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Takyi E, Nirmalkar K, Adams J, Krajmalnik-Brown R. Interventions targeting the gut microbiota and their possible effect on gastrointestinal and neurobehavioral symptoms in autism spectrum disorder. Gut Microbes 2025; 17:2499580. [PMID: 40376856 PMCID: PMC12087657 DOI: 10.1080/19490976.2025.2499580] [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: 08/25/2024] [Revised: 04/22/2025] [Accepted: 04/24/2025] [Indexed: 05/18/2025] Open
Abstract
Autism spectrum disorder (ASD) is a developmental disorder that is characterized by deficits in social communication and restricted, repetitive, and stereotyped behaviors. In addition to neurobehavioral symptoms, children with ASD often have gastrointestinal symptoms (e.g. constipation, diarrhea, gas, abdominal pain, reflux). Several studies have proposed the role of gut microbiota and metabolic disorders in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients; these results offer promising avenues for novel treatments of this disorder. Interventions targeting the gut microbiota - such as fecal microbiota transplant (FMT), microbiota transplant therapy (MTT), probiotics, prebiotics, synbiotics, antibiotics, antifungals, and diet - promise to improve gut health and can potentially improve neurological symptoms. The modulation of the gut microbiota using MTT in ASD has shown beneficial and long-term effects on GI symptoms and core symptoms of autism. Also, the modulation of the gut microbiota to resemble that of typically developing individuals seems to be the most promising intervention. As most of the studies carried out with MTT are open-label studies, more extensive double-blinded randomized control trials are needed to confirm the efficacy of MTT as a therapeutic option for ASD. This review examines the current clinical research evidence for the use of interventions that target the microbiome - such as antibiotics, antifungals, probiotics/prebiotics, synbiotics, and MTT - and their effectiveness in changing the gut microbiota and improving gastrointestinal and neurobehavioral symptoms in ASD.
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Affiliation(s)
- Evelyn Takyi
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
| | - Khemlal Nirmalkar
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
| | - James Adams
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
- School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, USA
| | - Rosa Krajmalnik-Brown
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, USA
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Wang X, Liu Y, Chang H, Tun HM, Xia X, Peng Y, Qin N. Goat Milk-Derived Extracellular Vesicles Alleviate Colitis Potentially Through Improved Gut Microbiota in Mice. Foods 2025; 14:1514. [PMID: 40361597 PMCID: PMC12071645 DOI: 10.3390/foods14091514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/18/2025] [Accepted: 04/21/2025] [Indexed: 05/15/2025] Open
Abstract
Ulcerative colitis (UC) is characterized clinically by intestinal inflammation and gut microbiota dysbiosis. The consumption of biologics, although effective in inflammation control, may lead to adverse effects and is inconvenient for at-home administration. Goat milk-derived extracellular vesicles (GMEVs) have been proposed as a supplement to prevent intestinal inflammation. However, their therapeutic potential for colitis remains elusive. This study aimed to explore the preventive effect of GMEVs on colitis and its underlying mechanisms through the microbiota-immune axis using a dextran sodium sulfate (DSS)-induced colitis mouse model. We found that a pre-treatment of 20 mg/kg/d GMEVs effectively prevented body weight loss, colon shortening, the depletion of colonic goblet cells, and the disappearance of crypts, while enhancing the intestinal mucosal barrier. Consistent with these phenotypes, GMEV pre-treatment increased levels of IL-22 and IL-10 and decreased levels of IL-1β, TNF-α, IL-6, and iNOS. However, GMEVs themselves had no effect on normal mice. Paralleling the alleviation of intestinal inflammation, GMEV pre-treatment also restored the reduction in unclassified Muribaculaceae, Dubosiella, and Lactobacillus and suppressed the expansion of Alistipes and Proteobacteria following DSS treatment. Additionally, GMEV intake significantly downregulated the expression of proteins in the NF-κB signaling pathway induced by DSS. In summary, GMEVs could prevent colitis by regulating intestinal inflammation, the intestinal mucosal barrier, gut microbiota, organ damage, and the immune microenvironment. This study demonstrated that GMEVs have potential application prospects for UC prevention.
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Affiliation(s)
- Xinru Wang
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Yi Liu
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Hong Chang
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Hein-Min Tun
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China
- Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Xiaodong Xia
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Ye Peng
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
- Microbiota I-Center (MagIC), Hong Kong SAR 999077, China
- Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
| | - Ningbo Qin
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, 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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Allegretti JR, Khanna S, Mullish BH, Feuerstadt P. The Progression of Microbiome Therapeutics for the Management of Gastrointestinal Diseases and Beyond. Gastroenterology 2024; 167:885-902. [PMID: 38754739 DOI: 10.1053/j.gastro.2024.05.004] [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: 12/01/2023] [Revised: 05/02/2024] [Accepted: 05/09/2024] [Indexed: 05/18/2024]
Abstract
There has been an increased ability to investigate the human microbiota through next-generation sequencing and functional assessment. This advancement has rapidly expanded our ability to study and manipulate the gastrointestinal microbiome to mitigate disease. Fecal microbiota transplantation, a therapy that broadly transfers the entire intestinal ecosystem, has been explored as a potential therapeutic in a variety of gastrointestinal, hepatic, and extraintestinal conditions. The field, however, continues to evolve, with a movement toward precision microbiome therapeutics, individualizing care for various disorders. This review will describe the use of fecal microbiota transplantation, microbiota restoration, and precision microbiome therapeutics, focusing on gastrointestinal and hepatic diseases.
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Affiliation(s)
- Jessica R Allegretti
- Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Sahil Khanna
- Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota
| | - Benjamin H Mullish
- Division of Digestive Diseases, Imperial College London, London, United Kingdom; Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom
| | - Paul Feuerstadt
- Division of Gastroenterology, Yale University School of Medicine, New Haven, Connecticut
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Allegretti JR, Axelrad J, Dalal RS, Kelly CR, Grinspan A, Fischer M. Outcomes After Fecal Microbiota Transplantation in Combination With Bezlotoxumab for Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection. Am J Gastroenterol 2024; 119:1433-1436. [PMID: 38501667 DOI: 10.14309/ajg.0000000000002770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 03/06/2024] [Indexed: 03/20/2024]
Abstract
ABSTRACT Fecal microbiota transplantation (FMT) prevents recurrent Clostridioides difficile infections (rCDI) in patients with inflammatory bowel disease. Bezlotoxumab is also indicated to prevent rCDI. We assess the impact of FMT in combination with bezlotoxumab in patients with inflammatory bowel disease and rCDI. We conducted a multicenter randomized placebo-controlled trial. All received a single colonoscopic FMT. Patients were randomized 1:1 to receive bezlotoxumab or placebo. Sixty-one patients were enrolled (30 received treatment and 31 received placebo). Overall, 5 participants (8%) experienced a CDI recurrence; 4 in the treatment arm, 1 in the placebo arm (13% vs 3%, P = 0.15). There was no clear benefit to the combination approach compared with FMT alone.
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Affiliation(s)
- Jessica R Allegretti
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Jordan Axelrad
- Division of Gastroenterology, NYU Grossman School of Medicine, New York, New York, USA
| | - Rahul S Dalal
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Colleen R Kelly
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Ari Grinspan
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Monika Fischer
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Tariq R, Loftus EV, Pardi D, Khanna S. Durability and outcomes of fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with moderate to severe inflammatory bowel disease. Intest Res 2024; 22:208-212. [PMID: 38191281 PMCID: PMC11079512 DOI: 10.5217/ir.2023.00100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 09/25/2023] [Accepted: 11/01/2023] [Indexed: 01/10/2024] Open
Affiliation(s)
- Raseen Tariq
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Darrell Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Peery AF, Kelly CR, Kao D, Vaughn BP, Lebwohl B, Singh S, Imdad A, Altayar O. AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases. Gastroenterology 2024; 166:409-434. [PMID: 38395525 DOI: 10.1053/j.gastro.2024.01.008] [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] [Indexed: 02/25/2024]
Abstract
BACKGROUND & AIMS Fecal microbiota-based therapies include conventional fecal microbiota transplant and US Food and Drug Administration-approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota-based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome. METHODS The guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of fecal microbiota-based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice. RESULTS The guideline panel made 7 recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of fecal microbiota-based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional fecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any fecal microbiota-based therapies to prevent recurrent C difficile. In adults hospitalized with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional fecal microbiota transplant. The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials. CONCLUSIONS Fecal microbiota-based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.
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Affiliation(s)
- Anne F Peery
- University of North Carolina, Chapel Hill, North Carolina
| | - Colleen R Kelly
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Dina Kao
- University of Alberta, Edmonton, Alberta, Canada
| | | | | | | | | | - Osama Altayar
- Washington University School of Medicine, St Louis, Missouri
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McMillan AS, Theriot CM. Bile acids impact the microbiota, host, and C. difficile dynamics providing insight into mechanisms of efficacy of FMTs and microbiota-focused therapeutics. Gut Microbes 2024; 16:2393766. [PMID: 39224076 PMCID: PMC11376424 DOI: 10.1080/19490976.2024.2393766] [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: 03/27/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/04/2024] Open
Abstract
Clostridioides difficile is a major nosocomial pathogen, causing significant morbidity and mortality worldwide. Antibiotic usage, a major risk factor for Clostridioides difficile infection (CDI), disrupts the gut microbiota, allowing C. difficile to proliferate and cause infection, and can often lead to recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as effective treatments for rCDI and aim to restore colonization resistance provided by a healthy gut microbiota. However, much is still unknown about the mechanisms mediating their success. Bile acids, extensively modified by gut microbes, affect C. difficile's germination, growth, and toxin production while also shaping the gut microbiota and influencing host immune responses. Additionally, microbial interactions, such as nutrient competition and cross-feeding, contribute to colonization resistance against C. difficile and may contribute to the success of microbiota-focused therapeutics. Bile acids as well as other microbial mediated interactions could have implications for other diseases being treated with microbiota-focused therapeutics. This review focuses on the intricate interplay between bile acid modifications, microbial ecology, and host responses with a focus on C. difficile, hoping to shed light on how to move forward with the development of new microbiota mediated therapeutic strategies to combat rCDI and other intestinal diseases.
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Affiliation(s)
- Arthur S. McMillan
- Genetics Program, Department of Biological Sciences, College of Science, North Carolina State University, Raleigh, NC, USA
- Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
| | - Casey M. Theriot
- Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
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Ghani R, Chrysostomou D, Roberts LA, Pandiaraja M, Marchesi JR, Mullish BH. Faecal (or intestinal) microbiota transplant: a tool for repairing the gut microbiome. Gut Microbes 2024; 16:2423026. [PMID: 39499189 PMCID: PMC11540080 DOI: 10.1080/19490976.2024.2423026] [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: 09/03/2024] [Revised: 10/21/2024] [Accepted: 10/24/2024] [Indexed: 11/07/2024] Open
Abstract
Faecal/intestinal microbiota transplant (FMT/IMT) is an efficacious treatment option for recurrent Clostridioides difficile infection, which has prompted substantial interest in FMT's potential role in the management of a much broader range of diseases associated with the gut microbiome. Despite its promise, the success rates of FMT in these other settings have been variable. This review critically evaluates the current evidence on the impact of clinical, biological, and procedural factors upon the therapeutic efficacy of FMT, and identifies areas that remain nebulous. Due to some of these factors, the optimal therapeutic approach remains unclear; for example, the preferred timing of FMT administration in a heavily antibiotic-exposed hematopoietic cell transplant recipient is not standardized, with arguments that can be made in alternate directions. We explore how these factors may impact upon more informed selection of donors, potential matching of donors to recipients, and aspects of clinical care of FMT recipients. This includes consideration of how gut microbiome composition and functionality may strategically inform donor selection criteria. Furthermore, we review how the most productive advances within the FMT space are those where clinical and translational outcomes are assessed together, and where this model has been used productively in recent years to better understand the contribution of the gut microbiome to human disease, and start the process toward development of more targeted microbiome therapeutics.
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Affiliation(s)
- Rohma Ghani
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
- Department of Infectious Diseases, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Despoina Chrysostomou
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Lauren A Roberts
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Madhumitha Pandiaraja
- Department of Gastroenterology, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Julian R. Marchesi
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Benjamin H. Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
- Department of Hepatology, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK
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10
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Kelly CR, Allegretti JR. Review Article: Gastroenterology and Clostridium difficile Infection: Past, Present, and Future. Clin Infect Dis 2023; 77:S463-S470. [PMID: 38051967 DOI: 10.1093/cid/ciad644] [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: 12/07/2023] Open
Abstract
Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.
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Affiliation(s)
- Colleen R Kelly
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Jessica R Allegretti
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
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Porcari S, Baunwall SMD, Occhionero AS, Ingrosso MR, Ford AC, Hvas CL, Gasbarrini A, Cammarota G, Ianiro G. Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: A systematic review and meta-analysis. J Autoimmun 2023; 141:103036. [PMID: 37098448 DOI: 10.1016/j.jaut.2023.103036] [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: 01/17/2023] [Revised: 03/26/2023] [Accepted: 04/04/2023] [Indexed: 04/27/2023]
Abstract
Fecal microbiota transplantation (FMT) is known to be highly effective in patients with recurrent Clostridioides difficile infection (rCDI), but its role in patients who also suffer from inflammatory bowel disease (IBD) is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT for the treatment of rCDI in patients with IBD. We searched the available literature until November 22, 2022 to identify studies that included patients with IBD treated with FMT for rCDI, reporting efficacy outcomes after at least 8 weeks of follow-up. The proportional effect of FMT was summarized with a generalized linear mixed-effect model fitting a logistic regression accounting for different intercepts among studies. We identified 15 eligible studies, containing 777 patients. Overall, FMT achieved high cure rates of rCDI, 81% for single FMT, based on all included studies and patients, and 92% for overall FMT, based on nine studies with 354 patients, respectively. We found a significant advantage of overall FMT over single FMT in improving cure rates of rCDI (from 80% to 92%, p = 0.0015). Serious adverse events were observed in 91 patients (12% of the overall population), with the most common being hospitalisation, IBD-related surgery, or IBD flare. In conclusion, in our meta-analysis FMT achieved high cure rates of rCDI in patients with IBD, with a significant advantage of overall FMT over single FMT, similar to data observed in patients without IBD. Our findings support the use of FMT as a treatment for rCDI in patients with IBD.
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Affiliation(s)
- Serena Porcari
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Annamaria Sara Occhionero
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Rosa Ingrosso
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alexander Charles Ford
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Ianiro
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
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Porcari S, Severino A, Rondinella D, Bibbò S, Quaranta G, Masucci L, Maida M, Scaldaferri F, Sanguinetti M, Gasbarrini A, Cammarota G, Ianiro G. Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis. J Autoimmun 2023; 141:103033. [PMID: 37085337 DOI: 10.1016/j.jaut.2023.103033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 03/05/2023] [Accepted: 03/17/2023] [Indexed: 04/23/2023]
Abstract
AIMS Clostridioides difficile infection (CDI) is a major challenge for healthcare systems. Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a risk factor for primary and recurrent CDI (rCDI). Moreover, CDI itself often worsens the clinical picture of IBD, increasing the risk of complications. Fecal microbiota transplantation (FMT) is a highly effective treatment for rCDI, but data from patients with IBD and CDI are limited and often referred to mixed cohorts. We aimed to report outcomes from a cohort of patients with UC treated with FMT for rCDI superinfection. METHODS AND RESULTS In a retrospective, single-centre cohort study we evaluated characteristics and outcomes of patients with UC who received FMT for rCDI. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Thirty-five patients were included in the analysis. Sixteen patients were cured after single FMT, while 19 patients received repeat FMT. Overall, FMT cured rCDI in 32 patients (91%), and repeat FMT was significantly associated with sustained cure of CDI compared with single FMT (84% vs 50%, p = 0.018). Twenty-four patients (69%) experienced remission or an amelioration of UC activity. Serious adverse events were not observed. CONCLUSIONS In our cohort of patients with UC, FMT was highly effective in curing rCDI without severe adverse events and repeat FMT was significantly associated with CDI cure. Most patients also experienced remission or amelioration of UC activity after FMT. Our findings suggest that a sequential FMT protocol may be used routinely in patients with UC and rCDI.
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Affiliation(s)
- Serena Porcari
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Severino
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Debora Rondinella
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Stefano Bibbò
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Quaranta
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Luca Masucci
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Marcello Maida
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital, Caltanissetta, Italy
| | - Franco Scaldaferri
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maurizio Sanguinetti
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
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Reasoner SA, Nicholson MR. Clostridioides difficile Infection in Pediatric Inflammatory Bowel Disease. Curr Gastroenterol Rep 2023; 25:316-322. [PMID: 37646895 PMCID: PMC10843265 DOI: 10.1007/s11894-023-00890-9] [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] [Accepted: 08/17/2023] [Indexed: 09/01/2023]
Abstract
PURPOSE OF REVIEW Children with inflammatory bowel disease (IBD) are at increased risk of C. difficile infection (CDI) and experience worse outcomes associated with an infection. In this article, we review recent research on the incidence, diagnosis, complications, and treatment options for CDI in children with IBD. RECENT FINDINGS Children with IBD have an elevated incidence of CDI, but their CDI risk does not associate with established risk factors in adults with IBD. Existing testing methodologies are inadequate at differentiating CDI from C. difficile colonization in children with IBD. Fecal microbiota transplantation offers a durable cure for recurrent CDI. CDI remains a frequent occurrence in children with IBD. Careful clinical monitoring should be used to diagnose CDI and patients with co-occurring IBD and CDI require careful surveillance for worse outcomes. Future research should explore the optimal diagnosis and treatment modalities in this unique patient population.
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Affiliation(s)
- Seth A Reasoner
- Division of Molecular Pathogenesis, Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Maribeth R Nicholson
- Immunology & Inflammation (VI4), Vanderbilt Institute for Infection, Vanderbilt University Medical Center, Nashville, TN, USA.
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Monroe Carrell Junior Children's Hospital at Vanderbilt, Nashville, TN, USA.
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Wu X, Ai RJ, Xu J, Wen Q, Pan HQ, Zhang ZH, Ning W, Fang Y, Ding DF, Wang Q, Han S, Liu X, Wu M, Jia ZY, Jia S, Lin T, Cui BT, Nie YZ, Wang X, Zhang FM. Washed microbiota transplantation for Clostridioides difficile infection: A national multicenter real-world study. J Dig Dis 2023; 24:540-549. [PMID: 37681235 DOI: 10.1111/1751-2980.13227] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 08/21/2023] [Accepted: 09/06/2023] [Indexed: 09/09/2023]
Abstract
OBJECTIVES Fecal microbiota transplantation (FMT) has been recommended for the treatment of recurrent Clostridioides difficile infection (CDI). We aimed to evaluate the therapeutic efficacy and safety of washed microbiota transplantation (WMT), a new method of FMT, for CDI across various medical settings. METHODS This multicenter real-world cohort study included CDI patients undergoing WMT. The primary outcome was the clinical cure rate of CDI within 8 weeks after WMT. Secondary outcomes included the CDI recurrence rate and reduction in total abdominal symptom score (TASS) during the follow-up period. Adverse events related to WMT were recorded. RESULTS Altogether 90.7% (49/54) of CDI patients achieved clinical cure after treated with WMT. The cure rate was 83.3% for cases with severe and complicated CDI (ScCDI) (n = 30) and 100% for non-ScCDI cases (n = 24) (P = 0.059). No difference was observed in the clinical cure rate between patients with first and recurrent CDI (91.9% vs 88.2%, P = 0.645). One week post-WMT, TASS showed a remarkable decrease compared to that at baseline (P < 0.001). Totally, 8.2% (4/49) of patients suffered CDI recurrence during the follow-up period. A WHO performance score of 4, age ≥65 years, higher TASS score, and higher Charlson comorbidity index score were potential risk factors for efficacy (P = 0.018, 0.03, 0.01, 0.034, respectively). Four (3.8%) transient adverse events related to WMT were observed. CONCLUSIONS This study emphasizes the attractive value of WMT for CDI. Early WMT may be recommended for CDI, especially for those in serious condition or with complex comorbidities. TRIAL REGISTRATION ClinicalTrials.gov, no. NCT03895593 (registered on 27 March 2019).
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Affiliation(s)
- Xia Wu
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Ru Jun Ai
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Jie Xu
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Quan Wen
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Hua Qin Pan
- Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Zhi Hua Zhang
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Wang Ning
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
| | - Ying Fang
- Department of Gastroenterology, The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Da Fa Ding
- Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Quan Wang
- Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Shuang Han
- Department of Gastroenterology, Honghui Hospital, Xi'an, Shaanxi Province, China
| | - Xiao Liu
- Department of Gastroenterology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi Province, China
| | - Mei Wu
- Department of Gastroenterology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China
| | - Zhen Yu Jia
- Department of General Practice, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Song Jia
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Tao Lin
- Department of Gastroenterology, Xi'an Daxing Hospital, Xi'an, Shaanxi Province, China
| | - Bo Ta Cui
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yong Zhan Nie
- Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, China
- National Clinical Research Center for Digestive Diseases, Xi'an, Shaanxi Province, China
| | - Xin Wang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
- National Clinical Research Center for Digestive Diseases, Xi'an, Shaanxi Province, China
| | - Fa Ming Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu Province, China
- National Clinical Research Center for Digestive Diseases, Xi'an, Shaanxi Province, China
- Division of Microbiotherapy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
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15
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Rossier L, Matter C, Burri E, Galperine T, Hrúz P, Juillerat P, Schoepfer A, Vavricka SR, Zahnd N, Décosterd N, Seibold F. Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice. Swiss Med Wkly 2023; 153:40100. [PMID: 37769622 DOI: 10.57187/smw.2023.40100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023] Open
Abstract
INTRODUCTION Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT. METHODS A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre). RESULTS The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future.
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Affiliation(s)
- Laura Rossier
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| | - Christoph Matter
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| | - Emanuel Burri
- Department of Gastroenterology and Hepatology, University Medical Clinic, Baselland Canton Hospital, Liestal, Switzerland
| | - Tatiana Galperine
- Fecal microbiota transplantation center, Department of infectious disease, Lausanne University Hospital, Lausanne, Switzerland
| | - Petr Hrúz
- Clarunis, Department of Gastroenterology, St Clara hospital and University hospital Basel, Basel, Switzerland
| | - Pascal Juillerat
- GastroGeb - Gastroenterology practice and Crohn-colitis Center, Lausanne - Bulle, Switzerland
| | - Alain Schoepfer
- Department of Gastroenterology, Lausanne University Hospital, Lausanne, Switzerland
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | - Natalie Décosterd
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
| | - Frank Seibold
- Intesto - Gastroenterology practice and Crohn-colitis Center, Bern, Switzerland
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Abstract
PURPOSE OF REVIEW The chronic inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis, are associated with an increased risk of symptomatic Clostridium difficile infection (CDI). CDI may also masquerade as an IBD flare and complicate IBD management. This review provides a comprehensive overview of the epidemiology, diagnosis, and treatment of CDI in IBD patients. RECENT FINDINGS CDI remains common in IBD with complications including flares in disease activity, recurrent CDI episodes, and prolonged hospital stays. Newer IBD therapeutics including vedolizumab, ustekinumab, and tofacitinib are less likely to cause severe CDI. A high index of suspicion, rapid testing via a two-step method, and prompt treatment with vancomycin or fidaxomicin are paramount to managing CDI in IBD patients. Strategies to prevent recurrent CDI (rCDI) include the monoclonal antibody bezlotoxumab as well as fecal microbiota transplantation (FMT). FMT has a robust profile of safety and effectiveness in preventing rCDI in adults and children. SUMMARY Clinicians must remain vigilant in the prompt diagnosis and treatment of CDI in IBD patients. Corticosteroids, unnecessary antibiotics, and ongoing colonic inflammatory disease are modifiable risk factors. Improved infection control measures, newer IBD medications, and using effective CDI treatments will facilitate a reduced burden of severe CDI and complications for IBD patients.
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Affiliation(s)
- Tamara Alhobayb
- Inflammatory Bowel Diseases Center and Division of Gastroenterology, Washington University School of Medicine, Saint Louis, Missouri, USA
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17
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Tariq R, Syed T, Yadav D, Prokop LJ, Singh S, Loftus EV, Pardi DS, Khanna S. Outcomes of Fecal Microbiota Transplantation for C. difficile Infection in Inflammatory Bowel Disease : A Systematic Review and Meta-analysis. J Clin Gastroenterol 2023; 57:285-293. [PMID: 34864789 DOI: 10.1097/mcg.0000000000001633] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 10/10/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridioides difficile infection (CDI). Data on FMT for CDI in patients with underlying inflammatory bowel disease (IBD) are emerging but conflicting. We performed a systematic review and meta-analysis to describe the efficacy and safety of FMT for CDI in IBD and its impact on IBD outcomes. METHODS A systematic search of multiple databases including Embase, Scopus, and Web of Science was performed. Our primary analysis focused on pooled rate of CDI resolution after single and multiple FMTs in IBD patients. Additional analyses included rates of IBD-associated outcomes (flare, surgery, symptom improvement) after FMT. The random-effects model was used to calculate pooled rates. RESULTS Among 457 adult patients, 363 had CDI resolution after first FMT with a pooled cure rate of 78% [95% confidence interval (CI): 73%-83%; I2 =39%]. Overall pooled rate cure rate with single and multiple FMTs was 88% (95% CI: 81%-94%; I2 =73%). The pooled rate of an IBD flare after FMT was 26.8% (95% CI: 22.5%-31.6%; I2 =9%) and of colectomy was 7.3% (95% CI: 4.7%-10.5%; I2 =56%). Among 141 pediatric patients, 106 had CDI resolution after first FMT with pooled cure rate of 78% (95% CI: 58%-93%; I2 =59%). Overall pooled cure rate with single and multiple FMTs was 77% (95% CI: 50%-96%; I2 =63%). The pooled rate of an IBD flare after FMT was 10.8% (95% CI: 5.7%-18.5% I2 =43%), and of colectomy was 10.3% (95% CI: 2.1%-30.2% I2 =23%). CONCLUSIONS FMT appears to be a highly effective therapy for preventing recurrent CDI in patients with IBD. Patients who fail a single FMT may benefit from multiple FMTs.
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Affiliation(s)
- Raseen Tariq
- Division of Gastroenterology and Hepatology
- Department of Internal Medicine, Rochester General Hospital
| | - Tausif Syed
- Department of Internal Medicine, Unity Hospital, Rochester, NY
| | | | | | - Siddharth Singh
- Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, CA
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Gholam-Mostafaei FS, Azimirad M, Naseri K, Nabavi-Rad A, Asadzadeh Aghdaei H, Shahrokh S, Ebrahimi Daryani N, Yadegar A, Zali MR. Intestinal microbiota changes pre- and post-fecal microbiota transplantation for treatment of recurrent Clostridioides difficile infection among Iranian patients with concurrent inflammatory bowel disease. Front Microbiol 2023; 14:1147945. [PMID: 36910213 PMCID: PMC9998922 DOI: 10.3389/fmicb.2023.1147945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 02/08/2023] [Indexed: 02/26/2023] Open
Abstract
INTRODUCTION Patients with inflammatory bowel disease (IBD) are at a greater risk for the recurrence of Clostridioides difficile infection (rCDI) that is triggered by intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) has emerged as a highly effective therapeutic option for this complication. However, little is known about the impact of FMT on intestinal microbiota alterations in rCDI patients suffering from IBD. In this study, we aimed to investigate post-FMT intestinal microbiota alterations in Iranian rCDI patients with underlying IBD. METHODS A total of 21 fecal samples were collected including 14 samples pre- and post-FMT and 7 samples from healthy donors. Microbial analysis was performed by quantitative real-time PCR (RT-qPCR) assay targeting the 16S rRNA gene. The pre-FMT profile and composition of the fecal microbiota were compared to the microbial changes of samples collected 28 days after FMT. RESULTS AND DISCUSSION Overall, the fecal microbiota profile of recipients was more similar to donor samples after the transplantation. We observed a significant increase in the relative abundance of Bacteroidetes post-FMT, compared to the pre-FMT microbial profile. Furthermore, there were remarkable differences between the microbial profile of pre-FMT, post-FMT, and healthy donor samples by PCoA analysis based on the ordination distance. This study demonstrates FMT as a safe and effective approach to restore the indigenous composition of the intestinal microbiota in rCDI patients and ultimately results in the treatment of concurrent IBD.
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Affiliation(s)
- Fahimeh Sadat Gholam-Mostafaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kaveh Naseri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi Daryani
- Department of Gastroenterology and Hepatology, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Bloom PP, Young VB. Microbiome therapeutics for the treatment of recurrent Clostridioides difficile infection. Expert Opin Biol Ther 2023; 23:89-101. [PMID: 36536532 DOI: 10.1080/14712598.2022.2154600] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The gut microbiome is implicated in Clostridioides difficile infection (CDI) and recurrent CDI (rCDI). AREAS COVERED This review covers the mechanisms by which microbiome therapeutics treat rCDI, their efficacy and safety, and clinical trial design considerations for future research. EXPERT OPINION Altering the chemical environment of the gut and reconstituting colonization resistance is a promising strategy for preventing and treating rCDI. Fecal microbiota transplant (FMT) is safe and effective for the treatment of rCDI. However, limitations of FMT have prompted investigation into alternative microbiome therapeutics. These alternative microbiome therapies require further evaluation, and adaptive trial designs should be strongly considered to more rapidly discern variables including the need for bowel preparation, timing and selection of pre-treatment antibiotics, and dose and duration of microbiome therapeutics. A broad range of adverse events must be prospectively evaluated in these controlled trials, as microbiome therapeutics have the potential for numerous effects. Future studies will lead to a greater understanding of the mechanisms by which microbiome therapies can break the cycle of rCDI, which should ultimately yield a personalized approach to rCDI treatment that restores an individual's specific deficit(s) in colonization resistance to C. difficile.
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Affiliation(s)
- Patricia P Bloom
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, USA
| | - Vincent B Young
- Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, USA.,Department of Microbiology and Immunology, University of Michigan, USA
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20
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van Lingen EE, Baunwall SSMD, Lieberknecht SSC, Benech NN, Ianiro GG, Sokol HH, Gasbarrini AA, Cammarota GG, Eriksen MMK, van der Meulen-de Jong AAE, Terveer EEM, Verspaget HHW, Vehreschild MM, Hvas CCL, Keller JJJ. Short- and long-term follow-up after fecal microbiota transplantation as treatment for recurrent Clostridioides difficile infection in patients with inflammatory bowel disease. Therap Adv Gastroenterol 2023; 16:17562848231156285. [PMID: 36910163 PMCID: PMC9998411 DOI: 10.1177/17562848231156285] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 01/09/2023] [Indexed: 03/14/2023] Open
Abstract
Background Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity. Objectives We performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD. Design This is a multicentre cohort study conducted in five European FMT centres. Methods Adult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death. Results In total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48 years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784 days (402-1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2 years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72 years). Conclusion FMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT.
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Affiliation(s)
- Emilie E van Lingen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Albinusdreef 2, Leiden, ZA 2333, The Netherlands.,Netherlands Donor Feces Bank, LUMC, Leiden, The Netherlands
| | - Simon S M D Baunwall
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Simone S C Lieberknecht
- Department of Internal Medicine, Infectious Diseases, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Nicolas N Benech
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology département, F-75012 Paris, France
| | - Gianluca G Ianiro
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Harry H Sokol
- Gastroenterology Département, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Sorbonne Université, Paris, France.,Paris Center for Microbiome Médicine (PaCeMM) FHU, Paris, France.,French Group of Fecal Microbiota Transplantation (GFTF; www.gftf.f), Paris, France
| | - Alessandro A Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Giovanni G Cammarota
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Marcel M K Eriksen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Elizabeth E M Terveer
- Department of Medical Microbiology, LUMC, Leiden, The Netherlands.,Netherlands Donor Feces Bank, LUMC, Leiden, The Netherlands
| | - Hein H W Verspaget
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.,Netherlands Donor Feces Bank, LUMC, Leiden, The Netherlands
| | - Maria M Vehreschild
- Department of Internal Medicine, Infectious Diseases, Goethe University Frankfurt, Frankfurt am Main, Germany.,Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital Cologne, Partner site Bonn-Cologne, Cologne, Germany.,German Centre for Infection Research (DZIF), Partner site Bonn-Cologne, Cologne, Germany
| | - Christian C L Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Josbert J J Keller
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Albinusdreef 2, Leiden, ZA 2333, The Netherlands.,Department of Gastroenterology and Hepatology, Haaglanden Medical Center (HMC), The Hague, The Netherlands.,Netherlands Donor Feces Bank, LUMC, Leiden, The Netherlands
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21
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Caetano MAF, Castelucci P. Role of short chain fatty acids in gut health and possible therapeutic approaches in inflammatory bowel diseases. World J Clin Cases 2022; 10:9985-10003. [PMID: 36246826 PMCID: PMC9561599 DOI: 10.12998/wjcc.v10.i28.9985] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 08/02/2022] [Accepted: 08/25/2022] [Indexed: 02/05/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are characterized by inflammation in the gastrointestinal tract and include Ulcerative Colitis and Crohn's Disease. These diseases are costly to health services, substantially reduce patients' quality of life, and can lead to complications such as cancer and even death. Symptoms include abdominal pain, stool bleeding, diarrhea, and weight loss. The treatment of these diseases is symptomatic, seeking disease remission. The intestine is colonized by several microorganisms, such as fungi, viruses, and bacteria, which constitute the intestinal microbiota (IM). IM bacteria promotes dietary fibers fermentation and produces short-chain fatty acids (SCFAs) that exert several beneficial effects on intestinal health. SCFAs can bind to G protein-coupled receptors, such as GPR41 and GPR43, promoting improvements in the intestinal barrier, anti-inflammatory, and antioxidant effects. Thus, SCFAs could be a therapeutic tool for IBDs. However, the mechanisms involved in these beneficial effects of SCFAs remain poorly understood. Therefore, this paper aims to provide a review addressing the main aspects of IBDs, and a more detailed sight of SCFAs, focusing on the main effects on different aspects of the intestine with an emphasis on IBDs.
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Affiliation(s)
| | - Patricia Castelucci
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508900, SP, Brazil
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22
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Shen Q, Huang Z, Ma L, Yao J, Luo T, Zhao Y, Xiao Y, Jin Y. Extracellular vesicle miRNAs promote the intestinal microenvironment by interacting with microbes in colitis. Gut Microbes 2022; 14:2128604. [PMID: 36176029 PMCID: PMC9542864 DOI: 10.1080/19490976.2022.2128604] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a global disease with no cure. Disruption of the microbial ecosystem is considered to be an important cause of IBD. Extracellular vesicles (EVs) are vital participants in cell-cell and cell-organism communication. Both host-derived EVs and bacteria-derived membrane vesicles (OMVs) contribute to homeostasis in the intestine. However, the roles of EVs-miRNAs and MVs in host-microbe interactions in colitis remain unclear. In the present study, the animal model of colitis was established by dextran sulfate sodium (DSS) to investigate the changes of miRNAs in colonic EVs from colitis. Several miRNAs were significantly altered in colitis EVs. miR-181b-5p transplantation inhibited M1 macrophage polarization and promoted M2 polarization to reduce the levels of inflammation both in acute and remission of chronic colitis. miR-200b-3p could interact with bacteria and regulate the composition of the microbiota, which contributed to intestinal barrier integrity and homeostasis. Notably, MVs from normal feces could effectively reverse the composition of the intestinal microbiota, restore the intestinal barrier and rescue colitis, and BMVs from colitis would also have similar effects after miR-200b-3p treatment. Our results preliminarily identify a vesicle-based host-microbe interaction cycle in colitis and provide new ideas for colitis treatment.
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Affiliation(s)
- Qichen Shen
- Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
| | - Zhuizui Huang
- Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
| | - Lingyan Ma
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Jiachen Yao
- Health Informatics Centre, Department of Learning, Informatics, Management and Ethics, Karolinska Institute, Stockholm, Sweden
| | - Ting Luo
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Yao Zhao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Yingping Xiao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China,Yingping Xiao Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, 298, Desheng Middle Road, Hangzhou, People’ Republic of China
| | - Yuanxiang Jin
- Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China,CONTACT Yuanxiang Jin College of Biotechnology and Bioengineering, Zhejiang University of Technology, 18, Chaowang Road, Hangzhou, People’ Republic of China
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23
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Risk Factors, Diagnosis, and Management of Clostridioides difficile Infection in Patients with Inflammatory Bowel Disease. Microorganisms 2022; 10:microorganisms10071315. [PMID: 35889034 PMCID: PMC9319314 DOI: 10.3390/microorganisms10071315] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/24/2022] [Accepted: 06/27/2022] [Indexed: 12/10/2022] Open
Abstract
Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are two pathologies that share a bidirectional causal nexus, as CDI is known to have an aggravating effect on IBD and IBD is a known risk factor for CDI. The colonic involvement in IBD not only renders the host more prone to an initial CDI development but also to further recurrences. Furthermore, IBD flares, which are predominantly set off by a CDI, not only create a need for therapy escalation but also prolong hospital stay. For these reasons, adequate and comprehensive management of CDI is of paramount importance in patients with IBD. Microbiological diagnosis, correct evaluation of clinical status, and consideration of different treatment options (from antibiotics and fecal microbiota transplantation to monoclonal antibodies) carry pivotal importance. Thus, the aim of this article is to review the risk factors, diagnosis, and management of CDI in patients with IBD.
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24
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Joachim A, Schwerd T, Hölz H, Sokollik C, Konrad LA, Jordan A, Lanzersdorfer R, Schmidt-Choudhury A, Hünseler C, Adam R. [Fecal Microbiota Transfer (FMT) in Children and Adolescents - Review and statement by the GPGE microbiome working group]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:963-969. [PMID: 35533688 DOI: 10.1055/a-1801-0284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The human microbiome and especially the gastrointestinal microbiota are associated with health and disease. Disturbance in the composition or function of fecal microbiota (dysbiosis) plays a role in the development of pediatric gastrointestinal diseases. Fecal microbiota transfer (FMT) is a special intervention, where microbiota are transferred from a healthy donor.In this review we describe the current state of knowledge for FMT in pediatric patients. There is satisfactory evidence concerning FMT in patients with recurrent C. difficile infection. For inflammatory bowel disease, few studies show a potential benefit.Adverse events occurred frequently in clinical studies, but were mostly mild and transient. There are hardly any data on long-term side effects of FMT, which are particularly significant for pediatrics. In practice, there is uncertainty as to which application route, dosage or frequency should be used. Legally, donor stool is considered a drug in German-speaking countries, for which no marketing authorization exists.In conclusion, knowledge about physiology, efficacy and side effects of FMT is insufficient and legal concerns complicate its implementation. More studies on this topic are needed urgently.
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Affiliation(s)
| | - Tobias Schwerd
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Klinikum der Universtität München, LMU München, München, Germany
| | - Hannes Hölz
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Klinikum der Universtität München, LMU München, München, Germany
| | - Christiane Sokollik
- Abteilung Pädiatrische Gastroenterologie, Hepatologie und Ernährung, Universitätsklinik für Kinderheilkunde, Inselspital, Universitätsspital Bern, Universität Bern, Bern, Switzerland
| | - Lukas Alfons Konrad
- Klinik für Neonatologie und allgemeine Pädiatrie, Gesundheit Nordhessen, Klinikum Kassel, Kassel, Germany
| | - Alexander Jordan
- Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Mannheim, Mannheim, Germany
| | | | - Anjona Schmidt-Choudhury
- Klinik für Kinder- und Jugendmedizin, Universitätsklinikum der Ruhr-Universität Bochum, Bochum, Germany
| | | | - Rüdiger Adam
- Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Mannheim, Mannheim, Germany
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25
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Gweon TG, Lee YJ, Kim KO, Yim SK, Soh JS, Kim SY, Park JJ, Shin SY, Lee TH, Choi CH, Cho YS, Yong D, Chung JW, Lee KJ, Lee OY, Choi MG, Choi M, Gut Microbiota Therapy Research Group Under the Korean Society of Neurogastroenterology Motility. Clinical Practice Guidelines for Fecal Microbiota Transplantation in Korea. J Neurogastroenterol Motil 2022; 28:28-42. [PMID: 34980687 PMCID: PMC8748844 DOI: 10.5056/jnm21221] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 12/08/2021] [Indexed: 12/05/2022] Open
Abstract
Fecal microbiota transplantation (FMT) is a highly efficacious and safe modality for the treatment of recurrent or refractory Clostridioides difficile infection (CDI), with overall success rates of 90%. Thus, FMT has been widely used for 10 years. The incidence and clinical characteristics of CDI, the main indication for FMT, differ between countries. To date, several guidelines have been published. However, most of them were published in Western countries and therefore cannot represent the Korean national healthcare systems. One of the barriers to performing FMT is a lack of national guidelines. Accordingly, multidisciplinary experts in this field have developed practical guidelines for FMT. The purpose of these guidelines is to aid physicians performing FMT, which can be adapted to treat CDI and other conditions.
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Affiliation(s)
- Tae-Geun Gweon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yoo Jin Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Kyeong Ok Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Sung Kyun Yim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jeonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-do, Korea
| | - Jae Seung Soh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Hallym College of Medicine, Hallym University, Anyang, Gyeonggi-do, Korea
| | - Seung Young Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do, Korea
| | - Jae Jun Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Yong Shin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Tae Hee Lee
- Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Chang Hwan Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Young-Seok Cho
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dongeun Yong
- Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea
| | - Jin-Won Chung
- Division of Infectious Diseases, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Kwang Jae Lee
- Department of Internal Medicine, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
| | - Oh Young Lee
- Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea
| | - Myung-Gyu Choi
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Miyoung Choi
- Division of Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaboration Agency, Seoul, Korea
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26
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Ianiro G, Bibbò S, Porcari S, Settanni CR, Giambò F, Curta AR, Quaranta G, Scaldaferri F, Masucci L, Sanguinetti M, Gasbarrini A, Cammarota G. Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center. Gut Microbes 2022; 13:1994834. [PMID: 34709989 PMCID: PMC8555518 DOI: 10.1080/19490976.2021.1994834] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8 weeks. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event.FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD.
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Affiliation(s)
- Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy,CONTACT Gianluca Ianiro Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Largo A. Gemelli 8, Rome00168, Italy
| | - Stefano Bibbò
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Serena Porcari
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Carlo Romano Settanni
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Federica Giambò
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Andreea Roxana Curta
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Gianluca Quaranta
- Microbiology Unit, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Franco Scaldaferri
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Luca Masucci
- Microbiology Unit, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Maurizio Sanguinetti
- Microbiology Unit, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Rome, Italy
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27
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Dose-Dependent Relationship between Protection of Thioacetamide-Induced Acute Liver Injury and Hyperammonemia and Concentration of Lactobacillus salivarius Li01 in Mice. Microbiol Spectr 2021; 9:e0184721. [PMID: 34937168 PMCID: PMC8694139 DOI: 10.1128/spectrum.01847-21] [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] [Indexed: 11/20/2022] Open
Abstract
Recently, probiotics have been widely used as an adjuvant therapy to cure, prevent, or improve certain diseases. However, no research has been carried out into the dose of probiotics, especially the maximum dose. Therefore, the effective and safe dosage of probiotics needs to be studied. Recently, L. Yang, X. Bian, W. Wu, L. Lv, et al. (Microb Biotechnol 13:1860–1876, 2020, https://doi.org/10.1111/1751-7915.13629) discovered that Lactobacillus salivarius Li01 had a protective effect on thioacetamide-induced acute liver injury and hyperammonemia, and a fixed concentration (3 × 109 CFU/mL) of L. salivarius Li01 was applied in their study. However, the most effective treatment concentration of L. salivarius Li01 remains unknown. Therefore, four concentration gradients of L. salivarius Li01 suspension were prepared for groups of mice to have different levels of bacterial colonization by gavage. Then, acute liver injury and hyperammonemia were induced via thioacetamide administration. By observation and detection, an inverted U-shaped protective effect from L. salivarius Li01 existed in thioacetamide-induced acute liver injury and hyperammonemia. Of note, significant deterioration was confirmed within the group that was orally administered with an excessive concentration of L. salivarius Li01 suspension, and this was attributed to endotoxemia that resulted from compromised immunity, a damaged intestinal barrier, and bacterial translocation. IMPORTANCE This research investigated the relationship between the concentration of Lactobacillus salivarius Li01 and its impact on mice that had a thioacetamide-induced acute liver injury and hyperammonemia. These findings could provide new insights into the effective, proper, and safe use of probiotics.
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28
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The Role of Fecal Microbiota Transplantation in the Treatment of Inflammatory Bowel Disease. J Clin Med 2021; 10:jcm10184055. [PMID: 34575166 PMCID: PMC8465860 DOI: 10.3390/jcm10184055] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 12/12/2022] Open
Abstract
The exact pathogenesis of inflammatory bowel disease (IBD) is still not completely understood. It is hypothesized that a genetic predisposition leads to an exaggerated immune response to an environmental trigger, leading to uncontrolled inflammation. As there is no known causative treatment, current management strategies for inflammatory bowel disease focus on correcting the excessive immune response to environmental (including microbial) triggers. In recent years, there has been growing interest in new avenues of treatment, including targeting the microbial environment itself. Fecal microbiota transplantation (FMT) is a novel treatment modality showing promising results in early studies. The article discusses the rationale for the use of FMT in inflammatory bowel disease and the yet-unresolved questions surrounding its optimal use in practice.
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29
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Conrad MA, Kelsen JR. Clostridioides difficile Infection in Pediatric Inflammatory Bowel Disease: A Clinician's Dilemma. J Pediatric Infect Dis Soc 2021; 10:S41-S45. [PMID: 34343321 PMCID: PMC8600020 DOI: 10.1093/jpids/piab069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 07/20/2021] [Indexed: 11/12/2022]
Abstract
Clostridioides difficile infection (CDI) in children with inflammatory bowel disease (IBD) can present and manifest differently from the general population with CDI, and it can worsen the underlying disease course. Furthermore, current clinical assays used to test for CDI do not accurately distinguish between true CDI or colonization. This uncertainty leads to difficulty in identifying the etiology and therapy for symptomatic patients with IBD. Improved diagnostic tests, biomarkers, and safe and effective treatment options are greatly needed for this vulnerable population.
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Affiliation(s)
- Máire A Conrad
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA,Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA,Corresponding Author: Máire A. Conrad, MD, Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Main Building 7NW, 3401 Civic Center Blvd, Philadelphia, PA 19104, USA. E-mail:
| | - Judith R Kelsen
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA,Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
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30
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Sehgal K, Yadav D, Khanna S. The interplay of Clostridioides difficile infection and inflammatory bowel disease. Therap Adv Gastroenterol 2021; 14:17562848211020285. [PMID: 34104215 PMCID: PMC8170344 DOI: 10.1177/17562848211020285] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 05/06/2021] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.
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Affiliation(s)
- Kanika Sehgal
- Division of Gastroenterology and
Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Devvrat Yadav
- Division of Gastroenterology and
Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Sahil Khanna
- Division of Gastroenterology and
Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905,
USA
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31
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Li Q, Ding X, Liu Y, Marcella C, Dai M, Zhang T, Bai J, Xiang L, Wen Q, Cui B, Zhang F. Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn's Disease. Front Pharmacol 2021; 12:658087. [PMID: 34079458 PMCID: PMC8166050 DOI: 10.3389/fphar.2021.658087] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 05/04/2021] [Indexed: 12/12/2022] Open
Abstract
Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn's disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation. Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The "one-hour FMT protocol" was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis. Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43-6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001-0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002). Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT01793831.
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Affiliation(s)
- Qianqian Li
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiao Ding
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Yujie Liu
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Cicilia Marcella
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Dai
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ting Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jianling Bai
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Liyuan Xiang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Quan Wen
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- National Clinical Research Center for Digestive Diseases, Xi’an, China
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Allegretti JR. Update on Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y) 2021; 17:31-34. [PMID: 34035760 PMCID: PMC8132680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Affiliation(s)
- Jessica R Allegretti
- Associate Director, Crohn's and Colitis Center Director, Fecal Microbiota Transplant Program Brigham and Women's Hospital Assistant Professor of Medicine Harvard Medical School Boston, Massachusetts
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