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Hou S, Yu J, Li Y, Zhao D, Zhang Z. Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413197. [PMID: 40013938 PMCID: PMC11967859 DOI: 10.1002/advs.202413197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/22/2025] [Indexed: 02/28/2025]
Abstract
This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.
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Affiliation(s)
- Shuna Hou
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Jiachen Yu
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Yongshuang Li
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Duoyi Zhao
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Zhiyu Zhang
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
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Azarfarin M, Moradikor N, Matin S, Dadkhah M. Association Between Stress, Neuroinflammation, and Irritable Bowel Syndrome: The Positive Effects of Probiotic Therapy. Cell Biochem Funct 2024; 42:e70009. [PMID: 39487668 DOI: 10.1002/cbf.70009] [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: 06/22/2024] [Revised: 09/23/2024] [Accepted: 10/14/2024] [Indexed: 11/04/2024]
Abstract
Stress refers to an organism's response to environmental threats in normal condition to maintain homeostasis in the body. In addition, strong inflammatory reactions induced by the hypothalamic-pituitary-adrenal (HPA) axis under stress condition during a long time. Reciprocally, chronic stress can induce the irritable bowel syndrome (IBS) which is a well-known gut disorder thereby play an important role in the promotion and pathophysiology of neuropsychiatric diseases. It has been demonstrated that leaky gut is a hallmark of IBS, leads to the entrance the microbiota into the bloodstream and consequent low-grade systemic inflammation. In the current review, we will discuss the mechanisms by which stress can influence the risk and severity of IBS and its relationship with neuroinflammation. Also, the role of probiotics in IBS co-existing with chronic stress conditions is highlighted.
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Affiliation(s)
- Maryam Azarfarin
- Department of Neuroscience, Faculty of Advanced Medical, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nasrollah Moradikor
- International Center for Neuroscience Research, Institute for Intelligent Research, Tbilisi, Georgia
| | - Somaieh Matin
- Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Masoomeh Dadkhah
- Lung Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
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Lee JY, Kim Y, Kim J, Kim JK. Fecal Microbiota Transplantation: Indications, Methods, and Challenges. J Microbiol 2024; 62:1057-1074. [PMID: 39557804 DOI: 10.1007/s12275-024-00184-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/25/2024] [Accepted: 10/16/2024] [Indexed: 11/20/2024]
Abstract
Over the past two decades, as the importance of gut microbiota to human health has become widely known, attempts have been made to treat diseases by correcting dysbiosis of gut microbiota through fecal microbiota transplantation (FMT). Apart from current knowledge of gut microbiota, FMT to treat disease has a long history, from the treatment of food poisoning in the fourth century to the treatment of Clostridioides difficile infections in the twentieth century. In 2013, FMT was recognized as a standard treatment for recurrent C. difficile because it consistently showed high efficacy. Though recurrent C. difficile is the only disease internationally recognized for FMT efficacy, FMT has been tested for other diseases and shown some promising preliminary results. Different FMT methods have been developed using various formulations and administration routes. Despite advances in FMT, some issues remain to be resolved, such as donor screening, manufacturing protocols, and unknown components in the fecal microbiota. In this review, we discuss the mechanisms, clinical indications, methods, and challenges of current FMT. We also discuss the development of alternative therapies to overcome the challenges of FMT.
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Affiliation(s)
- Jee Young Lee
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Yehwon Kim
- Department of Medicine, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Jiyoun Kim
- Department of Medicine, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Jiyeun Kate Kim
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea.
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El-Salhy M, Gilja OH, Hatlebakk JG. Factors underlying the long-term efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome. Microbes Infect 2024; 26:105372. [PMID: 38843950 DOI: 10.1016/j.micinf.2024.105372] [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: 01/17/2024] [Revised: 05/24/2024] [Accepted: 05/30/2024] [Indexed: 07/11/2024]
Abstract
The long-term effects of the transplant dose, its administration route and repeated faecal microbiota transplantation (FMT) on the outcomes of FMT for patients with irritable bowel syndrome (IBS) are unknown. This study included 171 patients (125 females and 46 males): 90 g of donor feces was administered into the large intestine (LI) in 58, into the small intestine (SI) in 57, and into the SI twice (repeated SI) in 56. The patients provided a fecal sample and completed five questionnaires at the baseline and at 2 years after FMT. Fecal bacteria and the dysbiosis index were analyzed using 16S rRNA gene PCR DNA amplification/probe. The response rates at 2 years after FMT were 47.2%, 80.9%, and 76.6% in the LI, SI, and repeated-SI groups, respectively. The response rate was significantly higher in the SI and repeated SI groups than in the LI group. IBS symptoms at 2 years after FMT were less severe in the SI and repeated-SI groups than in the LI group. Fluorescent signals of several bacteria were significantly correlated with IBS symptoms and fatigue after FMT. No long-term adverse events were observed. In conclusion, administering the transplant to the SI increased the long-term response rate and reduced IBS symptom severity compared with administering it to the LI, and led to the long-term colonization of beneficial bacteria. There was no long-term difference between one and two FMT procedures (www.clinicaltrials.gov: NCT04236843).
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Affiliation(s)
- Magdy El-Salhy
- Department of Medicine, Stord Hospital, Stord, Norway; Department of Clinical Medicine and Department of Gastroenterology, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
| | - Odd Helge Gilja
- Department of Clinical Medicine and Department of Gastroenterology, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway
| | - Jan Gunnar Hatlebakk
- Department of Clinical Medicine and Department of Gastroenterology, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway
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Lo SW, Hung TH, Lin YT, Lee CS, Chen CY, Fang CJ, Lai PC. Clinical efficacy and safety of faecal microbiota transplantation in the treatment of irritable bowel syndrome: a systematic review, meta-analysis and trial sequential analysis. Eur J Med Res 2024; 29:464. [PMID: 39289768 PMCID: PMC11409544 DOI: 10.1186/s40001-024-02046-5] [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: 02/19/2024] [Accepted: 08/30/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND The aim of this study is to evaluate the efficacy and safety of faecal microbiota transplantation (FMT) for the treatment of irritable bowel syndrome (IBS). METHODS We searched four databases for randomised controlled trials (RCTs) that compared FMT with a control intervention in patients with IBS. The revised Cochrane risk-of-bias (RoB) tool was chosen for appraisal. Meta-analysis with trial sequential analysis (TSA) was conducted. Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence (CoE). RESULTS We included 12 RCTs with a total of 615 participants. Meta-analyses showed no significant difference between the FMT and control groups in terms of clinical responses (relative risk [RR] = 1.44, 95% confidence interval [CI] 0.88-2.33) and changes in IBS Severity Scoring System (IBS-SSS) scores (standardised mean difference [SMD] = - 0.31, 95% CI - 0.72 to 0.09) and IBS Quality of Life (IBS-QOL) scores (SMD = 0.30, 95% CI - 0.09 to 0.69). Subgroup analysis revealed that in studies with low RoB and using endoscopy, nasojejunal tube and rectal enema delivery, FMT led to a significant improvement in clinical responses and changes in IBS-SSS and IBS-QOL scores. TSA suggested that the current evidence is inconclusive and that the CoE is very low. CONCLUSION This study suggests that patients with IBS may benefit from FMT especially when it is administered via endoscopy, nasojejunal tube or rectal enema. However, the certainty of evidence is very low. Further research is needed to confirm the efficacy and safety of FMT for IBS treatment. TRIAL REGISTRATION PROSPERO registration number CRD42020211002.
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Affiliation(s)
- Shao-Wei Lo
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
| | - Tsung-Hsuan Hung
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
| | - Yen-Tsen Lin
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
| | - Chun-Shen Lee
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
| | - Chiung-Yu Chen
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Ching-Ju Fang
- Medical Library, National Cheng Kung University, Tainan, Taiwan
- Department of Secretariat, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Pei-Chun Lai
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan.
- Department of Paediatrics, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
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Hartikainen AK, Jalanka J, Lahtinen P, Ponsero AJ, Mertsalmi T, Finnegan L, Crispie F, Cotter PD, Arkkila P, Satokari R. Fecal microbiota transplantation influences microbiota without connection to symptom relief in irritable bowel syndrome patients. NPJ Biofilms Microbiomes 2024; 10:73. [PMID: 39191760 PMCID: PMC11349920 DOI: 10.1038/s41522-024-00549-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 08/20/2024] [Indexed: 08/29/2024] Open
Abstract
Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients' clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient's microbiota in the colonization of donor's strains.
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Affiliation(s)
- Anna K Hartikainen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
| | - Jonna Jalanka
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Perttu Lahtinen
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Gastroenterology, Päijät-Häme Central Hospital, Lahti, Finland
| | - Alise J Ponsero
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- BIO5 Institute and Department of Biosystems Engineering, University of Arizona, Tucson, AZ, USA
| | - Tuomas Mertsalmi
- Department of Neurology, Helsinki University Hospital HUS, Helsinki, Finland
- Department of Clinical Neurosciences, University of Helsinki, HUS, PO Box 800, FI-00029, Helsinki, Finland
| | - Laura Finnegan
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
- APC Microbiome, Ireland, Cork, Ireland
| | - Fiona Crispie
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
- APC Microbiome, Ireland, Cork, Ireland
| | - Paul D Cotter
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
- APC Microbiome, Ireland, Cork, Ireland
| | - Perttu Arkkila
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| | - Reetta Satokari
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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Zhang Y, Wang S, Wang H, Cao M, Wang M, Zhang B, Xiao C, Zhu H, Du S. Efficacy of Donor-Recipient-Matched Faecal Microbiota Transplantation in Patients with IBS-D: A Single-Centre, Randomized, Double-Blind Placebo-Controlled Study. Digestion 2024; 105:457-467. [PMID: 39084197 DOI: 10.1159/000540420] [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: 12/12/2023] [Accepted: 07/14/2024] [Indexed: 08/02/2024]
Abstract
INTRODUCTION The imbalance in gut microbiota is contributing to the development and progression of IBS. FMT can improve the gut microbiota, and donor-recipient-matched FMT can help develop individualized treatment plans according to different enterotypes. This study aimed to explore the efficacy of donor-recipient-matched FMT in IBS with predominant diarrhoea (IBS-D) and evaluate its effects on gut microbiota. METHODS Twenty-seven patients with IBS-D were randomly divided into donor-recipient-matched FMT group (group P), random-donor FMT group (group R), and placebo group (group B). All participants received corresponding FMT treatment after filling in IBS-S, IBS-QoL, GSRS, and HADS questionnaires and having their stool samples collected at 4, 8, and 12 weeks after treatment. The improvement in the symptoms and the changes in the bacterial flora were analysed for three groups. RESULTS The IBS-SSS, IBS-QoL, GSRS, and anxiety scores of group P were significantly lower after treatment (p < 0.05). The IBS-QoL scores of group R were significantly lower after treatment (p < 0.05). Beta diversity analysis showed that the gut microbiota of group P had an obvious trend of classification after treatment. Seven bacterial genera were related to the differences in the IBS-SSS scores before and after treatment. CONCLUSION Donor-recipient-matched FMT significantly improved the clinical symptoms, quality of life, and anxiety scores of the patients with IBS-D than random-donor FMT.
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Affiliation(s)
- Yanli Zhang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Shuai Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Huifen Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Man Cao
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Miao Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Bangzhou Zhang
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Chuanxing Xiao
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Huiting Zhu
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Shiyu Du
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
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Wang Y, Hu Y, Shi P. A meta-analysis of randomized controlled trials evaluating the effectiveness of fecal microbiota transplantation for patients with irritable bowel syndrome. BMC Gastroenterol 2024; 24:217. [PMID: 38970007 PMCID: PMC11225114 DOI: 10.1186/s12876-024-03311-x] [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: 01/20/2024] [Accepted: 06/28/2024] [Indexed: 07/07/2024] Open
Abstract
OBJECTIVE Multiple randomized controlled trials (RCTs) have investigated the efficacy of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), but have yielded inconsistent results. We updated the short-term and long-term efficacy of FMT in treating IBS, and performed a first-of-its-kind exploration of the relationship between gut microbiota and emotions. METHODS We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library using various search strategies to identify all eligible studies. The inclusion criteria for data extraction were randomized controlled trials (RCTs) that investigated the efficacy of fecal microbiota transplantation (FMT) compared to placebo in adult patients (≥ 18 years old) with irritable bowel syndrome (IBS). A meta-analysis was then performed to assess the summary relative risk (RR) and corresponding 95% confidence intervals (CIs). RESULTS Out of 3,065 potentially relevant records, a total of 10 randomized controlled trials (RCTs) involving 573 subjects met the eligibility criteria for inclusion in the meta-analysis. The meta-analyses revealed no significant differences in short-term (12 weeks) (RR 0.20, 95% CI -0.04 to 0.44), long-term (52 weeks) global improvement (RR 1.38, 95% CI 0.87 to 2.21), besides short-term (12 weeks) (SMD - 48.16, 95% CI -102.13 to 5.81, I2 = 90%) and long-term (24 weeks) (SMD 2.16, 95% CI -60.52 to 64.83, I2 = 68%) IBS-SSS. There was statistically significant difference in short-term improvement of IBS-QoL (SMD 10.11, 95% CI 0.71 to 19.51, I2 = 82%), although there was a high risk of bias. In terms of long-term improvement (24 weeks and 54 weeks), there were no significant differences between the FMT and placebo groups (SMD 7.56, 95% CI 1.60 to 13.52, I2 = 0%; SMD 6.62, 95% CI -0.85 to 14.08, I2 = 0%). Sensitivity analysis indicated that there were visible significant effects observed when the criteria were based on Rome IV criteria (RR 16.48, 95% CI 7.22 to 37.62) and Gastroscopy (RR 3.25, 95%CI 2.37 to 4.47), Colonoscopy (RR 1.42, 95% CI 0.98 to 2.05). when using mixed stool FMT based on data from two RCTs, no significant difference was observed (RR 0.94, 95% CI 0.66 to -1.34). The remission of depression exhibited no significant difference between the FMT and placebo groups at the 12-week mark (SMD - 0.26, 95% CI -3.09 to 2.58), and at 24 weeks (SMD - 2.26, 95% CI -12.96 to 8.45). Furthermore, major adverse events associated with FMT were transient and self-limiting. DISCUSSION Based on the available randomized controlled trials (RCTs), the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term. The differential results observed in subgroup analyses raise questions about the accurate identification of suitable populations for FMT. Further investigation is needed to better understand the reasons behind these inconsistent findings and to determine the true potential of FMT as a treatment for IBS.
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Affiliation(s)
- Yu Wang
- Yuncheng Central Hospital affiliated of Shanxi Medical University, Shanxi, 044000, China
| | - Yongmei Hu
- Yuncheng Central Hospital affiliated of Shanxi Medical University, Shanxi, 044000, China
| | - Ping Shi
- Yuncheng Central Hospital affiliated of Shanxi Medical University, Shanxi, 044000, China.
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Yadegar A, Bar-Yoseph H, Monaghan TM, Pakpour S, Severino A, Kuijper EJ, Smits WK, Terveer EM, Neupane S, Nabavi-Rad A, Sadeghi J, Cammarota G, Ianiro G, Nap-Hill E, Leung D, Wong K, Kao D. Fecal microbiota transplantation: current challenges and future landscapes. Clin Microbiol Rev 2024; 37:e0006022. [PMID: 38717124 PMCID: PMC11325845 DOI: 10.1128/cmr.00060-22] [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] [Indexed: 06/14/2024] Open
Abstract
SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main "whole gut microbiome replacement" strategy and has been integrated into clinical practice guidelines for treating recurrent Clostridioides difficile infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease (IBD), metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research. However, the complex and variable nature of FMT makes it challenging to address its precise functionality and to assess clinical efficacy and safety in different disease contexts. In this review, we outline clinical applications, efficacy, durability, and safety of FMT and provide a comprehensive assessment of its procedural and administration aspects. The clinical applications of FMT in children and cancer immunotherapy are also described. We focus on data from human studies in IBD in contrast with rCDI to delineate the putative mechanisms of this treatment in IBD as a model, including colonization resistance and functional restoration through bacterial engraftment, modulating effects of virome/phageome, gut metabolome and host interactions, and immunoregulatory actions of FMT. Furthermore, we comprehensively review omics technologies, metagenomic approaches, and bioinformatics pipelines to characterize complex microbial communities and discuss their limitations. FMT regulatory challenges, ethical considerations, and pharmacomicrobiomics are also highlighted to shed light on future development of tailored microbiome-based therapeutics.
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Affiliation(s)
- Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Haggai Bar-Yoseph
- Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Tanya Marie Monaghan
- National Institute for Health Research Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | - Sepideh Pakpour
- School of Engineering, Faculty of Applied Sciences, UBC, Okanagan Campus, Kelowna, British Columbia, Canada
| | - Andrea Severino
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Ed J Kuijper
- Center for Microbiota Analysis and Therapeutics (CMAT), Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Wiep Klaas Smits
- Center for Microbiota Analysis and Therapeutics (CMAT), Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Elisabeth M Terveer
- Center for Microbiota Analysis and Therapeutics (CMAT), Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Sukanya Neupane
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Javad Sadeghi
- School of Engineering, Faculty of Applied Sciences, UBC, Okanagan Campus, Kelowna, British Columbia, Canada
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Estello Nap-Hill
- Department of Medicine, Division of Gastroenterology, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
| | - Dickson Leung
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Karen Wong
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Dina Kao
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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Chen J, Lan H, Li C, Xie Y, Cheng X, Xia R, Ke C, Liang X. Gut microbial signatures of patients with diarrhea-predominant irritable bowel syndrome and their healthy relatives. J Appl Microbiol 2024; 135:lxae118. [PMID: 38849305 DOI: 10.1093/jambio/lxae118] [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: 09/19/2023] [Revised: 04/24/2024] [Accepted: 05/12/2024] [Indexed: 06/09/2024]
Abstract
AIMS Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, encompassing diarrhea-predominant irritable bowel syndrome (IBS-D). Here, we utilized 16S rDNA gene sequencing to identify potential microbial drivers of IBS-D. METHODS AND RESULTS A total of 30 healthy relatives and 27 patients with IBS-D were recruited. Clinical data and fecal samples were collected from patients and controls. 16S rDNA gene sequencing was performed to obtain fecal bacterial data. Differences in community composition were evaluated utilizing analysis of similarity (ANOSIM) using Bray-Curtis dissimilarity. The Wilcoxon rank sum test was used to compare differences in taxa and functional pathways. Finally, the key gut microbiota was identified using the random forest algorithm. Gut microbiota diversity, estimated through the Observe, Chao1, and abundance-based coverage estimator (ACE) indices, was significantly lower in the IBS-D patients than in the healthy relatives. ANOSIM analysis further confirmed significant differences in the composition of the gut microbiota between IBS-D patients and healthy relatives, with an R value of 0.106 and a P-value of 0.005. Notably, the IBS-D patients exhibited a significant enrichment of specific bacterial genera, including Fusicatenibacter, Streptococcus, and Klebsiella, which may possess potential pathogenic properties. In particular, the bacterial genus Klebsiella demonstrated a positive correlation with irritable bowel syndrome severity scoring system scores. Conversely, healthy subjects showed enrichment of bacterial genera such as Alistipes, Akkermansia, and Dialister, which may be beneficial bacteria in IBS-D. Utilizing the random forest model, we developed a discriminative model for IBS-D based on differential bacterial genera. This model exhibited impressive performance, with an area under the curve value of 0.90. Additionally, our analysis did not reveal any gender-specific differences in the microbiota community composition among IBS-D patients. CONCLUSIONS Our findings offer preliminary insights into the potential relationship between intestinal microbiota and IBS-D. The identification model for IBS-D, grounded in gut microbiota, holds promising prospects for improving early diagnosis of IBS-D.
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Affiliation(s)
- Jie Chen
- Department of Gastroenterology, Northern Jiangsu People's Hospital, Yangzhou 225001, China
| | - Haibo Lan
- Department of Constipation, Chengdu Anorectal Hospital, Chengdu 610000, China
| | - Chenmeng Li
- Department of Clinical Laboratory, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen 361003, China
| | - Yongli Xie
- Department of Endocrinology, Pingxiang People's Hospital, Pingxiang 337000, China
| | - Xianhui Cheng
- Xiamen Treatgut Biotechnology Co., Ltd, Xiamen 361101, China
| | - Rongmu Xia
- Xiamen Treatgut Biotechnology Co., Ltd, Xiamen 361101, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350003, China
| | - Chunlin Ke
- Department of Radiotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Xuyang Liang
- Department of Gastroenterology, The Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People's Hospital of Lianyungang, Lianyungang 222061, China
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Dai C, Huang YH, Jiang M. Fecal microbiota transplantation for irritable bowel syndrome: Current evidence and perspectives. World J Gastroenterol 2024; 30:2179-2183. [PMID: 38690018 PMCID: PMC11056919 DOI: 10.3748/wjg.v30.i16.2179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Revised: 02/14/2024] [Accepted: 04/01/2024] [Indexed: 04/26/2024] Open
Abstract
In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology. We focus specifically on the mechanisms un-derlying the effects of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), the factors which affect the outcomes of FMT in IBS patients, and challenges. FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS. The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials, yielding divergent outcomes. The current frontier in this field seeks to elucidate these variations, underscore the existing knowledge gaps that necessitate exploration, and provide a guideline for successful FMT imple-mentation in IBS patients. At the same time, the application of FMT as a treatment for IBS confronts several challenges.
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Affiliation(s)
- Cong Dai
- Department of Gastroenterology, First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Yu-Hong Huang
- Department of Gastroenterology, First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Min Jiang
- Department of Gastroenterology, First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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12
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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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13
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Hao W, Ma Q, Wang L, Yuan N, Gan H, He L, Li X, Huang J, Chen J. Gut dysbiosis induces the development of depression-like behavior through abnormal synapse pruning in microglia-mediated by complement C3. MICROBIOME 2024; 12:34. [PMID: 38378622 PMCID: PMC10877840 DOI: 10.1186/s40168-024-01756-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 01/04/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND Remodeling eubiosis of the gut microenvironment may contribute to preventing the occurrence and development of depression. Mounting experimental evidence has shown that complement C3 signaling is associated with the pathogenesis of depression, and disruption of the gut microbiota may be an underlying cause of complement system activation. However, the mechanism by which complement C3 participates in gut-brain crosstalk in the pathogenesis of depression remains unknown. RESULTS In the present study, we found that chronic unpredictable mild stress (CUMS)-induced mice exhibited obvious depression-like behavior as well as cognitive impairment, which was associated with significant gut dysbiosis, especially enrichment of Proteobacteria and elevation of microbiota-derived lipopolysaccharides (LPS). In addition, peripheral and central complement C3 activation and central C3/CR3-mediated aberrant synaptic pruning in microglia have also been observed. Transplantation of gut microbiota from CUMS-induced depression model mice into specific pathogen-free and germ-free mice induced depression-like behavior and concomitant cognitive impairment in the recipient mice, accompanied by increased activation of the complement C3/CR3 pathway in the prefrontal cortex and abnormalities in microglia-mediated synaptic pruning. Conversely, antidepressants and fecal microbiota transplantation from antidepressant-treated donors improved depression-like behaviors and restored gut microbiome disturbances in depressed mice. Concurrently, inhibition of the complement C3/CR3 pathway, amelioration of abnormal microglia-mediated synaptic pruning, and increased expression of the synapsin and postsynaptic density protein 95 were observed. Collectively, our results revealed that gut dysbiosis induces the development of depression-like behaviors through abnormal synapse pruning in microglia-mediated by complement C3, and the inhibition of abnormal synaptic pruning is the key to targeting microbes to treat depression. CONCLUSIONS Our findings provide novel insights into the involvement of complement C3/CR3 signaling and aberrant synaptic pruning of chemotactic microglia in gut-brain crosstalk in the pathogenesis of depression. Video Abstract.
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Affiliation(s)
- Wenzhi Hao
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Qingyu Ma
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Lu Wang
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Naijun Yuan
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Hua Gan
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Liangliang He
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Xiaojuan Li
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
| | - Junqing Huang
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
| | - Jiaxu Chen
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
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14
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El-Salhy M, Gilja OH, Hatlebakk JG. Factors affecting the outcome of fecal microbiota transplantation for patients with irritable bowel syndrome. Neurogastroenterol Motil 2024; 36:e14641. [PMID: 37427566 DOI: 10.1111/nmo.14641] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 05/30/2023] [Accepted: 06/24/2023] [Indexed: 07/11/2023]
Abstract
BACKGROUND A previous study that introduced a Fecal microbiota transplantation (FMT) protocol with a high efficacy applied a combination of favorable factors. AIMS The present study aimed to evaluate some of these factors. METHODS This study included 186 patients with IBS randomized 1:1:1 into transplant administered to the colon (single LI), to the duodenum (single SI), or to the duodenum twice with a 1-week interval (repeated SI). The patients provided a fecal sample and were asked to complete five questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and dysbiosis index (DI) were analyzed using 16S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9. RESULTS The response rate was significantly higher in single SI than in single LI at 12 months after FMT. Symptoms and quality of life improved in all the treated groups at all time intervals after FMT. The abdominal symptoms were significantly reduced and the quality of life improved for repeated SI compared with for single SI. DI significantly decreased in all the treated groups at all observation times after FMT. The bacterial profiles changed in all groups at all observation intervals. However, these changes differed between single LI and single SI/repeated SI. CONCLUSION Administrating transplant to the small intestine had a long-term higher response rate than that administrated to the large intestine, and led to long-term colonization of beneficial bacteria. Repeating FMT had more effect on symptoms and quality of life than a single FMT. (www. CLINICALTRIALS gov: NCT04236843).
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Affiliation(s)
- Magdy El-Salhy
- Department of Research and Innovation, Helse Fonna, Stord, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Odd Helge Gilja
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Jan Gunnar Hatlebakk
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
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15
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Hartikainen AK, Khan I, Karjalainen EK, Renkonen-Sinisalo L, Arkkila P, Jalanka J, Lepistö AH, Satokari R. Microbiota and mucosal gene expression of fecal microbiota transplantation or placebo treated patients with chronic pouchitis. Gut Microbes 2024; 16:2295445. [PMID: 38214604 PMCID: PMC10793679 DOI: 10.1080/19490976.2023.2295445] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 12/12/2023] [Indexed: 01/13/2024] Open
Abstract
Altered microbiota and impaired host immune function have been linked to the pathogenesis of pouchitis. We used 16S rRNA gene sequencing and RNA sequencing data from a previous randomized clinical trial (RCT) on fecal microbiota transplantation (FMT) therapy in 26 chronic pouchitis patients with one-year follow-up. We analyzed changes in both luminal and mucosal microbiota composition, as well as in host mucosal gene expression to gain insights into the host-microbiota interactions possibly underlying clinical outcomes of the patients. Antibiotic type and pattern of use were significant drivers of the luminal microbiota at baseline. Differential gene expression analysis indicated transition from ileal to colonic gene expression in the pouch, and upregulation in inflammation- and immune system-related pathways in the pouch. At 4 weeks, the non-relapsed FMT patients had a lower microbiota dissimilarity to the donor than the non-relapsed placebo patients (p = .02). While two FMT-treated patients showed a shift toward the donor's microbiota during the one-year follow-up, the overall FMT microbiota modulation effect was low. Patient's luminal and mucosal microbiota profiles were unstable in both FMT and placebo groups. Expression of the chemokine receptor CXCR4 was downregulated at 52 weeks compared to the baseline in the non-relapsed patients in both FMT and placebo groups. Microbiota modulation by FMT seems to be low in this patient group. The microbiota composition or alterations did not explain the relapse status of the patients. Some evidence for remission-related host gene expression pattern was found; specifically, CXCR4 expression may have a role in sustained remission.
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Affiliation(s)
- Anna K. Hartikainen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Imran Khan
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Essi K. Karjalainen
- Department of Gastrointestinal Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Laura Renkonen-Sinisalo
- Department of Gastrointestinal Surgery, Helsinki University Hospital, Helsinki, Finland
- Genome-Scale Biology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Perttu Arkkila
- Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
- Department of Medicine, University of Helsinki, Helsinki, Finland
| | - Jonna Jalanka
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Anna H. Lepistö
- Department of Gastrointestinal Surgery, Helsinki University Hospital, Helsinki, Finland
- Genome-Scale Biology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Reetta Satokari
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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16
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Zhang Z, Li Q, Zhang S, Liu Y, Lu G, Wen Q, Cui B, Zhang F, Zhang F. Washed microbiota transplantation targeting both gastrointestinal and extraintestinal symptoms in patients with irritable bowel syndrome. Prog Neuropsychopharmacol Biol Psychiatry 2023; 127:110839. [PMID: 37562707 DOI: 10.1016/j.pnpbp.2023.110839] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 07/27/2023] [Accepted: 08/07/2023] [Indexed: 08/12/2023]
Abstract
OBJECTIVE Fecal microbiota transplantation (FMT) has been reported with the treatment potential for irritable bowel syndrome (IBS). However, the knowledge of its effect on extraintestinal symptoms of IBS is limited. This study aimed to evaluate the efficacy of the improved methodology of FMT, washed microbiota transplantation (WMT), on sleep disturbances, and psychological and gastrointestinal symptoms among patients with IBS. METHODS This was a prospective observational study involving patients with IBS who underwent WMT. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Gastrointestinal Symptom Rating Scale (GSRS) and IBS Severity Scoring System (IBS-SSS) were used to evaluate gastrointestinal symptoms and IBS severity, respectively. The Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) were used to evaluate depression and anxiety, respectively. All the symptoms were evaluated at baseline and one month after WMT. A multiple logistic regression model was used to determine the predictive factors of sleep improvement one month after WMT. RESULTS Seventy-three patients with IBS were included in the study. Sleep quality (Z = -4.211, P < 0.001), anxiety (Z = -4.775, P < 0.001), depression (Z = -4.610, P < 0.001), gastrointestinal symptoms (Z = -5.364, P < 0.001), and IBS severity (Z = -6.468, P < 0.001) significantly improved one month after WMT in all patients. The scores of the five components of PSQI including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, and sleep disturbances decreased in 52 patients with poor sleep quality (all P < 0.05). Baseline sleep duration scores were identified as an independent predictive factor of sleep improvement one month after WMT in patients with poor sleep quality (OR 2.180 [95% CI = 1.017-4.673]; P = 0.045). Patients that experienced sleep improvement demonstrated greater alleviation in depression (Z = -1.990, P = 0.047) and IBS severity (Z = -2.486, P = 0.013) compared with patients without sleep improvement. CONCLUSION This study suggested that WMT might be a promising therapy for patients with IBS, especially those with comorbid sleep and psychological disorders.
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Affiliation(s)
- Zulun Zhang
- Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.
| | - Qianqian Li
- Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.
| | - Sheng Zhang
- Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.
| | - Yujie Liu
- Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.
| | - Gaochen Lu
- Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.
| | - Quan Wen
- Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.
| | - Bota Cui
- Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.
| | - Fuquan Zhang
- Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, China.
| | - Faming Zhang
- Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.
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17
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Liu XY, Wu SD. Fecal microbiota transplantation for treatment of irritable bowel syndrome: Current advances and future perspectives. Shijie Huaren Xiaohua Zazhi 2023; 31:922-932. [DOI: 10.11569/wcjd.v31.i22.922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/27/2023] [Accepted: 11/19/2023] [Indexed: 11/28/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a kind of functional gastroin-testinal disorder, characterized by recurrent abdominal pain and altered bowel habits. IBS adversely affects the quality of life of patients for the lack of effective treatment. The etiology of IBS remains poorly known. Previous studies suggested a possible role of gut dysbiosis in IBS pathogenesis. Fecal microbiota transplantation (FMT), which aims to reverse the gut dysbiosis, is a promising strategy in IBS management. In this review, we summarize the role of the gut microbiota in IBS pathogenesis from different aspects. We also review recent studies on efficacy evaluation of FMT in IBS. Besides, we discuss factors affecting the efficacy of FMT, hoping to provide a reference for future IBS treatment strategies targeting the gut microbiota.
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Affiliation(s)
- Xin-Yi Liu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
| | - Sheng-Di Wu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
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18
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Yau YK, Su Q, Xu Z, Tang W, Ching JYL, Mak JWY, Cheung CP, Fung M, Ip M, Chan PKS, Wu JCY, Chan FKL, Ng SC. Randomised clinical trial: Faecal microbiota transplantation for irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther 2023; 58:795-804. [PMID: 37667968 DOI: 10.1111/apt.17703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/11/2023] [Accepted: 08/23/2023] [Indexed: 09/06/2023]
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) has been shown to improve symptoms in a proportion of patients with irritable bowel syndrome (IBS). AIM We performed a randomised trial to assess the efficacy of FMT in patients with IBS. METHODS We randomised 56 patients with diarrhoea-predominant IBS 1:1 to FMT or placebo via the duodenal route at baseline and week 4. The primary outcome was > 50 points decrease in IBS severity scoring system (IBS-SSS) score at week 12. Secondary outcomes were improvement in bloating and change in gut microbiota at week 12. After 12-week follow-up, those in the placebo group were assigned to receive open-label FMT. RESULTS At week 12, 57.1% in the FMT group and 46.4% in the placebo group achieved the primary endpoint (p = 0.42). More patients receiving FMT than placebo had improvement in bloating (72% vs 30%; p = 0.005). In an open-label extension, 65.2% and 82.4% of patients achieved, respectively, the primary endpoint and improvement in bloating. Faecal microbiome of patients in the FMT group showed a reduction in bacteria like Ruminococcus gnavus and enrichment of bacteria such as Lawsonibacter at week 12, while no change in the placebo group. Functional analyses showed that the hydrogen sulphide-producing pathway decreased in patients who had FMT (p < 0.05) accompanied by a reduction in contributing bacteria. There were no serious adverse events related to FMT. CONCLUSION FMT performed twice at an interval of four weeks did not significantly reduce IBS-SSS score. However, more patients had improvement in abdominal bloating, which was associated with a reduction in hydrogen sulphide-producing bacteria. (ClinicalTrials.gov NCT03125564).
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Affiliation(s)
- Yuk Kam Yau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Qi Su
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Zhilu Xu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Whitney Tang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jessica Y L Ching
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
| | - Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Chun Pan Cheung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Matthew Fung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Margaret Ip
- Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Paul Kay Sheung Chan
- Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Justin Che Yuen Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Francis Ka Leung Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Siew C Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
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19
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Jamshidi P, Farsi Y, Nariman Z, Hatamnejad MR, Mohammadzadeh B, Akbarialiabad H, Nasiri MJ, Sechi LA. Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Mol Sci 2023; 24:14562. [PMID: 37834010 PMCID: PMC10573019 DOI: 10.3390/ijms241914562] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 09/05/2023] [Accepted: 09/15/2023] [Indexed: 10/15/2023] Open
Abstract
Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.
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Affiliation(s)
- Parnian Jamshidi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran or (P.J.)
| | - Yeganeh Farsi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
| | - Zahra Nariman
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
| | - Mohammad Reza Hatamnejad
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran
| | - Benyamin Mohammadzadeh
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran or (P.J.)
| | - Hossein Akbarialiabad
- NVH Global Health Academy, Nuvance Health, Danbury, CT 06810, USA
- St George and Sutherland Clinical School, UNSW Medicine, Sydney, NSW 2217, Australia
| | - Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran or (P.J.)
| | - Leonardo A. Sechi
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
- SC Microbiologia e Virologia, Azienda Ospedaliera Universitaria, 07100 Sassari, Italy
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20
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Salonen T, Jokinen E, Satokari R, Lahtinen P. Randomized, double-blinded, placebo-controlled pilot study: efficacy of faecal microbiota transplantation on chronic fatigue syndrome. J Transl Med 2023; 21:513. [PMID: 37516837 PMCID: PMC10386223 DOI: 10.1186/s12967-023-04227-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 05/25/2023] [Indexed: 07/31/2023] Open
Abstract
BACKGROUND Chronic fatigue syndrome (CFS) is a disabling illness of unknown aetiology. Disruption of gut microbiota may play a role in several neurological disorders. In this study, the effect of faecal microbiota transplantation (FMT) on fatigue severity and health-related quality of life (HRQOL) in patients with CFS was evaluated. METHODS Randomized, placebo-controlled pilot trial. Patients and researchers were blinded to treatment assignment. 11 patients with CFS (10 female and 1 male, mean age 42.2 years and mean duration of CFS 6.3 years) were randomly assigned to receive either FMT from a universal donor (n = 5) or autologous FMT (n = 6) via colonoscopy. Patients' HRQOL was assessed by using visual analog scale (VAS) and self-reporting questionnaires Modified Fatigue Impact Scale (MFIS), 15D and EQ-5D-3L. Patients' HRQOL was evaluated at baseline, and 1 and 6 months after the FMT. RESULTS The baseline VAS scores in the FMT and placebo groups were 62.4 and 76.0 (p = 0.29). 1-month scores were 60.0 and 73.7 and 6-months scores 72.8 and 69.5, respectively. Total MFIS scores in the FMT and placebo groups were 59.6 and 61.0 at the baseline (p = 0.80), 53.5 and 62.0 at 1 month and 58.6 and 56.2 at 6 months. Compared to the baseline scores, differences at 1 and 6 months were statistically insignificant both in VAS and in MFIS. The 15D and EQ-5D-3L profiles did not change after the FMT or placebo. FMT-related adverse events were not reported. CONCLUSION FMT was safe but did not relieve symptoms or improve the HRQOL of patients with CFS. Small number of study subjects limits the generalizability of these results. Trial Registration ClinicalTrials.gov Identifier NCT04158427, https://register. CLINICALTRIALS gov , date of registration 08/08/2019.
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Affiliation(s)
- Tapani Salonen
- Department of Medicine, Tampere University Hospital, BOX 2000, FIN, 33521, Tampere, Finland.
| | - Elina Jokinen
- Department of Gastroenterology, Tampere University Hospital, Tampere, Finland
| | - Reetta Satokari
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Perttu Lahtinen
- Department of Gastroenterology, Päijät-Häme Central Hospital, Lahti, Finland
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21
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Kriger-Sharabi O, Malnick SDH, Fisher D. Manipulation of the intestinal microbiome-a slow journey to primetime. World J Clin Cases 2023; 11:4975-4988. [PMID: 37583860 PMCID: PMC10424025 DOI: 10.12998/wjcc.v11.i21.4975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/17/2023] [Accepted: 06/30/2023] [Indexed: 07/26/2023] Open
Abstract
The gut microbiota has important functions in the regulation of normal body functions. Alterations of the microbiota are being increasingly linked to various disease states. The microbiome has been manipulated via the administration of stool from animals or humans, for more than 1000 years. Currently, fecal microbiota transplantation can be performed via endoscopic administration of fecal matter to the duodenum or colon or via capsules of lyophilized stools. More recently fecal microbial transplantation has been shown to be very effective for recurrent Clostridoides difficile infection (CDI). In addition there is some evidence of efficacy in the metabolic syndrome and its hepatic manifestation, metabolic associated fatty liver disease (MAFLD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We review the current literature regarding the microbiome and the pathogenesis and treatment of CDI, MAFLD, IBS and IBD.
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Affiliation(s)
- Ofra Kriger-Sharabi
- Institute of Gastroenterology, Assuta Medical Center, Ashdod 7747629, Israel
| | - Stephen D H Malnick
- Department of Internal Medicine, Kaplan Medical Center, Rehovot 76100, Israel
| | - David Fisher
- Department of Endocrinology, Soroka Medical Center, Beer Sheva POB 151, Israel
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22
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Mohan BP, Loganathan P, Khan SR, Garg G, Muthusamy A, Ponnada S, Pasam RT, Chandan S, Tuteja A. Fecal microbiota transplant delivered via invasive routes in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials. Indian J Gastroenterol 2023; 42:315-323. [PMID: 37247177 PMCID: PMC10225764 DOI: 10.1007/s12664-023-01373-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 04/15/2023] [Indexed: 05/30/2023]
Abstract
BACKGROUND AND AIMS Irritable bowel syndrome (IBS) results in significant loss of quality of life. Management guidelines do not recommend fecal microbiota transplant (FMT) for IBS based on weak evidence as refined data is lacking. We performed a systematic review and meta-analysis to ascertain the pooled clinical outcomes of FMT in IBS, delivered via invasive routes. METHODS Multiple databases were searched through January 2023 to identify studies that reported on FMT treatment in IBS by invasive routes. Standard meta-analysis methodology using the random-effects model was used. Heterogeneity was assessed by I2% and 95% predication interval. RESULTS Five studies were included. As many as 377 IBS patients were assessed, of which 238 received FMT and 139 received placebo. One study used nasojejunal tubes, one esophagogastroduodenoscopy and three colonoscopy for FMT delivery. FMT via colonoscopy was performed as a one-time procedure instilled into the cecum. Two studies used 30 g of stool from a single universal donor and one study used 50-80 g of pooled donor feces. The pooled odds ratio of improvement in IBS symptoms with FMT was significantly better as compared to that of placebo OR = 2.9 (95% CI [1.6-5.2, I2 = 62%, p < 0.001]). This was true for studies that exclusively used colonoscopy (OR = 2.1 [1.1-4.2, p = 0.04]). In the FMT arm, 10 patients (10.6%) reported abdomen pain and worsening of symptoms with bloating and six patients (6.3%) reported diarrhea. CONCLUSION FMT delivered via invasive routes, especially colonoscopy, demonstrated significant improvement in IBS symptoms. A single FMT consisting of 30 g or more of single universal donor feces instilled into the cecum is the predominant modality.
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Affiliation(s)
- Babu P Mohan
- Gastroenterology and Hepatology, Veterans Affairs Medical Center and University of Utah Health School of Medicine, 30 N 1900 E SOM 4R118, Salt Lake City, UT, 84132, USA.
| | | | - Shahab R Khan
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Gauri Garg
- Gastroenterology and Hepatology, Veterans Affairs Medical Center and University of Utah Health School of Medicine, 30 N 1900 E SOM 4R118, Salt Lake City, UT, 84132, USA
| | | | - Suresh Ponnada
- Internal Medicine, Carilion Roanoke Medical Center, Roanoke, VA, USA
| | | | - Saurabh Chandan
- Gastroenterology and Hepatology, CHI Creighton School of Medicine, Omaha, NE, USA
| | - Ashok Tuteja
- Gastroenterology and Hepatology, Veterans Affairs Medical Center and University of Utah Health School of Medicine, 30 N 1900 E SOM 4R118, Salt Lake City, UT, 84132, USA
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23
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Halkjær SI, Lo B, Cold F, Højer Christensen A, Holster S, König J, Brummer RJ, Aroniadis OC, Lahtinen P, Holvoet T, Gluud LL, Petersen AM. Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis. World J Gastroenterol 2023; 29:3185-3202. [PMID: 37346153 PMCID: PMC10280798 DOI: 10.3748/wjg.v29.i20.3185] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/06/2023] [Accepted: 04/18/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients’ quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as ‘gut dysbiosis’. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS.
AIM To assess the efficacy and safety of FMT for the treatment of IBS.
METHODS We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence.
RESULTS Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision.
CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.
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Affiliation(s)
- Sofie Ingdam Halkjær
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | - Bobby Lo
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | - Frederik Cold
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
| | | | - Savanne Holster
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70362, Sweden
| | - Julia König
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70362, Sweden
| | - Robert Jan Brummer
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70362, Sweden
| | - Olga C Aroniadis
- Department of Internal Medicine, Division of Gastroenterology, Renaissance School of Medicine, Stony Brook University Hospital, New York, NY 11794-8434, United States
| | - Perttu Lahtinen
- Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti 15850, Finland
- Department of Medicine, University of Helsinki, Helsinki 00014, Finland
| | - Tom Holvoet
- Department of Gastroenterology, University Hospital Ghent, Ghent 9000, Belgium
| | - Lise Lotte Gluud
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark
| | - Andreas Munk Petersen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Copenhagen IBD Center, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark
- Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
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24
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Wang M, Xie X, Zhao S, Ma X, Wang Z, Zhang Y. Fecal microbiota transplantation for irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Front Immunol 2023; 14:1136343. [PMID: 37275867 PMCID: PMC10234428 DOI: 10.3389/fimmu.2023.1136343] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 04/27/2023] [Indexed: 06/07/2023] Open
Abstract
Objective Whether fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS) is effective in improving outcomes remains controversial. We assessed the safety and efficacy of FMT for patients with IBS. Methods In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, the Cochrane Library, the clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) up to February 25, 2022, updated to March 28, 2023. Randomized controlled trials (RCTs) compared the stool and capsule FMT with placebo in patients with IBS were included. Two authors independently assessed study eligibility, extracted the data, and assessed risk of bias. We did meta-analysis with RevMan, and the Stata software was used for sensitivity analysis and meta-regression. The GRADE system was used to assess the quality of evidences. Mean difference (MD) or standardized Mean difference (SMD) with 95% CI for continuous data, and risk ratios (RR) with 95% CI for dichotomous data were used with random-effects models. The primary outcomes included the clinical response rate and IBS-SSS score. This study is registered with PROSPERO: CRD42022328377. Results Nineteen reports from nine RCTs were included finally. Compared with the placebo, a single stool FMT could significantly decrease the IBS-SSS score at 1 month (MD=-65.75, 95%CI [-129.37, -2.13]), 3 months (MD=-102.11, 95% CI [-141.98, -62.24]), 6 months (MD=-84.38, 95%CI [-158.79, -9.97]), 24 months (MD=-110.41, 95%CI [-145.37, -75.46]), and 36 months (MD=-104.71, 95%CI [-137.78, -71.64]). It also could improve the clinical response rate at 3 months (RR=1.91, 95% [1.12, 3.25]), 24 months (RR=2.97, 95% [1.94, 4.54]), and 36 months (RR=2.48, 95% [1.65, 3.72]), and increase the IBS-QoL score at 3 months, 24 months, and 36 months. FMT did not increase the serious adverse event. The risk of bias was low, and the quality of evidence based on GRADE system was moderate in the stool FMT group. However, we did not find positive effect of capsule FMT on patients with IBS based on the current available data. Conclusion A single stool FMT is effective and safe for patients with IBS. However, some factors may affect the effectiveness of FMT, and the relationship between the gut microbiome and the effect of FMT for IBS is still unclear. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42022328377.
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Affiliation(s)
- Mancai Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
| | - Xiaofeng Xie
- Department of Histology and Embryology, Medical College of Northwest Minzu University, Lanzhou, China
| | - Songbo Zhao
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
| | - Xiaojuan Ma
- Department of Histology and Embryology, Medical College of Northwest Minzu University, Lanzhou, China
| | - Zheyuan Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
| | - Youcheng Zhang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
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25
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Lahtinen P, Jalanka J, Mattila E, Tillonen J, Bergman P, Satokari R, Arkkila P. Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis: A randomized controlled trial. World J Gastroenterol 2023; 29:2666-2678. [PMID: 37213403 PMCID: PMC10198050 DOI: 10.3748/wjg.v29.i17.2666] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/06/2023] [Accepted: 04/11/2023] [Indexed: 05/23/2023] Open
Abstract
BACKGROUND Fecal microbial transplantation (FMT) is a promising new method for treating active ulcerative colitis (UC), but knowledge regarding FMT for quiescent UC is scarce.
AIM To investigate FMT for the maintenance of remission in UC patients.
METHODS Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy. The primary endpoint was set to the maintenance of remission, a fecal calprotectin level below 200 μg/g, and a clinical Mayo score below three throughout the 12-mo follow-up. As secondary endpoints, we recorded the patient’s quality of life, fecal calprotectin, blood chemistry, and endoscopic findings at 12 mo.
RESULTS The main endpoint was achieved by 13 out of 24 (54%) patients in the FMT group and by 10 out of 24 (41%) patients in the placebo group (log-rank test, P = 0.660). Four months after FMT, the quality-of-life scores decreased in the FMT group compared to the placebo group (P = 0.017). In addition, the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point (P = 0.003). There were no differences in blood chemistry, fecal calprotectin, or endoscopic findings among the study groups at 12 mo. The adverse events were infrequent, mild, and distributed equally between the groups.
CONCLUSION There were no differences in the number of relapses between the study groups at the 12-mo follow-up. Thus, our results do not support the use of a single-dose FMT for the maintenance of remission in UC.
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Affiliation(s)
- Perttu Lahtinen
- Department of Gastroenterology, Päijät-Häme Central Hospital, Lahti 15610, Finland
- Department of Medicine, University of Helsinki, Helsinki 00014, Finland
| | - Jonna Jalanka
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland
| | - Eero Mattila
- Department of Infectious Diseases, Helsinki University Hospital, Helsinki 00029, Uusimaa, Finland
| | - Jyrki Tillonen
- Department of Gastroenterology, Päijät-Häme Central Hospital, Lahti 15610, Finland
| | - Paula Bergman
- Department of Bioinformatics, Helsinki University Hospital, Helsinki 00014, Finland
| | - Reetta Satokari
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland
| | - Perttu Arkkila
- Department of Gastroenterology, University Helsinki, Center Hospital, Helsinki 00029, Uusimaa, Finland
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26
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Rodrigues T, Rodrigues Fialho S, Araújo JR, Rocha R, Moreira-Rosário A. Procedures in Fecal Microbiota Transplantation for Treating Irritable Bowel Syndrome: Systematic Review and Meta-Analysis. J Clin Med 2023; 12:jcm12051725. [PMID: 36902512 PMCID: PMC10003588 DOI: 10.3390/jcm12051725] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/07/2023] [Accepted: 02/13/2023] [Indexed: 02/25/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease with no effective treatment. Altered microbiota composition seems implicated in disease etiology and therefore fecal microbial transplantation (FMT) has emerged as a possible treatment therapy. To clarify the clinical parameters impacting FMT efficacy, we conducted a systematic review with subgroup analysis. METHODS A literature search was performed identifying randomized controlled trials (RCTs) comparing FMT with placebo in IBS adult patients (8-week follow-up) with a reported improvement in global IBS symptoms. RESULTS Seven RCTs (489 participants) met the eligibility requirements. Although FMT seems not to be effective in global improvement of IBS symptoms, subgroup analysis shows that FMT through gastroscopy or nasojejunal tube are effective IBS treatments (RR 3.03; 95% CI 1.94-4.73; I2 = 10%, p < 0.00001). When considering non-oral ingestion routes, IBS patients with constipation symptoms are more likely to benefit from FMT administration (p = 0.003 for the difference between IBS subtypes regarding constipation). Fresh fecal transplant and bowel preparation seem also to have impact on FMT efficacy (p = 0.03 and p = 0.01, respectively). CONCLUSION Our meta-analysis revealed a set of critical steps that could affect the efficacy of FMT as clinical procedure to treat IBS, nevertheless more RCTs are needed.
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Affiliation(s)
- Tânia Rodrigues
- NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
| | - Sofia Rodrigues Fialho
- NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
| | - João Ricardo Araújo
- NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
- CINTESIS@RISE, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
| | - Rita Rocha
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
| | - André Moreira-Rosário
- NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
- CINTESIS@RISE, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
- Correspondence: ; Tel.: +351-218-803-000
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27
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Barbara G, Cremon C, Bellini M, Corsetti M, Di Nardo G, Falangone F, Fuccio L, Galeazzi F, Iovino P, Sarnelli G, Savarino EV, Stanghellini V, Staiano A, Stasi C, Tosetti C, Turco R, Ubaldi E, Zagari RM, Zenzeri L, Marasco G. Italian guidelines for the management of irritable bowel syndrome: Joint Consensus from the Italian Societies of: Gastroenterology and Endoscopy (SIGE), Neurogastroenterology and Motility (SINGEM), Hospital Gastroenterologists and Endoscopists (AIGO), Digestive Endoscopy (SIED), General Medicine (SIMG), Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP) and Pediatrics (SIP). Dig Liver Dis 2023; 55:187-207. [PMID: 36517261 DOI: 10.1016/j.dld.2022.11.015] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/21/2022] [Accepted: 11/24/2022] [Indexed: 01/29/2023]
Abstract
The irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction. IBS is still associated with areas of uncertainties, especially regarding the optimal diagnostic work-up and the more appropriate management. Experts from 7 Italian Societies conducted a Delphi consensus with literature summary and voting process on 27 statements. Recommendations and quality of evidence were evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was defined as >80% agreement and reached for all statements. In terms of diagnosis, the consensus supports a positive diagnostic strategy with a symptom-based approach, including the psychological comorbidities assessment and the exclusion of alarm symptoms, together with the digital rectal examination, full blood count, C-reactive protein, serology for coeliac disease, and fecal calprotectin assessment. Colonoscopy should be recommended in patients with alarm features. Regarding treatment, the consensus strongly supports a dietary approach for patients with IBS, the use of soluble fiber, secretagogues, tricyclic antidepressants, psychologically directed therapies and, only in specific IBS subtypes, rifaximin. A conditional recommendation was achieved for probiotics, polyethylene glycol, antispasmodics, selective serotonin reuptake inhibitors and, only in specific IBS subtypes, 5-HT3 antagonists, 5-HT4 agonists, bile acid sequestrants.
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Affiliation(s)
- Giovanni Barbara
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy.
| | - Cesare Cremon
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Sciences and New Technologies in Medicine and Surgery, University of Pisa, 56010 Pisa, Italy
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham Digestive Diseases Biomedical Research Centre, Nottingham, United Kingdom
| | - Giovanni Di Nardo
- NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
| | - Francesca Falangone
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, University Sapienza, Rome, Italy
| | - Lorenzo Fuccio
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy
| | - Francesca Galeazzi
- Gastroenterology Unit, Azienda Ospedale Università di Padova, 35128 Padua, Italy
| | - Paola Iovino
- Gastrointestinal Unit Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy
| | - Giovanni Sarnelli
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
| | | | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Annamaria Staiano
- Department of Translational Medical Sciences-Section of Pediatric, University Federico II, 80100 Naples, Italy
| | - Cristina Stasi
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | | | - Rossella Turco
- Department of Translational Medical Sciences-Section of Pediatric, University Federico II, 80100 Naples, Italy
| | - Enzo Ubaldi
- Primary Care, Health Care Agency of Ascoli Piceno, Ascoli Piceno, Italy
| | - Rocco Maurizio Zagari
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy
| | - Letizia Zenzeri
- NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
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Vasiliu O. Is fecal microbiota transplantation a useful therapeutic intervention for psychiatric disorders? A narrative review of clinical and preclinical evidence. Curr Med Res Opin 2023; 39:161-177. [PMID: 36094098 DOI: 10.1080/03007995.2022.2124071] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The therapeutic management of psychiatric disorders is currently confronted with a critical need to find new therapeutic interventions due to the high rates of non-responsivity or low responsivity in the key pathologies, e.g. schizophrenia spectrum disorders, alcohol use disorders, or major depressive disorder. The modulation of intestinal microbiota has been explored in various organic and psychiatric dysfunctions, with different degrees of success. However, this type of intervention may represent a helpful add-on at a conceptual level since it does not associate negative pharmacokinetics interactions, significant adverse events, or risk for non-adherence in the long term. Oral administration of pre-, pro-, or synbiotics, and especially the treatment with fecal microbiota transplantation (FMT), are methods still in their early research phase for patients with psychiatric disorders, therefore an exploration of data regarding the potential benefits and adverse events of FMT was considered necessary. In order to accomplish this purpose, the available results of research dedicated to each category of psychiatric disorders, starting with depressive and anxiety disorders, continuing with schizophrenia, substance use disorders, and finishing with disorders diagnosed during childhood, were presented in this paper. Seven clinical trials, 16 preclinical studies, three meta-analyses/systematic reviews, and six case reports, all of these representing ten distinct categories of psychiatric disorders or manifestations, have been reviewed. Mood disorders, anxiety disorders, and alcohol dependence have been the most extensively investigated clinical entities from the FMT efficacy and tolerability perspective, and reviewed data are generally promising. Based on the current status of research, FMT may be considered a helpful intervention in specific psychiatric pathologies. Still, this review showed that most of the information is derived from entirely preclinical studies. Therefore, clinical trials with sound methodology and more participants are needed to clarify FMT's benefits and risks in psychiatric disorders.
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Affiliation(s)
- Octavian Vasiliu
- Spitalul Universitar de Urgenţă Militar Central Dr Carol Davila Ringgold standard institution, Bucuresti, Romania
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Samuthpongtorn C, Kantagowit P, Pittayanon R, Patcharatrakul T, Gonlachanvit S. Fecal microbiota transplantation in irritable bowel syndrome: A meta-analysis of randomized controlled trials. Front Med (Lausanne) 2022; 9:1039284. [PMID: 36405622 PMCID: PMC9669599 DOI: 10.3389/fmed.2022.1039284] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 10/18/2022] [Indexed: 09/15/2023] Open
Abstract
Introduction Fecal microbiota transplantation (FMT) has been proposed as a potential treatment for irritable bowel syndrome (IBS); however, the consensus regarding its efficacy and safety is limited. Materials and Methods We performed a systematic search of the literature using PubMed, EMBASE, Ovid MEDLINE, and Cochrane. Meta-analyses were conducted in relative risk (RR) or standard mean difference (SMD) using 95% confidence intervals (CI). Cochrane risk-of-bias 2 tool (RoB2) was employed to evaluate the study quality. Result Of 2,589 potential records, 7 studies with 9 cohorts involving 505 participants were included. Meta-analyses showed no significant difference in the short-term (12 weeks) and long-term (12 months) global improvement of IBS symptoms of FMT vs. placebo (RR 0.63, 95% CI 0.39-1.00 and RR 0.88, 95% CI 0.53-1.45, respectively). There were statistically significant differences of short-term IBS-SSS improvement (SMD -0.58, 95% CI -1.09 to -0.88) and short-term IBS-QoL improvement (SMD 0.67, 95% CI 0.43-0.91). Eight from 9 studies (88.9%) had a low risk of bias. The subgroup analysis revealed the short-term global symptoms improvement in studies with low-risk of bias (RR 0.53, 95% CI 0.35-0.81), studies with well-defined donors (RR 0.31, 95% CI 0.14-0.72), and studies with FMT using colonoscopy (RR 0.66, 95% CI 0.47-0.92). Major FMT adverse events are transient and rapidly self-limiting. Conclusion FMT significantly improved IBS-SSS and IBS-QoL in the short-term period in IBS patients. However, global symptom improvement showed no significance. Well-defined donors and appropriate fecal administration routes appear to be important factors for the successful outcomes of FMT in IBS. Systematic review registration [www.crd.york.ac.uk/prospero], identifier [CRD42021246101].
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Affiliation(s)
| | | | - Rapat Pittayanon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Tanisa Patcharatrakul
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence in Neurogastroenterology and Motility, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sutep Gonlachanvit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence in Neurogastroenterology and Motility, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Zhang YW, Cao MM, Li YJ, Zhang RL, Wu MT, Yu Q, Rui YF. Fecal microbiota transplantation as a promising treatment option for osteoporosis. J Bone Miner Metab 2022; 40:874-889. [PMID: 36357745 PMCID: PMC9649400 DOI: 10.1007/s00774-022-01375-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 10/04/2022] [Indexed: 11/12/2022]
Abstract
Osteoporosis is a systemic metabolic bone disease characterized by the descending bone mass and destruction of bone microstructure, which tends to result in the increased bone fragility and associated fractures, as well as high disability rate and mortality. The relation between gut microbiota and bone metabolism has gradually become a research hotspot, and it has been verified that gut microbiota is closely associated with reduction of bone mass and incidence of osteoporosis recently. As a novel "organ transplantation" technique, fecal microbiota transplantation (FMT) mainly refers to the transplantation of gut microbiota from healthy donors to recipients with gut microbiota imbalance, so that the gut microbiota in recipients can be reshaped and play a normal function, and further prevent or treat the diseases related to gut microbiota disorder. Herein, based on the gut-bone axis and proven regulatory effects of gut microbiota on osteoporosis, this review expounds relevant basic researches and clinical practice of FMT on osteoporosis, thus demonstrating the potentials of FMT as a therapeutic option for osteoporosis and further providing certain reference for the future researches.
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Affiliation(s)
- Yuan-Wei Zhang
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, 210009, Jiangsu, People's Republic of China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Mu-Min Cao
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, 210009, Jiangsu, People's Republic of China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Ying-Juan Li
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- Department of Geriatrics, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Ruo-Lan Zhang
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Meng-Ting Wu
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Qian Yu
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- Department of Gastroenterology, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Yun-Feng Rui
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, 210009, Jiangsu, People's Republic of China.
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China.
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China.
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, People's Republic of China.
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Algera JP, Törnblom H, Simrén M. Treatments targeting the luminal gut microbiota in patients with irritable bowel syndrome. Curr Opin Pharmacol 2022; 66:102284. [PMID: 36067685 DOI: 10.1016/j.coph.2022.102284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 07/07/2022] [Accepted: 08/03/2022] [Indexed: 11/03/2022]
Abstract
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction affecting 4% of the world's population. Patients with IBS experience chronic or recurrent abdominal pain in combination with altered bowel habits (diarrhea and/or constipation), and have reduced quality of life. Despite the high prevalence and substantial burden of IBS, its pathophysiology is incompletely understood and remains to be elucidated. The importance of the gut microenvironment has been highlighted in IBS, as there are signs that the gut microbiota of patients differs from healthy controls. Recent studies have aimed to alter the gut microbiota and thereby, attempted to alleviate gastrointestinal symptoms in IBS patients. We highlighted recent advances in common treatments that are targeting the luminal gut microbiota in IBS.
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Affiliation(s)
- Joost P Algera
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Center for Functional GI & Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Fecal Microbiota Transplantation Combined with a Low FODMAP Diet for the Treatment of Irritable Bowel Syndrome with Predominant Diarrhea. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:5121496. [PMID: 36187337 PMCID: PMC9519354 DOI: 10.1155/2022/5121496] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 09/06/2022] [Indexed: 12/02/2022]
Abstract
Background. Fecal microbiota transplantation (FMT) has been found to be effective in irritable bowel syndrome with predominant diarrhea (IBS-D). We conducted this study to determine the impact of a low FODMAP diet (LFD) on the gut microbiota and the efficacy of FMT in the treatment of IBS-D. Methods. A retrospective analysis of a single-arm open-label prospective study was conducted to investigate the impact of FMT alone (
) and FMT+LFD (
) in refractory IBS-D. The IBS-quality of life (QOL), IBS-severity scoring system (SSS), gastrointestinal symptom rating scale (GSRS), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD) were used to evaluate the efficacy, and partial 16S rDNA amplicon sequencing was used to profile the microbiota. Results. The response rates were higher in the FMT+LFD group than in the FMT group (1 mo, 3 mo, 6 mo: 70.0% vs. 55.0%, 67.5% vs. 57.5%, 62.5% vs. 27.5%, respectively). The FMT+LFD group showed significantly better improvement in IBS-QOL at 1, 3, and 6 months; IBS-SSS at 6 months; and GSRS at 1 month compared to FMT alone. Changes in HAMA and HAMD were similar in the two groups. The LFD significantly upregulated the FMT-induced microbial diversity (OTUs: 666 vs. 574, Adonis:
) and significantly strengthened the upregulation of Bacteroides, Alistipes, and Ruminococcaceae_UCG-002 and the downregulation of Bifidobacterium. Conclusion. An LFD enhanced the efficacy of FMT, increased the gut microbial diversity after FMT, and strengthened the inhibitory effect of FMT on conditional pathogens.
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El-Salhy M, Mazzawi T, Hausken T, Hatlebakk JG. The fecal microbiota transplantation response differs between patients with severe and moderate irritable bowel symptoms. Scand J Gastroenterol 2022; 57:1036-1045. [PMID: 35486073 DOI: 10.1080/00365521.2022.2064725] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Fecal microbiota transplantation (FMT) is a promising intervention for patients with irritable bowel syndrome (IBS). The present study aimed to identify any differences in FMT response between patients with severe and moderate IBS symptoms. MATERIALS AND METHOD The study included the 164 patients who participated in our previous study, of which 96 (58.5%) and 68 (41.5%) had severe (S-IBS-S) and moderate (Mo-IBS-S) IBS, respectively. The patients were randomly divided into a placebo group (own feces) and 30-g and 60-g (donor feces) FMT groups. Patients completed three questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT, and provided fecal samples before and 1 month after FMT. The fecal bacteria were analyzed using the 16S rRNA gene in PCR DNA amplification covering the V3-V9 variable genes. RESULTS Response rates of the placebo group did not differ between S-IBS-S and Mo-IBS-S patients at 2 weeks, 1 month and 3 months after FMT. The response rates in the active treatment group were higher in S-IBS-S patients than in Mo-IBS-S patients at each observation time. FMT reduced abdominal symptoms and fatigue and improved the quality of life in patients with both severe and moderate IBS. Patients with S-IBS-S had higher levels of Eubacterium siraeum, and lower levels of Eubacterium rectale than Mo-IBS-S, after FMT. CONCLUSION Patients with S-IBS-S have a higher response rate to FMT and a marked improvement in fatigue and in quality of life compared with those with Mo-IBS-S. The clinical trial registration number is NCT03822299 and is available at www.clinicaltrials.gov.
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Affiliation(s)
- Magdy El-Salhy
- Department of Medicine, Stord Hospital, Stord, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Tarek Mazzawi
- Faculty of Medicine, Department of Medicine, Al-Balqa Applied University, Salt, Jordan
| | - Trygve Hausken
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
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Abdelghafar YA, AbdelQadir YH, Motawea KR, Nasr SA, Omran HAM, Belal MM, Elhashash MM, AbdelAzim AA, Shah J. Efficacy and safety of fecal microbiota transplant in irritable bowel syndrome: An update based on meta-analysis of randomized control trials. Health Sci Rep 2022; 5:e814. [PMID: 36110348 PMCID: PMC9466358 DOI: 10.1002/hsr2.814] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 07/12/2022] [Accepted: 08/08/2022] [Indexed: 11/21/2022] Open
Abstract
Background and Aims Fecal microbiota transfer (FMT) is a potential treatment for irritable bowel syndrome (IBS). Several randomized trials have tested FMT effects using different routes of administration, doses, and sample sizes. We aim to assess the overall efficacy of FMT for IBS patients and the safety of the intervention. Methods We systematically searched four databases for randomized control trials that studied the efficacy and safety of FMT in IBS patients. Results We included 8 randomized trials (472 patients) that compared FMT with placebo in IBS patients. Pooled results showed no statistically significant difference between FMT and control groups in the overall change in IBS symptom severity (IBS-SSS) at 1 month (p = 0.94), 3/4 months (p = 0.82), and at the end of trials (p = 0.67). No significant difference in the total number of respondents between the FMT and control groups (risk ratios = 1.84, [95% confidence interval (CI) = 0.82-2.65], p = 0.19). Although the oral route of administration showed a significant difference in the number of respondents (p = 0.004), there was no statistically significant difference in the IBS-SSS when subgrouping the oral route of administration (mean difference = 47.57, [95% CI = -8.74-103.87], p = 0.10). Conclusion FMT is not an effective treatment to relieve all the symptoms of IBS. Even in the groups that showed relatively significant improvement after FMT, the effect was proven to wear off over time and the re-administration carries a low success rate. Future research should consider different bacterial-based interventions such as probiotics or specific antibiotics.
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Affiliation(s)
| | | | | | - Sara Amr Nasr
- Faculty of MedicineAlexandria UniversityAlexandriaEgypt
| | | | | | | | | | - Jaffer Shah
- New York State Department of HealthNew YorkNYUSA
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35
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Hojo M, Nagahara A. Current perspectives on irritable bowel syndrome: a narrative review. J Int Med Res 2022; 50:3000605221126370. [PMID: 36171718 PMCID: PMC9523849 DOI: 10.1177/03000605221126370] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
The pathophysiology of irritable bowel syndrome (IBS) has not yet been fully elucidated. We reviewed articles addressing IBS that have been published in the last 2 years and selected papers related to IBS pathophysiology and treatment. Studies of intestinal bacteria, low-grade mucosal inflammation, and increased mucosal permeability—factors involved in the pathophysiology of IBS—have been conducted. In addition, the involvement of intestinal bacteria in IBS pathology has been clarified; many studies of treatments related to intestinal bacteria have been reported. Moreover, several studies address the effect on IBS of antidepressants and psychotherapy through the brain–gut axis. The contents of these papers are described in this narrative review.
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Affiliation(s)
- Mariko Hojo
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
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36
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Iribarren C, Maasfeh L, Öhman L, Simrén M. Modulating the gut microenvironment as a treatment strategy for irritable bowel syndrome: a narrative review. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2022; 3:e7. [PMID: 39295774 PMCID: PMC11406401 DOI: 10.1017/gmb.2022.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 06/02/2022] [Accepted: 07/26/2022] [Indexed: 09/21/2024]
Abstract
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with a complex pathophysiology. Growing evidence suggests that alterations of the gut microenvironment, including microbiota composition and function, may be involved in symptom generation. Therefore, attempts to modulate the gut microenvironment have provided promising results as an indirect approach for IBS management. Antibiotics, probiotics, prebiotics, food and faecal microbiota transplantation are the main strategies for alleviating IBS symptom severity by modulating gut microbiota composition and function (eg. metabolism), gut barrier integrity and immune activity, although with varying efficacy. In this narrative review, we aim to provide an overview of the current approaches targeting the gut microenvironment in order to indirectly manage IBS symptoms.
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Affiliation(s)
- Cristina Iribarren
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lujain Maasfeh
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA
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Biazzo M, Deidda G. Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases. J Clin Med 2022; 11:jcm11144119. [PMID: 35887883 PMCID: PMC9320118 DOI: 10.3390/jcm11144119] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/08/2022] [Accepted: 07/12/2022] [Indexed: 02/01/2023] Open
Abstract
The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota dysbiosis, thereby suggesting that the reinstatement of physiological microflora balance and composition might ameliorate the clinical symptoms. Among possible microbiota-targeted interventions, pre/pro-biotics supplementations were shown to provide effective results, but the main limitation remains in the limited microbial species available as probiotics. Differently, fecal microbiota transplantation involves the transplantation of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition aiming to confer a health benefit. Firstly used in the 4th century in traditional Chinese medicine, nowadays, it has been exploited so far to treat recurrent Clostridioides difficile infections, but accumulating data coming from a number of clinical trials clearly indicate that fecal microbiota transplantation may also carry the therapeutic potential for a number of other conditions ranging from gastrointestinal to liver diseases, from cancer to inflammatory, infectious, autoimmune diseases and brain disorders, obesity, and metabolic syndrome. In this review, we will summarize the commonly used preparation and delivery methods, comprehensively review the evidence obtained in clinical trials in different human conditions and discuss the variability in the results and the pivotal importance of donor selection. The final aim is to stimulate discussion and open new therapeutic perspectives among experts in the use of fecal microbiota transplantation not only in Clostridioides difficile infection but as one of the first strategies to be used to ameliorate a number of human conditions.
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Affiliation(s)
- Manuele Biazzo
- The BioArte Limited, Life Sciences Park, Triq San Giljan, SGN 3000 San Gwann, Malta;
- SienabioACTIVE, University of Siena, Via Aldo Moro 1, 53100 Siena, Italy
| | - Gabriele Deidda
- Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy
- Correspondence: ; Tel.: +39-049-827-6125
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Hamazaki M, Sawada T, Yamamura T, Maeda K, Mizutani Y, Ishikawa E, Furune S, Yamamoto K, Ishikawa T, Kakushima N, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M, Nakamura M, Fujishiro M. Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan. BMC Gastroenterol 2022; 22:342. [PMID: 35836115 PMCID: PMC9284895 DOI: 10.1186/s12876-022-02408-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 06/29/2022] [Indexed: 12/31/2022] Open
Abstract
Background Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients. Methods Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12 weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12 weeks after FMT. For the microbiome, we analyzed the V3–V4 region of the 16S rRNA gene. Results IBS-SI decreased an average of 115.58 points after 12 weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. α-diversity was increased only in the responder group (p = 0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT. Conclusions Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased α-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects. Trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363. The study was registered prospectively. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02408-5.
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Affiliation(s)
- Motonobu Hamazaki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Tsunaki Sawada
- Department of Endoscopy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.
| | - Keiko Maeda
- Department of Endoscopy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Yasuyuki Mizutani
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Eri Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Satoshi Furune
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Naomi Kakushima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan
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Gut Microbiota Manipulation in Irritable Bowel Syndrome. Microorganisms 2022; 10:microorganisms10071332. [PMID: 35889051 PMCID: PMC9319495 DOI: 10.3390/microorganisms10071332] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 06/24/2022] [Accepted: 06/29/2022] [Indexed: 02/05/2023] Open
Abstract
Increased knowledge suggests that disturbed gut microbiota, termed dysbiosis, might promote the development of irritable bowel syndrome (IBS) symptoms. Accordingly, gut microbiota manipulation has evolved in the last decade as a novel treatment strategy in order to improve IBS symptoms. In using different approaches, dietary management stands first in line, including dietary fiber supplements, prebiotics, and probiotics that are shown to change the composition of gut microbiota, fecal short-chain fatty acids and enteroendocrine cells densities and improve IBS symptoms. However, the exact mixture of beneficial bacteria for each individual remains to be identified. Prescribing nonabsorbable antibiotics still needs confirmation, although using rifaximin has been approved for diarrhea-predominant IBS. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and five out of seven placebo-controlled trials investigating FMT in IBS obtain promising results regarding symptom reduction and gut microbiota manipulation. However, more data, including larger cohorts and studying long-term effects, are needed before FMT can be regarded as a treatment for IBS in clinical practice.
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Doroftei B, Ilie OD, Diaconu R, Hutanu D, Stoian I, Ilea C. An Updated Narrative Mini-Review on the Microbiota Changes in Antenatal and Post-Partum Depression. Diagnostics (Basel) 2022; 12:diagnostics12071576. [PMID: 35885482 PMCID: PMC9315700 DOI: 10.3390/diagnostics12071576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 06/26/2022] [Accepted: 06/27/2022] [Indexed: 12/02/2022] Open
Abstract
Background: Antenatal depression (AND) and post-partum depression (PPD) are long-term debilitating psychiatric disorders that significantly influence the composition of the gut flora of mothers and infants that starts from the intrauterine life. Not only does bacterial ratio shift impact the immune system, but it also increases the risk of potentially life-threatening disorders. Material and Methods: Therefore, we conducted a narrative mini-review aiming to gather all evidence published between 2018–2022 regarding microflora changes in all three stages of pregnancy. Results: We initially identified 47 potentially eligible studies, from which only 7 strictly report translocations; 3 were conducted on rodent models and 4 on human patients. The remaining studies were divided based on their topic, precisely focused on how probiotics, breastfeeding, diet, antidepressants, exogenous stressors, and plant-derived compounds modulate in a bidirectional way upon behavior and microbiota. Almost imperatively, dysbacteriosis cause cognitive impairments, reflected by abnormal temperament and personality traits that last up until 2 years old. Thankfully, a distinct technique that involves fecal matter transfer between individuals has been perfected over the years and was successfully translated into clinical practice. It proved to be a reliable approach in diminishing functional non- and gastrointestinal deficiencies, but a clear link between depressive women’s gastrointestinal/vaginal microbiota and clinical outcomes following reproductive procedures is yet to be established. Another gut-dysbiosis-driving factor is antibiotics, known for their potential to trigger inflammation. Fortunately, the studies conducted on mice that lack microbiota offer, without a shadow of a doubt, insight. Conclusions: It can be concluded that the microbiota is a powerful organ, and its optimum functionality is crucial, likely being the missing puzzle piece in the etiopathogenesis of psychiatric disorders.
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Affiliation(s)
- Bogdan Doroftei
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (I.S.); (C.I.)
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania;
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Ovidiu-Dumitru Ilie
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, No. 20A, 700505 Iasi, Romania
- Correspondence:
| | - Roxana Diaconu
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania;
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Delia Hutanu
- Department of Biology, Faculty of Chemistry-Biology-Geography, West University of Timisoara, Vasile Pârvan Avenue, No. 4, 300115 Timisoara, Romania;
| | - Irina Stoian
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (I.S.); (C.I.)
| | - Ciprian Ilea
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (I.S.); (C.I.)
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania;
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Hurych J, Vejmelka J, Hlinakova L, Kramna L, Larionov V, Kulich M, Cinek O, Kohout P. Protocol for faecal microbiota transplantation in irritable bowel syndrome: the MISCEAT study - a randomised, double-blind cross-over study using mixed microbiota from healthy donors. BMJ Open 2022; 12:e056594. [PMID: 35760542 PMCID: PMC9237876 DOI: 10.1136/bmjopen-2021-056594] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
INTRODUCTION Several studies have demonstrated dysbiosis in irritable bowel syndrome (IBS). Therefore, faecal microbiota transplantation, whose effect and safety have been proven in Clostridioides difficile infections, may hold promise in other conditions, including IBS. Our study will examine the effectiveness of stool transfer with artificially increased microbial diversity in IBS treatment. METHODS AND ANALYSIS A three-group, double-blind,randomised, cross-over, placebo-controlled study of two pairs of gut microbiota transfer will be conducted in 99 patients with diarrhoeal or mixed type of IBS. Patients aged 18-65 will be randomised into three equally sized groups: group A will first receive two enemas of study microbiota mixture (deep-frozen stored stool microbiota mixed from eight healthy donors); after 8 weeks, they will receive two enemas with placebo (autoclaved microbiota mixture), whereas group B will first receive placebo, then microbiota mixture. Finally, group C will receive placebos only. The IBS Severity Symptom Score (IBS-SSS) questionnaires will be collected at baseline and then at weeks 3, 5, 8, 11, 13, 32. Faecal bacteriome will be profiled before and regularly after interventions using 16S rDNA next-generation sequencing. Food records, dietary questionnaires, anthropometry, bioimpedance, biochemistry and haematology workup will be obtained at study visits during the follow-up period. The primary outcome is the change in the IBS-SSS between the baseline and 4 weeks after the intervention for each patient compared with placebo. Secondary outcomes are IBS-SSS at 2 weeks after the intervention and 32 weeks compared with placebo and changes in the number of loose stools, Bristol stool scale, abdominal pain and bloating, anthropometric parameters, psychological evaluation and the gut microbiome composition. ETHICS AND DISSEMINATION The study was approved by the Ethics Committee of Thomayer University Hospital, Czechia (G-18-26); study results will be published in peer-reviewed journals and presented at international conferences and patient group meetings. TRIAL REGISTRATION NUMBER NCT04899869.
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Affiliation(s)
- Jakub Hurych
- Department of Medical Microbiology, Charles University Second Faculty of Medicine, Prague, Czech Republic
- Department of Paediatrics, Charles University Second Faculty of Medicine, Prague, Czech Republic
| | - Jiri Vejmelka
- Department of Internal Medicine, Charles University Third Faculty of Medicine, Prague, Czech Republic
| | - Lucie Hlinakova
- Department of Paediatrics, Charles University Second Faculty of Medicine, Prague, Czech Republic
| | - Lenka Kramna
- Department of Paediatrics, Charles University Second Faculty of Medicine, Prague, Czech Republic
| | - Vladyslav Larionov
- Department of Paediatrics, Charles University Second Faculty of Medicine, Prague, Czech Republic
| | - Michal Kulich
- Department of Probability and Statistics, Charles University, Prague, Czech Republic
| | - Ondrej Cinek
- Department of Medical Microbiology, Charles University Second Faculty of Medicine, Prague, Czech Republic
- Department of Paediatrics, Charles University Second Faculty of Medicine, Prague, Czech Republic
| | - Pavel Kohout
- Department of Internal Medicine, Charles University Third Faculty of Medicine, Prague, Czech Republic
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Zhao HJ, Zhang XJ, Zhang NN, Yan B, Xu KK, Peng LH, Pan F. Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials. Front Nutr 2022; 9:890357. [PMID: 35719141 PMCID: PMC9202577 DOI: 10.3389/fnut.2022.890357] [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: 03/05/2022] [Accepted: 04/26/2022] [Indexed: 12/15/2022] Open
Abstract
Background: Gut microbiota has been identified as an imbalance in patients with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is a novel method to restore microbiota and treat IBS patients. Objective To conduct a meta-analysis and estimate the efficacy and safety of FMT for the treatment of IBS patients with subgroup analyses to explore the most effective way of FMT for IBS. Methods All eligible studies were searched from PubMed, Embase, Web of Science, and the Cochrane Library through multiple search strategies. Data were extracted from studies comprising the following criteria: double-blind, randomized controlled trials (RCTs) that compared the efficacy of FMT with placebo for adult patients (≥18 years old) with IBS. A meta-analysis was performed to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs). Results A total of seven RCTs comprising 489 subjects were eligible for this meta-analysis. Pooled data showed no significant improvement of global IBS symptoms in patients with FMT compared with placebo (RR = 1.34; 95% CI 0.75–2.41, p = 0.32). A significant heterogeneity was observed among the studies (I2 = 83%, p < 0.00001). There was no significant evidence of funnel plot asymmetry (Egger's test, p = 0.719; Begg's test, p = 1.000), indicating no existence of publication bias. Subgroup analyses revealed that FMT operated by invasive routes, including gastroscope, colonoscope, and nasojejunal tube, significantly improved global IBS symptoms (RR = 1.96; 95% CI 1.23–3.11, p = 0.004) with heterogeneity (I2 = 57%, p = 0.06) and an NNT of 3 (95% CI 2–14). However, FMT delivered via oral capsules showed a negative impact on patients with IBS (RR = 0.56; 95% CI 0.33–0.96, p = 0.03) with a low heterogeneity (I2 = 39%, p = 0.2) and an NNH of 3 (95% CI 2–37). Conclusion The current evidence from RCTs with all routes of FMT does not show significant global improvement in patients with IBS. However, FMT operated by invasive routes significantly improved global IBS symptoms.
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Affiliation(s)
- Hui-jun Zhao
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- Department of Gastroenterology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Xiao-jing Zhang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Na-na Zhang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Bin Yan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Ke-ke Xu
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Li-hua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- *Correspondence: Fei Pan
| | - Fei Pan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- Li-hua Peng
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Chen C, Chen L, Sun D, Li C, Xi S, Ding S, Luo R, Geng Y, Bai Y. Adverse events of intestinal microbiota transplantation in randomized controlled trials: a systematic review and meta-analysis. Gut Pathog 2022; 14:20. [PMID: 35619175 PMCID: PMC9134705 DOI: 10.1186/s13099-022-00491-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 04/11/2022] [Indexed: 01/04/2025] Open
Abstract
Background Intestinal microbiota transplantation (IMT) has been recognized as an effective treatment for recurrent Clostridium difficile infection (rCDI) and a novel treatment option for other diseases. However, the safety of IMT in patients has not been established. Aims This systematic review and meta-analysis was conducted to assess the safety of IMT. Methods We systematically reviewed all randomized controlled trials (RCTs) of IMT studies published up to 28 February 2021 using databases including PubMed, EMBASE and the Cochrane Library. Studies were excluded if they did not report adverse events (AEs). Two authors independently extracted the data. The relative risk (RR) of serious adverse events (SAEs) and common adverse events (CAEs) were estimated separately, as were predefined subgroups. Publication bias was evaluated by a funnel plot and Egger’s regression test. Results Among 978 reports, 99 full‐text articles were screened, and 20 articles were included for meta-analysis, involving 1132 patients (603 in the IMT group and 529 in the control group). We found no significant difference in the incidence of SAEs between the IMT group and the control group (RR = 1.36, 95% CI 0.56–3.31, P = 0.50). Of these 20 studies, 7 described the number of patients with CAEs, involving 360 patients (195 in the IMT group and 166 in the control group). An analysis of the eight studies revealed that the incidence of CAEs was also not significantly increased in the IMT group compared with the control group (RR = 1.06, 95% CI 0.91–1.23, P = 0.43). Subgroup analysis showed that the incidence of CAEs was significantly different between subgroups of delivery methods (P(CAE) = 0.04), and the incidence of IMT-related SAEs and CAEs was not significantly different in the other predefined subgroups. Conclusion Currently, IMT is widely used in many diseases, but its associated AEs should not be ignored. To improve the safety of IMT, patients' conditions should be fully evaluated before IMT, appropriate transplantation methods should be selected, each operative step of faecal bacteria transplantation should be strictly controlled, AE management mechanisms should be improved, and a close follow-up system should be established.
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Affiliation(s)
- Chong Chen
- Department of Gastroenterology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518037, China
| | - Liyu Chen
- Department of Gastroenterology, 923Th Hospital of PLA Joint Logistics Support Force, Nanning, 530021, China
| | - Dayong Sun
- Department of Gastroenterology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518037, China
| | - Cailan Li
- Department of Gastroenterology, 923Th Hospital of PLA Joint Logistics Support Force, Nanning, 530021, China
| | - Shiheng Xi
- Department of Gastroenterology, 923Th Hospital of PLA Joint Logistics Support Force, Nanning, 530021, China
| | - Shihua Ding
- Department of Gastroenterology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518037, China
| | - Rongrong Luo
- Department of Gastroenterology, 923Th Hospital of PLA Joint Logistics Support Force, Nanning, 530021, China
| | - Yan Geng
- Department of Gastroenterology, 923Th Hospital of PLA Joint Logistics Support Force, Nanning, 530021, China.
| | - Yang Bai
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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Kindt S, Louis H, De Schepper H, Arts J, Caenepeel P, De Looze D, Gerkens A, Holvoet T, Latour P, Mahler T, Mokaddem F, Nullens S, Piessevaux H, Poortmans P, Rasschaert G, Surmont M, Vafa H, Van Malderen K, Vanuytsel T, Wuestenberghs F, Tack J. Belgian consensus on irritable bowel syndrome. Acta Gastroenterol Belg 2022; 85:360-382. [PMID: 35709780 DOI: 10.51821/85.2.10100] [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: 11/11/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.
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Affiliation(s)
- S Kindt
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - H Louis
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium
| | - H De Schepper
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - J Arts
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Gastroenterology, AZ Sint-Lucas, Brugge, Belgium
| | - P Caenepeel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Gastroenterology, Ziekenhuis Oost-Limburg, Campus Sint-Jan, Genk, Belgium
- UHasselt, Hasselt, Belgium
| | - D De Looze
- Department of Gastroenterology and Hepatology, University Hospital Ghent, Gent, Belgium
| | - A Gerkens
- Boitsfort Medical Center, Brussels, Belgium
| | - T Holvoet
- Department of Gastroenterology and Hepatology, University Hospital Ghent, Gent, Belgium
- Department of Gastroenterology, AZ Nikolaas, Sint Niklaas, Belgium
| | - P Latour
- Department of Gastroenterology, Hepatology and Digestive Oncology, Centre Hospitalier Universitaire de Liège, Liège, Belgium
| | - T Mahler
- Department of Pediatrics, Universitair Ziekenuis Brussel, Brussel, Belgium
| | - F Mokaddem
- Department of Gastroenterology and Hepatology, Vivalia-Centre Sud Luxembourg, Arlon, Belgium
| | - S Nullens
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - H Piessevaux
- Department of Hepato-gastroenterology, Cliniques universitaires St-Luc, Université catholique de Louvain, Brussels, Belgium
| | - P Poortmans
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - G Rasschaert
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - M Surmont
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - H Vafa
- Department of Gastroenterology and Hepatology, Chirec-Site Delta, Brussels, Belgium
| | - K Van Malderen
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - T Vanuytsel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - F Wuestenberghs
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université catholique de Louvain, Yvoir, Belgium
| | - J Tack
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
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Wu J, Lv L, Wang C. Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials. Front Cell Infect Microbiol 2022; 12:827395. [PMID: 35295757 PMCID: PMC8919053 DOI: 10.3389/fcimb.2022.827395] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/07/2022] [Indexed: 12/11/2022] Open
Abstract
Background Randomized controlled trials (RCTs) have examined the efficacy of fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) with inconsistent results. We performed a meta-analysis to assess both the short- and long-term efficacy of FMT in IBS. Methods MEDLINE, EMBASE, and the Cochrane Central Register were searched through September 2021. RCTs recruiting adult patients with IBS that compared FMT with placebo with dichotomous data of response to therapy were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of symptom not improving after therapy. RR was also pooled for adverse events (AEs). Continuous data were calculated using a mean difference for IBS-Quality of Life (IBS-QoL). GRADE methodology was used to assess quality of evidence. Results The search strategy generated 658 citations. Seven RCTs comprising 472 patients with IBS were included. FMT was not associated with a significant improvement in global symptom in IBS at 12 weeks in comparison with placebo (RR 0.75, 95% CI 0.43–1.31) with high heterogeneity between studies (I2 87%). Subgroup analyses showed that FMT was superior to placebo when administered via colonoscopy or gastroscope (RR 0.70, 95% CI 0.51–0.96; RR 0.37, 95% CI 0.14–0.99, respectively, while FMT was inferior to placebo when administered via oral capsules (RR 1.88, 95% CI 1.06–3.35). FMT induced a significant improvement in IBS-QoL compared to placebo (mean difference 9.39, 95% CI 3.86–14.91) at 12 weeks. No significant difference in the total number of AEs was observed between FMT and placebo (RR 1.20, 95% CI 0.59–2.47). FMT did not significantly improve global symptom in IBS at 1-year follow-up compared with placebo (RR 0.90, 95% CI 0.72–1.12). The GRADE quality evidence to support recommending FMT in IBS was very low. Conclusion IBS patients may benefit from FMT when administered via colonoscopy or gastroscope. FMT may improve the quality of life of IBS. The long-term use of FMT in IBS warrants further investigation. There is very-low-quality evidence to support recommending FMT in IBS.
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Waller KMJ, Leong RW, Paramsothy S. An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases. J Gastroenterol Hepatol 2022; 37:246-255. [PMID: 34735024 DOI: 10.1111/jgh.15731] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 10/17/2021] [Accepted: 10/18/2021] [Indexed: 12/13/2022]
Abstract
Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.
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Affiliation(s)
- Karen M J Waller
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia.,Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia.,Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.,Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Sudarshan Paramsothy
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia.,Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.,Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
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Chen M, Ruan G, Chen L, Ying S, Li G, Xu F, Xiao Z, Tian Y, Lv L, Ping Y, Cheng Y, Wei Y. Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome. Front Endocrinol (Lausanne) 2022; 13:817100. [PMID: 35250873 PMCID: PMC8888441 DOI: 10.3389/fendo.2022.817100] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 01/05/2022] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of unknown etiology. IBS is caused by a disruption in the gut-brain axis. Given the importance of the gut microbiota in maintaining local and systemic homeostasis of immunity, endocrine, and other physiological processes, the microbiota-gut-brain axis has been proposed as a key regulator in IBS. Neurotransmitters have been shown to affect blood flow regulation, intestinal motility, nutrient absorption, the gastrointestinal immune system, and the microbiota in recent studies. It has the potential role to play a function in the pathophysiology of the gastrointestinal and neurological systems. Transmitters and their receptors, including 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, and histamine, play an important role in IBS, especially in visceral sensitivity and gastrointestinal motility. Studies in this field have shed light on revealing the mechanism by which neurotransmitters act in the pathogenesis of IBS and discovering new therapeutic strategies based on traditional pharmacological approaches that target the nervous system or novel therapies that target the microbiota.
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Affiliation(s)
- Minjia Chen
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- Department of Pathogenic Biology and Immunology, School of Basic Medicine, Ningxia Medical University, Yinchuan, China
| | - Guangcong Ruan
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Lu Chen
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Senhong Ying
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Guanhu Li
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Fenghua Xu
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhifeng Xiao
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yuting Tian
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Linling Lv
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yi Ping
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yi Cheng
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Yanling Wei, ; Yi Cheng,
| | - Yanling Wei
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Yanling Wei, ; Yi Cheng,
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Elhusein AM, Fadlalmola HA. Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome Patients: An Updated Systematic Review and Meta-Analysis. Gastroenterol Nurs 2022; 45:11-20. [PMID: 35108241 DOI: 10.1097/sga.0000000000000652] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 10/13/2021] [Indexed: 12/16/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disease characterized by abdominal discomfort and bloating, diarrhea, and/or constipation. Fecal microbiota transplantation (FMT) is transferring the fecal bacteria and other microorganisms from a healthy person to another. We performed this systematic review and meta-analysis to assess the efficacy of FMT in treating IBS patients. We searched Scopus, PubMed, Cochrane, and Web of Science databases through June 2021 using relevant key words. We included 19 studies. Fecal microbiota transplantation was significantly superior to placebo in IBS quality of life after 4 weeks (mean difference [MD] = 7.47, 95% confidence interval [CI]: 2.05-12.89, p = .04), 12 weeks (MD = 9.99, 95% CI: 5.78-14.19, p < .00001), and 24 weeks (MD = 8.49, 95% CI: 0.47-16.52, p = .04), with no difference regarding IBS improvement symptoms and the IBS Severity Scoring System (SSS). Single-arm analysis revealed that the incidence of improvement of IBS symptoms was 57.8% (45.6%-69.9%) with reduction in IBS-SSS (MD = -74, 95% CI: -101.7 to -46.3). Fecal microbiota transplantation was superior to placebo in improving quality of life after 4, 12, and 24 weeks. Also, FMT improved IBS symptoms and reduced the IBS-SSS score. However, no deference was detected between FMT and placebo in IBS-SSS score and IBS symptoms improvement.
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Affiliation(s)
- Amal Mohamed Elhusein
- Amal Mohamed Elhusein, PhD, RN, MCH , is Assistant Professor, College of Applied Medical Science, Nursing Department, Bisha University, Bisha, Saudi Arabia; and Assistant Professor, Faculty of Nursing, Khartoum University, Khartoum, Sudan
- Hammad Ali Fadlalmola, PhD, RN, CHN , is Associate Professor, Department of Community Health Nursing, Taibah University, Nursing College, Almadinah, Saudi Arabia
| | - Hammad Ali Fadlalmola
- Amal Mohamed Elhusein, PhD, RN, MCH , is Assistant Professor, College of Applied Medical Science, Nursing Department, Bisha University, Bisha, Saudi Arabia; and Assistant Professor, Faculty of Nursing, Khartoum University, Khartoum, Sudan
- Hammad Ali Fadlalmola, PhD, RN, CHN , is Associate Professor, Department of Community Health Nursing, Taibah University, Nursing College, Almadinah, Saudi Arabia
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Browne PD, Cold F, Petersen AM, Halkjær SI, Christensen AH, Günther S, Hestbjerg Hansen L. Engraftment of strictly anaerobic oxygen-sensitive bacteria in irritable bowel syndrome patients following fecal microbiota transplantation does not improve symptoms. Gut Microbes 2021; 13:1-16. [PMID: 34074214 PMCID: PMC8183560 DOI: 10.1080/19490976.2021.1927635] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Dysbiosis of the gut microbiome has been correlated with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is being explored as a therapeutic option. Little is known of the mechanisms of engraftment of microbes following FMT and whether the engraftment of certain microbes correlate with clinical improvement in IBS. Microbiome data, from a previously reported placebo-controlled trial of treatment of IBS with FMT or placebo capsules, were used to investigate microbial engraftment 15 days, 1, 3 and 6 months after treatment through assessment of gains, losses and changes in abundance of amplicon sequence variants (ASVs) and microbial diversity (CHAO-1 richness) between the FMT group and the placebo group. These data were compared to changes in IBS Symptom Severity Scores (IBS-SSS). Twelve days of treatment with 25 daily multi-donor FMT capsules induced significant short- and long-term changes in the recipients' microbiomes for at least 6 months, with persistent engraftment of a variety of anaerobic bacteria from keystone genera, such as Faecalibacterium, Prevotella and Bacteroides and increased microbial diversity, particularly in patients with low initial diversity. FMT recipients lost ASVs after treatment, which was seen to a much lesser extent in the placebo group. No ASVs increased to a greater extent between FMT responders and non-responders following treatment. Major long-term changes, lasting for at least 6 months, in the gut microbiomes of IBS patients are seen following treatment with FMT capsules. None of these changes correlated with clinical improvement. The relationship between the microbiome and the etiology of IBS still remains unsolved.
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Affiliation(s)
- Patrick Denis Browne
- Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark
| | - Frederik Cold
- Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark,Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark,Department of Gastroenterology, Aleris-Hamlet Hospitals Copenhagen, Soeborg, Denmark
| | - Andreas Munk Petersen
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark,Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Sofie Ingdam Halkjær
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | | | - Stig Günther
- Department of Gastroenterology, Aleris-Hamlet Hospitals Copenhagen, Soeborg, Denmark
| | - Lars Hestbjerg Hansen
- Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark,CONTACT Lars Hestbjerg Hansen Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Denmark
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50
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El-Salhy M, Hausken T, Hatlebakk JG. Current status of fecal microbiota transplantation for irritable bowel syndrome. Neurogastroenterol Motil 2021; 33:e14157. [PMID: 34236740 DOI: 10.1111/nmo.14157] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 03/21/2021] [Accepted: 03/23/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common gastrointestinal functional disorder. Although IBS is a benign condition, it reduces the quality of life considerably. While there is currently no effective treatment for this disorder, fecal microbiota transplantation (FMT) seems to be promising. PURPOSE The aim of this review was to analysis possible factors affecting the success or failure of the randomized controlled trials (RCTs) of FMT for IBS and highlighting the gaps in our knowledge that need to be filled and of sketching a possible model for successful FMT in IBS patients. METHODS A systematic search was conducted of literature published in English from January 2015 to December 2020 using the keywords: fecal microbiota transplantation, randomized trials, and IBS. KEY RESULTS Seven randomized controlled trials (RCTs) on the efficacy of FMT for IBS were found in the literature. Four of the seven RCTs found various positive effects, while the other three did not find any effect. CONCLUSIONS AND INFERENCES The efficacy of FMT for IBS appears to be donor-dependent. The effective (super) donor would need to have a favorable microbiota signature, and 11 clinical criteria that are known to be associated with a favorable microbiota have been suggested for selecting FMT donors for IBS. Comparing the microbiota of the effective donors with those of healthy subjects would reveal the favorable microbiota signature required for a super-donor. However, the studies reviewed were not designed to compare efficacy of different donor types. The dose of the fecal transplant is also an important factor influencing the outcome of FMT for IBS. However, further studies designed to test the effect of fecal transplant dose are needed to answer this question. Administering the fecal transplant to either the small or large intestine seems to be effective, but the optimal route of administration remains to be determined. Moreover, whether single or repeated FMT is more effective is also still unclear. A 1-year follow-up of IBS patients who received FMT showed that adverse events of abdominal pain, diarrhea, and constipation were both mild and self-limiting.
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Affiliation(s)
- Magdy El-Salhy
- Department of Medicine, Stord Hospital, Stord, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, National Centre for Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway
| | - Trygve Hausken
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, National Centre for Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway
| | - Jan Gunnar Hatlebakk
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, National Centre for Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway
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