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Moutsoglou D, Syal A, Lopez S, Nelson EC, Chen L, Kabage AJ, Fischer M, Khoruts A, Vaughn BP, Staley C. Novel Microbial Engraftment Trajectories Following Microbiota Transplant Therapy in Ulcerative Colitis. J Crohns Colitis 2025; 19:jjae142. [PMID: 39240145 DOI: 10.1093/ecco-jcc/jjae142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND AND AIMS Microbiota transplant therapy (MTT) is an emerging treatment for ulcerative colitis (UC). One proposed mechanism for the benefit of MTT is through engraftment of donor microbiota; however, engraftment kinetics are unknown. We identified SourceTracker as an efficient method both to determine engraftment and for the kinetic study of engrafting donor taxa to aid in determining the mechanism of how this therapy may treat UC. METHODS Ulcerative colitis patients received either encapsulated (drug name MTP-101C) or placebo capsules daily for 8 weeks followed by a 4-week washout period. Amplicon sequence data from donors and patients were analyzed using the Bayesian algorithm SourceTracker. RESULTS Twenty-seven patients were enrolled, 14 to placebo and 13 to MTT. Baseline Shannon and Chao1 indices negatively correlated with week 12 donor engraftment for patients treated with active drug capsules but not for placebo patients. SourceTracker engraftment positively correlated with the week 12 distance from donors measured using the Bray-Curtis similarity metric in treated patients but not with placebo. Engraftment at week 12 was significantly higher in the MTT group than in the placebo group. We identified engrafting taxa from donors in our patients and quantified the proportion of donor similarity or engraftment during weeks 1 through 8 (active treatment) and week 12, 4 weeks after the last dose. CONCLUSION SourceTracker can be used as a simple and reliable method to quantify donor microbial community engraftment and donor taxa contribution in patients with UC and other inflammatory conditions treated with MTT.
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Affiliation(s)
- Daphne Moutsoglou
- Department of Gastroenterology, Minneapolis VA Health Care System, MN 55417, USA
- Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
| | - Aneesh Syal
- Division of Basic and Translational Research, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Sharon Lopez
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Elizabeth C Nelson
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Lulu Chen
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Amanda J Kabage
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Monika Fischer
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Alexander Khoruts
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Byron P Vaughn
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN 55355, USA
| | - Christopher Staley
- Division of Basic and Translational Research, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA
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Bénard MV, de Goffau MC, Blonk J, Hugenholtz F, van Buuren J, Paramsothy S, Kaakoush NO, D'Haens GRAM, Borody TJ, Kamm MA, Ponsioen CY. Gut Microbiota Features in Relation to Fecal Microbiota Transplantation Outcome in Ulcerative Colitis: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00907-8. [PMID: 39442743 DOI: 10.1016/j.cgh.2024.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 10/10/2024] [Accepted: 10/13/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND & AIMS Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis, yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition. METHODS MEDLINE, Embase, and Cochrane were systematically searched through August 2024 for relevant studies. The quality of studies was analyzed with JBI tools and a composite critical appraisal score. Additionally, species-level data from 2 landmark FMT trials (the Transplantation of Feces in Ulcerative Colitis; Returning Nature's Homeostasis [TURN] and Fecal Microbiota Transplantation for Chronic Active Ulcerative Colitis [FOCUS] trials) were reanalyzed from a compositional perspective. RESULTS Out of 3755 citations identified, 56 met the inclusion criteria, of which 29 fulfilled quality standards. Higher microbial α-diversity, either in donors or recipients (at baseline or following FMT treatment), was associated with better clinical response rates. Engraftment of the donors' microbiota could not be clearly linked with clinical response, possibly because not every donor has an ideal microbiome. Butyrate-producing species from the Lachnospiraceae and Oscillospiraceae families were often related with response, whereas the reverse was true for Fusobacteria, many Proteobacteria, and Ruminococcus gnavus. Compositional analyses showed that clinical response is associated with a shift from a low-diversity, often Bacteroides-dominant composition to one with higher diversity, either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network, or a moderate/high-diversity composition with abundant but not excessive levels of Prevotella copri. CONCLUSIONS This systematic review/meta-analysis yielded a coherent picture from a compositional perspective, which may help identify beneficial donor profiles and guide personalized FMT approaches.
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Affiliation(s)
- Mèlanie V Bénard
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Inflammatory Bowel Disease Centre, Amsterdam UMC, Amsterdam, the Netherlands
| | | | - Justine Blonk
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Floor Hugenholtz
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Amsterdam Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Joep van Buuren
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Sudarshan Paramsothy
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney, New South Wales, Australia; Department of Gastroenterology, Concord Repatriation General Hospital, Concord, New South Wales, Australia; Department of Gastroenterology, Macquarie University Hospital, Sydney, New South Wales, Australia
| | - Nadeem O Kaakoush
- School of Biomedical Sciences, University of New South Wales, Sydney, New South Wales, Australia
| | - Geert R A M D'Haens
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Inflammatory Bowel Disease Centre, Amsterdam UMC, Amsterdam, the Netherlands
| | - Thomas J Borody
- Centre for Digestive Diseases, Sydney, New South Wales, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Inflammatory Bowel Disease Centre, Amsterdam UMC, Amsterdam, the Netherlands.
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Foppa C, Rizkala T, Repici A, Hassan C, Spinelli A. Microbiota and IBD: Current knowledge and future perspectives. Dig Liver Dis 2024; 56:911-922. [PMID: 38008696 DOI: 10.1016/j.dld.2023.11.015] [Citation(s) in RCA: 5] [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] [Received: 08/19/2023] [Revised: 10/18/2023] [Accepted: 11/09/2023] [Indexed: 11/28/2023]
Abstract
Inflammatory Bowel Disease (IBD) is a chronic relapsing-remitting disease with a remarkable increase in incidence worldwide and a substantial disease burden. Although the pathophysiology is not fully elucidated yet an aberrant immune reaction against the intestinal microbiota and the gut microbial dysbiosis have been identified to play a major role. The composition of gut microbiota in IBD patients is distinct from that of healthy individuals, with certain organisms predominating over others. Differences in the microbial dysbiosis have been also observed between Crohn Disease (CD) and Ulcerative Colitis (UC). A disruption of the microbiota's balance can lead to inflammation and intestinal damage. Microbiota composition in IBD can be affected both by endogenous (i.e., interaction with the immune system and intestinal epithelial cells) and exogenous (i.e., medications, surgery, diet) factors. The complex interplay between the gut microbiota and IBD is an area of great interest for understanding disease pathogenesis and developing new treatments. The purpose of this review is to summarize the latest evidence on the role of microbiota in IBD pathogenesis and to explore possible future areas of research.
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Affiliation(s)
- Caterina Foppa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy; IRCCS Humanitas Research Hospital, Division of Colon and Rectal Surgery, via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - Tommy Rizkala
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy; IRCCS Humanitas Research Hospital, Division of Gastroenterology and Digestive Endoscopy Unit, via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - Cesare Hassan
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy; IRCCS Humanitas Research Hospital, Division of Gastroenterology and Digestive Endoscopy Unit, via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy; IRCCS Humanitas Research Hospital, Division of Colon and Rectal Surgery, via Manzoni 56, Rozzano, 20089, Milan, Italy.
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Xu B, Fu Y, Yin N, Qin W, Huang Z, Xiao W, Huang H, Mei Q, Fan J, Zeng Y, Huang C. Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii served as key components of fecal microbiota transplantation to alleviate colitis. Am J Physiol Gastrointest Liver Physiol 2024; 326:G607-G621. [PMID: 38502145 PMCID: PMC11376976 DOI: 10.1152/ajpgi.00303.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 02/28/2024] [Accepted: 03/15/2024] [Indexed: 03/20/2024]
Abstract
Fecal microbiota transplantation (FMT) is a promising therapy for inflammatory bowel disease (IBD) via rectifying gut microbiota. The aim of this study was to identify a mechanism of how specific bacteria-associated immune response contributes to alleviated colitis. Forty donors were divided into high (donor H) and low (donor L) groups according to the diversity and the abundance of Bacteroides and Faecalibacterium by 16S rRNA sequencing. FMT was performed on dextran sulfate sodium (DSS)-induced colitis in mice. Mice with colitis showed significant improvement in intestinal injury and immune imbalance after FMT with group donor H (P < 0.05). Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii were identified as targeted strains in donor feces by real-time PCR and droplet digital PCR. Mice with colitis were treated with mono- or dual-bacterial gavage therapy. Dual-bacterial therapy significantly ameliorated intestinal injury compared with mono-bacterial therapy (P < 0.05). Dual-bacterial therapy increased the M2/M1 macrophage polarization and improved the Th17/Treg imbalance and elevated IL-10 production by Tregs compared with the DSS group (P < 0.05). Metabolomics showed increased abundance of lecithin in the glycerophospholipid metabolism pathway. In conclusion, B. thetaiotaomicron and F. prausnitzii, as the key bacteria in donor feces, alleviate colitis in mice. The mechanism may involve increasing lecithin and regulating IL-10 production of intestinal Tregs.NEW & NOTEWORTHY We demonstrate that donors with high abundance of Bacteroides and Faecalibacterium ameliorate dextran sulfate sodium (DSS)-induced colitis in mice by fecal microbiota transplantation (FMT). The combination therapy of Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii is superior to mono-bacterial therapy in ameliorating colitis in mice, of which mechanism may involve promoting lecithin and inducing IL-10 production of intestinal Tregs.
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Affiliation(s)
- Binqiang Xu
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Yang Fu
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Nuoming Yin
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Wenfei Qin
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People's Republic of China
| | - Zehua Huang
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Wei Xiao
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People's Republic of China
| | - Huizhen Huang
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- Shanghai General Hospital of Nanjing Medical University, Shanghai, People's Republic of China
| | - Qixiang Mei
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Junjie Fan
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Yue Zeng
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Chunlan Huang
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
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Wu R, Xiong R, Li Y, Chen J, Yan R. Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation. J Autoimmun 2023; 141:103062. [PMID: 37246133 DOI: 10.1016/j.jaut.2023.103062] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 05/05/2023] [Accepted: 05/08/2023] [Indexed: 05/30/2023]
Abstract
Gut dysbiosis has been associated with inflammatory bowel disease (IBD), one of the most common gastrointestinal diseases. The microbial communities play essential roles in host physiology, with profound effects on immune homeostasis, directly or via their metabolites and/or components. There are increasing clinical trials applying fecal microbiota transplantation (FMT) with Crohn's disease (CD) and ulcerative colitis (UC). The restoration of dysbiotic gut microbiome is considered as one of the mechanisms of FMT therapy. In this work, latest advances in the alterations in gut microbiome and metabolome features in IBD patients and experimental mechanistic understanding on their contribution to the immune dysfunction were reviewed. Then, the therapeutic outcomes of FMT on IBD were summarized based on clinical remission, endoscopic remission and histological remission of 27 clinical trials retrieved from PubMed which have been registered on ClinicalTrials.gov with the results been published in the past 10 years. Although FMT is established as an effective therapy for both subtypes of IBD, the promising outcomes are not always achieved. Among the 27 studies, only 11 studies performed gut microbiome profiling, 5 reported immune response alterations and 3 carried out metabolome analysis. Generally, FMT partially restored typical changes in IBD, resulted in increased α-diversity and species richness in responders and similar but less pronounced shifts of patient microbial and metabolomics profiles toward donor profiles. Measurements of immune responses to FMT mainly focused on T cells and revealed divergent effects on pro-/anti-inflammatory functions. The very limited information and the extremely confounding factors in the designs of the FMT trials significantly hindered a reasonable conclusion on the mechanistic involvement of gut microbiota and metabolites in clinical outcomes and an analysis of the inconsistencies.
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Affiliation(s)
- Rongrong Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Rui Xiong
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Yan Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Junru Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Ru Yan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
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Liu Y, Ji X, Huang Y, Li Q, Ding X, Wang Y, Zhang S, Wen Q, Cui B, Lu X, Zhang F. Older patients benefit more from sequential courses of washed microbiota transplantation than younger population with ulcerative colitis. Scand J Gastroenterol 2023; 58:890-899. [PMID: 36864569 DOI: 10.1080/00365521.2023.2185476] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 02/19/2023] [Accepted: 02/23/2023] [Indexed: 03/04/2023]
Abstract
OBJECTIVES The short-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) has increasingly been evaluated. However, few studies have examined the long-term efficacy and its predictors. This study aimed to assess the clinical factors affecting the long-term efficacy of FMT for patients with UC. METHODS This is a retrospective analysis of a prospective trial (NCT01790061) for patients with UC undergoing washed microbiota transplantation (WMT), which is the improved methodology of FMT. The long-term clinical efficacy of WMT and the factors affecting efficacy were analyzed. RESULTS A total of 259 patients were included for analysis. Of 70.7% (183/259) of patients achieved a clinical response at 1 month after WMT and 29.7% (77/259) achieved steroid-free clinical remission 6 months after WMT. Total 44 patients maintained a clinical response for ≥24 months, and 33 (17.1%, 33/193) achieved steroid-free clinical remission for ≥24 months with WMT monotherapy. Patients with age at UC onset of ≥60 years, mild disease severity and undergoing ≥2 courses of WMT during the response within 6 months were more likely to achieve steroid-free clinical remission 6 months after WMT. Besides, independent factors associated with the long-term response of WMT for UC were age at onset of ≥60 years and ≥2 courses of WMT during the response. CONCLUSIONS This study indicated WMT could induce short-term steroid-free clinical remission and maintain long-term response in UC, especially for older patients and patients undergoing sequential courses.
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Affiliation(s)
- Yujie Liu
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
- Department of Geriatrics, Sir Run Run Hospital at Nanjing Medical University, Nanjing, China
| | - Xinghui Ji
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Yihao Huang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Qianqian Li
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Xiao Ding
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong, China
| | - Yun Wang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Sheng Zhang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Quan Wen
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Xiang Lu
- Department of Geriatrics, Sir Run Run Hospital at Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
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Li H, Li Y, Qian J. What is the "optimal formula" for donor selection and feces processing for fecal microbiota transplantation in ulcerative colitis? Chin Med J (Engl) 2023; 136:1410-1412. [PMID: 37166218 PMCID: PMC10278737 DOI: 10.1097/cm9.0000000000002704] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Indexed: 05/12/2023] Open
Affiliation(s)
- Haiyue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- School of Medicine, Tsinghua University, Haidian District, Beijing 100084, China
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
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Levast B, Fontaine M, Nancey S, Dechelotte P, Doré J, Lehert P. Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: A Systematic Review and Meta-analysis. Clin Transl Gastroenterol 2023; 14:e00568. [PMID: 37232579 PMCID: PMC10208705 DOI: 10.14309/ctg.0000000000000568] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 01/31/2023] [Indexed: 05/27/2023] Open
Abstract
INTRODUCTION Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis was performed to compare the efficacy of single-donor (SDN) and multidonor (MDN) strategies for product preparation. METHODS Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 nonrandomized). The treatment response was assessed by using fixed- and random-effects models, and the significance of the indirect difference between the interventions was assessed using a network approach. RESULTS Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios [RRs]: 4.41 and 1.57, respectively [P ≤ 0.001 for both]), and MDN was superior to SDN (RR: 2.81, P = 0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P = 0.042). Results were identical for both models. DISCUSSION There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation.JOURNAL/cltg/04.03/01720094-202305000-00002/2FFU1/v/2023-05-23T220055Z/r/image-tiff.
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Affiliation(s)
| | | | - Stéphane Nancey
- Department of Gastroenterology, CHU de Lyon, Lyon-Sud Hospital, University Claude Bernard Lyon 1 and CIRI-INSERM U1111, Lyon, France
| | | | - Joël Doré
- Université Paris-Saclay, INRAE, MetaGenoPolis, AgroParis Tech, MICALIS, 78350, Jouy-en-Josas, France
| | - Philippe Lehert
- Faculty of Management, UCL, Louvain, Belgium
- Faculty of Medicine, University of Melbourne, Australia
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Haneishi Y, Furuya Y, Hasegawa M, Picarelli A, Rossi M, Miyamoto J. Inflammatory Bowel Diseases and Gut Microbiota. Int J Mol Sci 2023; 24:ijms24043817. [PMID: 36835245 PMCID: PMC9958622 DOI: 10.3390/ijms24043817] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/13/2023] [Accepted: 02/13/2023] [Indexed: 02/17/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal tract, the incidence of which has rapidly increased worldwide, especially in developing and Western countries. Recent research has suggested that genetic factors, the environment, microbiota, and immune responses are involved in the pathogenesis; however, the underlying causes of IBD are unclear. Recently, gut microbiota dysbiosis, especially a decrease in the abundance and diversity of specific genera, has been suggested as a trigger for IBD-initiating events. Improving the gut microbiota and identifying the specific bacterial species in IBD are essential for understanding the pathogenesis and treatment of IBD and autoimmune diseases. Here, we review the different aspects of the role played by gut microbiota in the pathogenesis of IBD and provide a theoretical basis for modulating gut microbiota through probiotics, fecal microbiota transplantation, and microbial metabolites.
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Affiliation(s)
- Yuri Haneishi
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi 183-8509, Tokyo, Japan
| | - Yuma Furuya
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi 183-8509, Tokyo, Japan
| | - Mayu Hasegawa
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi 183-8509, Tokyo, Japan
| | - Antonio Picarelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Mauro Rossi
- Institute of Food Sciences, National Research Council (CNR), Via Roma 64, 83100 Avellino, Italy
| | - Junki Miyamoto
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi 183-8509, Tokyo, Japan
- Correspondence: ; Tel.: +81-42-367-5684
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Shang Y, Zhai Z, Huang J, Li L, Zuo X. Specific alterations in mucosa-associated bacterial composition in ulcerative colitis (UC) patients with different degrees of inflammation. BIOTECHNOL BIOTEC EQ 2022. [DOI: 10.1080/13102818.2022.2060134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Affiliation(s)
- Yansheng Shang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
- Department of Gastroenterology, Jinan City People’s Hospital, Jinan, Shandong, PR China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
| | - Zhenzhen Zhai
- Department of Gastroenterology, Dezhou People’s Hospital, Dezhou, Shandong, PR China
| | - Jiaguo Huang
- Department of Gastroenterology, Jinan City People’s Hospital, Jinan, Shandong, PR China
| | - Lixiang Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
| | - Xiuli Zuo
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
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11
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Guo XH, Zhu YL, Yang L, Li WJ, Du XF. The Effects of Multi-Donor Fecal Microbiota Transplantation Capsules Combined with Thalidomide on Hormone-Dependent Ulcerative Colitis. Infect Drug Resist 2022; 15:7495-7501. [PMID: 36570710 PMCID: PMC9784385 DOI: 10.2147/idr.s385485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 11/14/2022] [Indexed: 12/23/2022] Open
Abstract
Objective This study aimed to assess the effects of multi-donor fecal microbiota transplantation (FMT) capsules combined with thalidomide on hormone-dependent ulcerative colitis (UC). Methods A total of 59 patients with steroid-dependent UC treated at the Gastroenterology Department of the First Affiliated Hospital of Xinxiang Medical University between January 2017 and January 2019 were enrolled in this study. Using a random number table, the patients were divided into two groups: a group treated with FMT capsules (the FMT group) and a group treated with FMT capsules and thalidomide (the FMT+S group). Multi-donor FMT capsules were prepared, and all subjects and stool donors followed the FMT pathway for FMT transplantation. Each patient's Mayo score, C-reactive protein (CRP) level, and level of fecal calprotectin before FMT treatment and at week 1 and week 13 after treatment were recorded. All patients were followed up for 15 weeks. Results A total of 56.7% of the patients (34/59) achieved a therapeutic response at the end of the research period. Compared with the FMT group, the FMT+S group had better clinical benefit (P < 0.05). In the comparison of efficacy at week 1 and week 13 after treatment, the Mayo scores, calprotectin levels, and CRP indexes in the FMT+S group were better than those in the FMT group (P < 0.05). There were no serious adverse events in the treatment process or during follow-up. Conclusion A combination of FMT capsules and thalidomide provides a treatment choice for patients with hormone-dependent UC, and it can be used as an adjuvant therapy. However, large-scale, multi-center, and prospective trials are required to further verify the reliability of this treatment.
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Affiliation(s)
- Xiao-He Guo
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China
| | - Yan-Li Zhu
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China,Correspondence: Yan-Li Zhu, Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, No. 88 of Jiankang Road, Weihui District, Henan, 453100, People’s Republic of China, Tel +86 15036615840, Email
| | - Lu Yang
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China
| | - Wen-Jing Li
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China
| | - Xue-Fang Du
- Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China
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12
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Ramos RJ, Zhu C, Joseph DF, Thaker S, Lacomb JF, Markarian K, Lee HJ, Petrov JC, Monzur F, Buscaglia JM, Chawla A, Small-Harary L, Gathungu G, Morganstern JA, Yang J, Li J, Pamer EG, Robertson CE, Frank DN, Cross JR, Li E. Metagenomic and bile acid metabolomic analysis of fecal microbiota transplantation for recurrent Clostridiodes difficile and/or inflammatory bowel diseases. MEDICAL RESEARCH ARCHIVES 2022; 10:10.18103/mra.v10i10.3318. [PMID: 36618438 PMCID: PMC9817289 DOI: 10.18103/mra.v10i10.3318] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infections (rCDI), but has more limited efficacy in treating either ulcerative colitis (UC) or Crohn's disease (CD), two major forms of inflammatory bowel diseases (IBD). We hypothesize that FMT recipients with rCDI and/or IBD have baseline fecal bile acid (BA) compositions that differ significantly from that of their healthy donors and that FMT will normalize the BA compositions. AIM To study the effect of single colonoscopic FMT on microbial composition and function in four recipient groups: 1.) rCDI patients without IBD (rCDI-IBD); 2.) rCDI with IBD (rCDI+IBD); 3.) UC patients without rCDI (UC-rCDI); 4.) CD patients without rCDI (CD-rCDI). METHODS We performed 16S rRNA gene sequence, shotgun DNA sequence and quantitative bile acid metabolomic analyses on stools collected from 55 pairs of subjects and donors enrolled in two prospective single arm FMT clinical trials (Clinical Trials.gov ID NCT03268213, 479696, UC no rCDI ≥ 2x IND 1564 and NCT03267238, IND 16795). Fitted linear mixed models were used to examine the effects of four recipient groups, FMT status (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on microbial diversity and composition, bile acid metabolites and bile acid metabolizing enzyme gene abundance. RESULTS The pre-FMT stools collected from rCDI ± IBD recipients had reduced α-diversity compared to the healthy donor stools and was restored post-FMT. The α-diversity in the pre-FMT stools collected from UC-rCDI or CD-rCDI recipients did not differ significantly from donor stools. FMT normalized some recipient/donor ratios of genus level taxa abundance in the four groups. Fecal secondary BA levels, including some of the secondary BA epimers that exhibit in vitro immunomodulatory activities, were lower in rCDI±IBD and CD-rCDI but not UC-rCDI recipients compared to donors. FMT restored secondary BA levels. Metagenomic baiE gene and some of the eight bile salt hydrolase (BSH) phylotype abundances were significantly correlated with fecal BA levels. CONCLUSION Restoration of multiple secondary BA levels, including BA epimers implicated in immunoregulation, are associated with restoration of fecal baiE gene counts, suggesting that the 7-α-dehydroxylation step is rate-limiting.
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13
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Piazzesi A, Putignani L. Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention. Front Microbiol 2022; 13:958346. [PMID: 36071979 PMCID: PMC9441770 DOI: 10.3389/fmicb.2022.958346] [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: 05/31/2022] [Accepted: 07/25/2022] [Indexed: 11/15/2022] Open
Abstract
Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.
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Affiliation(s)
- Antonia Piazzesi
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Lorenza Putignani
- Department of Diagnostic and Laboratory Medicine, Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
- *Correspondence: Lorenza Putignani,
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14
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Nishida A, Nishino K, Ohno M, Sakai K, Owaki Y, Noda Y, Imaeda H. Update on gut microbiota in gastrointestinal diseases. World J Clin Cases 2022; 10:7653-7664. [PMID: 36158494 PMCID: PMC9372855 DOI: 10.12998/wjcc.v10.i22.7653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 04/20/2022] [Accepted: 06/22/2022] [Indexed: 02/06/2023] Open
Abstract
The human gut is a complex microbial ecosystem comprising approximately 100 trillion microbes collectively known as the "gut microbiota". At a rough estimate, the human gut microbiome contains almost 3.3 million genes, which are about 150 times more than the total human genes present in the human genome. The vast amount of genetic information produces various enzymes and physiologically active substances. Thus, the gut microbiota contributes to the maintenance of host health; however, when healthy microbial composition is perturbed, a condition termed "dysbiosis", the altered gut microbiota can trigger the development of various gastrointestinal diseases. The gut microbiota has consequently become an extremely important research area in gastroenterology. It is also expected that the results of research into the gut microbiota will be applied to the prevention and treatment of human gastrointestinal diseases. A randomized controlled trial conducted by a Dutch research group in 2013 showed the positive effect of fecal microbiota transplantation (FMT) on recurrent Clostridioides difficile infection (CDI). These findings have led to the development of treatments targeting the gut microbiota, such as probiotics and FMT for inflammatory bowel diseases (IBD) and other diseases. This review focuses on the association of the gut microbiota with human gastrointestinal diseases, including CDI, IBD, and irritable bowel syndrome. We also summarize the therapeutic options for targeting the altered gut microbiota, such as probiotics and FMT.
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Affiliation(s)
- Atsushi Nishida
- Department of Gastroenterology and Hepatology, Nagahama City Hospital, Nagahama 526-8580, Japan
| | - Kyohei Nishino
- Department of Gastroenterology and Hepatology, Nagahama City Hospital, Nagahama 526-8580, Japan
| | - Masashi Ohno
- Department of Gastroenterology and Hepatology, Nagahama City Hospital, Nagahama 526-8580, Japan
| | - Keitaro Sakai
- Department of Gastroenterology and Hepatology, Nagahama City Hospital, Nagahama 526-8580, Japan
| | - Yuji Owaki
- Department of Gastroenterology and Hepatology, Nagahama City Hospital, Nagahama 526-8580, Japan
| | - Yoshika Noda
- Department of Gastroenterology and Hepatology, Nagahama City Hospital, Nagahama 526-8580, Japan
| | - Hirotsugu Imaeda
- Department of Gastroenterology and Hepatology, Nagahama City Hospital, Nagahama 526-8580, Japan
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15
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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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16
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Rees NP, Shaheen W, Quince C, Tselepis C, Horniblow RD, Sharma N, Beggs AD, Iqbal TH, Quraishi MN. Systematic review of donor and recipient predictive biomarkers of response to faecal microbiota transplantation in patients with ulcerative colitis. EBioMedicine 2022; 81:104088. [PMID: 35660786 PMCID: PMC9163485 DOI: 10.1016/j.ebiom.2022.104088] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/14/2022] [Accepted: 05/16/2022] [Indexed: 12/14/2022] Open
Affiliation(s)
- Nia Paddison Rees
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK
| | - Walaa Shaheen
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK
| | | | - Chris Tselepis
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Clinical Sciences, School of Biomedical Sciences, University of Birmingham, UK
| | - Richard D Horniblow
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Clinical Sciences, School of Biomedical Sciences, University of Birmingham, UK
| | - Naveen Sharma
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Andrew D Beggs
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Tariq H Iqbal
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Microbiology and Infection, University of Birmingham, UK
| | - Mohammed Nabil Quraishi
- University of Birmingham Microbiome Treatment Centre, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
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17
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Zhang J, Guo Y, Duan L. Features of Gut Microbiome Associated With Responses to Fecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review. Front Med (Lausanne) 2022; 9:773105. [PMID: 35721102 PMCID: PMC9198717 DOI: 10.3389/fmed.2022.773105] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 04/19/2022] [Indexed: 12/14/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has been seen as a novel treatment for inflammatory bowel disease (IBD). The results on microbial alterations and their relationship to treatment efficacy are varied among studies. We performed a systematic review to explore the association between microbial features and therapy outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to November 2020. Studies that investigated the efficacy of FMT and baseline microbial features or dynamic alteration of the microbiome during FMT were included. The methodological quality of the included cohort studies and randomized controlled trials (RCTs) was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane risk of bias tool, respectively. A total of 30 studies were included in the analysis. Compared to non-responders, the microbial structure of patients who responded to FMT had a higher similarity to that of their donors after FMT. Donors of responders (R-d) and non-responders (NR-d) had different microbial taxa, but the results were inconsistent. After FMT, several beneficial short-chain fatty acids- (SCFA-) producing taxa, such as Faecalibacterium, Eubacterium, Roseburia, and species belonging to them, were enriched in responders, while pathogenic bacteria (Escherichia coli and Escherichia-Shigella) belonging to the phylum Proteobacteria were decreased. Alterations of microbial functional genes and metabolites were also observed. In conclusion, the response to FMT was associated with the gut microbiota and their metabolites. The pre-FMT microbial features of recipients, the comparison of pre- and post-FMT microbiota, and the relationship between recipients and donors at baseline should be further investigated using uniform and standardized methods.
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Affiliation(s)
- Jindong Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yangyang Guo
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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18
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Li W, Zhang L, Xu Q, Yang W, Zhao J, Ren Y, Yu Z, Ma L. Taxifolin Alleviates DSS-Induced Ulcerative Colitis by Acting on Gut Microbiome to Produce Butyric Acid. Nutrients 2022; 14:nu14051069. [PMID: 35268045 PMCID: PMC8912346 DOI: 10.3390/nu14051069] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/25/2022] [Accepted: 02/28/2022] [Indexed: 01/27/2023] Open
Abstract
Taxifolin is a bioflavonoid which has been used to treat Inflammatory Bowel Disease. However, taxifolin on DSS-induced colitis and gut health is still unclear. Here, we studied the effect of taxifolin on DSS-induced intestinal mucositis in mice. We measured the degree of intestinal mucosal injury and inflammatory response in DSS treated mice with or without taxifolin administration and studied the changes of fecal metabolites and intestinal microflora using 16S rRNA. The mechanism was further explored by fecal microbiota transplantation. The results showed that the weight loss and diarrhea score of the mice treated with taxifolin decreased in DSS-induced mice and longer colon length was displayed after taxifolin supplementation. Meanwhile, the expression of GPR41 and GPR43 in the colon was significantly increased by taxifolin treatment. Moreover, the expression of TNF-α, IL-1β, and IL-6 in colon tissue was inhibited by taxifolin treatment. The fecal metabolism pattern changed significantly after DSS treatment, which was reversed by taxifolin treatment. Importantly, taxifolin significantly increased the levels of butyric acid and isobutyric acid in the feces of DSS-treated mice. In terms of gut flora, taxifolin reversed the changes of Akkermansia, and further decreased uncultured_bacterium_f_Muribaculaceae. Fecal transplantation from taxifolin-treated mice showed a lower diarrhea score, reduced inflammatory response in the colon, and reduced intestinal mucosal damage, which may be related to the increased level of butyric acid in fecal metabolites. In conclusion, this study provides evidence that taxifolin can ameliorate DSS-induced colitis by altering gut microbiota to increase the production of SCFAs.
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Affiliation(s)
| | | | | | | | | | | | | | - Libao Ma
- Correspondence: ; Tel.: +86-13317192322
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19
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Qiu P, Ishimoto T, Fu L, Zhang J, Zhang Z, Liu Y. The Gut Microbiota in Inflammatory Bowel Disease. Front Cell Infect Microbiol 2022; 12:733992. [PMID: 35273921 PMCID: PMC8902753 DOI: 10.3389/fcimb.2022.733992] [Citation(s) in RCA: 213] [Impact Index Per Article: 71.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 01/24/2022] [Indexed: 12/16/2022] Open
Abstract
Epidemiological surveys indicate that the incidence of inflammatory bowel disease (IBD) is increasing rapidly with the continuous growth of the economy. A large number of studies have investigated the relationship between the genetic factors related to the susceptibility to IBD and the gut microbiota of patients by using high-throughput sequencing. IBD is considered the outcome of the interaction between host and microorganisms, including intestinal microbial factors, abnormal immune response, and a damaged intestinal mucosal barrier. The imbalance of microbial homeostasis leads to the colonization and invasion of opportunistic pathogens in the gut, which increases the risk of the host immune response and promotes the development of IBD. It is critical to identify the specific pathogens related to the pathogenesis of IBD. An in-depth understanding of various pathogenic factors is of great significance for the early detection of IBD. This review highlights the role of gut microbiota in the pathogenesis of IBD and provides a theoretical basis for the personalized approaches that modulate the gut microbiota to treat IBD.
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Affiliation(s)
- Peng Qiu
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Takatsugu Ishimoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Gastrointestinal Cancer Biology, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Lingfeng Fu
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Gastrointestinal Cancer Biology, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Jun Zhang
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Gastrointestinal Cancer Biology, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Zhenyong Zhang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yang Liu
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Yang Liu, ; orcid.org/0000-0002-2129-9086
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20
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Murata M, Sugimoto M, Miyamoto S, Kawai T. Long-term improvement in constipation-related symptoms after Helicobacter pylori eradication therapy. Helicobacter 2022; 27:e12863. [PMID: 34791741 DOI: 10.1111/hel.12863] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 10/29/2021] [Accepted: 11/07/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND Helicobacter pylori eradication therapy effectively improves the abnormal bowel habits and abdominal symptoms of patients for a few months post-treatment (PT). However, it is unclear whether the improvement in abnormal bowel habits and symptoms continues long term. Here, we investigated the association of successful H. pylori eradication therapy with improvements in abdominal symptoms in the short- and long-term PT. MATERIALS AND METHODS We evaluated the severity of constipation-related abdominal symptoms in 287 H. pylori-positive patients who underwent eradication therapy at pre-treatment and 2 and 12 months PT using two measures: the Gastrointestinal Symptom Rating Scale (GSRS) and the Izumo scale. RESULTS In patients with constipation at pre-treatment, constipation-related symptom scores in the GSRS improved significantly from 7.91 ± 3.15 at pre-treatment to 6.07 ± 2.75 at 2 months PT (p < 0.01) and 6.85 ± 3.46 at 12 months PT (p = 0.04). Patients with improved symptom scores at 2 months PT also experienced an improvement at 12 months PT. In contrast, patients who did not experience an improvement in constipation-related symptoms at 2 months PT likewise did not experience an improvement at 12 months PT. CONCLUSIONS Patients who experience an improvement at 2 months PT with H. pylori eradication therapy continue to experience improved symptoms in the long term. Therefore, H. pylori -positive patients with abnormal bowel habits should be recommended eradication therapy to prevent gastric cancer development and to alleviate abnormal bowel habits and abdominal symptoms.
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Affiliation(s)
- Masaki Murata
- Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Mitsushige Sugimoto
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Shin'ichi Miyamoto
- Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Takashi Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
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21
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Michailidis L, Currier AC, Le M, Flomenhoft DR. Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. Ann Gastroenterol 2021; 34:802-814. [PMID: 34815646 PMCID: PMC8596209 DOI: 10.20524/aog.2021.0655] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 03/08/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) has shown excellent efficacy in treating Clostridioides difficile infection, as well as promise in several other diseases. The heightened interest is accompanied by concerns over adverse events (AE) and safety. To further understand that in FMT, we performed a systematic review of the literature and a meta-analysis of high-quality, prospective randomized controlled trials FMT. METHODS Studies were selected based on predefined exclusion criteria and were assessed for quality. Only prospective, randomized, controlled studies of high quality were included in the final analysis. Data were extracted on demographics, AE, indication, delivery method and follow-up duration. RESULTS Out of 334 articles reviewed, 9 high quality studies with 756 FMTs were selected for final analysis. The pooled rate of AE was 39.3% (95% confidence interval [CI] 0.19-0.642) as they were reported by 112 patients who received FMT. The SAE rate was 5.3% (95%CI 3.1-8.8%). The most common AE reported was abdominal pain, followed by diarrhea. The most common SAE was Clostridium difficile infection. Upper gastrointestinal tract delivery was associated with a higher rate of total AE, but not SAE. CONCLUSIONS Based on the selected studies, the AE rate of FMT is 39.3%, with most AE being mild and self-limiting. SAE were uncommon at 5.3%, and many were only possibly related to the FMT. Adherence to standardized reporting of AE as well as longitudinal studies and registries will help further clarify the safety of FMT in the future.
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Affiliation(s)
- Lamprinos Michailidis
- Department of Digestive Diseases and Nutrition, University of Kentucky College of Medicine, Lexington, KY, USA
- Correspondence to: Lamprinos Michailidis, MD, University of Kentucky College of Medicine 800 Rose Street Room MN649, Lexington, KY 40536, USA, e-mail:
| | - Alden C. Currier
- Department of Digestive Diseases and Nutrition, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Michelle Le
- Department of Digestive Diseases and Nutrition, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Deborah R. Flomenhoft
- Department of Digestive Diseases and Nutrition, University of Kentucky College of Medicine, Lexington, KY, USA
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Fitzgerald RS, Sanderson IR, Claesson MJ. Paediatric Inflammatory Bowel Disease and its Relationship with the Microbiome. MICROBIAL ECOLOGY 2021; 82:833-844. [PMID: 33666710 PMCID: PMC8551107 DOI: 10.1007/s00248-021-01697-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 01/19/2021] [Indexed: 05/07/2023]
Abstract
Paediatric inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract, comprising of Crohn's disease (CD), ulcerative colitis (UC), and, where classification is undetermined, inflammatory bowel disease unclassified (IBDU). Paediatric IBD incidence is increasing globally, with prevalence highest in the developed world. Though no specific causative agent has been identified for paediatric IBD, it is believed that a number of factors may contribute to the development of the disease, including genetics and the environment. Another potential component in the development of IBD is the microbiota in the digestive tract, particularly the gut. While the exact role that the microbiome plays in IBD is unclear, many studies acknowledge the complex relationship between the gut bacteria and pathogenesis of IBD. In this review, we look at the increasing number of studies investigating the role the microbiome and other biomes play in paediatric patients with IBD, particularly changes associated with IBD, varying disease states, and therapeutics. The paediatric IBD microbiome is significantly different to that of healthy children, with decreased diversity and differences in bacterial composition (such as a decrease in Firmicutes). Changes in the microbiome relating to various treatments of IBD and disease severity have also been observed in multiple studies. Changes in diversity and composition may also extend to other biomes in paediatric IBD, such as the virome and the mycobiome. Research into biome differences in IBD paediatric patients may help progress our understanding of the aetiology of the disease.
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Affiliation(s)
- Rachel S Fitzgerald
- School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Ian R Sanderson
- Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Marcus J Claesson
- School of Microbiology, University College Cork, Cork, Ireland.
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
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23
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Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes. Clin Transl Gastroenterol 2021; 11:e00224. [PMID: 32955197 PMCID: PMC7431231 DOI: 10.14309/ctg.0000000000000224] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION: The previous researches aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) in a short-term observation. The present study aimed to explore the optimum timing of FMT for maintaining the long-term clinical benefits and to target the gut microbiota that may help to predict the long-term success or failure of FMT in UC. METHODS: Two hundred two patients with UC were recruited from November 2012 to September 2018. The primary endpoint of this study was the maintaining time of the first and second courses of FMT. Relapse was defined as partial Mayo score ≥2 after achieving clinical remission and an increase of partial Mayo score ≥1 after achieving clinical response. The stool samples were analyzed by 16S rRNA gene sequencing. RESULTS: The median maintaining time of the efficacy was 120 days (IQR, 45–180) and 182.5 days (IQR, 105–311.25) from the first course and second course of FMT, respectively. No FMT-related serious adverse events were observed. The differences of the relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission (P < 0.05). DISCUSSION: This study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits. The short-term alterations of microbiota after FMT may be conducive to predicting the long-term efficacy of FMT in UC (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/CTG/A363).
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24
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Olesen SW, Gerardin Y. Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease. J Crohns Colitis 2021; 15:453-461. [PMID: 32808030 DOI: 10.1093/ecco-jcc/jjaa170] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Faecal microbiota transplantation [FMT] is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions such as inflammatory bowel disease [IBD]. Previous FMT clinical trials have considered the possibility of a 'donor effect', that is, that FMT material from different donors has different clinical efficacies. METHODS Here we re-evaluate evidence for donor effects in published FMT clinical trials for IBD. RESULTS In ten of 12 published studies, no statistically significant donor effect was detected when rigorously re-evaluating the original analyses. One study showed statistically significant separation of microbiota composition of pools of donor stool when stratified by patient outcome. One study reported a significant effect but did not have underlying data available for re-evaluation. When quantifying the uncertainty on the magnitude of the donor effect, confidence intervals were large, including both zero donor effects and very substantial donor effects. CONCLUSION Although we found very little evidence for donor effects, the existing data cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are probably needed to determine if donor effects are clinically relevant for IBD.
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Affiliation(s)
- Scott W Olesen
- OpenBiome, Cambridge, MA, USA.,Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
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25
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Mocanu V, Rajaruban S, Dang J, Kung JY, Deehan EC, Madsen KL. Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis. J Clin Med 2021; 10:959. [PMID: 33804464 PMCID: PMC7957789 DOI: 10.3390/jcm10050959] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/17/2021] [Accepted: 02/19/2021] [Indexed: 12/13/2022] Open
Abstract
The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies-antibiotic pre-treatment and repeated FMT dosing-on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.
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Affiliation(s)
- Valentin Mocanu
- Department of Surgery, University of Alberta Hospital, University of Alberta, 8440 112 Street NW, Edmonton, AB T6G 2B7, Canada;
| | - Sabitha Rajaruban
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada; (S.R.); (E.C.D.); (K.L.M.)
| | - Jerry Dang
- Department of Surgery, University of Alberta Hospital, University of Alberta, 8440 112 Street NW, Edmonton, AB T6G 2B7, Canada;
| | - Janice Y. Kung
- John W. Scott Health Sciences Library, University of Alberta, 2K3.28 Walter C. Mackenzie Health Sciences Centre, Edmonton, AB T6G 2R7, Canada;
| | - Edward C. Deehan
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada; (S.R.); (E.C.D.); (K.L.M.)
| | - Karen L. Madsen
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada; (S.R.); (E.C.D.); (K.L.M.)
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26
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Banfi D, Moro E, Bosi A, Bistoletti M, Cerantola S, Crema F, Maggi F, Giron MC, Giaroni C, Baj A. Impact of Microbial Metabolites on Microbiota-Gut-Brain Axis in Inflammatory Bowel Disease. Int J Mol Sci 2021; 22:1623. [PMID: 33562721 PMCID: PMC7915037 DOI: 10.3390/ijms22041623] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/29/2021] [Accepted: 02/02/2021] [Indexed: 02/07/2023] Open
Abstract
The complex bidirectional communication system existing between the gastrointestinal tract and the brain initially termed the "gut-brain axis" and renamed the "microbiota-gut-brain axis", considering the pivotal role of gut microbiota in sustaining local and systemic homeostasis, has a fundamental role in the pathogenesis of Inflammatory Bowel Disease (IBD). The integration of signals deriving from the host neuronal, immune, and endocrine systems with signals deriving from the microbiota may influence the development of the local inflammatory injury and impacts also more distal brain regions, underlying the psychophysiological vulnerability of IBD patients. Mood disorders and increased response to stress are frequently associated with IBD and may affect the disease recurrence and severity, thus requiring an appropriate therapeutic approach in addition to conventional anti-inflammatory treatments. This review highlights the more recent evidence suggesting that alterations of the microbiota-gut-brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as "postbiotics", such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. The last section covers a critical evaluation of the main clinical evidence pointing to the microbiome-based therapeutic approaches for the treatment of IBD-related gastrointestinal and neuropsychiatric symptoms.
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Affiliation(s)
- Davide Banfi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Elisabetta Moro
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy; (E.M.); (F.C.)
| | - Annalisa Bosi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Michela Bistoletti
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Silvia Cerantola
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy; (S.C.); (M.C.G.)
| | - Francesca Crema
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy; (E.M.); (F.C.)
| | - Fabrizio Maggi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Maria Cecilia Giron
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy; (S.C.); (M.C.G.)
| | - Cristina Giaroni
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
- Centre of Neuroscience, University of Insubria, 21100 Varese, Italy
| | - Andreina Baj
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
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Ding X, Yang X, Wang H. Methodology, efficacy and safety of fecal microbiota transplantation in treating inflammatory bowel disease. MEDICINE IN MICROECOLOGY 2020. [DOI: 10.1016/j.medmic.2020.100028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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28
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Olesen SW. Power calculations for detecting differences in efficacy of fecal microbiota donors. Contemp Clin Trials Commun 2020; 20:100674. [PMID: 33241161 PMCID: PMC7672275 DOI: 10.1016/j.conctc.2020.100674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 10/27/2020] [Indexed: 12/26/2022] Open
Abstract
Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of other indications, notably inflammatory bowel disease. The immense variability in human stool, combined with anecdotal reports from FMT studies, have suggested the existence of “donor effects”, in which stool from some FMT donors is more efficacious than stool from other donors. In this study, simulated clinical trials were used to estimate the number of patients that would be required to detect donor effects under a variety of study designs. In most cases, reliable detection of donor effects required more than 100 patients treated with FMT. These results suggest that previous reports of donor effects need to be verified with results from large clinical trials and that patient biomarkers may be the most promising route to robustly identifying donor effects.
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Affiliation(s)
- Scott W Olesen
- OpenBiome, 2067 Massachusetts Avenue, Cambridge, MA, 02140, USA
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29
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Chen M, Liu XL, Zhang YJ, Nie YZ, Wu KC, Shi YQ. Efficacy and safety of fecal microbiota transplantation by washed preparation in patients with moderate to severely active ulcerative colitis. J Dig Dis 2020; 21:621-628. [PMID: 32909356 PMCID: PMC7756426 DOI: 10.1111/1751-2980.12938] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 06/17/2020] [Accepted: 08/05/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE We aimed to evaluate the short-term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC. METHODS An open-label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end-point was a clinical response at week 2 post-FMT. The secondary end-points were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression. RESULTS Of the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti-tumor necrosis factor-α therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P > 0.05). Adverse events, all mild and self-limiting, were observed in 33.3% (3/9) of the patients. CONCLUSIONS FMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short-term follow-up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings.
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Affiliation(s)
- Min Chen
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Xiao Lei Liu
- Department of Medical InsuranceXijing Hospital, Air Force Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Yu Jie Zhang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Yong Zhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Kai Chun Wu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
| | - Yong Quan Shi
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxi ProvinceChina
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30
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Zhao HL, Chen SZ, Xu HM, Zhou YL, He J, Huang HL, Xu J, Nie YQ. Efficacy and safety of fecal microbiota transplantation for treating patients with ulcerative colitis: A systematic review and meta-analysis. J Dig Dis 2020; 21:534-548. [PMID: 33439534 DOI: 10.1111/1751-2980.12933] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 07/30/2020] [Accepted: 08/14/2020] [Indexed: 01/30/2023]
Abstract
OBJECTIVES To assess the effect of donor selection, stool procedures and pretreatment with antibiotics on the efficacy and safety of fecal microbiota transplantation (FMT)-treated ulcerative colitis (UC). METHODS A systematic review and meta-analysis was conducted including studies on UC treated with FMT as the primary therapeutic agent published up to June 30, 2020. Primary end-point data included clinical remission (CR) or CR combined with endoscopic remission. RESULTS A total of 37 studies (seven random controlled trials [RCTs], five controlled and 25 uncontrolled cohort studies) and 959 patients with UC were enrolled. In controlled cohort studies and RCTs, FMT had a significantly greater benefit than placebo (pooled odds ratio [P-OR] 3.392, 95% CI 2.196-5.240, P < 0.001), with no heterogeneity (I2 = 0%). Furthermore, administration of FMT via the lower gastrointestinal (GI) tract was more effective in achieving CR than via the upper GI tract (44.3% vs 31.7%). The remission rate was also higher when the total stool dosage was over 275 g compared with less than 275 g (51.9% vs 29.5%). Overall, the incidence of serious adverse events of FMT was 5.9%. There was no significant difference between single and multiple donors, fresh and frozen stool sample used, and whether or not antibiotic pretreatment was administered before FMT. CONCLUSION FMT administration via the lower GI tract and using higher dosage appear to be effective and safe in inducing remission of active UC.
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Affiliation(s)
- Hai Lan Zhao
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Shu Zhen Chen
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Hao Ming Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - You Lian Zhou
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Jie He
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Hong Li Huang
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Jing Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
| | - Yu Qiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, China
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31
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Caldeira LDF, Borba HH, Tonin FS, Wiens A, Fernandez-Llimos F, Pontarolo R. Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis. PLoS One 2020; 15:e0238910. [PMID: 32946509 PMCID: PMC7500646 DOI: 10.1371/journal.pone.0238910] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 08/25/2020] [Indexed: 02/07/2023] Open
Abstract
Objectives Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease. Methods Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted. Results Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn’s disease patients seemed to benefit more from the procedure. Conclusions The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn’s disease.
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Affiliation(s)
| | - Helena H. Borba
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Fernanda S. Tonin
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Astrid Wiens
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
| | - Fernando Fernandez-Llimos
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Roberto Pontarolo
- Pharmaceutical Sciences Postgraduate Research Program, Universidade Federal do Paraná, Curitiba, Brazil
- * E-mail:
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The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study. Biomedicines 2020; 8:biomedicines8080268. [PMID: 32756350 PMCID: PMC7459721 DOI: 10.3390/biomedicines8080268] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 07/27/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove–Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients’ microbiota and resulted in the remission of patients with active UC.
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33
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Zatorski H, Nakov R. Faecal Microbiota Transplantation in Inflammatory Bowel Disease: Current Concepts and Future Challenges. Curr Drug Targets 2020; 21:1440-1447. [PMID: 32484770 DOI: 10.2174/1389450121666200602125507] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 04/08/2020] [Accepted: 04/09/2020] [Indexed: 12/26/2022]
Abstract
Dysbiosis has been repeatedly observed in inflammatory bowel disease (IBD) and is now recognized as an essential factor in the gut inflammatory process. IBD is a significant burden to health-care systems, mainly due to treatment-related costs. Available treatments have several limitations: up to 30% of patients are primary non-responders, and between 10 and 20% lose response per year, requiring a dose-escalation or a switch to another biologic. Hence, the current IBD treatment is not sufficient, and there is an urgent need to introduce new therapies in the management of these patients. Recently, the correction of dysbiosis has become an attractive approach from a therapeutic point of view. Faecal microbiota transplantation (FMT) appears as a reliable and potentially beneficial therapy in IBD patients. There is developing data that FMT for mild-to-moderately active UC is a safe and efficient therapy for the induction of remission. However, the current studies have different designs and have a short follow up, which makes clinical interpretation significantly difficult. There is a need for RCTs with a well-defined study cohort using FMT for the therapy of CD patients. The location, behavior, and severity of the disease should be taken into account. The goal of this manuscript is to review the data currently available on FMT and IBD, to explain FMT principles and methodology in IBD patients and to discuss some unresolved issues.
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Affiliation(s)
- Hubert Zatorski
- Department of Digestive Tract Diseasesx,Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Radislav Nakov
- Clinic of Gastroenterology, Tsaritsa Yoanna University Hospital, Medical University of Sofia, Sofia, Bulgaria
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Guo XY, Liu XJ, Hao JY. Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment. J Dig Dis 2020; 21:147-159. [PMID: 32040250 DOI: 10.1111/1751-2980.12849] [Citation(s) in RCA: 184] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 01/16/2020] [Accepted: 02/06/2020] [Indexed: 12/11/2022]
Abstract
Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem-based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.
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Affiliation(s)
- Xiao Yan Guo
- Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xin Juan Liu
- Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jian Yu Hao
- Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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Chen HT, Huang HL, Xu HM, Luo QL, He J, Li YQ, Zhou YL, Nie YQ, Zhou YJ. Fecal microbiota transplantation ameliorates active ulcerative colitis. Exp Ther Med 2020; 19:2650-2660. [PMID: 32256746 PMCID: PMC7086197 DOI: 10.3892/etm.2020.8512] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 01/03/2020] [Indexed: 12/11/2022] Open
Abstract
Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.
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Affiliation(s)
- Hui-Ting Chen
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Hong-Li Huang
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Hao-Ming Xu
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Qing-Ling Luo
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Jie He
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yong-Qiang Li
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - You-Lian Zhou
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yu-Qiang Nie
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yong-Jian Zhou
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
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Ding X, Li Q, Li P, Zhang T, Cui B, Ji G, Lu X, Zhang F. Long-Term Safety and Efficacy of Fecal Microbiota Transplant in Active Ulcerative Colitis. Drug Saf 2020; 42:869-880. [PMID: 30972640 DOI: 10.1007/s40264-019-00809-2] [Citation(s) in RCA: 104] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND OBJECTIVE The therapeutic role of fecal microbiota transplantation in ulcerative colitis varies across different reports. This study aims to evaluate the long-term safety and efficacy of a strategy called step-up fecal microbiota transplantation for ulcerative colitis. METHODS Two clinical trials (NCT01790061, NCT02560727) for moderate-to-severe ulcerative colitis (Mayo score range 6-12) were performed from November 2012 to July 2017. Both studies were pooled for analysis on the safety and efficacy of fecal microbiota transplantation in patients with ulcerative colitis over a 1-year follow-up. The step-up fecal microbiota transplantation strategy included step 1: single fecal microbiota transplantation; step 2: two or more fecal microbiota transplantations; and step 3: fecal microbiota transplantations followed by immunosuppressants. Long-term clinical efficacy and adverse events were assessed, and multiple factors related to fecal microbiota transplantation were evaluated. RESULTS Of 134 eligible patients in this real-word study, 81.3% (109/134) were included for analysis. The follow-up ranged from 1 to 5 years. Fecal microbiota transplantation-related adverse events were observed in 17.4% (43/247) of fecal microbiota transplantation procedures including one serious adverse event (myasthenia gravis) and 56 non-serious adverse events. Multivariable logistic regression analysis showed that both the method of preparation of microbiota from stool using the automatic system and the delivery method of colonic transendoscopic enteral tubing were associated with a lower rate of fecal microbiota transplantation-related adverse events (p = 0.023, p = 0.017, respectively). In total, 74.3% (81/109) and 51.4% (56/109) of patients achieved clinical response at 1 month and 3 months after step-up fecal microbiota transplantation, respectively. CONCLUSIONS Fecal microbiota transplantation should be a safe and promising therapy for ulcerative colitis. The improved fecal microbiota preparation and colonic transendoscopic enteral tubing might reduce the rate of adverse events in ulcerative colitis. TRIAL REGISTRATION ClinicalTrials.gov NCT01790061, NCT02560727.
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Affiliation(s)
- Xiao Ding
- Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, China.,Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Ave, Nanjing, 211166, China
| | - Qianqian Li
- Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, China
| | - Pan Li
- Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, China.,Key Laboratory of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Ting Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, China
| | - Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, China.,Key Laboratory of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Guozhong Ji
- Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, China.,Key Laboratory of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Xiang Lu
- Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Ave, Nanjing, 211166, China.
| | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, China. .,Key Laboratory of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China.
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Effects of Antibiotic Pretreatment of an Ulcerative Colitis-Derived Fecal Microbial Community on the Integration of Therapeutic Bacteria In Vitro. mSystems 2020; 5:5/1/e00404-19. [PMID: 31992630 PMCID: PMC6989129 DOI: 10.1128/msystems.00404-19] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Fecal microbiota transplantation (FMT) is a proposedly useful strategy for the treatment of gastrointestinal (GI) disorders through remediation of the patient gut microbiota. However, its therapeutic success has been variable, necessitating research to uncover mechanisms that improve patient response. Antibiotic pretreatment has been proposed as one method to enhance the success rate by increasing niche availability for introduced species. Several limitations hinder exploring this hypothesis in clinical studies, such as deleterious side effects and the development of antimicrobial resistance in patients. Thus, the purpose of this study was to evaluate the use of an in vitro, bioreactor-based, colonic ecosystem model as a form of preclinical testing by determining how pretreatment with the antibiotic rifaximin influenced engraftment of bacterial strains sourced from a healthy donor into an ulcerative colitis-derived defined microbial community. Distinct species integrated under the pretreated and untreated conditions, with the relative rifaximin resistance of the microbial strains being an important influencer. However, both conditions resulted in the integration of taxa from Clostridium clusters IV and XIVa, a concomitant reduction of Proteobacteria, and similar decreases in metabolites associated with poor health status. Our results agree with the findings of similar research in the clinic by others, which observed no difference in primary patient outcomes whether or not patients were given rifaximin prior to FMT. We therefore conclude that our model is useful for screening for antibiotics that could improve efficacy of FMT when used as a pretreatment.IMPORTANCE Patients with gastrointestinal disorders often exhibit derangements in their gut microbiota, which can exacerbate their symptoms. Replenishing these ecosystems with beneficial bacteria through fecal microbiota transplantation is thus a proposedly useful therapeutic; however, clinical success has varied, necessitating research into strategies to improve outcomes. Antibiotic pretreatment has been suggested as one such approach, but concerns over harmful side effects have hindered testing this hypothesis clinically. Here, we evaluate the use of bioreactors supporting defined microbial communities derived from human fecal samples as models of the colonic microbiota in determining the effectiveness of antibiotic pretreatment. We found that relative antimicrobial resistance was a key determinant of successful microbial engraftment with rifaximin (broad-spectrum antibiotic) pretreatment, despite careful timing of the application of the therapeutic agents, resulting in distinct species profiles from those of the control but with similar overall outcomes. Our model had results comparable to the clinical findings and thus can be used to screen for useful antibiotics.
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Berberine regulates fecal metabolites to ameliorate 5-fluorouracil induced intestinal mucositis through modulating gut microbiota. Biomed Pharmacother 2020; 124:109829. [PMID: 31958765 DOI: 10.1016/j.biopha.2020.109829] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Revised: 01/08/2020] [Accepted: 01/10/2020] [Indexed: 12/25/2022] Open
Abstract
Berberine (BBR) is an isoquinoline alkaloid, which has been used in the treatment of intestinal mucositis. However, BBR on chemotherapy-induced mucositis in cancer patients remains largely unknown. Here, we investigated the effect of BBR on intestinal mucositis induced by 5-fluorouracil (5-Fu) using rat model. We detected the degree of intestinal mucosal damage and inflammatory response in 5-Fu treated rats with or without BBR administration, and investigated the changes of fecal metabolites and gut microbiota using 1H NMR spectroscopy and 16S rRNA. The mechanism was further explored by fecal microbiota transplantation (FMT). Results showed that BBR treated rats displayed less weight loss, lower diarrhea score and longer colon length in 5-Fu treated rats. Meanwhile, BBR treatment significantly increased the expression of Occludin in ileum and decreased the d-lactate content in serum. Moreover, the expression of IL-1β, IL-6 and TNF-α in ileum were suppressed by BBR treatment. The pattern of fecal metabolism changed obviously after treated with 5-Fu, which was reversed by BBR. Importantly, BBR significantly increased the levels of butyrate and glutamine in feces from 5-Fu treated rats. In terms of gut microbiota, BBR enriched the relative abundance of Firmicutes and decreased Proteobacteria at the phylum level. Meanwhile, BBR increased the propotion of unclassified_f_ Porphyromonadaceae, unclassified_f_ Lachnospiraceae, Lactobacillus, unclassified_o_ Clostridiales, Ruminococcus, Prevotella, Clostridium IV, and decreased Escherichia/Shigella at the genera level. Furthermore, principal component analysis (PCA) showed that fecal transplantation led to changes in fecal metabolites. Fecal transplantation from BBR treated rats had low diarrhea score, reduced inflammatory response in ileum, and relieved intestinal mucosal injury, which may be caused by the increased of butyrate level in fecal metabolites. In conclusion, our study provides evidence that BBR regulates fecal metabolites to ameliorate 5-Fu induced intestinal mucositis by modifying gut microbiota.
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Newman KM, Vaughn BP. Efficacy of intestinal microbiota transplantation in ulcerative colitis: a review of current literature and knowledge. MINERVA GASTROENTERO 2020; 65. [DOI: 10.23736/s1121-421x.19.02610-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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40
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Zhao R, Ji Y, Chen X, Su A, Ma G, Chen G, Hu Q, Zhao L. Effects of a β-type glycosidic polysaccharide from Flammulina velutipes on anti-inflammation and gut microbiota modulation in colitis mice. Food Funct 2020; 11:4259-4274. [DOI: 10.1039/c9fo03017d] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Using the Flammulina velutipes polysaccharide (FVP) extracted from our previous study, herein, we investigated the improvement of this β-type glycosidic polysaccharide in alleviating dextran sodium sulfate-induced ulcerative colitis (UC) in mice.
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Affiliation(s)
- Ruiqiu Zhao
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
| | - Yang Ji
- College of Food Science and Engineering
- Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety
- Nanjing 210023
- People's Republic of China
| | - Xin Chen
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
| | - Anxiang Su
- College of Food Science and Engineering
- Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety
- Nanjing 210023
- People's Republic of China
| | - Gaoxing Ma
- College of Food Science and Engineering
- Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety
- Nanjing 210023
- People's Republic of China
| | - Guitang Chen
- Department of Food Quality and Safety
- China Pharmaceutical University
- Nanjing 211198
- People's Republic of China
| | - Qiuhui Hu
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
- College of Food Science and Engineering
| | - Liyan Zhao
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
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Zhang F, Zhang T, Zhu H, Borody TJ. Evolution of fecal microbiota transplantation in methodology and ethical issues. Curr Opin Pharmacol 2019; 49:11-16. [PMID: 31059962 DOI: 10.1016/j.coph.2019.04.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 04/01/2019] [Accepted: 04/01/2019] [Indexed: 02/07/2023]
Abstract
Fecal microbiota transplantation (FMT), the core therapy for remodeling the gut microbiota with a long medical history, has gained great attention worldwide in recent years. Increasing studies have explored its indications, methodology, efficacy, safety, and ethics. Purified forms of FMT, using an automated method for the purification of fecal microbiota from stool, has become a reality. Colonic transendoscopic enteral tubing makes frequent FMT delivery into the whole colon feasible. This review focuses on the recent progress in laboratory preparation, updated clinical strategies, novel delivery methods, and ethical issues surrounding FMT in clinical studies.
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Affiliation(s)
- Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China.
| | - Ting Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China
| | - Heming Zhu
- Department of Acupuncture and Oriental Medicine, Maryland University of Integrative Health, Laurel, MD, United States
| | - Thomas J Borody
- Centre for Digestive Diseases, Five Dock, NSW 2046, Australia
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The Clinical and Steroid-Free Remission of Fecal Microbiota Transplantation to Patients with Ulcerative Colitis: A Meta-Analysis. Gastroenterol Res Pract 2019; 2019:1287493. [PMID: 31178906 PMCID: PMC6501134 DOI: 10.1155/2019/1287493] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 03/14/2019] [Accepted: 03/17/2019] [Indexed: 12/26/2022] Open
Abstract
Background and Purpose Since the first case of fecal microbiota transplantation for the treatment of ulcerative colitis was described in the year 1989, there have been an increment of case reports, case series, cohort studies, and randomized controlled trials (RCTs). In this study, we were going to investigate general clinical remission, clinical response, and steroid-free remission of fecal microbiota transplantation. Methods We searched Ovid Medline, Ovid EMBASE, and Cochrane Library, focusing prospective studies including randomized controlled trials and cohort studies. The outcomes were clinical remission, clinical response, steroid-free remission, and serious adverse events. We used RevMan 5.3 software for meta-analyses. Key Results A total of 4 RCTs and 2 cohort studies (340 cases from 5 countries) were included. We found that FMT might be more effective than placebo on clinical remission (OR, 3.85 [2.21, 6.7]; P < 0.001; I 2 = 0%) and clinical response (OR, 2.75 [1.33, 5.67]; P = 0.006; I 2 = 49%), but no statistical difference on steroid-free remission (OR, 2.08 [0.41, 10.5]; P = 0.37; I 2 = 69%) and serious adverse events (OR, 2.0 [0.17, 22.97]; P = 0.44; I 2 = 0%). Conclusions and Inferences Fecal microbiota transplantations were associated with significant clinical remission and response in ulcerative colitis patients while there was no significant difference found between FMT and placebo in steroid-free remission. Moreover, a common consensus on the route, volume, timing, preferred donor characteristics, and frequency of fecal administration is necessary to achieve remission.
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Nishida A, Imaeda H, Inatomi O, Bamba S, Sugimoto M, Andoh A. The efficacy of fecal microbiota transplantation for patients with chronic pouchitis: A case series. Clin Case Rep 2019; 7:782-788. [PMID: 30997086 PMCID: PMC6452488 DOI: 10.1002/ccr3.2096] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Accepted: 02/21/2019] [Indexed: 01/07/2023] Open
Abstract
Pouchitis is one of the most common complications that develop after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Single fecal microbiota transplantation (FMT) by colonoscopy was performed safely on three patients with pouchitis. However, the efficacy of FMT on pouchitis was limited.
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Affiliation(s)
- Atsushi Nishida
- Department of MedicineShiga University of Medical ScienceOtsuJapan
| | - Hirotsugu Imaeda
- Department of MedicineShiga University of Medical ScienceOtsuJapan
| | - Osamu Inatomi
- Department of MedicineShiga University of Medical ScienceOtsuJapan
| | - Shigeki Bamba
- Division of Clinical NutritionShiga University of Medical ScienceOtsuJapan
| | | | - Akira Andoh
- Department of MedicineShiga University of Medical ScienceOtsuJapan
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Chen CC, Chen YN, Liou JM, Wu MS. From germ theory to germ therapy. Kaohsiung J Med Sci 2019; 35:73-82. [DOI: 10.1002/kjm2.12011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 11/22/2018] [Indexed: 12/16/2022] Open
Affiliation(s)
- Chieh-Chang Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; National Taiwan University Hospital; Taipei Taiwan
- Department of Internal Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Yen-Nien Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; National Taiwan University Hospital; Taipei Taiwan
- Department of Internal Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Jyh-Ming Liou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; National Taiwan University Hospital; Taipei Taiwan
- Department of Internal Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
| | - Ming-Shiang Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; National Taiwan University Hospital; Taipei Taiwan
- Department of Internal Medicine, College of Medicine; National Taiwan University; Taipei Taiwan
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Meng X, Zhou HY, Shen HH, Lufumpa E, Li XM, Guo B, Li BZ. Microbe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity. Autoimmun Rev 2019; 18:455-475. [PMID: 30844549 DOI: 10.1016/j.autrev.2019.03.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 11/05/2018] [Indexed: 12/14/2022]
Abstract
The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.
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Affiliation(s)
- Xiang Meng
- School of Stomatology, Anhui Medical University, Hefei, Anhui, China
| | - Hao-Yue Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China
| | - Hui-Hui Shen
- Department of Clinical Medicine, The second School of Clinical Medicine, Anhui Medical University, Anhui, Hefei, China
| | - Eniya Lufumpa
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Xiao-Mei Li
- Department of Rheumatology & Immunology, Anhui Provincial Hospital, Anhui, Hefei, China
| | - Biao Guo
- The Second Affiliated Hospital of Anhui Medical University, Anhui, Hefei, China
| | - Bao-Zhu Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China.
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Abu-Sbeih H, Ali FS, Wang Y. Clinical Review on the Utility of Fecal Microbiota Transplantation in Immunocompromised Patients. Curr Gastroenterol Rep 2019; 21:8. [PMID: 30815766 DOI: 10.1007/s11894-019-0677-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Fecal microbiota transplantation (FMT) represents a promising management modality for Clostridium difficile infection (CDI). In immunocompromised patients, FMT is utilized for CDI as well as emerging non-CDI indications such as inflammatory bowel disease and graft versus host disease. PURPOSE OF REVIEW: This review aims to shed light on the safety and efficacy of FMT in immunocompromised patients, including patients suffering for human immunodeficiency virus infection, solid organ and hematopoietic stem cell transplant recipients, cancer patients, and patients on immunosuppressive therapies. RECENT FINDINGS: Though the body of evidence concerning the use of FMT in immunocompromised is growing, no clinical trials exist to date. Present literature weighs in favor of FMT in immunocompromised patients, with an acceptable adverse effect profile and minimal risk of infectious adverse events. Further large scale studies and randomized controlled trials to validate the utility of FMT in immunocompromised individuals will be a welcomed endeavor.
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Affiliation(s)
- Hamzah Abu-Sbeih
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1466, Houston, TX, 77030, USA
| | - Faisal S Ali
- Department of Internal Medicine, Presence Saint Joseph Hospital, Chicago, IL, USA
| | - Yinghong Wang
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1466, Houston, TX, 77030, USA.
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Lai CY, Sung J, Cheng F, Tang W, Wong SH, Chan PKS, Kamm MA, Sung JJY, Kaplan G, Chan FKL, Ng SC. Systematic review with meta-analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation. Aliment Pharmacol Ther 2019; 49:354-363. [PMID: 30628108 DOI: 10.1111/apt.15116] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Revised: 07/20/2018] [Accepted: 12/06/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) is effective for Clostridium difficile infections (CDI) refractory to standard treatment and is being studied in other diseases. AIM To evaluate donor characteristics, procedures and clinical outcomes of FMT. METHODS We systematically reviewed FMT studies published up to 29 August 2018 using MEDLINE (R) and EMBASE and identified clinical studies with FMT donor information. We reported data on donor characteristics, screening criteria, administration, clinical outcomes and adverse events. RESULTS Among 5267 reports, 239 full-text articles were screened and 168 articles were included. FMT was performed commonly for CDI (n = 108) and inflammatory bowel disease (IBD) (n = 31). We reported characteristics of 1513 donors [58% male; mean age, 34.3 years; mean body mass index, 21.6]. Donors in Asia were younger than the West (mean age 30.7 vs 32.9, P = 0.00075). Less than 50% of studies screened donors for transmittable pathogens. Final cure rate for CDI was 95.6% (95% confidence interval [CI], 93.9%-97.1%) and final remission rates for ulcerative colitis (UC) and Crohn's disease (CD) were 39.6% (95% CI, 25.4%-54.6%) and 47.5% (95% CI, 29.4%-65.8%), respectively. Cure rates in CDI and final remission rates for CD and UC were comparable across all routes of FMT administration. Overall adverse event incidence was <1%, mostly GI-related. Adverse event rates did not differ significantly between routes of FMT administration or indication. CONCLUSIONS In a systematic review assessing donor characteristics and FMT efficacy, we observed heterogeneity in donor selection, application and outcomes of FMT. These data can facilitate standardisation of FMT protocols for various diseases.
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Affiliation(s)
- Cheuk Yin Lai
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Joanne Sung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Felix Cheng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Whitney Tang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Sunny H Wong
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Paul K S Chan
- Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China.,Center for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China
| | - Michael A Kamm
- St Vincent's Hospital and University of Melbourne, Melbourne, Victoria, Australia
| | - Joseph J Y Sung
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Gilaad Kaplan
- Departments of Medicine and Community Health Sciences, The University of Calgary, Calgary, Alberta, Canada
| | - Francis K L Chan
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.,Center for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.,Center for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China
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Wilson BC, Vatanen T, Cutfield WS, O'Sullivan JM. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front Cell Infect Microbiol 2019; 9:2. [PMID: 30719428 PMCID: PMC6348388 DOI: 10.3389/fcimb.2019.00002] [Citation(s) in RCA: 247] [Impact Index Per Article: 41.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 01/03/2019] [Indexed: 12/13/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has become a highly effective bacteriotherapy for recurrent Clostridium difficile infection. Meanwhile the efficacy of FMT for treating chronic diseases associated with microbial dysbiosis has so far been modest with a much higher variability in patient response. Notably, a number of studies suggest that FMT success is dependent on the microbial diversity and composition of the stool donor, leading to the proposition of the existence of FMT super-donors. The identification and subsequent characterization of super-donor gut microbiomes will inevitably advance our understanding of the microbial component of chronic diseases and allow for more targeted bacteriotherapy approaches in the future. Here, we review the evidence for super-donors in FMT and explore the concept of keystone species as predictors of FMT success. Possible effects of host-genetics and diet on FMT engraftment and maintenance are also considered. Finally, we discuss the potential long-term applicability of FMT for chronic disease and highlight how super-donors could provide the basis for dysbiosis-matched FMTs.
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Affiliation(s)
- Brooke C. Wilson
- The Liggins Institute, University of Auckland, Auckland, New Zealand
| | - Tommi Vatanen
- The Liggins Institute, University of Auckland, Auckland, New Zealand
- The Broad Institute of MIT and Harvard, Cambridge, MA, United States
| | - Wayne S. Cutfield
- The Liggins Institute, University of Auckland, Auckland, New Zealand
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Zhang J, Chen X, Song JL, Qian Y, Yi R, Mu J, Zhao X, Yang Z. Preventive Effects of Lactobacillus plantarum CQPC07 on Colitis Induced by Dextran Sodium Sulfate in Mice. FOOD SCIENCE AND TECHNOLOGY RESEARCH 2019. [DOI: 10.3136/fstr.25.413] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
- Jing Zhang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University (BTBU)
- College of Environmental and Quality Inspection, Chongqing Chemical Industry Vocational College
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education
| | - Xiaoliang Chen
- Dean's Office, Chongqing Chemical Industry Vocational College
| | - Jia-Le Song
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education
- Department of Nutrition and Food Hygiene, School of Public Health, Guilin Medical University
| | - Yu Qian
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education
| | - Ruokun Yi
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education
| | - Jianfei Mu
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education
| | - Xin Zhao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University (BTBU)
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education
| | - Zhennai Yang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University (BTBU)
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Levy AN, Allegretti JR. Insights into the role of fecal microbiota transplantation for the treatment of inflammatory bowel disease. Therap Adv Gastroenterol 2019; 12:1756284819836893. [PMID: 30906424 PMCID: PMC6421596 DOI: 10.1177/1756284819836893] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 02/16/2019] [Indexed: 02/04/2023] Open
Abstract
Fecal microbiota transplantation (FMT) has changed the treatment landscape of Clostridium difficile infection (CDI). Emerging evidence has shown that FMT can also be an effective and safe treatment strategy in CDI with underlying inflammatory bowel disease (IBD). Recently, randomized controlled trials of FMT in ulcerative colitis support its expanding role in restoring gut homeostasis in this disease. However, heterogeneous study designs leave several questions yet to be answered, including how to best position this novel therapy in the treatment approach of Crohn's disease and pouchitis. Additional studies are needed to validate whether FMT can assume a complementary role in the standard treatment of IBD.
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Affiliation(s)
- Alexander N. Levy
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA, USA
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