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Xiao Y, Yue X, Zhang X, Yang Y, Zhang Y, Sun L. The role of bacteriophage in inflammatory bowel disease and its therapeutic potential. Crit Rev Microbiol 2025:1-15. [PMID: 40219702 DOI: 10.1080/1040841x.2025.2492154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 03/25/2025] [Accepted: 04/07/2025] [Indexed: 04/14/2025]
Abstract
Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory disorders impacting the gastrointestinal (GI) tract. It represents a significant public health challenge due to its rising global incidence and substantial impact on patients' quality of life. Emerging research suggests a pivotal role of the human microbiome in IBD pathogenesis. Bacteriophages, integral components of the human microbiome, are indicated to influence the disease onset, progression, and therapeutic strategies. Here, we review the effect of bacteriophages on the pathogenesis of IBD and, more specifically, on the gut bacteria, the systemic immunity, and the susceptibility genes. Additionally, we explore the potential therapeutic use of the bacteriophages to modify gut microbiota and improve the health outcomes of IBD patients. This review highlights the potential of therapeutic bacteriophages in regulating gut microbiota and modulating the immune response to improve health outcomes in IBD patients. Future studies on personalized bacteriophage therapy and its integration into clinical practice could advance treatment strategies for IBD.
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Affiliation(s)
- Yuyang Xiao
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Xinyu Yue
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Xupeng Zhang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Yifei Yang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Yibo Zhang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Lang Sun
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
- Department of Microbiology, Xiangya School of the Basic Medical Science, Central South University, Changsha, Hunan Province, China
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Chen S, Zhang D, Li D, Zeng F, Chen C, Bai F. Microbiome characterization of patients with Crohn disease and the use of fecal microbiota transplantation: A review. Medicine (Baltimore) 2025; 104:e41262. [PMID: 39854760 PMCID: PMC11771716 DOI: 10.1097/md.0000000000041262] [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: 02/18/2024] [Revised: 03/19/2024] [Accepted: 11/15/2024] [Indexed: 01/26/2025] Open
Abstract
Inflammatory bowel disease is a chronic inflammatory condition predominantly affecting the intestines, encompassing both ulcerative colitis and Crohn disease (CD). As one of the most common gastrointestinal disorders, CD's pathogenesis is closely linked with the intestinal microbiota. Recently, fecal microbiota transplantation (FMT) has gained attention as a potential treatment for CD, with the effective reestablishment of intestinal microecology considered a crucial mechanism of FMT therapy. This article synthesizes the findings of population-based cohort studies to enhance our understanding of gut microbial characteristics in patients with CD. It delves into the roles of "beneficial" and "pathogenic" bacteria in CD's development. This article systematically reviews and compares data on clinical response rates, remission rates, adverse events, and shifts in bacterial microbiota. Among these studies, gut microbiome analysis was conducted in only 7, and a single study examined the metabolome. Overall, FMT has demonstrated a partial restoration of typical CD-associated microbiological alterations, leading to increased α-diversity in responders and a moderate shift in patient microbiota toward the donor profile. Several factors, including donor selection, delivery route, microbial state (fresh or frozen), and recipient condition, are identified as pivotal in influencing FMT's effectiveness. Future prospective clinical studies with larger patient cohorts and improved methodologies are imperative. In addition, standardization of FMT procedures, coupled with advanced genomic techniques such as macroproteomics and culture genomics, is necessary. These advancements will further clarify the bacterial microbiota alterations that significantly contribute to FMT's therapeutic effects in CD treatment, as well as elucidate the underlying mechanisms of action.
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Affiliation(s)
- Shiju Chen
- Graduate School, Hainan Medical University, Haikou, China
| | - Daya Zhang
- Graduate School, Hainan Medical University, Haikou, China
| | - Da Li
- Graduate School, Hainan Medical University, Haikou, China
| | - Fan Zeng
- Graduate School, Hainan Medical University, Haikou, China
| | - Chen Chen
- Graduate School, Hainan Medical University, Haikou, China
| | - Feihu Bai
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
- The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, China
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Soo N, Farinre O, Chahroudi A, Boliar S, Goswami R. A gut check: understanding the interplay of the gastrointestinal microbiome and the developing immune system towards the goal of pediatric HIV remission. Retrovirology 2024; 21:15. [PMID: 39425183 PMCID: PMC11490017 DOI: 10.1186/s12977-024-00648-9] [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] [Received: 05/20/2024] [Accepted: 10/10/2024] [Indexed: 10/21/2024] Open
Abstract
Despite the efficacy of antiretroviral therapy (ART) in reducing the global incidence of vertical HIV transmissions, more than 120,000 children are still infected with the virus each year. Since ART cannot clear the HIV reservoir that is established soon after infection, children living with HIV (CLWH) are forced to rely on therapy for their lives and suffer from long-term drug-related complications. Pediatric HIV infection, like adult infection, is associated with gut microbial dysbiosis, loss of gut epithelial integrity, bacterial translocation, CD4 + T cell depletion, systemic immune activation, and viral reservoir establishment. However, unlike in adults, HIV that is vertically acquired by infants interacts with a gut microbiome that is continuously evolving while concomitantly shaping the infant's immune ontogeny. Therefore, to determine whether there may be interventions that target the HIV reservoir through microbiome-directed approaches, understanding the complex tripartite interactions between the transmitted HIV, the maturing gut microbiome, and the developing immune system during early life is crucial. Importantly, early life is the time when the gut microbiome of an individual is highly dynamic, and this temporal development of the gut microbiome plays a crucial role in educating the maturing immune system of a child. Therefore, manipulation of the gut microbiome of CLWH to a phenotype that can reduce HIV persistence by fostering an antiviral immune system might be an opportune strategy to achieve ART-free viral suppression in CLWH. This review summarizes the current state of knowledge on the vertical transmission of HIV, the developing gut microbiome of CLWH, and the immune landscape of pediatric elite controllers, and explores the prospect of employing microbial modulation as a potential therapeutic approach to achieve ART-free viral suppression in the pediatric population.
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Affiliation(s)
- Nicole Soo
- Department of Pediatrics, Weill Cornell Medicine, New York, NY, 10021, USA
| | - Omotayo Farinre
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Ann Chahroudi
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA
- Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta and Emory University, Atlanta, GA, 30322, USA
| | - Saikat Boliar
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
- Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, 14203, USA
| | - Ria Goswami
- Department of Pediatrics, Weill Cornell Medicine, New York, NY, 10021, USA.
- Gale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, 10021, USA.
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Lauwers E, Sabino J, Hoffman I, van Hoeve K. Faecal microbiota transplantation in children: A systematic review. Acta Paediatr 2024; 113:1991-2002. [PMID: 38391047 DOI: 10.1111/apa.17167] [Citation(s) in RCA: 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: 09/15/2023] [Revised: 01/25/2024] [Accepted: 02/13/2024] [Indexed: 02/24/2024]
Abstract
AIM Novel technologies offer insights into the potential role of the intestinal microbiota in human health and disease. Dysbiosis has been associated with several diseases, and it is thought to play a role in the pathogenesis of different gastrointestinal diseases. Faecal microbiota transplantation (FMT) is emerging as a method to modulate the gastrointestinal microbial ecosystem. While recurrent Clostridioides difficile infection is the recognised FMT indication, exploration of other therapeutic uses is ongoing. METHODS Following PRISMA guidelines, we conducted a systematic review, extracting 583 articles from Embase and PubMed (index date to October 2022). RESULTS The search yielded 58 studies for full review, with 50 included in the systematic review. Articles were categorised by FMT indication, study design, efficacy, adverse events, donor selection and administration route. FMT appears safe and effective for recurrent Clostridioides difficile infection, although severe adverse events are reported in children. However, there are currently insufficient data to support the use of FMT for other potential therapeutic indications (such as irritable or inflammatory bowel disease or obesity), beside the potential to decolonise multi-drug resistant organisms. CONCLUSION This underscores the need for randomised, controlled, prospective cohort studies in children to assess FMT effectiveness in diverse conditions and counteract publication bias.
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Affiliation(s)
- Ella Lauwers
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
| | - João Sabino
- TARGID, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
- Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Ilse Hoffman
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
| | - Karen van Hoeve
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
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Ottria R, Xynomilakis O, Casati S, Ciuffreda P. Pre- to Postbiotics: The Beneficial Roles of Pediatric Dysbiosis Associated with Inflammatory Bowel Diseases. Microorganisms 2024; 12:1582. [PMID: 39203424 PMCID: PMC11356122 DOI: 10.3390/microorganisms12081582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 09/03/2024] Open
Abstract
Probiotics are "live microorganisms which, when administered in adequate amount, confer health benefits on the host". They can be found in certain foods like yogurt and kefir and in dietary supplements. The introduction of bacterial derivatives has not only contributed to disease control but has also exhibited promising outcomes, such as improved survival rates, immune enhancement, and growth promotion effects. It is interesting to note that the efficacy of probiotics goes beyond the viability of the bacteria, giving rise to concepts like paraprobiotics, non-viable forms of probiotics, and postbiotics. Paraprobiotics offer various health benefits in children with intestinal dysbiosis, contributing to improved digestive health, immune function, and overall well-being. In this review, the potential of these therapeutic applications as alternatives to pharmacological agents for treating pediatric intestinal dysbiosis will be thoroughly evaluated. This includes an analysis of their efficacy, safety, long-term benefits, and their ability to restore gut microbiota balance, improve digestive health, enhance immune function, and reduce inflammation. The aim is to determine if these non-pharmacological interventions can effectively and safely manage intestinal dysbiosis in children, reducing the need for conventional medications and their side effects.
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Affiliation(s)
- Roberta Ottria
- Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, 20157 Milan, Italy; (O.X.); (S.C.); (P.C.)
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Gu X, Chen ZH, Zhang SC. Fecal microbiota transplantation in childhood: past, present, and future. World J Pediatr 2023; 19:813-822. [PMID: 36484871 PMCID: PMC9734408 DOI: 10.1007/s12519-022-00655-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 11/13/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) has been well described in the treatment of pediatric diseases; however, the latest updates regarding its use in children are unclear and the concepts involved need to be revisited. DATA SOURCES We performed advanced searches in the MEDLINE, EMBASE, and Cochrane databases using the keywords "Fecal microbiota transplantation OR Fecal microbiota transfer" in the [Title/Abstract] to identify relevant articles published in English within the last five years. To identify additional studies, reference lists of review articles and included studies were manually searched. Retrieved manuscripts (case reports, reviews, and abstracts) were assessed by the authors. RESULTS Among the articles, studies were based on the mechanism (n = 28), sample preparation (n = 9), delivery approaches (n = 23), safety (n = 26), and indications (n = 67), including Clostridium difficile infection (CDI) and recurrent C. difficile infection (rCDI; n = 21), non-alcoholic fatty liver disease (NAFLD; n = 10), irritable bowel syndrome (IBS; n = 5), inflammatory bowel disease (IBD; n = 15), diabetes (n = 5), functional constipation (FC; n = 4), and autism spectrum disorder (ASD; n = 7). CONCLUSIONS Concepts of FMT in pediatric diseases have been updated with respect to underlying mechanisms, methodology, indications, and safety. Evidence-based clinical trials for the use of FMT in pediatric diseases should be introduced to resolve the challenges of dosage, duration, initiation, and the end point of treatment.
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Affiliation(s)
- Xu Gu
- Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang, 110004, China
| | - Zhao-Hong Chen
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shu-Cheng Zhang
- Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang, 110004, China.
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Hasan N, Yang H. Evaluation of microbial and vancomycin treatments in ulcerative colitis in murine models. PLoS One 2023; 18:e0285613. [PMID: 37167242 PMCID: PMC10174502 DOI: 10.1371/journal.pone.0285613] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 04/26/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Despite the number of available therapies for ulcerative colitis (UC), severe side effects and high cost has limited their clinical application. Thus, finding new alternative strategies with minimal side effects is inevitable. Therefore, this study aimed to compare the effectiveness of different therapeutic approaches in DSS-induced colitis. METHODS Firstly, we designed oral bio-therapeutic products, Live Bacterial Products (LBP), which include a mixture of fecal bacteria strains isolated from healthy mice and prepared by microencapsulation and freeze-dried techniques. Then we investigated the efficiency of 7 days of freeze-dried FMT, LBP, and vancomycin treatments in DSS-induced colitis. Secondly, we compared the effect of 15 days of microbial therapies (freeze-dried powder of FMT and LBP microcapsules) and seven days of oral vancomycin on the severity of colitis in mice. Furthermore, the levels of IL-1β and TNF-α were measured in serum by ELISA, and the fecal microbiota diversity was analyzed by high-throughput sequencing for all mice groups. RESULTS After seven days of treatments, our results indicated that oral vancomycin reduced the severity of DSS-induced colitis in mice, where weight gain and a decrease in IL-1 β and TNF-α levels were observed in the vancomycin group compared with other treatment groups. While after two weeks of treatment, the LBP microcapsules were able to reduce the severity of colitis. And at the end of the treatment period, weight gain and a decrease in the DAI scores and the levels of IL-1β and TNF-α were noted in the LBP treatment group compared to other treatment groups. By high-throughput sequencing of the 16S rRNA gene, our results showed that while the microcapsules LBP treatment increased the fecal microbial diversity, after vancomycin therapy, most of the fecal microbiota genera and operational taxonomic units (OTUs) were depleted. CONCLUSION Our results concluded that treatment duration and preparation methods affect the microbial therapies' efficiency in UC. Furthermore, this study highlighted the negative consequences of oral vancomycin administration on gut health that should be known before using this medication.
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Affiliation(s)
- Nihal Hasan
- Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, People’s Republic of China
- Faculty of Health Science, Al-Baath University, Homs, Syria
| | - Hongyi Yang
- Department of Microbiology, Northeast Forestry University, Harbin, Heilongjiang, People’s Republic of China
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Levast B, Fontaine M, Nancey S, Dechelotte P, Doré J, Lehert P. Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: A Systematic Review and Meta-analysis. Clin Transl Gastroenterol 2023; 14:e00568. [PMID: 37232579 PMCID: PMC10208705 DOI: 10.14309/ctg.0000000000000568] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 01/31/2023] [Indexed: 05/27/2023] Open
Abstract
INTRODUCTION Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis was performed to compare the efficacy of single-donor (SDN) and multidonor (MDN) strategies for product preparation. METHODS Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 nonrandomized). The treatment response was assessed by using fixed- and random-effects models, and the significance of the indirect difference between the interventions was assessed using a network approach. RESULTS Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios [RRs]: 4.41 and 1.57, respectively [P ≤ 0.001 for both]), and MDN was superior to SDN (RR: 2.81, P = 0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P = 0.042). Results were identical for both models. DISCUSSION There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation.JOURNAL/cltg/04.03/01720094-202305000-00002/2FFU1/v/2023-05-23T220055Z/r/image-tiff.
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Affiliation(s)
| | | | - Stéphane Nancey
- Department of Gastroenterology, CHU de Lyon, Lyon-Sud Hospital, University Claude Bernard Lyon 1 and CIRI-INSERM U1111, Lyon, France
| | | | - Joël Doré
- Université Paris-Saclay, INRAE, MetaGenoPolis, AgroParis Tech, MICALIS, 78350, Jouy-en-Josas, France
| | - Philippe Lehert
- Faculty of Management, UCL, Louvain, Belgium
- Faculty of Medicine, University of Melbourne, Australia
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Imdad A, Pandit NG, Zaman M, Minkoff NZ, Tanner-Smith EE, Gomez-Duarte OG, Acra S, Nicholson MR. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev 2023; 4:CD012774. [PMID: 37094824 PMCID: PMC10133790 DOI: 10.1002/14651858.cd012774.pub3] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT). OBJECTIVES To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022. SELECTION CRITERIA We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD. DATA COLLECTION AND ANALYSIS Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias. Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI -3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC. Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC. None of the included studies assessed use of FMT for induction of remission in people with CD. One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD. AUTHORS' CONCLUSIONS FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.
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Affiliation(s)
- Aamer Imdad
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Natasha G Pandit
- Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Muizz Zaman
- Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Nathan Zev Minkoff
- Pediatric Gastroenterology, Hepatology and Nutrition, Valley Children's Hospital, Madera, CA, USA
| | - Emily E Tanner-Smith
- Counseling Psychology and Human Services, University of Oregon, Eugene, Oregon, USA
| | - Oscar G Gomez-Duarte
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University at Buffalo, State University of New York, Buffalo, New York, USA
| | - Sari Acra
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Maribeth R Nicholson
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
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Zhou S, Cui Y, Zhang Y, Zhao T, Cong J. Fecal microbiota transplantation for induction of remission in Crohn's disease: a systematic review and meta-analysis. Int J Colorectal Dis 2023; 38:62. [PMID: 36882658 DOI: 10.1007/s00384-023-04354-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 03/09/2023]
Abstract
PURPOSE Fecal microbiota transplantation (FMT) has been found to be a potential treatment for Crohn's disease (CD). We sought to perform a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD. METHODS Electronic databases were searched for studies until January 2023. Clinical remission was established as the primary outcome. The secondary outcome was clinical response, endoscopic remission, minor adverse events, serious adverse events, and changes in disease activity indices, biochemical indicators, and microbial diversities. Pooled effect sizes and 95% confidence intervals (CIs) were calculated under the random effects model. RESULTS Eleven cohort studies and one randomized controlled trial involving 228 patients were included. In a meta-analysis, the pooled proportion of adult patients with active CD that achieved clinical remission 2 to 4 weeks after FMT was 57% (95% CI = 49-64%) with a low risk of heterogeneity (I2 = 37%). Furthermore, our results showed that FMT significantly (standardized mean difference = -0.66; 95% CI = -1.12 to -0.20; I2 = 0) reduced Crohn's disease activity index scores 4 to 8 weeks after FMT. Subgroup analyses showed no difference between FMT methodologies, except for pre-FMT treatment with antibiotics (P = 0.02). Most adverse events were self-limiting and disappeared spontaneously within hours or days after FMT. Microbiota analysis showed an increased Shannon diversity and a shift toward donor-like microbiome after FMT. CONCLUSION FMT could be a promising therapy in the short-term treatment of active CD. More placebo-controlled randomized trials with a long-term follow-up treatment are necessary. TRIAL REGISTRATION https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322694 No. CRD42022322694.
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Affiliation(s)
- Siyu Zhou
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266000, People's Republic of China
| | - Ying Cui
- Department of Oncology, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital, Siliu South Road No.127, Qingdao, 266000, People's Republic of China
| | - Yun Zhang
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266000, People's Republic of China
| | - Tianyu Zhao
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266000, People's Republic of China
| | - Jing Cong
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266000, People's Republic of China.
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Yan XX, Wu D. Intestinal microecology-based treatment for inflammatory bowel disease: Progress and prospects. World J Clin Cases 2023; 11:47-56. [PMID: 36687179 PMCID: PMC9846986 DOI: 10.12998/wjcc.v11.i1.47] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 11/11/2022] [Accepted: 12/15/2022] [Indexed: 01/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, recurrent, and debilitating disorder, and includes Crohn’s disease and ulcerative colitis. The pathogenesis of IBD is closely associated with intestinal dysbiosis, but has not yet been fully clarified. Genetic and environmental factors can influence IBD patients’ gut microbiota and metabolism, disrupt intestinal barriers, and trigger abnormal immune responses. Studies have reported the alteration of gut microbiota and metabolites in IBD, providing the basis for potential therapeutic options. Intestinal microbiota-based treatments such as pre/probiotics, metabolite supplementation, and fecal microbiota transplantation have been extensively studied, but their clinical efficacy remains controversial. Repairing the intestinal barrier and promoting mucosal healing have also been proposed. We here review the current clinical trials on intestinal microecology and discuss the prospect of research and practice in this field.
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Affiliation(s)
- Xia-Xiao Yan
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
| | - Dong Wu
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
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12
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Zou B, Liu S, Li X, He J, Dong C, Ruan M, Huang Z, Shu S. Repeated and multiple fecal microbiota transplantations plus partial enteral nutrition as the first-line treatment in active pediatric Crohn's disease. Front Cell Infect Microbiol 2023; 13:1083236. [PMID: 36909725 PMCID: PMC9996013 DOI: 10.3389/fcimb.2023.1083236] [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: 10/28/2022] [Accepted: 02/09/2023] [Indexed: 02/25/2023] Open
Abstract
Background Most studies have reported fecal microbiota transplantation (FMT) as an effective secondary option for Crohn's disease (CD). However, there is little data on FMT as a first-line treatment for CD. In our study we explore the rates of clinical and endoscopic remission and mucosal healing after FMT plus partial enteral nutrition (PEN), as a first-line treatment for active CD in children. Methods We retrospectively enrolled pediatric CD patients who underwent PEN or PEN plus FMT treatment at diagnosis from November 2016 to July 2019 at the Pediatric Department, Tongji Hospital. The two groups were defined as FMT group (repeated and multiple doses of FMT plus PEN) or PEN group (PEN alone). All the patients received PEN intervention. At baseline and week 8- 10, the FMT group was administered multiple doses of FMT to help induce and maintain remission. All patients were evaluated at week 8- 10 and 18-22 via clinical and relevant laboratory parameters and endoscopic results. The clinical and endoscopic remission and mucosal healing rates were compared between the two groups at different time points after the therapy. Results Twenty-five newly diagnosed active CD patients were included in the study, containing 7 females and 18 males with a median age of 11. 1 ± 2.3 years. 13 and 12 patients were assigned to the PEN and FMT groups, respectively. At week 8-10, clinical remission was obtained in 83.3% and 53.8% of the FMT and PEN groups, respectively (p=0.202). The endoscopic remission rates were 72.7% for FMT and 25.0% for PEN (p=0.039), whereas the mucosal healing rates were 27.2% for FMT and 0% for PEN (p=0.093). At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups, respectively (p=0.03). Theendoscopic remission rates were 66.6% and 12.5% in the FMT and PEN groups, respectively (p=0.05), whereas the mucosal healing rates were 55.5% and 0% in FMT and PEN groups, respectively (p=0.029). Conclusion This study demonstrate that FMT plus PEN can be used as a first-line treatment for active CD in children.
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Zhang X, Ishikawa D, Ohkusa T, Fukuda S, Nagahara A. Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease. Front Med (Lausanne) 2022; 9:1068567. [PMID: 36530877 PMCID: PMC9755187 DOI: 10.3389/fmed.2022.1068567] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 11/21/2022] [Indexed: 11/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic intestinal mucosal inflammatory disease with complex etiology. Traditional anti-inflammatory treatment regimens have yielded unsatisfactory results. As research continues to deepen, it has been found that the gut microbiota of patients with IBD is generally altered. The presence of microorganisms in the human gastrointestinal tract is inextricably linked to the regulation of health and disease. Disruption of the microbiotic balance of microbiota in the gastrointestinal tract is called dysbiosis, which leads to disease. Therefore, in recent years, the exploration of therapeutic methods to restore the homeostasis of the gut microbiota has attracted attention. Moreover, the use of the well-established fecal microbiota transplantation (FMT) regimen for the treatment of Clostridioides difficile infection has attracted the interest of IBD researchers. Therefore, there are an increasing number of clinical studies regarding FMT for IBD treatment. However, a series of questions regarding FMT in the treatment of IBD warrants further investigation and discussion. By reviewing published studies, this review explored hot topics such as the efficacy, safety, and administration protocol flow of FMT in the treatment of IBD. Different administration protocols have generally shown reassuring results with significant efficacy and safety. However, the FMT treatment regimen needs to be further optimized. We believe that in the future, individual customized or standard FMT implementation will further enhance the relevance of FMT in the treatment of IBD.
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Affiliation(s)
- Xiaochen Zhang
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Dai Ishikawa
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Toshifumi Ohkusa
- Department of Microbiota Research, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Department of Gastroenterology and Hepatology, The Jikei University Kashiwa Hospital, Chiba, Japan
| | - Shinji Fukuda
- Department of Regenerative Microbiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University School of Medicine, Tokyo, Japan
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14
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Wang JG, Liang Q, Dou HH, Ou Y. The global incidence of adverse events associated with fecal microbiota transplantation in children over the past 20 years: A systematic review and meta-analysis. J Gastroenterol Hepatol 2022; 37:2031-2038. [PMID: 36066910 DOI: 10.1111/jgh.15996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 08/25/2022] [Accepted: 09/03/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To understand the global incidence of the adverse events associated with fecal microbiota transplantation (FMT) in children over the past 20 years. METHODS We searched PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and Chongqing Weipu) for high-quality articles written over the past 20 years and made selections based on the quality standard score. The study characteristics and incidences of adverse events were extracted from each article, meta-analysis was performed using the R.3.6.3 software, and randomized-effect or fixed-effect meta-analyses were used to determine the incidence of adverse events. Subgroup analysis was performed to determine heterogeneity. RESULTS A total of 18 articles involving 681 children were included in the analysis. The total effective rate of FMT in children was 85.75% (95% CI: 76.23-93.15%), of which the overall efficacy of FMT for the treatment of Clostridium difficile infection was 91.22% (95% CI: 83.49-96.68%) and the overall adverse event rate was 28.86% (95% CI: 19.56-39.15%), with a mild to moderate adverse event rate of 27.72% (95% CI: 17.86-38.83%) and a severe adverse event rate of 0.90% (95% CI: 0.33-1.76%). The most common mild to moderate adverse events were as follows: bellyache, 14.02% (95% CI: 5.43-25.77%); diarrhea, 7.75% (95% CI: 2.69-15.11%); and bloating, 7.36% (95% CI: 1.79-16.28%). Other adverse events included fever, 2.34%; vomiting, 3.12%; nausea, 1.50%; hematochezia, 2.30%; anorexia, 1.94%; and fatigue, 0.03%. The only death reported was in a study from China, in which the patient died of sepsis and liver failure 4 weeks after FMT. The other serious adverse event was an immunodeficiency patient with severe hematochezia. Another study in the United States described seven serious adverse events including one death that was not considered to be related to FMT; however, they did not describe the events in detail. There was no difference in the incidence of adverse events between the upper and lower gastrointestinal tracts (OR = 0.61, 95% CI: 0.02-15.42, P = 0.76). CONCLUSION Adverse events related to FMT in children are mostly mild to moderate, of short duration, and self-limiting. Therefore, the use of FMT in children is safe and worthy of widespread promotion.
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Affiliation(s)
- Ji-Gan Wang
- Department of Pediatrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, China
| | - Qing Liang
- Department of Pediatrics, Ethnic Hospital of Guangxi Zhuang Autonomous Region, Affiliated Ethnic Hospital of Guangxi Medical University, Nanning, China
| | - Hui-Hong Dou
- Department of Pediatrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, China
| | - Yuan Ou
- Department of Pediatrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, China
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15
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Huang T, Xu J, Wang M, Pu K, Li L, Zhang H, Liang Y, Sun W, Wang Y. An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis. Medicine (Baltimore) 2022; 101:e29790. [PMID: 35905229 PMCID: PMC9333500 DOI: 10.1097/md.0000000000029790] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) as a promising therapy for ulcerative colitis (UC) remains controversial. We conducted a systematic review and meta-analysis to assess the efficiency and safety of FMT as a treatment for UC. METHODS The target studies were identified by searching PubMed, EMBASE, the Cochrane Library, Web of Science, and ClinicalTrials and by manual supplementary retrieval. We conducted a general review and quantitative synthesis of included studies. We used the RevMan and Stata programs in the meta-analysis. The outcomes were total remission, clinical remission, steroid-free remission, and serious adverse events. We also performed subgroup analyses based on different populations. RESULTS A total of 34 articles were included in the general review. Only 16 articles, including 4 randomized controlled trials, 2 controlled clinical trials, and 10 cohort studies, were selected for the meta-analysis. We found that donor FMT might be more effective than placebo for attaining total remission (risk ratio [RR]: 2.77, 95% confidence interval [CI]: 1.54-4.98; P = .0007), clinical remission (RR: 0.33, 95% CI: 0.24-0.41; P < .05), and steroid-free remission (RR: 3.63, 95% CI: 1.57-8.42; P = .003), but found no statistically significant difference in the incidence of serious adverse events (RR: 0.88, 95% CI: 0.34-2.31, P = .8). The subgroup analyses revealed significant differences between the pooled clinical remission rates for different regions, degrees of severity of the disease, and patients with steroid- or nonsteroid-dependent UC. CONCLUSIONS FMT can achieve clinical remission and clinical response in patients with UC.
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Affiliation(s)
- Taobi Huang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Jinlan Xu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Maoying Wang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Ke Pu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Longquan Li
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Huiyun Zhang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Yuan Liang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Weiming Sun
- Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, China
- *Correspondence: Yu Ping Wang, Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, No.1 West Donggang Road, Lanzhou, Gansu 730000, China (e-mail:
| | - Yuping Wang
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
- *Correspondence: Yu Ping Wang, Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, No.1 West Donggang Road, Lanzhou, Gansu 730000, China (e-mail:
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Chen CC, Chiu CH. Current and future applications of fecal microbiota transplantation for children. Biomed J 2021; 45:11-18. [PMID: 34781002 PMCID: PMC9133305 DOI: 10.1016/j.bj.2021.11.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 10/23/2021] [Accepted: 11/07/2021] [Indexed: 12/18/2022] Open
Abstract
Fecal microbiota transplantation (FMT) is a new and adequate route to modify the microbial ecosystem in gastrointestinal tract of the hosts. Intestinal microbiota is highly associated with human health and disease. According to the reports of human clinical trials or case series, the application of FMT ranged from Clostridiodes difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome, refractory diarrhea, diabetes mellitus, metabolic syndrome, and even neurologic diseases, including Parkinson disease, and neuropsychiatric disorder (autism spectrum disorder, ASD). Although the current allowed indication of FMT is CDI in Taiwan, more application and development are expectable in the future. There is a relative rare data available for children in application of fecal microbiota transplantation. Thus, we review previous published research inspecting FMT in children, and address particular considerations when conducting FMT in pediatric patients.
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Affiliation(s)
- Chien-Chang Chen
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Cheng-Hsun Chiu
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
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17
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Fehily SR, Basnayake C, Wright EK, Kamm MA. Fecal microbiota transplantation therapy in Crohn's disease: Systematic review. J Gastroenterol Hepatol 2021; 36:2672-2686. [PMID: 34169565 DOI: 10.1111/jgh.15598] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The gastrointestinal microbiota is the key antigenic drive in the inflammatory bowel diseases. Randomized controlled trials (RCTs) in ulcerative colitis have established fecal microbiota transplantation (FMT) as an effective therapy. We have conducted a systematic review to evaluate the efficacy of FMT in Crohn's disease. METHODS A systematic literature search was performed through to August 2020 (MEDLINE; Embase). Studies were included if they reported FMT administration in patients with Crohn's disease, and reported on clinical outcomes. RESULTS Fifteen studies published between 2014 and 2020, comprising 13 cohort studies and two RCTs, were included in the analysis. The majority of trials evaluated FMT for induction of remission, with follow-up duration varying from 4 to 52 weeks. One RCT in 21 patients, of single-dose FMT versus placebo, following steroid-induced remission, showed a higher rate of steroid-free clinical remission in the FMT group compared to the control group: 87.5% vs 44.4% at week 10 (P = 0.23). Another RCT, two-dose FMT in 31 patients, showed an overall clinical remission rate of 36% at week 8, however, with no difference in clinical or endoscopic endpoints between FMT administered by gastroscopy and colonoscopy. Considering all studies, the clinical response rates in early follow up were higher following multiple FMT than with single FMT. FMT dose did not appear to influence clinical outcomes, nor did whether FMT was fresh or frozen. FMT delivered via upper gastrointestinal route demonstrated higher early efficacy rates of 75 to 100% compared with lower delivery route rates of 30% to 58%, but on follow up beyond 8 weeks, this difference was not maintained. Whether pre-FMT antibiotic administration was beneficial was not able to be determined due to the limited number of patients receiving antibiotics and varying antibiotic regimens. No serious adverse events were reported. CONCLUSIONS Preliminary studies suggest that FMT may be an effective therapy in Crohn's disease. However large controlled trials are needed. No serious safety concerns have been identified.
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Affiliation(s)
- Sasha R Fehily
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Chamara Basnayake
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
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18
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Żebrowska P, Łaczmańska I, Łaczmański Ł. Future Directions in Reducing Gastrointestinal Disorders in Children With ASD Using Fecal Microbiota Transplantation. Front Cell Infect Microbiol 2021; 11:630052. [PMID: 33718277 PMCID: PMC7952982 DOI: 10.3389/fcimb.2021.630052] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 01/22/2021] [Indexed: 12/16/2022] Open
Abstract
Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.
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Affiliation(s)
- Paulina Żebrowska
- Laboratory of Genomics and Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | | | - Łukasz Łaczmański
- Laboratory of Genomics and Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
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19
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Ding X, Yang X, Wang H. Methodology, efficacy and safety of fecal microbiota transplantation in treating inflammatory bowel disease. MEDICINE IN MICROECOLOGY 2020. [DOI: 10.1016/j.medmic.2020.100028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Zhao HL, Chen SZ, Xu HM, Zhou YL, He J, Huang HL, Xu J, Nie YQ. Efficacy and safety of fecal microbiota transplantation for treating patients with ulcerative colitis: A systematic review and meta-analysis. J Dig Dis 2020; 21:534-548. [PMID: 33439534 DOI: 10.1111/1751-2980.12933] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 07/30/2020] [Accepted: 08/14/2020] [Indexed: 01/30/2023]
Abstract
OBJECTIVES To assess the effect of donor selection, stool procedures and pretreatment with antibiotics on the efficacy and safety of fecal microbiota transplantation (FMT)-treated ulcerative colitis (UC). METHODS A systematic review and meta-analysis was conducted including studies on UC treated with FMT as the primary therapeutic agent published up to June 30, 2020. Primary end-point data included clinical remission (CR) or CR combined with endoscopic remission. RESULTS A total of 37 studies (seven random controlled trials [RCTs], five controlled and 25 uncontrolled cohort studies) and 959 patients with UC were enrolled. In controlled cohort studies and RCTs, FMT had a significantly greater benefit than placebo (pooled odds ratio [P-OR] 3.392, 95% CI 2.196-5.240, P < 0.001), with no heterogeneity (I2 = 0%). Furthermore, administration of FMT via the lower gastrointestinal (GI) tract was more effective in achieving CR than via the upper GI tract (44.3% vs 31.7%). The remission rate was also higher when the total stool dosage was over 275 g compared with less than 275 g (51.9% vs 29.5%). Overall, the incidence of serious adverse events of FMT was 5.9%. There was no significant difference between single and multiple donors, fresh and frozen stool sample used, and whether or not antibiotic pretreatment was administered before FMT. CONCLUSION FMT administration via the lower GI tract and using higher dosage appear to be effective and safe in inducing remission of active UC.
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Affiliation(s)
- Hai Lan Zhao
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Shu Zhen Chen
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Hao Ming Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - You Lian Zhou
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Jie He
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Hong Li Huang
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Jing Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Yu Qiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
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Quagliariello A, Del Chierico F, Reddel S, Russo A, Onetti Muda A, D’Argenio P, Angelino G, Romeo EF, Dall’Oglio L, De Angelis P, Putignani L. Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations. Microorganisms 2020; 8:microorganisms8101486. [PMID: 32992653 PMCID: PMC7599854 DOI: 10.3390/microorganisms8101486] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/11/2020] [Accepted: 09/23/2020] [Indexed: 01/10/2023] Open
Abstract
Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.
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Affiliation(s)
- Andrea Quagliariello
- Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.Q.); (S.R.)
| | - Federica Del Chierico
- Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.Q.); (S.R.)
- Correspondence: ; Tel.: +39-0668594061; Fax: +39-0668592904
| | - Sofia Reddel
- Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.Q.); (S.R.)
| | - Alessandra Russo
- Department of Laboratories, Unit of Parasitology, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Andrea Onetti Muda
- Department of Laboratories, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Patrizia D’Argenio
- Academic Department of Pediatrics, Unit of Immune and Infectious Diseases, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Giulia Angelino
- Digestive Surgery and Endoscopy Unit, Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy; (G.A.); (E.F.R.); (L.D.); (P.D.A.)
| | - Erminia Francesca Romeo
- Digestive Surgery and Endoscopy Unit, Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy; (G.A.); (E.F.R.); (L.D.); (P.D.A.)
| | - Luigi Dall’Oglio
- Digestive Surgery and Endoscopy Unit, Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy; (G.A.); (E.F.R.); (L.D.); (P.D.A.)
| | - Paola De Angelis
- Digestive Surgery and Endoscopy Unit, Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy; (G.A.); (E.F.R.); (L.D.); (P.D.A.)
| | - Lorenza Putignani
- Department of Laboratories, Unit of Parasitology and Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
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22
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Caldeira LDF, Borba HH, Tonin FS, Wiens A, Fernandez-Llimos F, Pontarolo R. Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis. PLoS One 2020; 15:e0238910. [PMID: 32946509 PMCID: PMC7500646 DOI: 10.1371/journal.pone.0238910] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 08/25/2020] [Indexed: 02/07/2023] Open
Abstract
Objectives Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease. Methods Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted. Results Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn’s disease patients seemed to benefit more from the procedure. Conclusions The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn’s disease.
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Affiliation(s)
| | - Helena H. Borba
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Fernanda S. Tonin
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Astrid Wiens
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Fernando Fernandez-Llimos
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Roberto Pontarolo
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
- * E-mail:
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Park S, Kang Y, Koh H, Kim S. Increasing incidence of inflammatory bowel disease in children and adolescents: significance of environmental factors. Clin Exp Pediatr 2020; 63:337-344. [PMID: 32024322 PMCID: PMC7462828 DOI: 10.3345/cep.2019.00500] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 11/22/2019] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated disease of the intestinal tract. Although its prevalence is reportedly lower in Asia than in Western countries, the rapid increase in the incidence of IBD has drawn attention to its etiology, including genetic susceptibility and environmental factors. Specifically, recent studies concerning dietary treatments and intestinal microbiota suggest that these factors may interact with the immune system, and the imbalance of this relationship may lead to immune dysregulation in IBD. Changes in diet or alterations in the composition of the intestinal microbiota may be associated with the increasing incidence of IBD in Asia. Here, we aim to review recent studies on the role of diet and intestinal microbiota in IBD pathogenesis and the results of the investigations performed to modulate these factors.
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Affiliation(s)
- Sowon Park
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Pediatric IBD Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yunkoo Kang
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Wonju Severance Christian Hospital, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Hong Koh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Pediatric IBD Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Kim
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Pediatric IBD Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea
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24
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Ghouri YA, Tahan V, Shen B. Secondary causes of inflammatory bowel diseases. World J Gastroenterol 2020; 26:3998-4017. [PMID: 32821067 PMCID: PMC7403802 DOI: 10.3748/wjg.v26.i28.3998] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/15/2020] [Accepted: 07/16/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD), conventionally consist of Crohn's disease (CD) and ulcerative colitis. They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors. The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis, which in turn is triggered due to exposure to various inciting environmental factors. But there is no clearly defined etiology of IBD and this type of disease is termed as "idiopathic IBD", "classic IBD", or "primary IBD". We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions, and we consider this form of de novo IBD as "secondary IBD". Currently known factors that are potentially responsible for giving rise to secondary IBD are medications; bowel altering surgeries and transplantation of organs, stem cells or fecal microbiome. Medications associated with the development of secondary IBD include; immunomodulators, anti-tumor necrosis factor alpha agents, anti-interleukin agents, interferons, immune stimulating agents and checkpoint inhibitors. Colectomy can in some cases give rise to de novo CD, pouchitis of the ileal pouch, or postcolectomy enteritis syndrome. After solid organ transplantation or hematopoietic stem cell transplantation, the recipient may develop de novo IBD or IBD flare. Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.
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Affiliation(s)
- Yezaz A Ghouri
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri- School of Medicine, Columbia, MO 65201, United States
| | - Veysel Tahan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri- School of Medicine, Columbia, MO 65201, United States
| | - Bo Shen
- Department of Medicine and Surgery, Interventional IBD Center, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY 10032, United States
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Abstract
PURPOSE OF REVIEW Administration of fecal material into the gastrointestinal tract, termed fecal microbiota transplantation (FMT), is increasingly recognized as an effective treatment option for recurrent Clostridium difficile infection (RCDI). The impact of FMT on host microbial communities and subsequent disease states has also been explored in recent years for conditions as varied as inflammatory bowel disease especially ulcerative colitis, metabolic diseases, such as diabetes, graft-versus-host disease in hematopoietic stem cell transplant recipients, and autism and autism spectrum disorders. The purpose of this article is to review the evidence for FMT as a treatment option in various pediatric illnesses. RECENT FINDINGS The rate of C. difficile infection is rising among children, and is associated with significant morbidity and disease, with recurrence in up to 20% of pediatric patients. Several randomized controlled trials evaluating the utility of FMT in RCDI in comparison to vancomycin have been published and demonstrate high rates of efficacy between 70 and 100%. In addition, the safety of FMT in the treatment of RCDI has been well described in the adult population, with several pediatric case series demonstrating similar rates of tolerability and adverse events. FMT in ulcerative colitis appears promising, especially with multiple infusions administered via the lower gastrointestinal tract. However, there are several limitations, including the lack of uniformity of protocols used, source of FMT, route of administration and the lack of standardization of concomitant therapies. The data on usage of FMT for other indications are preliminary and limited. SUMMARY FMT is recognized as an effective treatment option for RCDI and is increasing sought by parents. Although limited, pediatric studies to date on the use of FMT for RCDI demonstrate similar efficacy rates as in the adult population. FMT has been proposed as a treatment option for an increasing number of pediatric conditions, and additional studies are needed to delineate the efficacy of FMT outside of RCDI, as well as its short and long-term impacts on human health.
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26
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Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation. J Immunol Res 2019; 2019:1603758. [PMID: 31143780 PMCID: PMC6501133 DOI: 10.1155/2019/1603758] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 04/01/2019] [Indexed: 12/19/2022] Open
Abstract
Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient's intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.
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Dalzell AM, Ba'Ath ME. Paediatric inflammatory bowel disease: review with a focus on practice in low- to middle-income countries. Paediatr Int Child Health 2019; 39:48-58. [PMID: 30900526 DOI: 10.1080/20469047.2019.1575056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Inflammatory bowel disease (IBD) should be considered in any child with a persistently altered bowel habit. Growth failure may be a consequence and there may also be extra-intestinal manifestations. Oesophago-gastroduodenoscopy and colonoscopy and conventional histopathology are the diagnostic tools of choice in IBD. The identification and management of children with IBD in resource-poor settings is difficult and there are few data on its prevalence in low- and middle-income countries. The main challenges are a lack of resources and infrastructure including trained personnel in settings where there are other priorities for maintaining the health and wellbeing of children. The identification and management of children with inflammatory bowel conditions often depends on the enthusiasm, skill and commitment of a few dedicated individuals. Abbreviations: ADA: Adalimumab; CD: Crohn disease; ECCO: European Crohn's and Colitis Organisation; EEN: exclusive enteral nutrition; ESPGHAN: European Society for Paediatric Gastroenterology Hepatology and Nutrition; FMT: faecal microbiota transplantation; GDP: gross domestic product; HIC: high-income countries; IBD: inflammatory bowel disease; IBDU: inflammatory bowel disease unclassified; IC: ileocolonoscopy; IFX: infliximab; IPAA: ileal pouch anal anastomosis; LMIC: low- and middle-income countries; MH: mucosal healing; OGD: oesophago-gastroduodenoscopy; PCDAI: Paediatric Crohn's Disease Activity Index; PIBD: paediatric inflammatory bowel disease; PUCAI: Paediatric Ulcerative Colitis Activity Index; UC: ulcerative colitis; UGIT: upper gastrointestinal tract; VEO-IBD: very early-onset IBD; WLE: white light endoscopy; 5-ASA: 5 aminosalicylic acid; 6-MP: 6-mercaptopurine.
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The Safety of Fecal Microbiota Transplantation for Crohn's Disease: Findings from A Long-Term Study. Adv Ther 2018; 35:1935-1944. [PMID: 30328062 PMCID: PMC6223988 DOI: 10.1007/s12325-018-0800-3] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2018] [Indexed: 12/12/2022]
Abstract
Introduction Fecal microbiota transplantation (FMT) has been used as a potential treatment option for Crohn’s disease (CD). However, there is still lack of safety and efficacy evidence based on large samples of CD undergoing FMT. This study aimed to evaluate the risk factors of adverse event (AE) in the long term and the efficacy of FMT in the short term for patients with CD. Methods FMT via mid-gut for mild to severe CD in a single center trial (NCT01793831) was performed from October 2012 to December 2016. The possible factors with AE and efficacy after FMT were prospectively recorded. Results A total of 184 frequencies of FMT were performed for 139 patients who received FMT. During 1 month after FMT, 13.6% of mild AEs occurred, including increased frequency of defecation, fever, abdominal pain, flatulence, hematochezia, vomiturition, bloating and herpes zoster. No AE beyond 1 month was observed. Therefore, a 1 month cut-off could be suggested to define short-term and long-term AEs of FMT. Among the possible risk factors, only fecal microbiota purification methods were closely associated with the occurrence of AEs. The rate of AEs in patients undergoing manual methods for the preparation of fecal microbiota was 21.7%, which was significantly higher than the 8.7% in those experiencing an automatic method. The manual or automatic purification of fecal microbiota had no correlation with the efficacy of FMT. Conclusion This cohort study based on the largest size of cases demonstrated that improved fecal microbiota preparation reduced the rates of AEs, but did not affect the clinical efficacy in patients with CD.
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Huang L, Gao R, Yu N, Zhu Y, Ding Y, Qin H. Dysbiosis of gut microbiota was closely associated with psoriasis. SCIENCE CHINA-LIFE SCIENCES 2018; 62:807-815. [PMID: 30264198 DOI: 10.1007/s11427-018-9376-6] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Accepted: 08/09/2018] [Indexed: 02/06/2023]
Abstract
Psoriasis is an autoimmune disease and gut microbiota participate in the establishment of intestinal immunity. This study was performed to identify the fecal microbial composition of psoriasis patients, and investigated the influence of subgroup (type and severity) on the fecal microbial composition, and to define the key microbiota in the pathogenesis of psoriasis. Fecal samples from 35 psoriasis patients and 27 healthy controls were sequenced by 16S rRNA and then analyzed by informatics methods. We found that the microbiota of the psoriasis group differed from that of the heathy group. The relative abundances of Firmicutes and Bacteroidetes were inverted at the phylum level, and 16 kinds of phylotype at the genus level were found with significant difference. No microbial diversity and composition alteration were observed among the four types of psoriasis. The microbiota of psoriasis patients in the severe state differs from those of psoriasis patients with more mild conditions and also the healthy controls. The veillonella in fecal microbiota showed a positive relationship with h-CRP in blood. This research proved that psoriasis patients have a significant disturbed microbiota profiles. Further study of psoriasis based on microbiota may provide novel insights into the pathogenesis of psoriasis and more evidence for the prevention and treatment of psoriasis.
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Affiliation(s)
- Linsheng Huang
- Shanghai Clinical College, Anhui Medical University, Shanghai, 200072, China.,Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, 200072, China
| | - Renyuan Gao
- Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, 200072, China
| | - Ning Yu
- Department of Dermatology, Shanghai Dermatology Hospital, Shanghai, 200043, China
| | - Yefei Zhu
- Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, 200072, China
| | - Yangfeng Ding
- Department of Dermatology, Shanghai Dermatology Hospital, Shanghai, 200043, China.
| | - Huanlong Qin
- Shanghai Clinical College, Anhui Medical University, Shanghai, 200072, China. .,Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, 200072, China.
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