Deleu S, Puca P, Abreu MT, Armuzzi A, Barbara G, Caprioli F, Chieng S, Costello SP, Damiani A, Danese S, Del Chierico F, D'Haens G, Dotan I, Facciotti F, Falony G, Fantini MC, Fiorino G, Gionchetti P, Godny L, Hart A, Kupčinskas J, Iqbal T, Laterza L, Lombardini L, Maharshak N, Marasco G, Masucci L, Papa A, Paramsothy S, Petito V, Piovani D, Pugliese D, Putignani L, Raes J, Ribaldone DG, Sanguinetti M, Savarino EV, Sokol H, Vetrano S, Ianiro G, Cammarota G, Cominelli F, Pizarro TT, Tilg H, Gasbarrini A, Vermeire S, Scaldaferri F. Guidance for Fecal Microbiota Transplantation Trials in Ulcerative Colitis: The Second ROME Consensus Conference. Inflamm Bowel Dis 2025:izaf013. [PMID: 39932857 DOI: 10.1093/ibd/izaf013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Indexed: 02/13/2025]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodologies, current studies demonstrate its potential for inducing remission in UC patients. Therefore, standardized and robust randomized clinical trials (RCTs) are needed to further support its efficacy for managing UC. The aim of the second Rome Consensus Conference was to address gaps and uncertainties identified in previous research regarding FMT and to offer a robust framework for future studies applied to the treatment of UC. METHODS Global experts in the field of clinical IBD, mucosal immunology, and microbiology (N = 48) gathered to address the need for standardized clinical trials in FMT investigation. The group focused on key issues, such as stool donation, donor selection, characterization of fecal biomass, potential administration routes, as well as the process of induction, maintenance, and endpoint readouts. RESULTS AND CONCLUSIONS The consensus achieved during this conference established standardization of methods and protocols to enhance the current quality of research, with the aim of eventual implementation of FMT in managing UC and the ultimate goal of improving patient outcomes.
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Affiliation(s)
- Loris R Lopetuso
- IBD Unit, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Life Science, Health, and Health Professions, Link Campus University, Rome, Italy
| | - Sara Deleu
- IBD Unit, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Chronic Diseases, Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Pierluigi Puca
- IBD Unit, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Teresa Abreu
- Division of Gastroenterology, Department of Medicine, Crohn's and Colitis Center, University of Miami - Miller School of Medicine, Miami, FL, USA
| | - Alessandro Armuzzi
- IBD Unit, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Rome, Italy
- IRCCS Azienda Ospedaliero Universitaria Di Bologna, Bologna, Italy
| | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Siew Chieng
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Samuel Paul Costello
- Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, SA, Australia
| | - Andrea Damiani
- Real World Data Facility, Gemelli Generator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Silvio Danese
- Department of Gastroenterology and Digestive Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Federica Del Chierico
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Geert D'Haens
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel
| | - Federica Facciotti
- Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy
| | - Gwen Falony
- Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Massimo Claudio Fantini
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Italy
| | | | - Paolo Gionchetti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- IBD Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna,, Italy
| | - Lihi Godny
- Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel
| | - Ailsa Hart
- IBD Unit, St Mark's Hospital, Harrow, Middlesex, UK
| | - Juozas Kupčinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Tariq Iqbal
- Microbiome Treatment Center, University of Birmingham, Birmingham, UK
| | - Lucrezia Laterza
- IBD Unit, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Letizia Lombardini
- Centro Nazionale Trapianti (CNT), Istituto Superiore di Sanità, Rome, Italy
| | - Nitsan Maharshak
- Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero Universitaria Di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna,, Italy
| | - Luca Masucci
- Microbiology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Alfredo Papa
- IBD Unit, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Sudarshan Paramsothy
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, Australia
| | - Valentina Petito
- IBD Unit, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Daniela Pugliese
- IBD Unit, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Lorenza Putignani
- Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Research Area of Immunology, Rheumatology and Infectious Diseases, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Jeroen Raes
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
- Center for Microbiology, VIB, Gent, Belgium
| | | | - Maurizio Sanguinetti
- Microbiology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | - Harry Sokol
- INSERM, Centre de Recherche Saint-Antoine, CRSA, Sorbonne Université, Paris, France
- Department of Gastroenterology, Saint Antoine Hospital, Paris, France
| | - Stefania Vetrano
- Laboratory of Gastrointestinal Immunopathology, Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Gianluca Ianiro
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, UOC di Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giovanni Cammarota
- Dipartimento di Scienze Mediche e Chirurgiche, UOC di Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Fabio Cominelli
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Theresa T Pizarro
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Herbert Tilg
- Department of Gastroenterology, Saint Antoine Hospital, Paris, France
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Antonio Gasbarrini
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, UOC di Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Severine Vermeire
- Department of Chronic Diseases, Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Franco Scaldaferri
- IBD Unit, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
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Pinto S, Šajbenová D, Benincà E, Nooij S, Terveer EM, Keller JJ, van der Meulen–de Jong AE, Bogaards JA, Steyerberg EW. Dynamics of Gut Microbiota After Fecal Microbiota Transplantation in Ulcerative Colitis: Success Linked to Control of Prevotellaceae. J Crohns Colitis 2025; 19:jjae137. [PMID: 39225490 PMCID: PMC11836888 DOI: 10.1093/ecco-jcc/jjae137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 07/21/2024] [Accepted: 09/02/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is an experimental treatment for ulcerative colitis (UC). We aimed to study microbial families associated with FMT treatment success. METHODS We analyzed stools from 24 UC patients treated with 4 FMTs weekly after randomization for pretreatment during 3 weeks with budesonide (n = 12) or placebo (n = 12). Stool samples were collected 9 times pre-, during, and post-FMT. Clinical and endoscopic response was assessed 14 weeks after initiation of the study using the full Mayo score. Early withdrawal due to worsening of UC symptoms was classified as non-response. RESULTS Nine patients (38%) reached remission at week 14, and 15 patients had a partial response or non-response at or before week 14. With a Dirichlet multinomial mixture model, we identified 5 distinct clusters based on the microbiota composition of 180 longitudinally collected patient samples and 27 donor samples. A Prevotellaceae-dominant cluster was associated with poor response to FMT treatment. Conversely, the families Ruminococcaceae and Lachnospiraceae were associated with a successful clinical response. These associations were already visible at the start of the treatment for a subgroup of patients and were retained in repeated measures analyses of family-specific abundance over time. Responders were also characterized by a significantly lower Simpson dominance compared to non-responders. CONCLUSIONS The success of FMT treatment of UC patients appears to be associated with specific gut microbiota families, such as control of Prevotellaceae. Monitoring the dynamics of these microbial families could potentially be used to inform treatment success early during FMT. CLINICAL TRIAL REGISTRATION NUMBER The study was registered in the Netherlands Trial Register, with reference number NL9858.
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Affiliation(s)
- Susanne Pinto
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Dominika Šajbenová
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Elisa Benincà
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | - Sam Nooij
- Leiden University Center for Infectious Diseases (LUCID) Research, Leiden University Medical Center, Leiden, The Netherlands
| | - Elisabeth M Terveer
- Leiden University Center for Infectious Diseases (LUCID) Research, Leiden University Medical Center, Leiden, The Netherlands
- Netherlands Donor Feces Bank, LUCID Medical Microbiology & Infection Control, Leiden University Medical Center, Leiden, The Netherlands
| | - Josbert J Keller
- Netherlands Donor Feces Bank, LUCID Medical Microbiology & Infection Control, Leiden University Medical Center, Leiden, The Netherlands
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Gastroenterology, Haaglanden Medisch Centrum, The Hague, The Netherlands
| | | | - Johannes A Bogaards
- Department of Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Amsterdam Institute for Infection and Immunity (AI&I), Amsterdam UMC, Amsterdam, The Netherlands
| | - Ewout W Steyerberg
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
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Moutsoglou D, Syal A, Lopez S, Nelson EC, Chen L, Kabage AJ, Fischer M, Khoruts A, Vaughn BP, Staley C. Novel Microbial Engraftment Trajectories Following Microbiota Transplant Therapy in Ulcerative Colitis. J Crohns Colitis 2025; 19:jjae142. [PMID: 39240145 DOI: 10.1093/ecco-jcc/jjae142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND AND AIMS Microbiota transplant therapy (MTT) is an emerging treatment for ulcerative colitis (UC). One proposed mechanism for the benefit of MTT is through engraftment of donor microbiota; however, engraftment kinetics are unknown. We identified SourceTracker as an efficient method both to determine engraftment and for the kinetic study of engrafting donor taxa to aid in determining the mechanism of how this therapy may treat UC. METHODS Ulcerative colitis patients received either encapsulated (drug name MTP-101C) or placebo capsules daily for 8 weeks followed by a 4-week washout period. Amplicon sequence data from donors and patients were analyzed using the Bayesian algorithm SourceTracker. RESULTS Twenty-seven patients were enrolled, 14 to placebo and 13 to MTT. Baseline Shannon and Chao1 indices negatively correlated with week 12 donor engraftment for patients treated with active drug capsules but not for placebo patients. SourceTracker engraftment positively correlated with the week 12 distance from donors measured using the Bray-Curtis similarity metric in treated patients but not with placebo. Engraftment at week 12 was significantly higher in the MTT group than in the placebo group. We identified engrafting taxa from donors in our patients and quantified the proportion of donor similarity or engraftment during weeks 1 through 8 (active treatment) and week 12, 4 weeks after the last dose. CONCLUSION SourceTracker can be used as a simple and reliable method to quantify donor microbial community engraftment and donor taxa contribution in patients with UC and other inflammatory conditions treated with MTT.
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Affiliation(s)
- Daphne Moutsoglou
- Department of Gastroenterology, Minneapolis VA Health Care System, MN 55417, USA
- Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
| | - Aneesh Syal
- Division of Basic and Translational Research, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Sharon Lopez
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Elizabeth C Nelson
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Lulu Chen
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Amanda J Kabage
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Monika Fischer
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Alexander Khoruts
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Byron P Vaughn
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Christopher Staley
- Division of Basic and Translational Research, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA
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Liu Z, Wang M, Hu Y, Li J, Gong W, Guo X, Song S, Zhu B. Ulva lactuca polysaccharides combined with fecal microbiota transplantation ameliorated dextran sodium sulfate-induced colitis in C57BL/6J mice. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2025; 105:422-432. [PMID: 39212113 DOI: 10.1002/jsfa.13839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/26/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) of healthy donors improves ulcerative colitis (UC) patients by restoring the balance of the gut microbiota. However, donors vary in microbial diversity and composition, often resulting in weak or even ineffective FMT. Improving the efficacy of FMT through combination treatment has become a promising strategy. Ulva lactuca polysaccharides (ULP) have been found to benefit host health by regulating gut microbiota. The effect of the combination of ULP and FMT in ameliorating UC has not yet been evaluated. RESULTS The present study found that supplementation with ULP combined with FMT showed better effects in ameliorating UC than supplementation with FMT alone. Results suggested that FMT or ULP combined with FMT alleviated the symptoms of UC in mice, as evidenced by prevention of body weight loss, improvement of disease activity index and protection of the intestinal mucus. Notably, ULP in combination with FMT was more effective than FMT in reducing levels of cytokines and related inflammatory enzymes. In addition, ULP combined with FMT effectively restored the dysbiosis induced by dextran sulfate sodium (DSS) and further enriched probiotics (such as Bifidobacterium). The production of short-chain fatty acids, especially acetic acid, was also significantly enriched by ULP combined with FMT. CONCLUSION Supplementation of ULP combined with FMT could significantly ameliorate DSS-induced colitis in mice by inhibiting inflammation and restoring dysbiosis of gut microbiota. These results suggested that ULP combined with FMT has potential application in ameliorating UC. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Zhengqi Liu
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
- National Engineering Research Center of Seafood, National and Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, School of Food Science and Technology, Dalian Polytechnic University, Dalian, PR China
| | - Menghui Wang
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Yuanyuan Hu
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Jinjin Li
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Wei Gong
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Xiaoming Guo
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
| | - Shuang Song
- National Engineering Research Center of Seafood, National and Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, School of Food Science and Technology, Dalian Polytechnic University, Dalian, PR China
| | - Beiwei Zhu
- Shenzhen Key Laboratory of Food Nutrition and Health, College of Chemistry and Environmental Engineering, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, PR China
- National Engineering Research Center of Seafood, National and Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, School of Food Science and Technology, Dalian Polytechnic University, Dalian, PR China
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Jangi S, Zhao N, Hsia K, Park YS, Michaud DS, Yoon H. Specific Bacterial Co-abundance Groups Are Associated With Inflammatory Status in Patients With Ulcerative Colitis. J Crohns Colitis 2025; 19:jjae125. [PMID: 39126385 PMCID: PMC11725523 DOI: 10.1093/ecco-jcc/jjae125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Indexed: 08/12/2024]
Abstract
BACKGROUND AND AIMS While there is increasing interest in microbiome-directed therapies for patients with ulcerative colitis (UC), the identification of microbial targets remains elusive, underlining the need for novel approaches. METHODS Utilizing metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation, we used a tree-based dichotomous approach to assemble distinct clusters of species-level bacterial co-abundance groups (CAGs). We evaluated the abundance of bacterial CAGs and fungal taxa during remission (n = 166) and activity (n = 46). We examined if the bacterial CAGs identified in our cohorts were conserved in 2 healthy cohorts and a Korean UC cohort. RESULTS CAG3 and CAG8, dominated by bacteria from the family Lachnospiraceae, were associated with remission. Low abundance of CAG8 and elevated abundance of Candida genus were predictive of active UC. Constituents from CAG8 were influential hub species of the remission-associated microbial UC network, including Ruminococcus gnavus, Erysipelatoclostridium ramosum, Blautia, and Dorea species. These hub species interactions were preserved in 2 healthy cohorts and were partially recapitulated in a Korean UC cohort. CAG8 abundance correlated with the secondary bile acid production pathway. Bacterial CAGs did not correlate with Candida; however, Bifidobacterium adolescentis and Alistipes putredinis were negatively associated with Candida. CONCLUSIONS Lachnospiraceae-dominated bacterial CAGs were associated with remission in UC, with key bacterial interactions within the CAG also observed in 2 healthy cohorts and a Korean UC cohort. Bacterial CAG-based analyses may aid in designing candidate consortia for microbiome-based therapeutics.
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Affiliation(s)
- Sushrut Jangi
- Department of Medicine, Tufts Medical Center, Boston, MA, USA
| | - Naisi Zhao
- Tufts University School of Medicine, Public Health and Community Medicine, Boston, MA, USA
| | - Katie Hsia
- Department of Medicine, Tufts Medical Center, Boston, MA, USA
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Dominique S Michaud
- Tufts University School of Medicine, Public Health and Community Medicine, Boston, MA, USA
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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Shang J, Del Valle DM, Britton GJ, Mead K, Rajpal U, Chen-Liaw A, Mogno I, Li Z, Menon R, Gonzalez-Kozlova E, Elkrief A, Peled JU, Gonsalves TR, Shah NJ, Postow M, Colombel JF, Gnjatic S, Faleck DM, Faith JJ. Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis. J Exp Med 2025; 222:e20232079. [PMID: 39666007 PMCID: PMC11636624 DOI: 10.1084/jem.20232079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 09/17/2024] [Accepted: 11/21/2024] [Indexed: 12/13/2024] Open
Abstract
Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort. Leveraging a preclinical mouse model, predisease stools from irC subjects induced greater colitigenicity upon transfer to mice. The microbiota during the first 10 days of irC closely resembled inflammatory bowel disease microbiomes, with reduced diversity, increased Proteobacteria and Veillonella, and decreased Faecalibacterium, which normalized before irC remission. These findings highlight the irC gut microbiota as functionally distinct but phylogenetically similar to non-irC and healthy microbiomes, with the exception of an acute, transient disruption early in irC. We underscore the significance of longitudinal microbiome profiling in developing clinical avenues to detect, monitor, and mitigate irC in ICI therapy cancer patients.
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Affiliation(s)
- Joan Shang
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Diane Marie Del Valle
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Graham J. Britton
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - K.R. Mead
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Urvija Rajpal
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alice Chen-Liaw
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ilaria Mogno
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Zhihua Li
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Edgar Gonzalez-Kozlova
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Arielle Elkrief
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jonathan U. Peled
- Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Tina Ruth Gonsalves
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Neil J. Shah
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Michael Postow
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sacha Gnjatic
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - David M. Faleck
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Jeremiah J. Faith
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Hemachandra S, Rathnayake SN, Jayamaha AA, Francis BS, Welmillage D, Kaur DN, Zaw HK, Zaw LT, Chandra HA, Abeysekera ME. Fecal Microbiota Transplantation as an Alternative Method in the Treatment of Obesity. Cureus 2025; 17:e76858. [PMID: 39901991 PMCID: PMC11788455 DOI: 10.7759/cureus.76858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/03/2025] [Indexed: 02/05/2025] Open
Abstract
Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for various health conditions, particularly obesity and metabolic disorders. This review examines the mechanisms underlying FMT, including its role in restoring gut microbiota diversity and enhancing immunomodulatory functions, which are essential for maintaining overall health. Recent studies indicate that FMT can significantly improve body weight and metabolic parameters, suggesting its potential as an alternative or complementary treatment to current obesity therapies. However, the effectiveness of FMT depends on several factors, including the composition of the donor microbiota, recipient characteristics, and concomitant medications or dietary interventions. Despite its great promise, challenges such as standardized protocols, donor screening, and the need for a deeper understanding of gut microbiota dynamics remain key hurdles. Future research should focus on elucidating the specific microbial compositions necessary for optimal therapeutic outcomes and exploring personalized FMT approaches tailored to individual patient profiles. This evolving field presents exciting opportunities for innovative strategies in obesity treatment, warranting further investigation and clinical application.
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Affiliation(s)
| | | | | | | | | | | | - Hein K Zaw
- Gastroenterology, Nanjing Medical University, Nanjing, CHN
| | - Lin T Zaw
- Gastroenterology, Nanjing Medical University, Nanjing, CHN
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Saha S, Schnabl B. Modulating the microbiome in chronic liver diseases - current evidence on the role of fecal microbiota transplantation. Expert Rev Gastroenterol Hepatol 2025; 19:53-64. [PMID: 39760535 PMCID: PMC11882407 DOI: 10.1080/17474124.2025.2450707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 12/23/2024] [Accepted: 01/04/2025] [Indexed: 01/07/2025]
Abstract
INTRODUCTION The gut microbiota has a complex relationship with the human host and is key to maintaining health. Disruption of the healthy diverse gut microbial milieu plays an important role in the pathogenesis of several diseases including Clostridioides difficile infection (CDI), inflammatory bowel disease, irritable bowel syndrome, alcohol-related liver disease and metabolic-dysfunction associated steatotic liver disease (MASLD). Fecal microbiota transplantation (FMT) is highly effective in treating CDI, though its utility in other diseases is still being explored. AREAS COVERED In this narrative review, we explore the role of gut microbiota in liver diseases, focusing on key changes in the microbial composition and function. We summarize current evidence on the role of FMT, identifying gaps in current research and outlining future directions for investigation. We comprehensively searched PubMed through 15 October 2024 to identify relevant studies. EXPERT OPINION While data from available studies shows promise, more research is necessary before we can use FMT for liver diseases. Key areas that require further study are - determining the optimal FMT regimen for each disease, establishing efficacy and safety with larger clinical trials, ensuring safe and equitable access to the FMT product and mechanistic insights into the reasons for success or failure of FMT.
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Affiliation(s)
- Srishti Saha
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of California San Diego, San Diego, CA
| | - Bernd Schnabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of California San Diego, San Diego, CA
- Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA
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46
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Deraison C, Vergnolle N. Pharmacology of Intestinal Inflammation and Repair. Annu Rev Pharmacol Toxicol 2025; 65:301-314. [PMID: 39847467 DOI: 10.1146/annurev-pharmtox-051921-084536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2025]
Abstract
Chronic inflammation is a common trait in the pathogenesis of several diseases of the gut, including inflammatory bowel disease and celiac disease. Control of the inflammatory response is crucial in these pathologies to avoid tissue destruction and loss of intestinal function. Over the last 50 years, the identification of the mechanisms and mediators involved in the acute phase of the inflammatory response, which is characterized by massive leukocyte recruitment, has led to a number of therapeutic options. New drugs targeting inflammatory flares are still under development. However, interest on the other end of the spectrum-the resolution and repair phases-has emerged, as promoting tissue functional repair may maintain remission and counteract the chronicity of the disease. This review aims to discuss the current and future pharmacological approaches to the treatment of chronic intestinal inflammation and the restoration of functional tissues.
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Affiliation(s)
- Céline Deraison
- Institute of Digestive Health Research (IRSD), Toulouse University, INSERM 1022, INRAe, ENVT, University of Toulouse III Paul Sabatier, Toulouse, France;
| | - Nathalie Vergnolle
- Institute of Digestive Health Research (IRSD), Toulouse University, INSERM 1022, INRAe, ENVT, University of Toulouse III Paul Sabatier, Toulouse, France;
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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Zhang T, Li X, Li J, Sun F, Duan L. Gut microbiome-targeted therapies as adjuvant treatments in inflammatory bowel diseases: a systematic review and network meta-analysis. J Gastroenterol Hepatol 2025; 40:78-88. [PMID: 39482823 DOI: 10.1111/jgh.16795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 09/10/2024] [Accepted: 10/15/2024] [Indexed: 11/03/2024]
Abstract
BACKGROUND AND AIM Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD). METHODS We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values. RESULTS Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD. CONCLUSIONS FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.
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Affiliation(s)
- Tao Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xiaoang Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Jun Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Feng Sun
- China Center for Evidence Based Medical and Clinical Research, Peking University, Beijing, China
- Institute of Public Health, Peking University, Beijing, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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48
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Sin HCL, Haifer C. Faecal transplantation: the good, the bad and the ugly. Intern Med J 2025; 55:35-40. [PMID: 39629909 DOI: 10.1111/imj.16559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 10/13/2024] [Indexed: 01/18/2025]
Abstract
There continues to be significant interest from both clinicians and patients in using faecal transplantation, as the integral role of the gut microbiome is increasingly recognised in various disease conditions, both within and beyond the gut. This Clinical Perspectives article provides an overview of existing literature, factors limiting the use of faecal microbial transplantation in clinical practice and exciting new advancements on the horizon.
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Affiliation(s)
- Hiu C L Sin
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney, New South Wales, Australia
| | - Craig Haifer
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney, New South Wales, Australia
- School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
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49
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Chasov V, Gilyazova E, Ganeeva I, Zmievskaya E, Davletshin D, Valiullina A, Bulatov E. Gut Microbiota Modulation: A Novel Strategy for Rheumatoid Arthritis Therapy. Biomolecules 2024; 14:1653. [PMID: 39766360 PMCID: PMC11674688 DOI: 10.3390/biom14121653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 12/14/2024] [Accepted: 12/20/2024] [Indexed: 01/11/2025] Open
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint inflammation, progressive tissue damage and significant disability, severely impacting patients' quality of life. While the exact mechanisms underlying RA remain elusive, growing evidence suggests a strong link between intestinal microbiota dysbiosis and the disease's development and progression. Differences in microbial composition between healthy individuals and RA patients point to the role of gut microbiota in modulating immune responses and promoting inflammation. Therapies targeting microbiota restoration have demonstrated promise in improving treatment efficacy, enhancing patient outcomes and slowing disease progression. However, the complex interplay between gut microbiota and autoimmune pathways in RA requires further investigation to establish causative relationships and mechanisms. Here, we review the current understanding of the gut microbiota's role in RA pathogenesis and its potential as a therapeutic target.
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Affiliation(s)
- Vitaly Chasov
- Laboratory of Biomedical Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia (I.G.)
| | - Elvina Gilyazova
- Laboratory of Biomedical Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia (I.G.)
| | - Irina Ganeeva
- Laboratory of Biomedical Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia (I.G.)
| | - Ekaterina Zmievskaya
- Laboratory of Biomedical Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia (I.G.)
| | - Damir Davletshin
- Laboratory of Biomedical Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia (I.G.)
| | - Aygul Valiullina
- Laboratory of Biomedical Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia (I.G.)
| | - Emil Bulatov
- Laboratory of Biomedical Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia (I.G.)
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia
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50
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Dong D, Wang H, Bi H, Li Y, Gao T, Feng J, Li G, Guo S, Yuan H, Ni W. A pectic polysaccharide from Lycium ruthenicum Murray alleviates dextran sulfate sodium-induced colitis in mice. Curr Res Food Sci 2024; 10:100955. [PMID: 39807359 PMCID: PMC11728900 DOI: 10.1016/j.crfs.2024.100955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/03/2024] [Accepted: 12/10/2024] [Indexed: 01/16/2025] Open
Abstract
Inflammatory bowel disorders (IBD) can lead to severe complications like perforation, bleeding, and colon cancer, posing life-threatening risks. Lycium ruthenicum Murray (L. ruthenicum Murr.), rich in polysaccharides, has been utilized in traditional diets for thousands of years. This study explores the protective effects of the polysaccharide of L. ruthenicum on mice with dextran sulfate sodium (DSS)-induced colitis. In the present study, a pectic polysaccharide (LRWP-Ap) containing arabinogalactan (AG) and homogalacturonic acid (HG) structural domains with a Mw of 4.34 kDa was obtained from L. ruthenicum Murr. Fruit. The gavage administration of LRWP-Ap significantly alleviated symptoms of DSS-induced colitis in mice. In this process, LRWP-Ap modulated the balance of Arg-1/iNOS to regulate the metabolism of arginine, and the levels of intestinal tight junction (TJ) (ZO-1, Occludin, and Claudin 1) were increased by LRWP-Ap treatment, which promoted intestinal barrier function. In addition, LRWP-Ap alleviated the inflammatory response while increasing the anti-inflammatory response by reducing the level of proinflammatory factors, enhancing the level of anti-inflammatory factors (IL-10) and improving the balance of Treg/Th17 cells. These effects resulted in the maintenance of intestinal immune homeostasis. Moreover, LRWP-Ap modulated the gut microbiota composition and short-chain fatty acid (SCFA) content, which may maintain relatively favorable intestinal homeostasis. In general, LRWP-Ap has the potential to alleviate IBD, and the use of L. ruthenicum Murr. As a natural functional food to improve gut health in the context of DSS-induced colitis.
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Affiliation(s)
- Dai Dong
- Department of Immunology, College of Basic Medical Sciences, Jilin University, 126 Xin min Street, Changchun, 130021, China
| | - Hailiang Wang
- The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130033, China
| | - Hongtao Bi
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, CAS, 23 Xinning Road, Xining, 810008, China
| | - Yu Li
- Department of Immunology, College of Basic Medical Sciences, Jilin University, 126 Xin min Street, Changchun, 130021, China
| | - Tingting Gao
- School of Psychology, Chengdu Medical College, 783 Xindu Road, Chengdu, 610500, China
| | - Jingyue Feng
- Department of Immunology, College of Basic Medical Sciences, Jilin University, 126 Xin min Street, Changchun, 130021, China
| | - Guoqiang Li
- Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, CAS, 23 Xinning Road, Xining, 810008, China
| | - Shiqi Guo
- The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130033, China
| | - Hongyan Yuan
- Department of Immunology, College of Basic Medical Sciences, Jilin University, 126 Xin min Street, Changchun, 130021, China
| | - Weihua Ni
- Department of Immunology, College of Basic Medical Sciences, Jilin University, 126 Xin min Street, Changchun, 130021, China
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