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Deng Z, Mei S, Ouyang Z, Wang R, Wang L, Zou B, Dai J, Mao K, Li Q, Guo Q, Yi C, Meng F, Xie M, Zhang X, Wang R, Deng T, Wang Z, Li X, Wang Q, Liu B, Tian X. Dysregulation of gut microbiota stimulates NETs-driven HCC intrahepatic metastasis: therapeutic implications of healthy faecal microbiota transplantation. Gut Microbes 2025; 17:2476561. [PMID: 40099491 PMCID: PMC11925110 DOI: 10.1080/19490976.2025.2476561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 12/04/2024] [Accepted: 03/03/2025] [Indexed: 03/20/2025] Open
Abstract
The stringent regulation of intrahepatic metastases is essential for improving survival outcomes in patients with hepatocellular carcinoma (HCC). This study investigated the impact of gut microbiota on intrahepatic metastasis of HCC and evaluated the therapeutic potential of healthy fecal microbiota transplantation (FMT). Dysregulation of the gut microbiota, characterized by a significant reduction in the abundance of beneficial bacteria, such as Anaerotruncus colihominis and Dysosmobacter welbionis, was observed in patients with intrahepatic metastatic HCC. A human flora-associated (HFA) intrahepatic metastatic HCC mouse model was successfully established through consecutive 4 weeks of human-mouse FMT. Dysregulation of gut microbiota promoted intrahepatic metastasis in the mouse model, primarily by enhancing neutrophil-mediated inflammatory responses and lead to excessive formation of neutrophil extracellular traps (NETs). Consequently, it promoted tumor vascular growth and tissue necrosis, resulting in intrahepatic metastasis of HCC. Notably, FMT from healthy donors mitigated these pathological processes. This study elucidated the role and mechanism of dysregulated gut microbiota in promoting intrahepatic metastasis of HCC. Healthy FMT emerges as a promising novel therapeutic strategy for preventing and treating intrahepatic metastasis of HCC.
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Affiliation(s)
- Zhe Deng
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
| | - Si Mei
- Hunan Province University Key Laboratory of Oncology of Traditional Chinese Medicine, Changsha, Hunan, China
- Key Laboratory of Traditional Chinese Medicine for Mechanism of Tumor Prevention &Treatment, Changsha, Hunan, China
- Department of Physiology, Faculty of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Zhaoguang Ouyang
- School and Hospital of Stomatology, Tianjin Medical University, Tianjin, China
| | - Ruoyu Wang
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Lihuai Wang
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Bo Zou
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Jingjing Dai
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Kexin Mao
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Qian Li
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Qianqian Guo
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Chun Yi
- Department of Pathology, Faculty of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Fanying Meng
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Mingxia Xie
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Xue Zhang
- College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Rongrong Wang
- Hunan Province Integrated Traditional Chinese and Western Medicine Hospital, Changsha, Hunan, China
| | - Tianhao Deng
- Hunan Province Integrated Traditional Chinese and Western Medicine Hospital, Changsha, Hunan, China
| | - Zhenyu Wang
- JCY Biotech Ltd., Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen, China
| | - Xiaozheng Li
- College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China
- College of Biology, School of Biomedical Sciences, Hunan University, Changsha, China
| | - Qing Wang
- Shanghai OE Biotech Co. Ltd, Shanghai, China
| | - Bin Liu
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Xuefei Tian
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
- Hunan Province University Key Laboratory of Oncology of Traditional Chinese Medicine, Changsha, Hunan, China
- Key Laboratory of Traditional Chinese Medicine for Mechanism of Tumor Prevention &Treatment, Changsha, Hunan, China
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Jansen D, Deleu S, Caenepeel C, Marcelis T, Simsek C, Falony G, Machiels K, Sabino J, Raes J, Vermeire S, Matthijnssens J. Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses. Gut Microbes 2025; 17:2499575. [PMID: 40371968 DOI: 10.1080/19490976.2025.2499575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 04/02/2025] [Accepted: 04/24/2025] [Indexed: 05/16/2025] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplantation (FMT), which transfers healthy donor microbiota to patients. The role of viruses in this process, however, remains underexplored. To address this, we analyzed the gut virome using metagenomic sequencing of enriched viral particles from 320 longitudinal fecal samples of 44 patients enrolled in the RESTORE-UC FMT trial. Patients were treated with FMTs from healthy donors (allogenic, treatment) or themselves (autologous, control). We found that colonic inflammation, both its presence and location, had a greater impact on the gut virome than FMT itself. In autologous FMT patients, the virome was unstable and showed rapid divergence over time, a phenomenon we termed virome drift. In allogenic FMT patients, the virome temporarily shifted toward the healthy donor, lasting up to 5 weeks and primarily driven by microviruses. Notably, two distinct virome configurations were identified and linked to either healthy donors or patients. In conclusion, inflammation strongly affects the gut virome in UC patients, which may lead to instability and obstruct the engraftment of allogeneic FMT.
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Affiliation(s)
- Daan Jansen
- Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, Belgium
| | - Sara Deleu
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Clara Caenepeel
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Tine Marcelis
- Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, Belgium
| | - Ceren Simsek
- Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, Belgium
| | - Gwen Falony
- Department of Microbiology Immunology and Transplantation, Rega Institute, Laboratory of Molecular Bacteriology, KU Leuven, Leuven, Belgium
- Center for Microbiology, VIB, Leuven, Belgium
- Institute of Medical Microbiology and Hygiene and Research Centre for Immunotherapy (FZI), University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Kathleen Machiels
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - João Sabino
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Jeroen Raes
- Department of Microbiology Immunology and Transplantation, Rega Institute, Laboratory of Molecular Bacteriology, KU Leuven, Leuven, Belgium
- Center for Microbiology, VIB, Leuven, Belgium
| | - Séverine Vermeire
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Jelle Matthijnssens
- Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, KU Leuven, Leuven, Belgium
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Zhang F, Kamm MA, Wu X, Kao D, Borody TJ, Chen LA, He X, Fischer M, Wong SH, Ng SC, Cui B, Chan FKL, Nie Y, Sood A, Li J, Sun Y, Dai I, Chen Q, Lv M, Zhang Z, Ianiro G, Yang Y, Kelly CR. Preferred Reporting Items for Microbiotherapy (PRIM) Guidelines Across Medical Disciplines: An International Delphi Consensus. J Gastroenterol Hepatol 2025. [PMID: 40143713 DOI: 10.1111/jgh.16947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 02/06/2025] [Accepted: 03/14/2025] [Indexed: 03/28/2025]
Abstract
Microbiotherapy has opened new avenues for managing dysbiosis-related diseases. However, many studies did not cover all the necessary reporting items for microbiotherapy making the interpretation of results, safety assessment, technology extension, and even the transparency of legitimacy difficult. This project consisted of 2 phases. First, we proposed an initial preferred reporting items for microbiotherapy (PRIM) checklist and applied it to oncology studies from 2011 to 2023 according to Meta-Analyses guideline. Only 39.3% (n = 64) of these studies (n = 163) met all PRIM checklist items. The culture-based microbiotherapy (CMT) studies had higher score than non-culture-based (NMT) ones (p = 0.018). In the second phase, the expert panel consisting of 22 specialists from eight countries across Asia, Australia, Europe, and North America refined and finalized the PRIM guidelines (named as PRIM 2024) through Delphi consensus. The PRIM 2024 guidelines conclude 10 statements and 18 points on diagnosis, delivery route, source, classification, preparation, dosage, state, concomitant treatment, efficacy, and safety. The panel defined less than 80% of all PRIM points (14 points) as low-quality reports. These guidelines are recommended for reporting on microbiotherapy in clinical studies and reports on compassionate use, including but not limited to fecal microbiota transplantation, phage therapy, probiotics, and synbiotics. These consistent and transparent reporting items can help researchers and practitioners better evaluate, compare, implement research findings in microbiotherapy.
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Affiliation(s)
- Faming Zhang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Xia Wu
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dina Kao
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Thomas J Borody
- Center for Digestive Diseases, Sydney, New South Wales, Australia
| | - Lea Ann Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers, New Brunswick, USA
| | - Xingxiang He
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Monika Fischer
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Sunny H Wong
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, National Healthcare Group, Singapore
| | - Siew C Ng
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Bota Cui
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Francis K-L Chan
- Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Yongzhan Nie
- National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Yang Sun
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Ishikawa Dai
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Qiyi Chen
- Department of Colorectal Disease, Intestinal Microenvironment Treatment Center, Shanghai Tenth People's Hospital, Shanghai, China
| | - Muhan Lv
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Zulun Zhang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Gianluca Ianiro
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Yunsheng Yang
- National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Colleen R Kelly
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA
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Zhang S, Lu G, Wang W, Li Q, Wang R, Zhang Z, Wu X, Liang C, Liu Y, Li P, Wen Q, Cui B, Zhang F. A predictive machine-learning model for clinical decision-making in washed microbiota transplantation on ulcerative colitis. Comput Struct Biotechnol J 2024; 24:583-592. [PMID: 39281978 PMCID: PMC11399476 DOI: 10.1016/j.csbj.2024.08.021] [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: 04/09/2024] [Revised: 08/21/2024] [Accepted: 08/21/2024] [Indexed: 09/18/2024] Open
Abstract
Machine learning based on clinical data and treatment protocols for better clinical decision-making is a current research hotspot. This study aimed to build a machine learning model on washed microbiota transplantation (WMT) for ulcerative colitis (UC), providing patients and clinicians with a new evaluation system to optimize clinical decision-making. Methods Patients with UC who underwent WMT via mid-gut or colonic delivery route at an affiliated hospital of Nanjing Medical University from April 2013 to June 2022 were recruited. Model ensembles based on the clinical indicators were constructed by machine-learning to predict the clinical response of WMT after one month. Results A total of 366 patients were enrolled in this study, with 210 patients allocated for training and internal validation, and 156 patients for external validation. The low level of indirect bilirubin, activated antithrombin III, defecation frequency and cholinesterase and the elderly and high level of creatine kinase, HCO3 - and thrombin time were related to the clinical response of WMT at one month. Besides, the voting ensembles exhibited an area under curve (AUC) of 0.769 ± 0.019 [accuracy, 0.754; F1-score, 0.845] in the internal validation; the AUC of the external validation was 0.614 ± 0.017 [accuracy, 0.801; F1-score, 0.887]. Additionally, the model was available at https://wmtpredict.streamlit.app. Conclusions This study pioneered the development of a machine learning model to predict the one-month clinical response of WMT on UC. The findings demonstrate the potential value of machine learning applications in the field of WMT, opening new avenues for personalized treatment strategies in gastrointestinal disorders. Trial registration clinical trials, NCT01790061. Registered 09 February 2013 - Retrospectively registered, https://clinicaltrials.gov/study/NCT01790061.
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Affiliation(s)
- Sheng Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Gaochen Lu
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Weihong Wang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qianqian Li
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Rui Wang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zulun Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xia Wu
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chenchen Liang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yujie Liu
- Department of Medicine & Therapeutics, the Chinese University of Hong Kong, Hong Kong, China
| | - Pan Li
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Quan Wen
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- National Clinical Research Center for Digestive Diseases, Xi'an, China
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Wang Z, Wu X, Wang Y, Wen Q, Cui B, Zhang F. Colonic transendoscopic enteral tubing is revolutionizing intestinal therapeutics, diagnosis, and microbiome research. Therap Adv Gastroenterol 2024; 17:17562848241301574. [PMID: 39582897 PMCID: PMC11585053 DOI: 10.1177/17562848241301574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 10/14/2024] [Indexed: 11/26/2024] Open
Abstract
The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.
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Affiliation(s)
- Zheyu Wang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Xia Wu
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Yaxue Wang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, 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
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, 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
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, 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, 121 Jiang Jia Yuan, Nanjing 210011, China
- Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Key Lab of Holistic Integrative Enterology, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
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Khalaf R, Sciberras M, Ellul P. The role of the fecal microbiota in inflammatory bowel disease. Eur J Gastroenterol Hepatol 2024; 36:1249-1258. [PMID: 38973540 DOI: 10.1097/meg.0000000000002818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
The understanding of the potential role of the microbiota in the pathogenesis of inflammatory bowel disease (IBD) is ever-evolving. Traditionally, the management of IBD has involved medical therapy and/or surgical intervention. IBD can be characterized by gut microbiome alterations through various pathological processes. Various studies delve into nontraditional methods such as probiotics and fecal microbiota transplant and their potential therapeutic effects. Fecal microbiota transplant involves the delivery of a balanced composition of gut microorganisms into an affected patient via multiple possible routes and methods, while probiotics consist of live microorganisms given via the oral route. At present, neither method is considered first-line treatment, however, fecal microbiota transplant has shown potential success in inducing and maintaining remission in ulcerative colitis. In a study by Kruis and colleagues, Escherichia coli Nissle 1917 was considered to be equivalent to mesalamine in mild ulcerative colitis. Alteration of the microbiome in the management of Crohn's disease is less well defined. Furthermore, variation in the clinical usefulness of 5-aminosalicylic acid medication has been attributed, in part, to its acetylation and inactivation by gut microbes. In summary, our understanding of the microbiome's role is continually advancing, with the possibility of paving the way for personalized medicine based on the microbiome.
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Affiliation(s)
- Rami Khalaf
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | | | - Pierre Ellul
- Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
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Chen L, Peng J, Wang Y, Liu Y, Fu X, Li J. FMT Combined with Vedolizumab for the Treatment of Refractory Ulcerative Colitis. Dig Dis Sci 2024; 69:4006-4008. [PMID: 39460881 DOI: 10.1007/s10620-024-08666-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Accepted: 09/24/2024] [Indexed: 10/28/2024]
Affiliation(s)
- Lanfang Chen
- Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, 278# Bao guang Avenue, Xindu District, Chengdu, Sichuan, 610000, People's Republic of China
| | - Juan Peng
- Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, 278# Bao guang Avenue, Xindu District, Chengdu, Sichuan, 610000, People's Republic of China
| | - Yanwei Wang
- Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, 278# Bao guang Avenue, Xindu District, Chengdu, Sichuan, 610000, People's Republic of China
| | - Yuzhi Liu
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangsheng Fu
- Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, 278# Bao guang Avenue, Xindu District, Chengdu, Sichuan, 610000, People's Republic of China.
| | - Jun Li
- Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, 278# Bao guang Avenue, Xindu District, Chengdu, Sichuan, 610000, People's Republic of China
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Zhang H, Hao Z, Zhang R, Tong J, Wang X, Liu J, Gao Y, Wang X, Su Q, Wen H, Fan Y, Liu F, Li X, Tong C, Wang X. Artemisia argyi polyphenols Attenuates DSS-induced colitis in mice by regulating the structural composition of gut microbiota. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 132:155897. [PMID: 39032279 DOI: 10.1016/j.phymed.2024.155897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 07/05/2024] [Accepted: 07/16/2024] [Indexed: 07/23/2024]
Abstract
BACKGROUND Intestinal health is affected by heredity, lifestyle, and structure of gut microbiota. The imbalance of symbiotic and harmful bacteria in gut microbiota may increase the occurrence of colonic inflammation. Supplementary A. muciniphila can improve the survival rate of colitis mice, reduce colon tissue injury, and the expression of anti-inflammatory factors was upregulated. Artemisia argyi has been reported to have anti-inflammatory, antioxidant, bactericidal, and immunomodulatory effects. However, its anti-inflammatory effect and mechanism, and its influence on gut microbiota and metabolites are still unclear yet. PURPOSE To explore whether Artemisia argyi Polyphenols(AAPs) can alleviate ulcerative colitis (UC) by changing gut microbiota. METHODS The therapeutic effect of AAPs on colitis was investigated by inducing ulcerative colitis in mice using dextran sodium sulfate (DSS) and administering different doses of AAPs orally to mice. Exploring the levels of inflammatory proteins, oxidative stress proteins, and barrier proteins using western blotting and immunofluorescence, and explored the structural changes of gut microbiota and its metabolites. Meanwhile, in order to explore whether the role of AAPs in alleviating colitis is based on the regulation of gut microbiota structure, we conducted fecal microbiota transplantation (FMT). RESULTS It showed that AAPs and FMT trial alleviated DSS-induced colonic injury, including clinical parameters and pathological injury of colon tissue, reduction in the expression of inflammatory proteins: IL-6, TNF-α, p-p65, p-IκBα, and increase in the expression of antioxidant proteins: Nrf2, NQO-1 and HO-1 and barrier proteins: Claudin-1, Occludin, ZO-1 and MUC2. AAPs and FMT promoted the content of beneficial bacteria, such as Butyricimonas and Lactobacillus, and the content of beneficial metabolites for instance acetic acid, butyric acid, and valeric acid has also increased. CONCLUSION These results suggested that AAPs might improve DSS-induced colonic injury by changing the structural of gut microbiota while promoting the synthesis of fatty acids in the intestine, thereby providing a theoretical basis for using AAPs to treat ulcerative colitis.
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Affiliation(s)
- Huaqiang Zhang
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Henan High Tech Industry Co., Ltd., Henan Academy of Sciences, Zhengzhou 450000, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Zhonghua Hao
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Ruya Zhang
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Jiang Tong
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Xiaoke Wang
- Leicester International College, Dalian University of Technology, Dalian 116000, Liaoning province, PR China
| | - Jingjing Liu
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Yingkui Gao
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Xuefang Wang
- Henan High Tech Industry Co., Ltd., Henan Academy of Sciences, Zhengzhou 450000, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Qing Su
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Haojie Wen
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Yi Fan
- Henan High Tech Industry Co., Ltd., Henan Academy of Sciences, Zhengzhou 450000, PR China
| | - Fang Liu
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China
| | - Xiao Li
- Henan High Tech Industry Co., Ltd., Henan Academy of Sciences, Zhengzhou 450000, PR China.
| | - Chao Tong
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China.
| | - Xuebing Wang
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, Henan province, PR China; Henan High Tech Industry Co., Ltd., Henan Academy of Sciences, Zhengzhou 450000, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450000, Henan province, PR China.
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9
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Lauwers E, Sabino J, Hoffman I, van Hoeve K. Faecal microbiota transplantation in children: A systematic review. Acta Paediatr 2024; 113:1991-2002. [PMID: 38391047 DOI: 10.1111/apa.17167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/25/2024] [Accepted: 02/13/2024] [Indexed: 02/24/2024]
Abstract
AIM Novel technologies offer insights into the potential role of the intestinal microbiota in human health and disease. Dysbiosis has been associated with several diseases, and it is thought to play a role in the pathogenesis of different gastrointestinal diseases. Faecal microbiota transplantation (FMT) is emerging as a method to modulate the gastrointestinal microbial ecosystem. While recurrent Clostridioides difficile infection is the recognised FMT indication, exploration of other therapeutic uses is ongoing. METHODS Following PRISMA guidelines, we conducted a systematic review, extracting 583 articles from Embase and PubMed (index date to October 2022). RESULTS The search yielded 58 studies for full review, with 50 included in the systematic review. Articles were categorised by FMT indication, study design, efficacy, adverse events, donor selection and administration route. FMT appears safe and effective for recurrent Clostridioides difficile infection, although severe adverse events are reported in children. However, there are currently insufficient data to support the use of FMT for other potential therapeutic indications (such as irritable or inflammatory bowel disease or obesity), beside the potential to decolonise multi-drug resistant organisms. CONCLUSION This underscores the need for randomised, controlled, prospective cohort studies in children to assess FMT effectiveness in diverse conditions and counteract publication bias.
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Affiliation(s)
- Ella Lauwers
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
| | - João Sabino
- TARGID, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
- Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Ilse Hoffman
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
| | - Karen van Hoeve
- Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, Leuven, Belgium
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10
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Zeng C, Wan SR, Guo M, Tan XZ, Zeng Y, Wu Q, Xie JJ, Yan P, Long Y, Zheng L, Jiang ZZ, Teng FY, Xu Y. Fecal virome transplantation: A promising strategy for the treatment of metabolic diseases. Biomed Pharmacother 2024; 177:117065. [PMID: 38971010 DOI: 10.1016/j.biopha.2024.117065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/08/2024] Open
Abstract
Metabolic diseases are a group of disorders caused by metabolic abnormalities, including obesity, diabetes, non-alcoholic fatty liver disease, and more. Increasing research indicates that, beyond inherent metabolic irregularities, the onset and progression of metabolic diseases are closely linked to alterations in the gut microbiota, particularly gut bacteria. Additionally, fecal microbiota transplantation (FMT) has demonstrated effectiveness in clinically treating metabolic diseases, notably diabetes. Recent attention has also focused on the role of gut viruses in disease onset. This review first introduces the characteristics and influencing factors of gut viruses, then summarizes their potential mechanisms in disease development, highlighting their impact on gut bacteria and regulation of host immunity. We also compare FMT, fecal filtrate transplantation (FFT), washed microbiota transplantation (WMT), and fecal virome transplantation (FVT). Finally, we review the current understanding of gut viruses in metabolic diseases and the application of FVT in treating these conditions. In conclusion, FVT may provide a novel and promising treatment approach for metabolic diseases, warranting further validation through basic and clinical research.
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Affiliation(s)
- Chen Zeng
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Sheng-Rong Wan
- Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Man Guo
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Xiao-Zhen Tan
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Yan Zeng
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao 999078, China
| | - Qi Wu
- Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao 999078, China; Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Jia-Jie Xie
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Pijun Yan
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Institute of Cardiovascular Research, Peking University, Beijing 100871, China
| | - Yang Long
- Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Lemin Zheng
- Institute of Cardiovascular Research, Peking University, Beijing 100871, China
| | - Zong-Zhe Jiang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Fang-Yuan Teng
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Yong Xu
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
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11
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Ullah H, Arbab S, Tian Y, Chen Y, Liu CQ, Li Q, Li K. Crosstalk between gut microbiota and host immune system and its response to traumatic injury. Front Immunol 2024; 15:1413485. [PMID: 39144142 PMCID: PMC11321976 DOI: 10.3389/fimmu.2024.1413485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 06/04/2024] [Indexed: 08/16/2024] Open
Abstract
Millions of microorganisms make up the complex microbial ecosystem found in the human gut. The immune system's interaction with the gut microbiota is essential for preventing inflammation and maintaining intestinal homeostasis. Numerous metabolic products that can cross-talk between immune cells and the gut epithelium are metabolized by the gut microbiota. Traumatic injury elicits a great and multifaceted immune response in the minutes after the initial offense, containing simultaneous pro- and anti-inflammatory responses. The development of innovative therapies that improve patient outcomes depends on the gut microbiota and immunological responses to trauma. The altered makeup of gut microbes, or gut dysbiosis, can also dysregulate immunological responses, resulting in inflammation. Major human diseases may become more common as a result of chronic dysbiosis and the translocation of bacteria and the products of their metabolism beyond the mucosal barrier. In this review, we briefly summarize the interactions between the gut microbiota and the immune system and human disease and their therapeutic probiotic formulations. We also discuss the immune response to traumatic injury.
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Affiliation(s)
- Hanif Ullah
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Safia Arbab
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Yali Tian
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Yuwen Chen
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Chang-qing Liu
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Qijie Li
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Ka Li
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
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12
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Arora U, Kedia S, Ahuja V. The practice of fecal microbiota transplantation in inflammatory bowel disease. Intest Res 2024; 22:44-64. [PMID: 37981746 PMCID: PMC10850701 DOI: 10.5217/ir.2023.00085] [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: 07/19/2023] [Revised: 09/10/2023] [Accepted: 09/14/2023] [Indexed: 11/21/2023] Open
Abstract
Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.
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Affiliation(s)
- Umang Arora
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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13
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Zhang S, Huang Y, Lu G, Zhang Z, Wang Y, Liu Y, Wang W, Li Q, Li P, Wen Q, Cui B, Zhang F. Comparison between washed microbiota transplantation and infliximab: Medical cost during long-term management in patients with inflammatory bowel disease. J Chin Med Assoc 2024; 87:109-118. [PMID: 37988085 DOI: 10.1097/jcma.0000000000001025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND Both infliximab (IFX) and fecal microbiota transplantation (FMT) have shown the efficacy for inflammatory bowel disease (IBD). However, there has no head-to-head study on the cost-value of the such treatments on IBD. This study aimed to compare the medical costs using IFX and the new method of FMT (washed microbiota transplantation [WMT]) in the long-term management for IBD under the current health economic condition in China. METHODS Patients with IBD who underwent initial WMT via upper gastrointestinal endoscopy, mid-gut tube, or colonic transendoscopic enteral tubing at a university hospital between April 2013 and August 2021 and achieved the long-term sustainment with WMT or WMT combined with mesalazine until August 2022 were recruited in the real-world. The costs and hospitalizations were analyzed among two therapies mentioned above and IFX standard therapy. The charge of WMT was stable in the long term at our center, and the charge of IFX came from virtual statistics publicized by China Healthcare Security. RESULTS Sixty eligible patients with IBD were included in the study. The long-term costs of patients using WMT monotherapy annually or per hospitalization were lower than those on WMT combined with mesalazine, respectively ( p < 0.001, respectively). The cumulative costs of IFX at the time of 0.52 and 0.85 years exceeded that of the above WMT, respectively ( p < 0.001, respectively). Besides, patients on WMT monotherapy paid 51.1 k CNY annually in the nonsustain phase but cut down the costs by 7.2 k CNY and duration of hospitalization by 5.1 days per hospitalization when reaching the goal of sustainment. CONCLUSION This study demonstrated that WMT could dramatically reduce the cost and duration of hospitalizations in the long-term sustainment in the current Chinese IBD cohort. Compared with IFX, WMT could be a good way for the patients with IBD achieving long-term sustainment and saving medical costs.
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Affiliation(s)
- Sheng Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yihao Huang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Gaochen Lu
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zulun Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yun Wang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yujie Liu
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Weihong Wang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qianqian Li
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Pan Li
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Quan Wen
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Microbiotherapy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
- National Clinical Research Center for Digestive Diseases, Xi'an, China
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Pandey H, Jain D, Tang DWT, Wong SH, Lal D. Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease. Intest Res 2024; 22:15-43. [PMID: 37935653 PMCID: PMC10850697 DOI: 10.5217/ir.2023.00080] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/23/2023] [Accepted: 08/27/2023] [Indexed: 11/09/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.
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Affiliation(s)
| | | | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi, India
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15
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Van Dingenen L, Segers C, Wouters S, Mysara M, Leys N, Kumar-Singh S, Malhotra-Kumar S, Van Houdt R. Dissecting the role of the gut microbiome and fecal microbiota transplantation in radio- and immunotherapy treatment of colorectal cancer. Front Cell Infect Microbiol 2023; 13:1298264. [PMID: 38035338 PMCID: PMC10687483 DOI: 10.3389/fcimb.2023.1298264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 10/31/2023] [Indexed: 12/02/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and poses a major burden on the human health worldwide. At the moment, treatment of CRC consists of surgery in combination with (neo)adjuvant chemotherapy and/or radiotherapy. More recently, immune checkpoint blockers (ICBs) have also been approved for CRC treatment. In addition, recent studies have shown that radiotherapy and ICBs act synergistically, with radiotherapy stimulating the immune system that is activated by ICBs. However, both treatments are also associated with severe toxicity and efficacy issues, which can lead to temporary or permanent discontinuation of these treatment programs. There's growing evidence pointing to the gut microbiome playing a role in these issues. Some microorganisms seem to contribute to radiotherapy-associated toxicity and hinder ICB efficacy, while others seem to reduce radiotherapy-associated toxicity or enhance ICB efficacy. Consequently, fecal microbiota transplantation (FMT) has been applied to reduce radio- and immunotherapy-related toxicity and enhance their efficacies. Here, we have reviewed the currently available preclinical and clinical data in CRC treatment, with a focus on how the gut microbiome influences radio- and immunotherapy toxicity and efficacy and if these treatments could benefit from FMT.
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Affiliation(s)
- Lena Van Dingenen
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
- Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
| | - Charlotte Segers
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
| | - Shari Wouters
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
- Molecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
| | - Mohamed Mysara
- Bioinformatics Group, Center for Informatics Science, School of Information Technology and Computer Science, Nile University, Giza, Egypt
| | - Natalie Leys
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
| | - Samir Kumar-Singh
- Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
- Molecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
| | - Surbhi Malhotra-Kumar
- Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
| | - Rob Van Houdt
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
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16
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Shao T, Hsu R, Hacein-Bey C, Zhang W, Gao L, Kurth MJ, Zhao H, Shuai Z, Leung PSC. The Evolving Landscape of Fecal Microbial Transplantation. Clin Rev Allergy Immunol 2023; 65:101-120. [PMID: 36757537 PMCID: PMC9909675 DOI: 10.1007/s12016-023-08958-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2023] [Indexed: 02/10/2023]
Abstract
The human gastrointestinal tract houses an enormous microbial ecosystem. Recent studies have shown that the gut microbiota plays significant physiological roles and maintains immune homeostasis in the human body. Dysbiosis, an imbalanced gut microbiome, can be associated with various disease states, as observed in infectious diseases, inflammatory diseases, autoimmune diseases, and cancer. Modulation of the gut microbiome has become a therapeutic target in treating these disorders. Fecal microbiota transplantation (FMT) from a healthy donor restores the normal gut microbiota homeostasis in the diseased host. Ample evidence has demonstrated the efficacy of FMT in recurrent Clostridioides difficile infection (rCDI). The application of FMT in other human diseases is gaining attention. This review aims to increase our understanding of the mechanisms of FMT and its efficacies in human diseases. We discuss the application, route of administration, limitations, safety, efficacies, and suggested mechanisms of FMT in rCDI, autoimmune diseases, and cancer. Finally, we address the future perspectives of FMT in human medicine.
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Affiliation(s)
- Tihong Shao
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
- Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, CA, 95616, USA
| | - Ronald Hsu
- Division of Gastroenterology, University of California Davis School of Medicine, Davis, CA, 95616, USA
| | - Camelia Hacein-Bey
- Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, CA, 95616, USA
| | - Weici Zhang
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Lixia Gao
- Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Mark J Kurth
- Department of Chemistry, University of California Davis, Davis, CA, 95616, USA
| | - Huanhuan Zhao
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Zongwen Shuai
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Patrick S C Leung
- Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, CA, 95616, USA.
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17
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O’Reilly C, Mills S, Rea MC, Lavelle A, Ghosh S, Hill C, Ross RP. Interplay between inflammatory bowel disease therapeutics and the gut microbiome reveals opportunities for novel treatment approaches. MICROBIOME RESEARCH REPORTS 2023; 2:35. [PMID: 37849974 PMCID: PMC7615213 DOI: 10.20517/mrr.2023.41] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/19/2023] [Accepted: 09/22/2023] [Indexed: 10/19/2023]
Abstract
Inflammatory bowel disease (IBD) is a complex heterogeneous disorder defined by recurring chronic inflammation of the gastrointestinal tract, attributed to a combination of factors including genetic susceptibility, altered immune response, a shift in microbial composition/microbial insults (infection/exposure), and environmental influences. Therapeutics generally used to treat IBD mainly focus on the immune response and include non-specific anti-inflammatory and immunosuppressive therapeutics and targeted therapeutics aimed at specific components of the immune system. Other therapies include exclusive enteral nutrition and emerging stem cell therapies. However, in recent years, scientists have begun to examine the interplay between these therapeutics and the gut microbiome, and we present this information here. Many of these therapeutics are associated with alterations to gut microbiome composition and functionality, often driving it toward a "healthier profile" and preclinical studies have revealed that such alterations can play an important role in therapeutic efficacy. The gut microbiome can also improve or hinder IBD therapeutic efficacy or generate undesirable metabolites. For certain IBD therapeutics, the microbiome composition, particularly before treatment, may serve as a biomarker of therapeutic efficacy. Utilising this information and manipulating the interactions between the gut microbiome and IBD therapeutics may enhance treatment outcomes in the future and bring about new opportunities for personalised, precision medicine.
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Affiliation(s)
- Catherine O’Reilly
- Food Biosciences Department, Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork P61C996, Ireland
- Microbiology Department, University College Cork, Co. Cork T12TP07, Ireland
- APC Microbiome Ireland, University College Cork, Co. Cork T12YT20, Ireland
- Authors contributed equally
| | - Susan Mills
- APC Microbiome Ireland, University College Cork, Co. Cork T12YT20, Ireland
- Authors contributed equally
| | - Mary C. Rea
- Food Biosciences Department, Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork P61C996, Ireland
- APC Microbiome Ireland, University College Cork, Co. Cork T12YT20, Ireland
| | - Aonghus Lavelle
- APC Microbiome Ireland, University College Cork, Co. Cork T12YT20, Ireland
| | - Subrata Ghosh
- APC Microbiome Ireland, University College Cork, Co. Cork T12YT20, Ireland
| | - Colin Hill
- Microbiology Department, University College Cork, Co. Cork T12TP07, Ireland
- APC Microbiome Ireland, University College Cork, Co. Cork T12YT20, Ireland
| | - R. Paul Ross
- Microbiology Department, University College Cork, Co. Cork T12TP07, Ireland
- APC Microbiome Ireland, University College Cork, Co. Cork T12YT20, Ireland
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18
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Stoff R, Wolf Y, Boursi B. Fecal Microbiota Transplantation as a Cancer Therapeutic. Cancer J 2023; 29:102-108. [PMID: 36957981 DOI: 10.1097/ppo.0000000000000651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2023]
Abstract
ABSTRACT For decades, cancer research and treatment focused on the cellular level, viewing cancer as a genetic disease of cell transformation. In the era of chemotherapy and radiotherapy, studies from the second half of the 19th century suggesting an association between the microbiota and cancer were almost neglected. The main focus of the field was limited to identification of specific viruses and bacteria that may serve as direct carcinogens leading to the recognition of 7 viruses (i.e., human papillomavirus, hepatitis B virus, and Kaposi sarcoma-associated herpesvirus) and 1 bacterium (Helicobacter pylori) as human carcinogens by the International Agency for Research on Cancer (https://monographs.iarc.who.int/agents-classified-by-the-iarc/). Shortly after the publication of the first draft of the human genome project in February 2001, the Nobel laureate microbiologist Joshua Lederberg raised the question: "Is human identity all in the genes?" It took more than a decade later and the development of multiomic techniques to confirm that his answer "each one of us is a small ecological community" was correct (Lederberg J. Keynote Address: Beyond the Genome. Brooklyn Law Rev 67). This ecological notion became relevant to cancer prevention, prediction, and treatment following the immunotherapy revolution and the understanding of the metabolic and immunologic roles of the microbiota in health and disease. Recently, the microbiota was recognized as an emerging hallmark of cancer following a large body of research showing its role in tumorigenesis, treatment efficacy and toxicity, and initial data regarding the role of microbial modulation in cancer therapy (Cancer Discov 2022;12(1):31-46). In the current review, we will focus on the role of fecal microbiota transplantation, the first microbial modulation technique that is used mainly in low-complexity conditions such as recurrent Clostridium difficile infections (Aliment Pharmacol Ther 2017;46(5):479-493), as a possible cancer therapeutic. However, to better understand the suggested roles of fecal microbiota transplantation in medical oncology, we first need to understand cancer as an ecological niche and the role of the microbiota in tumorigenesis and cancer treatment, specifically immunotherapy.
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Affiliation(s)
- Ronen Stoff
- From the Ella Lemelbaum institute for immuno-oncology and melanoma, Sheba Medical Center, Ramat Gan
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19
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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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20
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Zhang X, Ishikawa D, Ohkusa T, Fukuda S, Nagahara A. Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease. Front Med (Lausanne) 2022; 9:1068567. [PMID: 36530877 PMCID: PMC9755187 DOI: 10.3389/fmed.2022.1068567] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 11/21/2022] [Indexed: 11/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic intestinal mucosal inflammatory disease with complex etiology. Traditional anti-inflammatory treatment regimens have yielded unsatisfactory results. As research continues to deepen, it has been found that the gut microbiota of patients with IBD is generally altered. The presence of microorganisms in the human gastrointestinal tract is inextricably linked to the regulation of health and disease. Disruption of the microbiotic balance of microbiota in the gastrointestinal tract is called dysbiosis, which leads to disease. Therefore, in recent years, the exploration of therapeutic methods to restore the homeostasis of the gut microbiota has attracted attention. Moreover, the use of the well-established fecal microbiota transplantation (FMT) regimen for the treatment of Clostridioides difficile infection has attracted the interest of IBD researchers. Therefore, there are an increasing number of clinical studies regarding FMT for IBD treatment. However, a series of questions regarding FMT in the treatment of IBD warrants further investigation and discussion. By reviewing published studies, this review explored hot topics such as the efficacy, safety, and administration protocol flow of FMT in the treatment of IBD. Different administration protocols have generally shown reassuring results with significant efficacy and safety. However, the FMT treatment regimen needs to be further optimized. We believe that in the future, individual customized or standard FMT implementation will further enhance the relevance of FMT in the treatment of IBD.
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Affiliation(s)
- Xiaochen Zhang
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Dai Ishikawa
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Toshifumi Ohkusa
- Department of Microbiota Research, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Department of Gastroenterology and Hepatology, The Jikei University Kashiwa Hospital, Chiba, Japan
| | - Shinji Fukuda
- Department of Regenerative Microbiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Department of Regenerative Microbiology, Juntendo University School of Medicine, Tokyo, Japan
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21
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Ma Y, Ke D, Li D, Zhang Q. Donors' experiences and attitudes of fecal microbiota transplantation: An empirical bioethics study from China. IMETA 2022; 1:e62. [PMID: 38867907 PMCID: PMC10989884 DOI: 10.1002/imt2.62] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 09/12/2022] [Accepted: 10/22/2022] [Indexed: 06/14/2024]
Abstract
Donor participation is a critical part of ensuring the development of human microbiome research and the clinical application of fecal microbiota transplantation (FMT). Most FMT donors are still not sufficiently aware of the risks associated with the act of donating gut microbiota, especially the risk of data privacy disclosure. Enhanced awareness of the moral responsibility of the researchers and ethical oversight by ethics committees are needed.
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Affiliation(s)
- Yonghui Ma
- Medical Humanities and Bioethics Center, School of MedicineXiamen UniversityXiamenChina
| | - Dawei Ke
- Medical Humanities and Bioethics Center, School of MedicineXiamen UniversityXiamenChina
| | - Danyi Li
- R Institute Co. Ltd.BeijingChina
| | - Quan Zhang
- National Institute for Data Science in Health and MedicineXiamen UniversityXiamenChina
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22
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Zhang Z, Cui B, Zhang F. Washed microbiota transplantation cured a patient with immune-mediated enteropathy induced by cryptosporidium infection. MEDICINE IN MICROECOLOGY 2022; 14:100060. [DOI: 10.1016/j.medmic.2022.100060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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23
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Huang HL, Zhu JQ, Yang LS, Wu Q, Shou DW, Chen HT, Ma J, Li YQ, Xu HM, Zhou YJ. Fecal Microbiota Transplantation Combined with a Low FODMAP Diet for the Treatment of Irritable Bowel Syndrome with Predominant Diarrhea. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:5121496. [PMID: 36187337 PMCID: PMC9519354 DOI: 10.1155/2022/5121496] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 09/06/2022] [Indexed: 12/02/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) has been found to be effective in irritable bowel syndrome with predominant diarrhea (IBS-D). We conducted this study to determine the impact of a low FODMAP diet (LFD) on the gut microbiota and the efficacy of FMT in the treatment of IBS-D. METHODS A retrospective analysis of a single-arm open-label prospective study was conducted to investigate the impact of FMT alone (n = 40) and FMT+LFD (n = 40) in refractory IBS-D. The IBS-quality of life (QOL), IBS-severity scoring system (SSS), gastrointestinal symptom rating scale (GSRS), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD) were used to evaluate the efficacy, and partial 16S rDNA amplicon sequencing was used to profile the microbiota. RESULTS The response rates were higher in the FMT+LFD group than in the FMT group (1 mo, 3 mo, 6 mo: 70.0% vs. 55.0%, 67.5% vs. 57.5%, 62.5% vs. 27.5%, respectively). The FMT+LFD group showed significantly better improvement in IBS-QOL at 1, 3, and 6 months; IBS-SSS at 6 months; and GSRS at 1 month compared to FMT alone. Changes in HAMA and HAMD were similar in the two groups. The LFD significantly upregulated the FMT-induced microbial diversity (OTUs: 666 vs. 574, Adonis: P = 0.02) and significantly strengthened the upregulation of Bacteroides, Alistipes, and Ruminococcaceae_UCG-002 and the downregulation of Bifidobacterium. CONCLUSION An LFD enhanced the efficacy of FMT, increased the gut microbial diversity after FMT, and strengthened the inhibitory effect of FMT on conditional pathogens.
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Affiliation(s)
- Hong-Li Huang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - Jia-Qi Zhu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - Liu-Si Yang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - Qiong Wu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - Di-Wen Shou
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - Hui-Ting Chen
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - Jun Ma
- Department of Traditional Chinese Medicine, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - Yong-Qiang Li
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China
| | - Yong-Jian Zhou
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China
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Siddiqui R, Mungroo MR, Alharbi AM, Alfahemi H, Khan NA. The Use of Gut Microbial Modulation Strategies as Interventional Strategies for Ageing. Microorganisms 2022; 10:microorganisms10091869. [PMID: 36144471 PMCID: PMC9506335 DOI: 10.3390/microorganisms10091869] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/07/2022] [Accepted: 09/14/2022] [Indexed: 11/16/2022] Open
Abstract
Gut microbial composition codevelops with the host from birth and is influenced by several factors, including drug use, radiation, psychological stress, dietary changes and physical stress. Importantly, gut microbial dysbiosis has been clearly associated with several diseases, including cancer, rheumatoid arthritis and Clostridium difficile-associated diarrhoea, and is known to affect human health and performance. Herein, we discuss that a shift in the gut microbiota with age and reversal of age-related modulation of the gut microbiota could be a major contributor to the incidence of numerous age-related diseases or overall human performance. In addition, it is suggested that the gut microbiome of long-lived animals such as reptiles should be investigated for their unique properties and contribution to the potent defense system of these species could be extrapolated for the benefit of human health. A range of techniques can be used to modulate the gut microbiota to have higher abundance of “beneficial” microbes that have been linked with health and longevity.
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Affiliation(s)
- Ruqaiyyah Siddiqui
- College of Arts and Sciences, American University of Sharjah, Sharjah P.O. Box 26666, United Arab Emirates
| | - Mohammad Ridwane Mungroo
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates
| | - Ahmad M. Alharbi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia
| | - Hasan Alfahemi
- Department of Medical Microbiology, Faculty of Medicine, Al-Baha University, Al-Baha 65799, Saudi Arabia
| | - Naveed Ahmed Khan
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates
- Correspondence:
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25
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Zhang W, Zhang J, Liu T, Xing J, Zhang H, Wang D, Tang D. Bidirectional effects of intestinal microbiota and antibiotics: a new strategy for colorectal cancer treatment and prevention. J Cancer Res Clin Oncol 2022; 148:2387-2404. [PMID: 35661254 DOI: 10.1007/s00432-022-04081-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 05/19/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE Colorectal cancer (CRC) is the third most common cancer worldwide, and its incidence and mortality rates are increasing every year. The intestinal microbiota has been called the "neglected organ" and there is growing evidence that the intestinal microbiota and its metabolites can be used in combination with immunotherapy, radiotherapy and chemotherapy to greatly enhance the treatment of colorectal cancer and to address some of the side effects and adverse effects of these therapies. Antibiotics have great potential to eliminate harmful microbiota, control infection, and reduce colorectal cancer side effects. However, the use of antibiotics has been a highly controversial issue, and numerous retrospective studies have shown that the use of antibiotics affects the effectiveness of treatment (especially immunotherapy). Understanding the bi-directional role of the gut microbiota and antibiotics will further enhance our research into the diagnosis and treatment of cancer. METHODS We searched the "PubMed" database and selected the following keywords "intestinal microbiota, antibiotics, treatment, prevention, colorectal cancer". In this review, we discuss the role of the intestinal microbiota in immunotherapy, radiotherapy, chemotherapy, diagnosis, and prevention of CRC. We also conclude that the intestinal microbiota and antibiotics work together to promote the treatment of CRC through a bidirectional effect. RESULTS We found that the intestinal microbiota plays a key role in promoting immunotherapy, chemotherapy, radiotherapy, diagnosis and prevention of CRC. In addition, gut microbiota and antibiotic interactions could be a new strategy for CRC treatment. CONCLUSION The bi-directional role of the intestinal microbiota and antibiotics plays a key role in the prevention, diagnosis, and treatment of colorectal cancer.
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Affiliation(s)
- Wenjie Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Jie Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Tian Liu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Juan Xing
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Huan Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Daorong Wang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu Province Hospital, Yangzhou University, Yangzhou, 225001, China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu Province Hospital, Yangzhou University, Yangzhou, 225001, China.
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Madhogaria B, Bhowmik P, Kundu A. Correlation between human gut microbiome and diseases. INFECTIOUS MEDICINE 2022; 1:180-191. [PMID: 38077626 PMCID: PMC10699709 DOI: 10.1016/j.imj.2022.08.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/07/2022] [Accepted: 08/16/2022] [Indexed: 03/21/2024]
Abstract
Human gut microbiome is a major source of human bacterial population and a significant contribution to both positive and harmful effects. Due to its involvement in a variety of interactions, gut microorganisms have a great impact on our health throughout our lives. The impact of gut microbial population is been studied intensively in last two decades. Extensive literature survey focusing developments in the field were searched in English language Electronic Databases like PubMed, Google Scholar, Pubag, Google books, and Research Gate were mostly used to understand the role of human gut mirobiome and its role in different human diseases. Gut microbiome in healthy subjects differs from those who suffer from diseases. Type 2 diabetes, obesity, non-alcoholic liver disease, and cardiometabolic diseases have all been linked to dysbiosis of the gut microbiota. Pathogenesis of many disorders is also linked to changes in gut microbiota. Other diseases like cancer, arithritis, autism, depression, anxiety, sleep disorder, HIV, hypertension, and gout are also related to gut microbiota dysbiosis. We focus in this review on recent studies looking into the link between gut microbiome dysbiosis and disease etiology. Research on how gut microbiota affects host metabolism has been changed in past decades from descriptive analyses to high throughput integrative omics data analysis such as metagenomics and metabolomics. Identification of molecular mechanisms behind reported associations is been carried out in human, animals, and cells for measure of host physiology and mechanics. Still many the mechanisms are not completely understood.
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Affiliation(s)
- Barkha Madhogaria
- Department of Microbiology, Techno India University, West Bengal EM-4 Sector-V, Salt Lake City, Kolkata 700091, West Bengal, India
| | - Priyanka Bhowmik
- Department of Biological Sciences, Adamas University, Barrackpore-Barasat Road, 24 Paragnas North, Jagannathpur, Kolkata, West Bengal, India
| | - Atreyee Kundu
- Department of Microbiology, Techno India University, West Bengal EM-4 Sector-V, Salt Lake City, Kolkata 700091, West Bengal, India
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Wang Y, Zhang S, Borody TJ, Zhang F. Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases. Chin Med J (Engl) 2022; 135:1927-1939. [PMID: 36103991 PMCID: PMC9746749 DOI: 10.1097/cm9.0000000000002339] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Indexed: 01/06/2023] Open
Abstract
ABSTRACT Fecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT from a global perspective. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota-gut-liver axis, microbiota-gut-brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.
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Affiliation(s)
- Yun Wang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu 210011, China
| | - Sheng Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu 210011, China
| | | | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, Jiangsu 210011, China
- National Clinical Research Center for Digestive Diseases, Xi’an, Shaanxi 710032, China
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Singh A, Mahajan R, Kahlon BK, Dhaliwal AS, Midha V, Mehta V, Bansal N, Singh D, Sood A. Early fecal microbiome transfer after donor defecation determines response in patients with moderate to severe ulcerative colitis. Indian J Gastroenterol 2022; 41:389-396. [PMID: 36121613 DOI: 10.1007/s12664-022-01257-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 03/02/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Fecal microbiome transfer (FMT) targeting gut microbiome dysbiosis is an emerging therapy for ulcerative colitis (UC). There is however no consensus on protocols for performing FMT in UC, especially in relation to time after donor feces defecation. METHODS This is a single-center retrospective analysis of patients with moderate-severe UC (total Mayo Clinic score ≥6 and endoscopic Mayo Clinic subscore of ≥2) treated with FMT between September 2017 and December 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Fresh fecal samples from unrelated healthy voluntary donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. Time interval between donor feces defecation and FMT procedure was recorded for each FMT session and the mean time of seven sessions was designated aika. Impact of aika on clinical response and safety of FMT was evaluated. RESULTS During the study period, 123 adult patients (mean age 33.75±11.97 years, 61.8% [n=76] males) with moderate-severe UC (mean total Mayo Clinic and endoscopic Mayo Clinic scores 7.49±1.60 and 2.50±0.50, respectively) were treated with FMT. The mean aika was 2.29±0.75 h. The aika was smaller in patients who responded to FMT as compared to non-responders (2.13±0.75 h vs. 2.71±0.76 h, p=0.0002) as well as in patients achieving clinical remission (2.15±0.76 h vs. 2.42±0.76 h, p=0.05). There was no significant impact of aika on adverse effects except for the incidence of borborygmi after FMT, which was higher in patients with aika ≤2 h. CONCLUSION Early FMT after donor feces defecation favorably impacts the clinical response rates in patients with active UC.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | | | | | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College, Ludhiana, 141 001, India
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Namita Bansal
- Research and Development Centre, Dayanand Medical College, Ludhiana, 141 001, India
| | - Dharmatma Singh
- Research and Development Centre, Dayanand Medical College, Ludhiana, 141 001, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India.
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Huang T, Xu J, Wang M, Pu K, Li L, Zhang H, Liang Y, Sun W, Wang Y. An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis. Medicine (Baltimore) 2022; 101:e29790. [PMID: 35905229 PMCID: PMC9333500 DOI: 10.1097/md.0000000000029790] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) as a promising therapy for ulcerative colitis (UC) remains controversial. We conducted a systematic review and meta-analysis to assess the efficiency and safety of FMT as a treatment for UC. METHODS The target studies were identified by searching PubMed, EMBASE, the Cochrane Library, Web of Science, and ClinicalTrials and by manual supplementary retrieval. We conducted a general review and quantitative synthesis of included studies. We used the RevMan and Stata programs in the meta-analysis. The outcomes were total remission, clinical remission, steroid-free remission, and serious adverse events. We also performed subgroup analyses based on different populations. RESULTS A total of 34 articles were included in the general review. Only 16 articles, including 4 randomized controlled trials, 2 controlled clinical trials, and 10 cohort studies, were selected for the meta-analysis. We found that donor FMT might be more effective than placebo for attaining total remission (risk ratio [RR]: 2.77, 95% confidence interval [CI]: 1.54-4.98; P = .0007), clinical remission (RR: 0.33, 95% CI: 0.24-0.41; P < .05), and steroid-free remission (RR: 3.63, 95% CI: 1.57-8.42; P = .003), but found no statistically significant difference in the incidence of serious adverse events (RR: 0.88, 95% CI: 0.34-2.31, P = .8). The subgroup analyses revealed significant differences between the pooled clinical remission rates for different regions, degrees of severity of the disease, and patients with steroid- or nonsteroid-dependent UC. CONCLUSIONS FMT can achieve clinical remission and clinical response in patients with UC.
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Affiliation(s)
- Taobi Huang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Jinlan Xu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Maoying Wang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Ke Pu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Longquan Li
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Huiyun Zhang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Yuan Liang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
| | - Weiming Sun
- Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, China
- *Correspondence: Yu Ping Wang, Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, No.1 West Donggang Road, Lanzhou, Gansu 730000, China (e-mail:
| | - Yuping Wang
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China
- Gansu Province Key Laboratory of Gastrointestinal Diseases in Lanzhou University, Lanzhou, China
- *Correspondence: Yu Ping Wang, Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, No.1 West Donggang Road, Lanzhou, Gansu 730000, China (e-mail:
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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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[How I treat gastrointestinal tract acute graft versus host disease with fecal microbiota transplantation]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2022; 43:365-369. [PMID: 35680592 PMCID: PMC9250952 DOI: 10.3760/cma.j.issn.0253-2727.2022.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Shang L, Tu J, Dai Z, Zeng X, Qiao S. Microbiota Transplantation in an Antibiotic-Induced Bacterial Depletion Mouse Model: Reproducible Establishment, Analysis, and Application. Microorganisms 2022; 10:902. [PMID: 35630347 PMCID: PMC9146686 DOI: 10.3390/microorganisms10050902] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/30/2022] [Accepted: 04/14/2022] [Indexed: 02/01/2023] Open
Abstract
The fecal bacteria transplantation (FMT) technique is indispensable when exploring the pathogenesis and potential treatments for microbiota-related diseases. For FMT clinical treatments, there are already systematic guidelines for donor selection, fecal bacterial separation, FMT frequency, and infusion methods. However, only a few studies have demonstrated the use of standardized FMT procedures for animal models used in theoretical research, creating difficulties for many new researchers in this field. In the present paper, we provide a brief overview of FMT and discuss its contribution to the current understanding of disease mechanisms that relate to microbiota. This protocol can be used to generate a commonly used FMT mouse model and provides a literature reference of customizable steps.
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Affiliation(s)
- Lijun Shang
- State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Centre, China Agricultural University, Beijing 100193, China; (L.S.); (J.T.); (Z.D.); (X.Z.)
- Beijing Bio-Feed Additives Key Laboratory, Beijing 100193, China
| | - Jiayu Tu
- State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Centre, China Agricultural University, Beijing 100193, China; (L.S.); (J.T.); (Z.D.); (X.Z.)
- Beijing Bio-Feed Additives Key Laboratory, Beijing 100193, China
| | - Ziqi Dai
- State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Centre, China Agricultural University, Beijing 100193, China; (L.S.); (J.T.); (Z.D.); (X.Z.)
- Beijing Bio-Feed Additives Key Laboratory, Beijing 100193, China
| | - Xiangfang Zeng
- State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Centre, China Agricultural University, Beijing 100193, China; (L.S.); (J.T.); (Z.D.); (X.Z.)
- Beijing Bio-Feed Additives Key Laboratory, Beijing 100193, China
| | - Shiyan Qiao
- State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Centre, China Agricultural University, Beijing 100193, China; (L.S.); (J.T.); (Z.D.); (X.Z.)
- Beijing Bio-Feed Additives Key Laboratory, Beijing 100193, China
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Wang Y, Cui B, Zhang F. Refractory ulcerative colitis stabilized by interval washed microbiota transplantation: less is more. Curr Med Res Opin 2022; 38:531-534. [PMID: 35040380 DOI: 10.1080/03007995.2022.2030563] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/31/2021] [Accepted: 01/14/2022] [Indexed: 01/06/2023]
Abstract
Ulcerative colitis (UC) is an autoimmune inflammatory disorder characterized by a relapsing and remitting course. The gut microbiota is implicated in the pathogenesis of UC. Fecal microbiota transplant (FMT) has been reported as a rescue therapy for refractory UC. The newly improved methodology of FMT was recently coined as washed microbiota transplantation (WMT) based on the automatic purification system and washing process. Colonic transendoscopic enteral tubing (TET) is a novel delivery of WMT within the whole colon. In this case, the patient with refractory UC underwent two different strategies of fresh FMT. The prior strategy conducted daily FMT through the percutaneous endoscopic cecostomy (PEC) tube for 60 days. We performed WMT every 3-35 months by colonic TET or gastroscopy. The patient was effectively responsive to both strategies. The repeated interval WMTs induced long-term clinical remission for the patient. The case encouraged the physicians to consider repeated interval WMTs into practice as a long-term treatment strategy for refractory UC. Moreover, we hope more physicians and researchers would be inspired to study clinical strategies, such as optimizing the frequency and interval of WMTs and the related delivering strategy.
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Affiliation(s)
- Yun Wang
- 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
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
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Huang HL, Xu HM, Liu YD, Shou DW, Chen HT, Nie YQ, Li YQ, Zhou YJ. First Application of Fecal Microbiota Transplantation in Adult Asperger Syndrome With Digestive Symptoms-A Case Report. Front Psychiatry 2022; 13:695481. [PMID: 35370847 PMCID: PMC8964519 DOI: 10.3389/fpsyt.2022.695481] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 02/21/2022] [Indexed: 12/12/2022] Open
Abstract
Asperger syndrome (AS) is a chronic neurodevelopmental disorder. Although all of the clinically diagnosed cases display normal intelligence and speech functions, barriers in social interaction and communication seriously affect mental health and psychological function. In addition to traditional psychological/behavioral training and symptomatic medication, in-depth studies of intestinal microbiota and mental health have indicated that probiotics (e.g., Lactobacillus rhamnosus) can effectively reduce the occurrence of AS. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe the first case of adult AS treated with FMT. The patient suffered from diarrhea-predominant irritable bowel syndrome for 6 years with symptoms of diarrhea and abdominal pain. After three rounds of FMT, the diarrhea and abdominal pain were significantly improved. Moreover, the symptoms of AS were also significantly ameliorated. We found that FMT changed the structure of the intestinal microbiota as well as the patient's serum metabolites, and these changes were consistent with the patient's symptoms. The metabolites may affect signaling pathways, as revealed by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The changes in microbial metabolites following FMT may affect other regions (e.g., the nervous system) via the circulatory system, such that the bacteria-gut-blood-brain axis may be the means through which FMT mitigates AS.
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Affiliation(s)
| | | | | | | | | | | | - Yong-Qiang Li
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yong-Jian Zhou
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
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Huang S, Hu S, Liu S, Tang B, Liu Y, Tang L, Lei Y, Zhong L, Yang S, He S. Lithium carbonate alleviates colon inflammation through modulating gut microbiota and Treg cells in a GPR43-dependent manner. Pharmacol Res 2022; 175:105992. [PMID: 34801681 DOI: 10.1016/j.phrs.2021.105992] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 11/12/2021] [Accepted: 11/15/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Recent evidence suggests that neuropsychiatric stabilizers have a place in resolving gastrointestinal disorders. Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we estimate the therapeutic function of LC against colitis and investigate the mechanism of intestinal flora and metabolism modulation. METHODS A colitis model was constructed by continuously administering 2.5% dextran sodium sulfate (DSS) solution daily for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene high-throughput sequencing. Spectrum antibiotic cocktail (ABX) and faecal microbiota transplantation (FMT) were employed to evaluate the protective effect of intestinal flora. Colonic Treg cells and related immune responses were detected by flow cytometry. RESULTS LC treatment significantly alleviated colon inflammation by regulating gut microbial diversity and altering flora composition. Notably, LC treatment upregulated short-chain fatty acid (SCFA)-producing bacteria, especially Akkermansia muciniphila (A. muciniphila), and transformed metabolite SCFA profiles. LC activated anti-inflammatory Treg cell responses in colonic lamina propria (LP) in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm the above mechanism. CONCLUSIONS As an intestinal microbiome and metabolite modulator, LC alleviates colon inflammation in a GPR43-dependent manner through activating Treg cell responses. Therefore, the therapeutic strategy of the microbiome-metabolite-immune axis, as observed in the A. muciniphila-SCFA-Treg cell axis in our study, might provide a new direction for the treatment of IBD.
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Affiliation(s)
- Shengjie Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Shiping Hu
- Department of Gastroenterology, Third Military Medical University Second Affiliated Hospital, Chongqing, 400037, China
| | - Shuang Liu
- Department of Gastroenterology, Third Military Medical University Second Affiliated Hospital, Chongqing, 400037, China
| | - Bo Tang
- Department of Gastroenterology, Third Military Medical University Second Affiliated Hospital, Chongqing, 400037, China
| | - Yaojiang Liu
- Department of Gastroenterology, Third Military Medical University Second Affiliated Hospital, Chongqing, 400037, China
| | - Li Tang
- Department of Gastroenterology, Third Military Medical University Second Affiliated Hospital, Chongqing, 400037, China
| | - Yuanyuan Lei
- Department of Gastroenterology, Third Military Medical University Second Affiliated Hospital, Chongqing, 400037, China
| | - Li Zhong
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Shiming Yang
- Department of Gastroenterology, Third Military Medical University Second Affiliated Hospital, Chongqing, 400037, China.
| | - Song He
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
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Liu L, Zhang J, Cheng Y, Zhu M, Xiao Z, Ruan G, Wei Y. Gut microbiota: A new target for T2DM prevention and treatment. Front Endocrinol (Lausanne) 2022; 13:958218. [PMID: 36034447 PMCID: PMC9402911 DOI: 10.3389/fendo.2022.958218] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 07/22/2022] [Indexed: 12/12/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM), one of the fastest growing metabolic diseases, has been characterized by metabolic disorders including hyperglycemia, hyperlipidemia and insulin resistance (IR). In recent years, T2DM has become the fastest growing metabolic disease in the world. Studies have indicated that patients with T2DM are often associated with intestinal flora disorders and dysfunction involving multiple organs. Metabolites of the intestinal flora, such as bile acids (BAs), short-chain fatty acids (SCFAs) and amino acids (AAs)may influence to some extent the decreased insulin sensitivity associated with T2DM dysfunction and regulate metabolic as well as immune homeostasis. In this paper, we review the changes in the gut flora in T2DM and the mechanisms by which the gut microbiota modulates metabolites affecting T2DM, which may provide a basis for the early identification of T2DM-susceptible individuals and guide targeted interventions. Finally, we also highlight gut microecological therapeutic strategies focused on shaping the gut flora to inform the improvement of T2DM progression.
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Affiliation(s)
- Lulu Liu
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jiheng Zhang
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yi Cheng
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Meng Zhu
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhifeng Xiao
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Guangcong Ruan
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Yanling Wei, ; Guangcong Ruan,
| | - Yanling Wei
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Yanling Wei, ; Guangcong Ruan,
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The role of enteric dysbacteriosis and modulation of gut microbiota in the treatment of inflammatory bowel disease. Microb Pathog 2021; 165:105381. [PMID: 34974123 DOI: 10.1016/j.micpath.2021.105381] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 12/27/2021] [Accepted: 12/28/2021] [Indexed: 12/12/2022]
Abstract
The incidence of inflammatory bowel disease (IBD) is globally increasing. This disorder seriously affects the quality of life in patients. Interestingly, studies have detected that the intestinal flora imbalance is a critical factor in the progression of IBD. One potential treatment strategy for IBD involves regulating the composition and function of the intestinal flora. To date, a multitude of experiments have confirmed the relationship between intestinal flora, immune regulation, and anti-inflammation. The intestinal flora can reduce intestinal inflammation by regulating immunity and increasing the secretion of metabolic short-chain fatty acids. In this review, we discuss the composition and function of the intestinal flora, the relationship between the intestinal flora and the host, the role of intestinal flora disorders in IBD, and the progress in IBD treatment. Combining the regulation of the intestinal flora with probiotics treatment is considered a promising strategy for substantially improving the treatment of IBD.
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Yang YP, Zhang XY, Cui BT, Zhang H, Wu ZF, Tan X, Cheng W, Zhu X, Zhang FM, Qin HL, Wei H. Preclinical safety, effectiveness evaluation, and screening of functional bacteria for fecal microbiota transplantation based on germ-free animals. World J Meta-Anal 2021; 9:496-504. [DOI: 10.13105/wjma.v9.i6.496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 10/14/2021] [Accepted: 12/24/2021] [Indexed: 02/06/2023] Open
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Huang HL, Xu HM, Liu YD, Shou DW, Nie YQ, Chen HT, Zhou YJ. Fecal microbiota transplantation as a novel approach for the treatment of atopic dermatitis. J Dermatol 2021; 48:e574-e576. [PMID: 34580907 DOI: 10.1111/1346-8138.16169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 07/28/2021] [Accepted: 08/12/2021] [Indexed: 12/18/2022]
Affiliation(s)
- Hong-Li Huang
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yan-Di Liu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Di-Wen Shou
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yu-Qiang Nie
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Hui-Ting Chen
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yong-Jian Zhou
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
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Zhao Y, Li X, Zhou Y, Gao J, Jiao Y, Zhu B, Wu D, Qi X. Safety and Efficacy of Fecal Microbiota Transplantation for Grade IV Steroid Refractory GI-GvHD Patients: Interim Results From FMT2017002 Trial. Front Immunol 2021; 12:678476. [PMID: 34220825 PMCID: PMC8248496 DOI: 10.3389/fimmu.2021.678476] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 06/04/2021] [Indexed: 01/17/2023] Open
Abstract
Gastrointestinal (GI) tract graft-versus-host disease (GvHD) is a major cause of post-allo-HSCT (hematopoietic stem cell transplantation) morbidity and mortality. Patients with steroid-refractory GI-GvHD have a poor prognosis and limited therapeutic options. FMT2017002 trial (#NCT03148743) was a non-randomized, open-label, phase I/II clinical study of FMT for treating patients with grade IV steroid-refractory GI-GvHD. A total of 55 patients with steroid-refractory GI-GvHD were enrolled in this study. Forty-one patients with grade IV steroid-refractory GI-GvHD were included in the final statistical analysis. Of them, 23 patients and 18 patients were assigned to the FMT group and the control group, respectively. On days 14 and 21 after FMT, clinical remission was significantly greater in the FMT group than in the control group. Within a follow-up period of 90 days, the FMT group showed a better overall survival (OS). At the end of the study, the median survival time was >539 days in the FMT group and 107 days in the control group (HR=3.51; 95% CI, 1.21–10.17; p=0.021). Both the event-free survival time (EFS) (HR=2.3, 95% CI, 0.99–5.4; p=0.08) and OS (HR=4.4, 95% CI, 1.5–13.04; p=0.008) were higher in the FMT group during the follow-up period. Overall, the mortality rate was lower in the FMT group (HR=3.97; 95% CI, 1.34–11.75; p=0.013). No differences in the occurrence of any other side effects were observed. Our data suggest that the diversity of the intestinal microbiota could be affected by allo-HSCT. Although its effectiveness and safety need further evaluation, FMT may serve as a therapeutic option for grade IV steroid-refractory GI-GvHD.
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Affiliation(s)
- Ye Zhao
- Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.,National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Suzhou, China.,Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China.,Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xuewei Li
- Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.,National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Suzhou, China.,Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, China.,Cyrus Tang Hematology Center, Soochow University, Suzhou, China
| | - Yujing Zhou
- Center for Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jin Gao
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Yang Jiao
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Baoli Zhu
- Chinese Academy of Sciences (CAS) Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.,Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.,Beijing Key Laboratory of Antimicrobial Resistance and Pathogen Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.,Department of Pathogenic Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, China
| | - Depei Wu
- Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.,National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Suzhou, China.,Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China.,Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, China.,State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Xiaofei Qi
- Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.,National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Suzhou, China.,Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China.,Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, China.,State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China.,Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Pavel FM, Vesa CM, Gheorghe G, Diaconu CC, Stoicescu M, Munteanu MA, Babes EE, Tit DM, Toma MM, Bungau S. Highlighting the Relevance of Gut Microbiota Manipulation in Inflammatory Bowel Disease. Diagnostics (Basel) 2021; 11:1090. [PMID: 34203609 PMCID: PMC8232187 DOI: 10.3390/diagnostics11061090] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/06/2021] [Accepted: 06/12/2021] [Indexed: 01/11/2023] Open
Abstract
Two different conditions are included in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), being distinguished by chronic recurrence of gut inflammation in persons that are genetically predisposed and subjected to environmental causative factors. The normal structure of the gut microbiome and its alterations in IBD were defined in several microbial studies. An important factor in the prolonged inflammatory process in IBD is the impaired microbiome or "dysbiosis". Thus, gut microbiome management is likely to be an objective in IBD treatment. In this review, we analyzed the existing data regarding the pathophysiological/therapeutic implications of intestinal microflora in the development and evolution of IBD. Furthermore, the main effects generated by the administration of probiotics, prebiotics, fecal transplantation, and phytochemicals supplementation were analyzed regarding their potential roles in improving the clinical and biochemical status of patients suffering from Crohn's disease (CD) and ulcerative colitis (UC), and are depicted in the sections/subsections of the present paper. Data from the literature give evidence in support of probiotic and prebiotic therapy, showing effects such as improving remission rate, improving macroscopic and microscopic aspects of IBD, reducing the pro-inflammatory cytokines and interleukins, and improving the disease activity index. Therefore, the additional benefits of these therapies should not be ignored as adjuvants to medical therapy.
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Affiliation(s)
- Flavia Maria Pavel
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (F.M.P.); (C.M.V.)
| | - Cosmin Mihai Vesa
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (F.M.P.); (C.M.V.)
| | - Gina Gheorghe
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (G.G.); (C.C.D.)
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Camelia C. Diaconu
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (G.G.); (C.C.D.)
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Manuela Stoicescu
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410041 Oradea, Romania; (M.S.); (M.A.M.); (E.E.B.)
| | - Mihai Alexandru Munteanu
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410041 Oradea, Romania; (M.S.); (M.A.M.); (E.E.B.)
| | - Elena Emilia Babes
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410041 Oradea, Romania; (M.S.); (M.A.M.); (E.E.B.)
| | - Delia Mirela Tit
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (D.M.T.); (M.M.T.)
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
| | - Mirela Marioara Toma
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (D.M.T.); (M.M.T.)
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (D.M.T.); (M.M.T.)
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
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42
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Li Q, Ding X, Liu Y, Marcella C, Dai M, Zhang T, Bai J, Xiang L, Wen Q, Cui B, Zhang F. Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn's Disease. Front Pharmacol 2021; 12:658087. [PMID: 34079458 PMCID: PMC8166050 DOI: 10.3389/fphar.2021.658087] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 05/04/2021] [Indexed: 12/12/2022] Open
Abstract
Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn's disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation. Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The "one-hour FMT protocol" was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis. Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43-6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001-0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002). Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT01793831.
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Affiliation(s)
- Qianqian Li
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiao Ding
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Yujie Liu
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Cicilia Marcella
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Dai
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ting Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jianling Bai
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Liyuan Xiang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Quan Wen
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- National Clinical Research Center for Digestive Diseases, Xi’an, China
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Su F, Luo Y, Yu J, Shi J, Zhao Y, Yan M, Huang H, Tan Y. Tandem fecal microbiota transplantation cycles in an allogeneic hematopoietic stem cell transplant recipient targeting carbapenem-resistant Enterobacteriaceae colonization: a case report and literature review. Eur J Med Res 2021; 26:37. [PMID: 33910622 PMCID: PMC8080403 DOI: 10.1186/s40001-021-00508-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 04/13/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Due to limited antibiotic options, carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Also, intestinal CRE colonization is a risk factor for subsequent CRE infection. Several clinical studies have reported successful fecal microbiota transplantation (FMT) for the gut decontamination of a variety of multidrug-resistant bacteria (MDRB), even in immunosuppressed patients. Similarly, other studies have also indicated that multiple FMTs may increase or lead to successful therapeutic outcomes. CASE PRESENTATION We report CRE colonization in an allo-HSCT patient with recurrent CRE infections, and its successful eradication using tandem FMT cycles at 488 days after allo-HSCT. We also performed a comprehensive microbiota analysis. No acute or delayed adverse events (AEs) were observed. The patient remained clinically stable with CRE-negative stool culture at 26-month follow-up. Our analyses also showed some gut microbiota reconstruction. We also reviewed the current literature on decolonization strategies for CRE. CONCLUSIONS CRE colonization led to a high no-relapse mortality after allo-HSCT; however, well-established decolonization strategies are currently lacking. The successful decolonization of this patient suggests that multiple FMT cycles may be potential options for CRE decolonization.
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Affiliation(s)
- Fengqin Su
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yi Luo
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Jian Yu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Jimin Shi
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yanmin Zhao
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Mengni Yan
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yamin Tan
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China. .,Hematology Department, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China.
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Wang Q, Luo Y, Chaudhuri KR, Reynolds R, Tan EK, Pettersson S. The role of gut dysbiosis in Parkinson's disease: mechanistic insights andtherapeutic options. Brain 2021; 144:2571-2593. [PMID: 33856024 DOI: 10.1093/brain/awab156] [Citation(s) in RCA: 142] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 01/23/2021] [Accepted: 03/23/2021] [Indexed: 12/02/2022] Open
Abstract
Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.
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Affiliation(s)
- Qing Wang
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China
| | - Yuqi Luo
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China
| | - K Ray Chaudhuri
- Parkinson Foundation International Centre of Excellence at King's College Hospital, and Kings College, Denmark Hill, London, SE5 9RS, UK
| | - Richard Reynolds
- Department of Brain Sciences, Imperial College London, Hammersmith Hospital Campus, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.,Centre for Molecular Neuropathology, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232
| | - Eng-King Tan
- Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore.,Duke-NUS Medical School, Singapore
| | - Sven Pettersson
- Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore.,Duke-NUS Medical School, Singapore.,LKC School of Medicine, NTU, Singapore.,Sunway University, Department of Medical Sciences, Kuala Lumpur, Malaysia
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Xu HM, Huang HL, Xu J, He J, Zhao C, Peng Y, Zhao HL, Huang WQ, Cao CY, Zhou YJ, Zhou YL, Nie YQ. Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation. Front Microbiol 2021; 12:658292. [PMID: 33912150 PMCID: PMC8071877 DOI: 10.3389/fmicb.2021.658292] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 03/11/2021] [Indexed: 12/15/2022] Open
Abstract
Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography-mass spectrometry (LC-MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - You-Lian Zhou
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yu-Qiang Nie
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, China
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46
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Xu F, Li N, Wang C, Xing H, Chen D, Wei Y. Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study. BMC Gastroenterol 2021; 21:54. [PMID: 33549047 PMCID: PMC7866462 DOI: 10.1186/s12876-021-01630-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 01/26/2021] [Indexed: 12/16/2022] Open
Abstract
Background Small intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated. Methods In this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy. Results Gastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none. Conclusions This study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO. Trial registry This study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).
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Affiliation(s)
- Fenghua Xu
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Ning Li
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Chun Wang
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Hanyang Xing
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Dongfeng Chen
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China
| | - Yanling Wei
- Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, No.10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China.
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Hmar EBL, Paul S, Boruah N, Sarkar P, Borah S, Sharma HK. Apprehending Ulcerative Colitis Management With Springing Up Therapeutic Approaches: Can Nanotechnology Play a Nascent Role? CURRENT PATHOBIOLOGY REPORTS 2021. [DOI: 10.1007/s40139-020-00218-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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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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Dang XF, Qing-Xi Wang, Yin Z, Sun L, Yang WH. Recurrence of moderate to severe ulcerative colitis after fecal microbiota transplantation treatment and the efficacy of re-FMT: a case series. BMC Gastroenterol 2020; 20:401. [PMID: 33243141 PMCID: PMC7691068 DOI: 10.1186/s12876-020-01548-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 11/18/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), the pathogenesis of which is complicated, and it is difficult to treat. In recent years, the emerging fecal microbiota transplantation (FMT) has shown good effects in UC treatment and is therefore accepted by increasing numbers of patients. Our hospital has carried out FMT since 2017, and has achieved good results in UC treatment. We have found in our clinical work that the efficacy of re-FMT after recurrence decreased. This is difference from reported literatures. In order to attract clinical attention, here we selected typical cases for analysis. METHODS Among all UC patients who received FMT in our hospital, 12 patients with moderate to severe UC were selected. They all received multiple FMT and were followed up for 52 weeks. Besides, none of them had other underlying diseases. Colonoscopy images of patients were presentated, SCCAI and UCDAI were used assess the effect of FMT. RESULTS On the whole, FMT has a significant effect on moderate to severe UC. Of the 12 patients, 11 (91.7%) achieved a clinical response, 9 (75.0%) achieved clinical remission, and only one patient did not respond to FMT treatment. However, 6 patients relapsed within 52 weeks after remission, with a recurrence rate of 54.5%. Four of the six relapsed patients received FMT again, but the efficacy of FMT after relapse was significantly lower than that of the initial FMT. Fortunately, compared to before the initial FMT treatment, the severity of the disease after relapse was significantly reduced. CONCLUSION FMT has a good effect on the relief of moderate to severe UC. However, the effect of FMT treatment after relapse is reduced. For patients who relapse after remission, the efficacy of FMT reapplication requires more experiments to verify.
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Affiliation(s)
- Xiao-Fei Dang
- Department of Clinical Microbiology, Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong, China
| | - Qing-Xi Wang
- Department of Clinical Microbiology, Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong, China
| | - Zhao Yin
- Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, China
| | - Lin Sun
- Department of Clinical Microbiology, Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong, China
| | - Wei-Hua Yang
- Department of Clinical Microbiology, Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong, China.
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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: 20] [Impact Index Per Article: 4.0] [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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