|
1
|
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.
Collapse
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
| |
Collapse
|
|
2
|
Ebrahimi R, Farsi Y, Nejadghaderi SA. Fecal microbiota transplantation for glaucoma; a potential emerging treatment strategy. CURRENT RESEARCH IN MICROBIAL SCIENCES 2024; 7:100314. [PMID: 39726974 PMCID: PMC11670420 DOI: 10.1016/j.crmicr.2024.100314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2024] Open
Abstract
Glaucoma is the primary cause of irreversible blindness globally. Different glaucoma subtypes are identified by their underlying mechanisms, and treatment options differ by its pathogenesis. Current management includes topical medications to lower intraocular pressure and surgical procedures like trabeculoplasty and glaucoma drainage implants. Fecal microbiota transplantation (FMT) is an almost effective and safe treatment option for recurrent Clostridium difficile infection. The relationship between bacterial populations, metabolites, and inflammatory pathways in retinal diseases indicates possible therapeutic strategies. Thus, incorporating host microbiota-based therapies could offer an additional treatment option for glaucoma patients. Here, we propose that combining FMT with standard glaucoma treatments may benefit those affected by this condition. Also, the potential safety, efficacy, cost-effectiveness and clinical applications are discussed.
Collapse
Affiliation(s)
- Rasoul Ebrahimi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Yeganeh Farsi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Aria Nejadghaderi
- HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
| |
Collapse
|
|
3
|
Wang Y, Dai M, Zheng M, Jin Y, Wen Q, Cui B, Zhang Z, Zhu J, Zhang F. Bowel preparation after mid-gut tubing enhanced the efficacy and compliance of magnetic resonance enterography in Crohn's disease: a randomized controlled trial. Therap Adv Gastroenterol 2024; 17:17562848241275337. [PMID: 39346010 PMCID: PMC11437563 DOI: 10.1177/17562848241275337] [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: 12/17/2023] [Accepted: 07/26/2024] [Indexed: 10/01/2024] Open
Abstract
BACKGROUND Magnetic resonance enterography (MRE) has become a routine intestinal imaging examination for Crohn's disease (CD). Sufficient bowel preparation is fundamental for MRE. OBJECTIVES To compare the efficacy and compliance of bowel preparation between through a mid-gut tube and oral administration for MRE in CD. DESIGN This was an open-label, prospective, multicenter, randomized controlled trial. METHODS Eligible patients were randomized at a 1:1 ratio into an oral group (bowel preparation by oral administration) and a tubing group (bowel preparation through a mid-gut tube). Bowel preparation for MRE included bowel cleaning and bowel distention. The primary outcomes were the degree of discomfort and grade of bowel distention. The secondary outcomes were diagnostic accuracy rate through MRE, mental stress, and bowel preparation method preference. RESULTS A total of 95 CD patients were included in the final analysis. Subjects in the tubing group complained of less vomiting during bowel preparation than those in the oral group (p < 0.05). The degree of nausea and bloating during bowel cleaning for MRE was lower in the tubing group than in the oral group (all p < 0.05). The distention grade was higher in the tubing group compared to the oral group in the splenic flexure of the colon and rectosigmoid colon. The tubing group demonstrated a higher overall diagnostic sensitivity in ulcers compared to the oral group (p = 0.048). Additionally, bowel preparation via the mid-gut tube ameliorated mental stress (p = 0.020) and increased bowel preparation preference (p < 0.001). CONCLUSION Bowel preparation through the mid-gut tube enhanced the efficacy and compliance for MRE in CD. This study highlighted the concept of physician-patient satisfaction using mid-gut tube for proper bowel preparation for MRE, enteral nutrition and microbial therapy. TRIAL REGISTRATION ClinicalTrials.gov, NCT03541733, registered 5 May 2018.
Collapse
Affiliation(s)
- Yun Wang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Min Dai
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Minghui Zheng
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Yan Jin
- Department of Gastroenterology, Jiangnan University Medical Center, Wuxi, China
| | - Quan Wen
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Zulun Zhang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Jianguo Zhu
- Department of Radiology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, 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
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
4
|
Zikou E, Koliaki C, Makrilakis K. The Role of Fecal Microbiota Transplantation (FMT) in the Management of Metabolic Diseases in Humans: A Narrative Review. Biomedicines 2024; 12:1871. [PMID: 39200335 PMCID: PMC11352194 DOI: 10.3390/biomedicines12081871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/02/2024] Open
Abstract
The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes.
Collapse
|
|
5
|
Zheng YM, Wu HY, Ye MM, Cai JY, Yuan Y, Xie WR, Xu JT, Liu T, He XX, Wu LH. Comparison of the use of a spiral nasojejunal tube and transendoscopic enteral tubing in washed microbiota transplantation via the mid-gut route. Heliyon 2024; 10:e30310. [PMID: 38742080 PMCID: PMC11089310 DOI: 10.1016/j.heliyon.2024.e30310] [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: 01/18/2024] [Revised: 04/20/2024] [Accepted: 04/23/2024] [Indexed: 05/16/2024] Open
Abstract
Background Methods for washed microbiota transplantation (WMT) through the mid-gut include transendoscopic enteral tubing (TET) and manual spiral nasojejunal tube (SNT) placement have not been studied. Methods This prospective interventional study was performed at a single centre. Patients were divided into the SNT and mid-gut TET groups based on their conditions and wishes. In the SNT group, an SNT was passively inserted into the stomach, and abdominal X-rays were taken within 24 h to confirm tube placement in the small intestine. In the mid-gut TET group, mid-gut TET was placed in the small intestine for gastroscopy. Data on the clinical efficacy of WMT, intubation time, cost, overall comfort score, adverse reactions, etc., were collected from the two groups. Results Sixty-three patients were included in the study (SNT group (n = 40) and mid-gut TET group (n = 23)). The clinical efficacy of WMT in the SNT and mid-gut TET groups was 90 % and 95.7 %, respectively (P = 0.644). Compared with the mid-gut TET group, the SNT group showed a shorter operation time (120 s vs. 258 s, P = 0.001) and a lower average cost (641.7 yuan vs. 1702.1 yuan, P = 0.001). There was no significant difference in the overall comfort score or the incidence of common discomfort symptoms between the two groups. Conclusion The different implantation methods have different advantages; compared with mid-gut TET placement, manual SNT placement provides some benefits.
Collapse
Affiliation(s)
- Ya-Mei Zheng
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| | - Hui-Yi Wu
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| | - Meng-Meng Ye
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| | - Jie-Yi Cai
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| | - Yu Yuan
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| | - Wen-Rui Xie
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| | - Jia-Ting Xu
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| | - Tao Liu
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| | - Xing-Xiang He
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| | - Li-Hao Wu
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, Guangzhou, 510080, Guangdong Province, China
| |
Collapse
|
|
6
|
Chen SJ, Zhang DY, Wu X, Zhang FM, Cui BT, Huang YH, Zhang ZL, Wang R, Bai FH. Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study. World J Gastroenterol 2024; 30:1572-1587. [PMID: 38617453 PMCID: PMC11008410 DOI: 10.3748/wjg.v30.i11.1572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 02/07/2024] [Accepted: 03/06/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported. AIM To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT. METHODS We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure. RESULTS Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT. CONCLUSION WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.
Collapse
Affiliation(s)
- Shi-Ju Chen
- Graduate School, Hainan Medical University, Haikou 571199, Hainan Province, China
| | - Da-Ya Zhang
- Graduate School, Hainan Medical University, Haikou 571199, Hainan Province, China
| | - Xia Wu
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Fa-Ming Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Bo-Ta Cui
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Yi-Hao Huang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Zu-Lun Zhang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Rui Wang
- Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Fei-Hu Bai
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570216, Hainan Province, China
| |
Collapse
|
|
7
|
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.
Collapse
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
| |
Collapse
|
|
8
|
Yang J, Yang X, Wu G, Huang F, Shi X, Wei W, Zhang Y, Zhang H, Cheng L, Yu L, Shang J, Lv Y, Wang X, Zhai R, Li P, Cui B, Fang Y, Deng X, Tang S, Wang L, Yuan Q, Zhao L, Zhang F, Zhang C, Yuan H. Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes. Cell Metab 2023; 35:1548-1562.e7. [PMID: 37451270 DOI: 10.1016/j.cmet.2023.06.010] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 03/17/2023] [Accepted: 06/19/2023] [Indexed: 07/18/2023]
Abstract
The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.
Collapse
Affiliation(s)
- Junpeng Yang
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Xueli Yang
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Guojun Wu
- State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, Rutgers-SJTU Joint Laboratory on Microbiome and Human Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Biochemistry and Microbiology and New Jersey Institute for Food, Nutrition, and Health, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ 08901, USA
| | - Fenglian Huang
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Xiaoyang Shi
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Wei Wei
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Yingchao Zhang
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Haihui Zhang
- Department of Gastroenterology of Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Lina Cheng
- Department of Gastroenterology of Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Lu Yu
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Jing Shang
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Yinghua Lv
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Xiaobing Wang
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Rui Zhai
- State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, Rutgers-SJTU Joint Laboratory on Microbiome and Human Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Pan Li
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Key Laboratory of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China
| | - Bota Cui
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Key Laboratory of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China
| | - Yuanyuan Fang
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Xinru Deng
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Shasha Tang
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Limin Wang
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Qian Yuan
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China
| | - Liping Zhao
- State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, Rutgers-SJTU Joint Laboratory on Microbiome and Human Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Biochemistry and Microbiology and New Jersey Institute for Food, Nutrition, and Health, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ 08901, USA.
| | - Faming Zhang
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Key Laboratory of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China.
| | - Chenhong Zhang
- State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, Rutgers-SJTU Joint Laboratory on Microbiome and Human Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Huijuan Yuan
- Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
| |
Collapse
|
|
9
|
Wu L, Yuan Q, Wu L, Hua-Xiang Xia H, Zhong M, Liu T, Ye X, Luo D, Xu J, Xie W, He X, Cai J. Efficacy of washed microbiota transplantation for therapeutic targets of refractory functional constipation and the influencing factors: a single-center, retrospective, 24-week follow-up study. BMC Gastroenterol 2023; 23:291. [PMID: 37641043 PMCID: PMC10463406 DOI: 10.1186/s12876-023-02929-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 08/19/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND The efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and influencing factors of WMT in treating refractory FC-related therapeutic targets. METHODS The clinical data of patients diagnosed with refractory FC and received with WMT were retrospectively collected. The therapeutic targets included straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, manual maneuvers, and decreased stool frequency. Each target was recorded as 1 (yes) or 0 (no). All patients were followed up for approximately 24 weeks from the end of the first course of WMT. The primary outcomes were the improvement rates for the individual therapeutic targets and the overall response in respect of the therapeutic targets decreased by 2 at weeks 4, 8, and 24. The secondary outcomes were the clinical remission rate (i.e., the proportion of patients with an average of 3 or more spontaneous complete bowel movements per week), clinical improvement rate (i.e., the proportion of patients with an average increase of 1 or more SCBMs/week or patients with remission), stool frequency, Wexner constipation score, Bristol Stool Form Scale (BSFS) score, and adverse events. The factors influencing the efficacy were also analyzed. RESULTS Overall, 63 patients with 112 WMT courses were enrolled. The improvement rates at weeks 8 and 24 were 45.6% and 35.0%, 42.9% and 38.6%, 45.0% and 35.7%, 55.6% and 44.4%, and 60.9% and 50.0%, respectively, for straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, and decreased stool frequency. The overall response rates were 49.2%, 50.8%, and 42.9%, respectively, at weeks 4, 8, and 24. The rates of clinical remission and clinical improvement were 54.0% and 68.3%, respectively, at weeks 4. The stool frequency, BSFS score, and Wexner constipation score tended to improve post-WMT. Only 22 mild adverse events were observed during the 112 WMT courses and the follow-up. The number of WMT courses was identified to be the independent factor influencing the efficacy. CONCLUSIONS WMT is efficacious in improving refractory FC-related therapeutic targets. The effectiveness of WMT in the management of FC is enhanced with the administration of multiple courses.
Collapse
Affiliation(s)
- Liquan Wu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Qingfen Yuan
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Lihao Wu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Harry Hua-Xiang Xia
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Muxiao Zhong
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Tao Liu
- Department of Medical Record, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China
| | - Xiaoyan Ye
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Danping Luo
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Jiating Xu
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Wenrui Xie
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Xingxiang He
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China
| | - Jieyi Cai
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, 510080, China.
| |
Collapse
|
|
10
|
Liu Y, Ji X, Huang Y, Li Q, Ding X, Wang Y, Zhang S, Wen Q, Cui B, Lu X, Zhang F. Older patients benefit more from sequential courses of washed microbiota transplantation than younger population with ulcerative colitis. Scand J Gastroenterol 2023; 58:890-899. [PMID: 36864569 DOI: 10.1080/00365521.2023.2185476] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 02/19/2023] [Accepted: 02/23/2023] [Indexed: 03/04/2023]
Abstract
OBJECTIVES The short-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) has increasingly been evaluated. However, few studies have examined the long-term efficacy and its predictors. This study aimed to assess the clinical factors affecting the long-term efficacy of FMT for patients with UC. METHODS This is a retrospective analysis of a prospective trial (NCT01790061) for patients with UC undergoing washed microbiota transplantation (WMT), which is the improved methodology of FMT. The long-term clinical efficacy of WMT and the factors affecting efficacy were analyzed. RESULTS A total of 259 patients were included for analysis. Of 70.7% (183/259) of patients achieved a clinical response at 1 month after WMT and 29.7% (77/259) achieved steroid-free clinical remission 6 months after WMT. Total 44 patients maintained a clinical response for ≥24 months, and 33 (17.1%, 33/193) achieved steroid-free clinical remission for ≥24 months with WMT monotherapy. Patients with age at UC onset of ≥60 years, mild disease severity and undergoing ≥2 courses of WMT during the response within 6 months were more likely to achieve steroid-free clinical remission 6 months after WMT. Besides, independent factors associated with the long-term response of WMT for UC were age at onset of ≥60 years and ≥2 courses of WMT during the response. CONCLUSIONS This study indicated WMT could induce short-term steroid-free clinical remission and maintain long-term response in UC, especially for older patients and patients undergoing sequential courses.
Collapse
Affiliation(s)
- Yujie Liu
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
- Department of Geriatrics, Sir Run Run Hospital at Nanjing Medical University, Nanjing, China
| | - Xinghui Ji
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Yihao Huang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Qianqian Li
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Xiao Ding
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong, China
| | - Yun Wang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Sheng Zhang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Quan Wen
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Xiang Lu
- Department of Geriatrics, Sir Run Run Hospital at Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Department of Microbiota Medicine and Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
11
|
Wang W, Lu G, Wu X, Wen Q, Zhang F. Colonic Transendoscopic Enteral Tubing Is a New Pathway to Microbial Therapy, Colonic Drainage, and Host-Microbiota Interaction Research. J Clin Med 2023; 12:780. [PMID: 36769429 PMCID: PMC9918197 DOI: 10.3390/jcm12030780] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 01/08/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
The limitation of traditional delivery methods for fecal microbiota transplantation (FMT) gave birth to colonic transendoscopic enteral tubing (TET) to address the requirement of frequent FMTs. Colonic TET as a novel endoscopic intervention has received increasing attention in practice since 2015 in China. Emerging studies from multiple centers indicate that colonic TET is a promising, safe, and practical delivery method for microbial therapy and administering medication with high patient satisfaction. Intriguingly, colonic TET has been used to rescue endoscopy-related perforations by draining colonic air and fluid through the TET tube. Recent research based on collecting ileocecal samples through a TET tube has contributed to demonstrating community dynamics in the intestine, and it is expected to be a novel delivery of proof-of-concept in host-microbiota interactions and pharmacological research. The present article aims to review the concept and techniques of TET and to explore microbial therapy, colonic drainage, and microbial research based on colonic TET.
Collapse
Affiliation(s)
- Weihong Wang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
| | - Gaochen Lu
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
| | - Xia Wu
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
| | - Quan Wen
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
- Key Lab of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China
- Department of Microbiotherapy, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Avenue, Nanjing 211166, China
| |
Collapse
|
|
12
|
Qiao X, Biliński J, Wang L, Yang T, Luo R, Fu Y, Yang G. Safety and efficacy of fecal microbiota transplantation in the treatment of graft-versus-host disease. Bone Marrow Transplant 2023; 58:10-19. [PMID: 36167905 DOI: 10.1038/s41409-022-01824-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/24/2022] [Accepted: 09/01/2022] [Indexed: 01/10/2023]
Abstract
This article evaluates the efficacy and safety of FMT in the treatment of GVHD after HSCT using a systematic literature search to conduct a meta-analysis constructed of studies involving GVHD patients treated with FMT. 23 studies were included, among which 2 prospective cohort studies, 10 prospective single arm studies, 2 retrospective single arm studies, 2 case series and 7 case reports, comprise a total of 242 patients with steroid-resistant or steroid-dependent GVHD secondary to HSCT who were treated with FMT. 100 cases achieved complete responses, while 61 cases showed partial responses, and 81 cases presented no effect after FMT treatment. The estimate of clinical remission odds ratio was 5.51 (95% CI 1.49-20.35) in cohort studies, and the pooled clinical remission rate is 64% (51-77%) in prospective single arm studies and 81% (62-95%) in retrospective studies, case series and case reports. Five (2.1%) patients had FMT-related infection events, but all recovered after treatment. Other adverse effects were mild and acceptable. Microbiota diversity and composition, donor type, and other related issues were also analyzed. The data proves that FMT is a promising treatment modality of GVHD, but further validation of its safety and efficacy is still needed with prospective control studies.Clinical trial registration: Registered in https://www.crd.york.ac.uk/PROSPERO/ CRD42022296288.
Collapse
Affiliation(s)
- Xiaoying Qiao
- Peking University Health Science Center, Beijing, 100191, China.,Peking University People'hospital, Beijing, China
| | - Jarosław Biliński
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
| | - Leyi Wang
- Peking University Health Science Center, Beijing, 100191, China
| | - Tianyu Yang
- Peking University Health Science Center, Beijing, 100191, China
| | - Rongmu Luo
- Department of Hematology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, China
| | - Yi Fu
- Department of Gastroenterology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, China
| | - Guibin Yang
- Department of Gastroenterology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, China.
| |
Collapse
|
|
13
|
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
|
|
14
|
Zhang YW, Cao MM, Li YJ, Zhang RL, Wu MT, Yu Q, Rui YF. Fecal microbiota transplantation as a promising treatment option for osteoporosis. J Bone Miner Metab 2022; 40:874-889. [PMID: 36357745 PMCID: PMC9649400 DOI: 10.1007/s00774-022-01375-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 10/04/2022] [Indexed: 11/12/2022]
Abstract
Osteoporosis is a systemic metabolic bone disease characterized by the descending bone mass and destruction of bone microstructure, which tends to result in the increased bone fragility and associated fractures, as well as high disability rate and mortality. The relation between gut microbiota and bone metabolism has gradually become a research hotspot, and it has been verified that gut microbiota is closely associated with reduction of bone mass and incidence of osteoporosis recently. As a novel "organ transplantation" technique, fecal microbiota transplantation (FMT) mainly refers to the transplantation of gut microbiota from healthy donors to recipients with gut microbiota imbalance, so that the gut microbiota in recipients can be reshaped and play a normal function, and further prevent or treat the diseases related to gut microbiota disorder. Herein, based on the gut-bone axis and proven regulatory effects of gut microbiota on osteoporosis, this review expounds relevant basic researches and clinical practice of FMT on osteoporosis, thus demonstrating the potentials of FMT as a therapeutic option for osteoporosis and further providing certain reference for the future researches.
Collapse
Affiliation(s)
- Yuan-Wei Zhang
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, 210009, Jiangsu, People's Republic of China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Mu-Min Cao
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, 210009, Jiangsu, People's Republic of China
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Ying-Juan Li
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- Department of Geriatrics, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Ruo-Lan Zhang
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Meng-Ting Wu
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Qian Yu
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China
- Department of Gastroenterology, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People's Republic of China
| | - Yun-Feng Rui
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, 210009, Jiangsu, People's Republic of China.
- Multidisciplinary Team (MDT) for Geriatric Hip Fracture Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China.
- School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China.
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, People's Republic of China.
| |
Collapse
|
|
15
|
Xu H, Cao C, Ren Y, Weng S, Liu L, Guo C, Wang L, Han X, Ren J, Liu Z. Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment. Front Immunol 2022; 13:949490. [PMID: 36177041 PMCID: PMC9513044 DOI: 10.3389/fimmu.2022.949490] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 08/04/2022] [Indexed: 11/20/2022] Open
Abstract
Fecal microbiome transplantation (FMT) from healthy donors is one of the techniques for restoration of the dysbiotic gut, which is increasingly being used to treat various diseases. Notably, mounting evidence in recent years revealed that FMT has made a breakthrough in the oncology treatment area, especially by improving immunotherapy efficacy to achieve antitumor effects. However, the mechanism of FMT in enhancing antitumor effects of immune checkpoint blockers (ICBs) has not yet been fully elucidated. This review systematically summarizes the role of microbes and their metabolites in the regulation of tumor immunity. We highlight the mechanism of action of FMT in the treatment of refractory tumors as well as in improving the efficacy of immunotherapy. Furthermore, we summarize ongoing clinical trials combining FMT with immunotherapy and further focus on refined protocols for the practice of FMT in cancer treatment, which could guide future directions and priorities of FMT scientific development.
Collapse
Affiliation(s)
- Hui Xu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Interventional Institute of Zhengzhou University, Zhengzhou, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, China
| | - Chenxi Cao
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuqing Ren
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Siyuan Weng
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Long Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chunguang Guo
- Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Libo Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Interventional Institute of Zhengzhou University, Zhengzhou, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, China
- *Correspondence: Xinwei Han, ; Jianzhuang Ren, ; Zaoqu Liu,
| | - Jianzhuang Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Xinwei Han, ; Jianzhuang Ren, ; Zaoqu Liu,
| | - Zaoqu Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Interventional Institute of Zhengzhou University, Zhengzhou, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, China
- *Correspondence: Xinwei Han, ; Jianzhuang Ren, ; Zaoqu Liu,
| |
Collapse
|
|
16
|
Lu G, Wang W, Li P, Wen Q, Cui B, Zhang F. Washed preparation of faecal microbiota changes the transplantation related safety, quantitative method and delivery. Microb Biotechnol 2022; 15:2439-2449. [PMID: 35576458 PMCID: PMC9437882 DOI: 10.1111/1751-7915.14074] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 04/30/2022] [Indexed: 01/06/2023] Open
Abstract
The safety, quantitative method and delivery of faecal microbiota transplantation (FMT) vary a lot from different countries in practice. Recently, the improved methodology of FMT based on the automatic filtration, washing process and the related delivery was named as washed microbiota transplantation (WMT). First, this study aimed to describe the methodology development of FMT from manual to washing preparation from 2012 to 2021 in China Microbiota Transplantation System (CMTS), a centralized stool bank for providing a national non-profit service. The secondary aim is to describe donor screenings, the correlation between faecal weight and treatment doses, incidence of adverse events and delivery decision. The retrospective analysis on the prospectively recorded data was performed. Results showed that the success rate of donor screening was 3.1% (32/1036). The incidence rate of fever decreased significantly from 19.4% (6/31) in manual FMT to 2.7% (24/902) in WMT in patients with ulcerative colitis (UC), which made UC a considerable disease model to reflect the quality control of faecal microbiota preparation. We defined one treatment unit as 10 cm3 microbiota precipitation (1.0 × 1013 bacteria) based on enriched microbiota instead of rough faecal weight. For delivering microbiota, colonic transendoscopic enteral tube is a promising way especially for multiple WMTs or frequent colonic administration of drugs combined with WMT. This study should help improve the better practice of FMT for helping more patients in the future.
Collapse
Affiliation(s)
- Gaochen Lu
- Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing210011China
| | - Weihong Wang
- Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing210011China
| | - Pan Li
- Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing210011China
| | - Quan Wen
- Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing210011China
| | - Bota Cui
- Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing210011China
| | - Faming Zhang
- Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing210011China
- Department of MicrobiotherapySir Run Run HospitalNanjing Medical UniversityNanjing211166China
- National Clinical Research Center for Digestive DiseasesXi'an710032China
| |
Collapse
|
|
17
|
Lu G, Xiang Q, Wang S, Pan M, Xiang X, Yang Y, Shi X. Endoscopic- versus x-ray-guidance for placement of nasojejunal tubes in critically ill patients: a systematic review and meta-analysis of randomized controlled trials. Am J Transl Res 2022; 14:2134-2146. [PMID: 35559401 PMCID: PMC9091079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 03/22/2022] [Indexed: 06/15/2023]
Abstract
Nasojejunal tubes (NJTs) are increasingly used in critically ill patients. NJT insertion with endoscopic- or x-ray-guidance can be achieved with success rates above 90%. This systematic review and meta-analysis of randomized controlled trials (RCTs) compares the efficiency and safety of these two methods in critically ill patients. We searched Chinese and English databases for RCTs comparing endoscopy- and x-ray-guided NJT placement published up to July 5, 2021. Meta-analyses were performed using RevMan5 software to compute mean differences (MDs) and odds ratios (ORs). Eleven RCTs (n=676) were included. The endoscopic group had a higher procedure success rate (OR=2.14, 95% CI [1.19, 3.85], Z=2.52, P=0.01) and shorter insertion time (MD=-3.70 min, 95% CI [-6.90, -0.50], Z=2.27, P=0.02) than the x-ray group. NJT indwelling time and post-insertion complications were similar between groups. The x-ray group had fewer complications during placement (OR=8.08, 95% CI [3.58, 18.22], Z=5.03, P<0.00001]; on subgroup analysis, only gastrointestinal non-bleeding adverse events differed significantly between groups (OR=2.78, 95% CI [1.43, 5.39], Z=3.03, P=0.002). Visual analog scale discomfort scores were better in the x-ray group (MD=4.10, 95% CI [3.57, 4.63], Z=15.07, P<0.00001). Compared with x-ray-guided NJT placement, endoscopy-guided placement was faster, had a higher success rate, and was associated with fewer gastrointestinal non-bleeding adverse events and less discomfort during insertion. Endoscopic guidance is recommended for NJT placement in critically ill patients to improve placement efficiency. X-ray guidance is a good alternative, depending on the hospital setting, as it is convenient, economical, and potentially safer.
Collapse
Affiliation(s)
- Guanzhen Lu
- Surgery Department, Huzhou Central Hospital, Affiliated Central Hospital, Huzhou UniversityHuzhou 313000, Zhejiang, China
| | - Qin Xiang
- Graduate School of Nursing, Huzhou UniversityHuzhou 313000, Zhejiang, China
| | - Sha Wang
- Graduate School of Nursing, Huzhou UniversityHuzhou 313000, Zhejiang, China
| | - Mingyue Pan
- Graduate School of Nursing, Huzhou UniversityHuzhou 313000, Zhejiang, China
| | - Xu Xiang
- Graduate School of Nursing, Huzhou UniversityHuzhou 313000, Zhejiang, China
| | - Yanling Yang
- Graduate School of Nursing, Huzhou UniversityHuzhou 313000, Zhejiang, China
| | - Xinyan Shi
- Surgery Department, Huzhou Central Hospital, Affiliated Central Hospital, Huzhou UniversityHuzhou 313000, Zhejiang, China
| |
Collapse
|
|
18
|
Xiang L, Yu Y, Ding X, Zhang H, Wen Q, Cui B, Zhang F. Exclusive Enteral Nutrition Plus Immediate vs. Delayed Washed Microbiota Transplantation in Crohn's Disease With Malnutrition: A Randomized Pilot Study. Front Med (Lausanne) 2021; 8:666062. [PMID: 34746161 PMCID: PMC8569231 DOI: 10.3389/fmed.2021.666062] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 09/28/2021] [Indexed: 12/12/2022] Open
Abstract
Background: The potential of washed microbiota transplantation (WMT) in Crohn's disease (CD) has been reported. This study aimed to explore the suitable timing of WMT in patients with CD complicated with malnutrition. Methods: This is a randomized, open-label study. Patients with active CD complicated with malnutrition were included and 1:1 randomized to undergo WMT at day 1 (group WMT-DAY1) or day 8 (group WMT-DAY8). The observation duration was 15 days. Exclusive enteral nutrition (EEN) was administered in both groups. The primary outcome was the improvement in nutritional parameters at day 8 and day 15 in two groups. The secondary outcome was the rate of clinical remission at day 15 in two groups. Results: Totally 19 patients completed the trial. At day 8, the lymphocyte count, albumin and prealbumin increased significantly compared to those at day 1 in group WMT-DAY1 (p = 0.018, p = 0.028, p = 0.028, respectively), while no significant increase in any nutritional parameter was shown in group WMT-DAY8. At day 15, albumin increased significantly compared to that at day 1 in both groups (p < 0.05), while significant increase in prealbumin was only shown in group WMT-DAY1 (p = 0.004) compared to that at day 1. The rate of clinical remission at day 15 in group WMT-DAY1 and group WMT-DAY8 was 87.5% (7/8) and 72.7% (8/11), respectively (p = 0.603). Conclusion: EEN combined with immediate WMT intervention could rapidly improve the nutritional status and induce clinical remission in malnourished patients with CD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02897661.
Collapse
Affiliation(s)
- Liyuan Xiang
- Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Yan Yu
- Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Gastroenterology, Changshu No. 2 People's Hospital, Suzhou, China
| | - Xiao Ding
- Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Hui Zhang
- Division of Clinical Nutrition, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Quan Wen
- Medical Center for Digestive Diseases, 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, 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, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
- Division of Microbiotherapy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
- National Clinical Research Center for Digestive Diseases, Xi'an, China
| |
Collapse
|
|
19
|
Fehily SR, Basnayake C, Wright EK, Kamm MA. Fecal microbiota transplantation therapy in Crohn's disease: Systematic review. J Gastroenterol Hepatol 2021; 36:2672-2686. [PMID: 34169565 DOI: 10.1111/jgh.15598] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The gastrointestinal microbiota is the key antigenic drive in the inflammatory bowel diseases. Randomized controlled trials (RCTs) in ulcerative colitis have established fecal microbiota transplantation (FMT) as an effective therapy. We have conducted a systematic review to evaluate the efficacy of FMT in Crohn's disease. METHODS A systematic literature search was performed through to August 2020 (MEDLINE; Embase). Studies were included if they reported FMT administration in patients with Crohn's disease, and reported on clinical outcomes. RESULTS Fifteen studies published between 2014 and 2020, comprising 13 cohort studies and two RCTs, were included in the analysis. The majority of trials evaluated FMT for induction of remission, with follow-up duration varying from 4 to 52 weeks. One RCT in 21 patients, of single-dose FMT versus placebo, following steroid-induced remission, showed a higher rate of steroid-free clinical remission in the FMT group compared to the control group: 87.5% vs 44.4% at week 10 (P = 0.23). Another RCT, two-dose FMT in 31 patients, showed an overall clinical remission rate of 36% at week 8, however, with no difference in clinical or endoscopic endpoints between FMT administered by gastroscopy and colonoscopy. Considering all studies, the clinical response rates in early follow up were higher following multiple FMT than with single FMT. FMT dose did not appear to influence clinical outcomes, nor did whether FMT was fresh or frozen. FMT delivered via upper gastrointestinal route demonstrated higher early efficacy rates of 75 to 100% compared with lower delivery route rates of 30% to 58%, but on follow up beyond 8 weeks, this difference was not maintained. Whether pre-FMT antibiotic administration was beneficial was not able to be determined due to the limited number of patients receiving antibiotics and varying antibiotic regimens. No serious adverse events were reported. CONCLUSIONS Preliminary studies suggest that FMT may be an effective therapy in Crohn's disease. However large controlled trials are needed. No serious safety concerns have been identified.
Collapse
Affiliation(s)
- Sasha R Fehily
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Chamara Basnayake
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| |
Collapse
|
|
20
|
PH van Trijp M, Wilms E, Ríos-Morales M, Masclee AA, Brummer RJ, Witteman BJ, Troost FJ, Hooiveld GJ. Using naso- and oro-intestinal catheters in physiological research for intestinal delivery and sampling in vivo: practical and technical aspects to be considered. Am J Clin Nutr 2021; 114:843-861. [PMID: 34036315 PMCID: PMC8408849 DOI: 10.1093/ajcn/nqab149] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 04/09/2021] [Indexed: 01/19/2023] Open
Abstract
Intestinal catheters have been used for decades in human nutrition, physiology, pharmacokinetics, and gut microbiome research, facilitating the delivery of compounds directly into the intestinal lumen or the aspiration of intestinal fluids in human subjects. Such research provides insights about (local) dynamic metabolic and other intestinal luminal processes, but working with catheters might pose challenges to biomedical researchers and clinicians. Here, we provide an overview of practical and technical aspects of applying naso- and oro-intestinal catheters for delivery of compounds and sampling luminal fluids from the jejunum, ileum, and colon in vivo. The recent literature was extensively reviewed, and combined with experiences and insights we gained through our own clinical trials. We included 60 studies that involved a total of 720 healthy subjects and 42 patients. Most of the studies investigated multiple intestinal regions (24 studies), followed by studies investigating only the jejunum (21 studies), ileum (13 studies), or colon (2 studies). The ileum and colon used to be relatively inaccessible regions in vivo. Custom-made state-of-the-art catheters are available with numerous options for the design, such as multiple lumina, side holes, and inflatable balloons for catheter progression or isolation of intestinal segments. These allow for multiple controlled sampling and compound delivery options in different intestinal regions. Intestinal catheters were often used for delivery (23 studies), sampling (10 studies), or both (27 studies). Sampling speed decreased with increasing distance from the sampling syringe to the specific intestinal segment (i.e., speed highest in duodenum, lowest in ileum/colon). No serious adverse events were reported in the literature, and a dropout rate of around 10% was found for these types of studies. This review is highly relevant for researchers who are active in various research areas and want to expand their research with the use of intestinal catheters in humans in vivo.
Collapse
Affiliation(s)
- Mara PH van Trijp
- Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands
| | - Ellen Wilms
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Melany Ríos-Morales
- Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Ad Am Masclee
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Robert Jan Brummer
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Ben Jm Witteman
- Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands,Hospital Gelderse Vallei, Department of Gastroenterology and Hepatology, Ede, The Netherlands
| | - Freddy J Troost
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands,Food Innovation and Health, Centre for Healthy Eating and Food Innovation, Maastricht University, Maastricht, The Netherlands
| | | |
Collapse
|
|
21
|
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.
Collapse
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
| |
Collapse
|
|
22
|
Iakupova AA, Abdulkhakov SR, Safin AG, Alieva IM, Oslopova JV, Abdulkhakov RA. [Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. TERAPEVT ARKH 2021; 93:215-221. [PMID: 36286640 DOI: 10.26442/00403660.2021.02.200615] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 04/06/2021] [Indexed: 12/12/2022]
Abstract
Fecal microbiota transplantation is a treatment method based on the introduction of donated fecal material to the recipient in order to restore the damaged composition of the intestinal microbiota. This review summarizes existing data on indications for fecal microbiota transplantation, recommendations for donor selection, processing and storage of donor biomaterial.
Collapse
Affiliation(s)
| | - S R Abdulkhakov
- Kazan (Volga Region) Federal University
- Kazan State Medical University
| | - A G Safin
- Kazan (Volga Region) Federal University
| | | | | | | |
Collapse
|
|
23
|
Marcella C, Cui B, Kelly CR, Ianiro G, Cammarota G, Zhang F. Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. Aliment Pharmacol Ther 2021; 53:33-42. [PMID: 33159374 DOI: 10.1111/apt.16148] [Citation(s) in RCA: 123] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 08/24/2020] [Accepted: 10/20/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) is an effective treatment in C. difficile infection (CDI) and is currently being investigated in other diseases. There is concern around the safety of FMT and that side effects or complications may be under-reported in the medical literature. AIM To evaluate the safety of FMT by summarising the overall reported Adverse Events (AEs) over a 20-year period METHODS: We searched EMBASE, MEDLINE, and Cochrane Library databases, and CNKI and Wanfang Data from January 2000 to April 2020. All original studies reporting FMT-related AEs were considered for inclusion. FMT-related AEs were further classified as delivery-related or microbiota-related. RESULTS Based on the inclusion criteria, 129 studies, which included 4241 patients (5688 FMT courses), were finally eligible. The most common indication for FMT was CDI. Overall, FMT-related AEs were observed in 19% of FMT procedures. The most frequently reported FMT-related AEs were diarrhoea (10%) and abdominal discomfort/pain/cramping (7%). FMT-related serious adverse events (SAEs), including infections and deaths, have been reported in 1.4% of patients who underwent FMT (0.99% microbiota-related SAEs). Four of five FMT-related deaths were reported in patients receiving FMT via the upper gastrointestinal route. Importantly, all reported FMT-related SAEs were in patients with mucosal barrier injury. CONCLUSION Most FMT-related AEs were mild or moderate and self-limiting. Although FMT appears to be highly safe, its methodology should be improved to reduce both delivery-related AEs and, microbiota-related AEs.
Collapse
Affiliation(s)
- Cicilia Marcella
- Medical Center of Digestive Disease, 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 of Digestive Disease, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Colleen R Kelly
- Division of Gastroenterology, Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Gianluca Ianiro
- Digestive Diseases Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Digestive Diseases Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Faming Zhang
- Medical Center of Digestive Disease, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
24
|
Guochen W, Feihong S. Video analysis method of basketball training assistant based on deep learning theory during COVID-19 spread. JOURNAL OF INTELLIGENT & FUZZY SYSTEMS 2020. [DOI: 10.3233/jifs-189271] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
During covid-19, basketball training was stopped. Instead, the basketball video analysis is used. In this paper, literature, theoretical analysis, numerical simulation, experimental research and other research methods are used. The ant colony algorithm model of deep learning optimization for basketball technical and tactical decision-making is established to solve the optimization problem of actual technical and tactical decision-making. In this paper, video image correlation algorithm is used. In the video of players’ free throw basket, there are many independent frames. The real frame set of free throw basket includes the whole process of jumping, arm lifting, squatting and stretching. The shooting frame set and shooting information of the ball are obtained. In this paper, a shot frame detection algorithm is proposed by analyzing multiple samples of multi shot video. The mathematical model of the shooting frame is established, which can locate the shooting frame quickly and accurately and determine the penalty frame set. Further obtain the basketball release status information for preparation. The reliability and robustness of the algorithm are verified by experiments on several samples. It provides a new method for basketball training during covid-19.
Collapse
Affiliation(s)
- Wan Guochen
- Ministry of Basic Science, Jilin University of Architecture and Technology, Jilin Changchun, Jilin, China
| | - Shan Feihong
- Ministry of Basic Science, Jilin University of Architecture and Technology, Jilin Changchun, Jilin, China
| |
Collapse
|
|
25
|
Guo W, Ren K, Ning R, Li C, Zhang H, Li D, Xu L, Sun F, Dai M. Fecal microbiota transplantation provides new insight into wildlife conservation. Glob Ecol Conserv 2020. [DOI: 10.1016/j.gecco.2020.e01234] [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
|
|
26
|
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
|
|
27
|
Zhong M, Sun Y, Wang HG, Marcella C, Cui BT, Miao YL, Zhang FM. Awareness and attitude of fecal microbiota transplantation through transendoscopic enteral tubing among inflammatory bowel disease patients. World J Clin Cases 2020; 8:3786-3796. [PMID: 32953854 PMCID: PMC7479546 DOI: 10.12998/wjcc.v8.i17.3786] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/28/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Transendoscopic enteral tubing (TET) has been used in China as a novel delivery route for fecal microbiota transplantation (FMT) into the whole colon with a high degree of patient satisfaction among adults. AIM To explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease (IBD). METHODS An anonymous questionnaire, evaluating their awareness and attitudes toward FMT and TET was distributed among IBD patients in two provinces of Eastern and Southwestern China. Question formats included single-choice questions, multiple-choice questions and sorting questions. Patients who had not undergone FMT were mainly investigated for their cognition and acceptance of FMT and TET. Patients who had experience of FMT, the way they underwent FMT and acceptance of TET were the main interest. Then all the patients were asked whether they would recommend FMT and TET. This study also analyzed the preference of FMT delivery in IBD patients and the patient-related factors associated with it. RESULTS A total of 620 eligible questionnaires were included in the analysis. The survey showed that 44.6% (228/511) of patients did not know that FMT is a therapeutic option in IBD, and 80.6% (412/511) of them did not know the concept of TET. More than half (63.2%, 323/511) of the participants stated that they would agree to undergo FMT through TET. Of the patients who underwent FMT via TET [62.4% (68/109)], the majority [95.6% (65/68)] of them were satisfied with TET. Patients who had undergone FMT and TET were more likely to recommend FMT than patients who had not (94.5% vs 86.3%, P = 0.018 and 98.5% vs 87.8%, P = 0.017). Patients' choice for the delivery way of FMT would be affected by the type of disease and whether the patient had the experience of FMT. When compared to patients without experience of FMT, Crohn's disease and ulcerative colitis patients who had experience of FMT preferred mid-gut TET (P < 0.001) and colonic TET (P < 0.001), respectively. CONCLUSION Patients' experience of FMT through TET lead them to maintain a positive attitude towards FMT. The present findings highlighted the significance of patient education on FMT and TET.
Collapse
Affiliation(s)
- Min Zhong
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Yang Sun
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming 650032, Yunnan, China
| | - Hong-Gang Wang
- Medical Center for Digestive Diseases, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian 223300, Jiangsu Province, China
| | - Cicilia Marcella
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Bo-Ta Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| | - Ying-Lei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming 650032, Yunnan, China
| | - Fa-Ming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
| |
Collapse
|
|
28
|
The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study. Biomedicines 2020; 8:biomedicines8080268. [PMID: 32756350 PMCID: PMC7459721 DOI: 10.3390/biomedicines8080268] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 07/27/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove–Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients’ microbiota and resulted in the remission of patients with active UC.
Collapse
|
|
29
|
Li Q, Ding X, Liu K, Marcella C, Liu X, Zhang T, Liu Y, Li P, Xiang L, Cui B, Wang J, Bai J, Zhang F. Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes. Clin Transl Gastroenterol 2020; 11:e00224. [PMID: 32955197 PMCID: PMC7431231 DOI: 10.14309/ctg.0000000000000224] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 07/09/2020] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION The previous researches aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) in a short-term observation. The present study aimed to explore the optimum timing of FMT for maintaining the long-term clinical benefits and to target the gut microbiota that may help to predict the long-term success or failure of FMT in UC. METHODS Two hundred two patients with UC were recruited from November 2012 to September 2018. The primary endpoint of this study was the maintaining time of the first and second courses of FMT. Relapse was defined as partial Mayo score ≥2 after achieving clinical remission and an increase of partial Mayo score ≥1 after achieving clinical response. The stool samples were analyzed by 16S rRNA gene sequencing. RESULTS The median maintaining time of the efficacy was 120 days (IQR, 45-180) and 182.5 days (IQR, 105-311.25) from the first course and second course of FMT, respectively. No FMT-related serious adverse events were observed. The differences of the relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission (P < 0.05). DISCUSSION This study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits. The short-term alterations of microbiota after FMT may be conducive to predicting the long-term efficacy of FMT in UC (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/CTG/A363).
Collapse
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
| | - Kangjian 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
| | - Xiaolin Liu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
| | - Ting Zhang
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yafei Liu
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Pan Li
- 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
| | - Liyuan Xiang
- 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
| | - Jun Wang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Jianling Bai
- Department of Biostatistics, School of Public Health, 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
- National Clinical Research Center for Digestive Diseases, Xi'an, China
| |
Collapse
|
|
30
|
Zhang T, Long C, Cui B, Buch H, Wen Q, Li Q, Ding X, Ji G, Zhang F. Colonic transendoscopic tube-delivered enteral therapy (with video): a prospective study. BMC Gastroenterol 2020; 20:135. [PMID: 32375675 PMCID: PMC7203978 DOI: 10.1186/s12876-020-01285-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 04/27/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Colonic transendoscopic enteral tubing (TET) refers to colonic transendoscopic tube-delivered enteral therapy. Colonic TET has been successfully used for frequent colonic administration of drugs or multiple fecal microbiota transplantations (FMTs). This prospective observational study aimed to evaluate possible factors affecting methodology, feasibility and safety of colonic TET. METHODS Patients who underwent colonic TET at our center from October 2014 to November 2018 were included. The feasibility, efficacy, and safety of TET were evaluated. RESULTS In total, 224 patients were analyzed. The success rate of TET was 100%. The median retention time of TET tube within the colonic lumen was 8.5 (IQR 7-11) days in 158 patients with tube falling out spontaneously, and the maximum retention time was up to 28 days. These patients were divided into the short-retention group (≤ 8.5 days) and the long-retention group (> 8.5 days). Univariate and multivariate analysis demonstrated that the type of endoscopic clip (p = 0.001) was an independent factor for the retention time. The larger clips as well as a greater number of clips significantly affected the retention time (p = 0.013). No severe adverse event was observed during and after TET. CONCLUSIONS Colonic TET is a feasible, practical, and safe colon-targeted drug delivery technique with a high degree of patients' satisfaction. Two to four large endoscopic clips are recommended to maintain stability of the TET tube within the colon for over 7 days.
Collapse
Affiliation(s)
- Ting Zhang
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Chuyan Long
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Bota Cui
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Heena Buch
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Quan Wen
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Qianqian Li
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Xiao Ding
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Guozhong Ji
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China.
| |
Collapse
|
|
31
|
Xiang L, Ding X, Li Q, Wu X, Dai M, Long C, He Z, Cui B, Zhang F. Efficacy of faecal microbiota transplantation in Crohn's disease: a new target treatment? Microb Biotechnol 2020; 13:760-769. [PMID: 31958884 PMCID: PMC7111085 DOI: 10.1111/1751-7915.13536] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 12/26/2019] [Accepted: 12/28/2019] [Indexed: 12/11/2022] Open
Abstract
The efficacy of faecal microbiota transplantation (FMT) in Crohn's disease (CD) remains unclear due to lack of data. This study aimed to assess the value of FMT in treating CD-related clinical targets. The use of FMT for CD as a registered trial (NCT01793831) was performed between October 2012 and December 2017. Seven therapeutic targets included abdominal pain, diarrhoea, hematochezia, fever, steroid-dependence, enterocutaneous fistula and active perianal fistula. Each target was recorded as 1 (yes) or 0 (no) during the long-term follow-up for each patient. The primary outcome was the rate of improvement in each therapeutic target. Overall, 174 patients completed the follow-up. The median follow-up duration was 43 (interquartile range, 28-59) months. The median score of the total targets was 2 (range, 1-4) before FMT, and it decreased significantly at 1, 3, 6, 12, 24 and 36 months after FMT (P < 0.001 respectively). At 1 month after FMT, 72.7% (101/139), 61.6% (90/146), 76% (19/25) and 70.6% (12/17) of patients achieved improvement in abdominal pain, diarrhoea, hematochezia and fever respectively. Furthermore, 50% (10/20) of steroid-dependent patients achieved steroid-free remission after FMT. The present findings indicate that it is important to understand the efficacy of FMT in CD as a targeted therapy, especially for abdominal pain, hematochezia, fever and diarrhoea.
Collapse
Affiliation(s)
- Liyuan Xiang
- Medical Center for Digestive Diseasesthe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing211100China
| | - Xiao Ding
- Medical Center for Digestive Diseasesthe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing211100China
| | - Qianqian Li
- Medical Center for Digestive Diseasesthe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing211100China
| | - Xia Wu
- Medical Center for Digestive Diseasesthe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing211100China
| | - Min Dai
- Medical Center for Digestive Diseasesthe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing211100China
| | - Chuyan Long
- Medical Center for Digestive Diseasesthe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing211100China
| | - Zhi He
- Medical Center for Digestive Diseasesthe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing211100China
| | - Bota Cui
- Medical Center for Digestive Diseasesthe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing211100China
| | - Faming Zhang
- Medical Center for Digestive Diseasesthe Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China
- Key Lab of Holistic Integrative EnterologyNanjing Medical UniversityNanjing211100China
- Division of MicrobiotherapySir Run Run Shaw HospitalNanjing Medical UniversityNanjing211166China
- National Clinical Research Center for Digestive DiseasesXi'an710032China
| |
Collapse
|
|
32
|
Chen HT, Huang HL, Xu HM, Luo QL, He J, Li YQ, Zhou YL, Nie YQ, Zhou YJ. Fecal microbiota transplantation ameliorates active ulcerative colitis. Exp Ther Med 2020; 19:2650-2660. [PMID: 32256746 PMCID: PMC7086197 DOI: 10.3892/etm.2020.8512] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 01/03/2020] [Indexed: 12/11/2022] Open
Abstract
Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.
Collapse
Affiliation(s)
- Hui-Ting Chen
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Hong-Li Huang
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Hao-Ming Xu
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Qing-Ling Luo
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Jie He
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yong-Qiang Li
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - You-Lian Zhou
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yu-Qiang Nie
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yong-Jian Zhou
- Department of Gastroenterology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| |
Collapse
|
|
33
|
Yang Z, Bu C, Yuan W, Shen Z, Quan Y, Wu S, Zhu C, Wang X. Fecal Microbiota Transplant via Endoscopic Delivering Through Small Intestine and Colon: No Difference for Crohn's Disease. Dig Dis Sci 2020; 65:150-157. [PMID: 31367877 DOI: 10.1007/s10620-019-05751-y] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 07/19/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Crohn's disease (CD) is a chronic inflammatory bowel disorder associated with intestinal dysbiosis. This study aimed to determine the efficacy and safety of different methods of fecal microbiota transplantation (FMT), a potential therapy for CD. METHODS Patients with CD were randomized to receive FMT by gastroscopy or colonoscopy; a second transplantation was performed 1 week later. Patients were assessed by clinical evaluation and serum testing (at weeks 1, 2, 4, 6, and 8) and endoscopy (8 weeks after transplantation). Fecal DNA was extracted and analyzed using the Illuminal sequencing platform. RESULTS Of the 27 patients included in the study, clinical remission was achieved in 18 (66.7%); no significant difference was seen between the two methods. 76.9% of gastroscopy group patients and 64.3% of colonoscopy group patients experienced mild adverse events during or shortly after treatment. Microbiota diversity analyses showed that, in comparison with the donors, patients had lower operational taxonomic units (OTU; 117 vs. 258, p < 0.05) and Shannon diversity index (2.05 vs. 3.46, p < 0.05). The CD patients showed a significant increase in OTU and Shannon diversity index 2 weeks after FMT. In comparison with the donors, CD patients had lower levels of Bacteroides, Eubacterium, faecalibacterium, and Roseburia, and higher levels of Clostridium, Cronobacter, Fusobacterium, and Streptococcus. CONCLUSIONS FMT was seen to be safe and effective in this cohort of patients with CD. No significant differences in clinical remission rate and adverse events were seen between the gastroscopy and colonoscopy groups. FMT was seen to increase the species richness in CD patients.
Collapse
Affiliation(s)
- Zhenyu Yang
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Chibin Bu
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Wei Yuan
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Zhaohua Shen
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Yongsheng Quan
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Shuai Wu
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Changxin Zhu
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Xiaoyan Wang
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China.
| |
Collapse
|
|
34
|
Wu X, Dai M, Buch H, Bai J, Long W, Long C, Tang X, Tu H, Zhang R, Zhu C, Yang S, Cui B, Ji G, Zhang F. The recognition and attitudes of postgraduate medical students toward fecal microbiota transplantation: a questionnaire study. Therap Adv Gastroenterol 2019; 12:1756284819869144. [PMID: 31516555 PMCID: PMC6724572 DOI: 10.1177/1756284819869144] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 06/28/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Physicians and medical students in the world do not have high awareness of fecal microbiota transplantation (FMT). This study aimed to explore the recognition and attitude of postgraduate medical students towards FMT and to create awareness for it. METHODS A self-administered questionnaire was distributed to first-year Chinese postgraduate medical students across six medical universities. Basic descriptive statistical analyses were performed. RESULTS A total of 1828 eligible questionnaires were included into analysis. 47.76% of students did not know FMT prior to this survey. Respondents with a high-level recognition of FMT were more willing to donate feces or receive FMT therapy than those with a low-level recognition (80.26% vs. 69.62%, p = 0.000 and 56.80% vs. 41.45%, p = 0.000). The respondents from a leading institution of FMT in China showed better awareness compared with others, and 42.26% of them knew about FMT from medical lectures. The main reasons for respondents not supporting FMT were: limited reported clinical evidence (67.94%), raw technology (42.56%), and lack of analysis of patient willingness or cost-effectiveness (36.71%). However, the life-saving value (84.41%), the automatic purification system (38.68%), low expenses (36.00%), and convenient delivering ways (35.67%) were the major considerations for supporting FMT. CONCLUSIONS This study revealed the low recognition level of postgraduate medical students about FMT. Therefore, medical education should not neglect the knowledge of FMT. Studies of FMT and standardized FMT should be carried out to promote its development.
Collapse
Affiliation(s)
- Xia Wu
- 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
| | - Heena Buch
- 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
| | - Wenwu Long
- Jiangxi Medical College of Nanchang University, Nanchang, China
| | - Chuyan Long
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xianyan Tang
- Department of Epidemiology and Biostatistics, School of Public Health, Guangxi Medical University, Guangxi Zhuang Autonomous Region, China
| | - Hua Tu
- Department of Gastroenterology, Hubei Provincial Hospital Traditional Chinese Medicine, Wuhan, China
| | - Renjie Zhang
- Hubei University of Chinese Medicine, Wuhan, China
| | - Cairong Zhu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Shaoqi Yang
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Guozhong Ji
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, China
| |
Collapse
|
|
35
|
Jagessar SAR, Long C, Cui B, Zhang F. Improvement of Good's syndrome by fecal microbiota transplantation: the first case report. J Int Med Res 2019; 47:3408-3415. [PMID: 31218940 PMCID: PMC6683929 DOI: 10.1177/0300060519854913] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 05/14/2019] [Indexed: 12/21/2022] Open
Abstract
Good’s syndrome (GS) is a rare primary immunodeficiency defined as hypogammaglobulinemia associated with the presence of a thymoma. Patients with GS usually have increased susceptibility to a wide range of infections, and clinical treatment is a challenge for physicians. Fecal microbiota transplantation (FMT), which is a safe strategy for reconstruction of the gut microbiota, has a positive influence on the treatment of refractory infections such as those in patients with GS. We herein report a case involving a 73-year-old woman who had been previously diagnosed with a thymoma. After thymectomy, she complained of respiratory and gastrointestinal symptoms. Her laboratory analysis strongly suggested GS. Infusion of immunoglobulin and albumin was the only treatment of choice until FMT was considered as an alternative therapy. The patient’s manifestations were subsequently relieved, and several FMTs were required to maintain clinical remission. Management of GS remains quite challenging to physicians because of the intricate organ involvement and limited and costly existing therapies. FMT is usually well tolerated by patients, and its cost-effectiveness and safety profile allow it to be considered as an alternative therapy for GS.
Collapse
Affiliation(s)
- Sabreen Abdul Rahman Jagessar
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Jiang Jia Yuan, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Jiang Jia Yuan, Nanjing, China
| | - Chuyan Long
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Jiang Jia Yuan, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Jiang Jia Yuan, Nanjing, China
| | - Bota Cui
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Jiang Jia Yuan, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Jiang Jia Yuan, Nanjing, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Jiang Jia Yuan, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Jiang Jia Yuan, Nanjing, China
- National Clinical Research Center for Digestive Diseases, Xi'an, China
| |
Collapse
|
|
36
|
Microbiota transplantation: Targeting cancer treatment. Cancer Lett 2019; 452:144-151. [DOI: 10.1016/j.canlet.2019.03.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 02/26/2019] [Accepted: 03/08/2019] [Indexed: 02/07/2023]
|
|
37
|
Zhang F, Zhang T, Zhu H, Borody TJ. Evolution of fecal microbiota transplantation in methodology and ethical issues. Curr Opin Pharmacol 2019; 49:11-16. [PMID: 31059962 DOI: 10.1016/j.coph.2019.04.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 04/01/2019] [Accepted: 04/01/2019] [Indexed: 02/07/2023]
Abstract
Fecal microbiota transplantation (FMT), the core therapy for remodeling the gut microbiota with a long medical history, has gained great attention worldwide in recent years. Increasing studies have explored its indications, methodology, efficacy, safety, and ethics. Purified forms of FMT, using an automated method for the purification of fecal microbiota from stool, has become a reality. Colonic transendoscopic enteral tubing makes frequent FMT delivery into the whole colon feasible. This review focuses on the recent progress in laboratory preparation, updated clinical strategies, novel delivery methods, and ethical issues surrounding FMT in clinical studies.
Collapse
Affiliation(s)
- Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China.
| | - Ting Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China
| | - Heming Zhu
- Department of Acupuncture and Oriental Medicine, Maryland University of Integrative Health, Laurel, MD, United States
| | - Thomas J Borody
- Centre for Digestive Diseases, Five Dock, NSW 2046, Australia
| |
Collapse
|
|
38
|
Sarin SK, Pande A, Schnabl B. Microbiome as a therapeutic target in alcohol-related liver disease. J Hepatol 2019; 70:260-272. [PMID: 30658727 DOI: 10.1016/j.jhep.2018.10.019] [Citation(s) in RCA: 183] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 10/23/2018] [Indexed: 02/08/2023]
Abstract
Alcohol-related liver disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced liver disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related liver disease. A major mechanism by which gut microbiota influence the development of alcohol-related liver disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related liver disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related liver disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related liver disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related liver disease. These approaches are likely to add to the therapeutic options for alcohol-related liver disease independently or in conjunction with steroids.
Collapse
Affiliation(s)
- Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - Apurva Pande
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA.
| |
Collapse
|
|
39
|
Dai M, Zhang T, Li Q, Cui B, Xiang L, Ding X, Rong R, Bai J, Zhu J, Zhang F. The bowel preparation for magnetic resonance enterography in patients with Crohn's disease: study protocol for a randomized controlled trial. Trials 2019; 20:1. [PMID: 30606236 PMCID: PMC6318891 DOI: 10.1186/s13063-018-3101-x] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 12/04/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Adequate bowel preparation is required for magnetic resonance enterography (MRE), which can be achieved by administering contrast solution after mid-gut tubing or taking contrast solution orally. We present the design of randomized controlled trial (RCT) to compare the efficacy and compliance of bowel preparation between mid-gut tubing and oral administering for MRE in patients with Crohn's disease (CD). METHODS/DESIGN This is an open-label, multicenter RCT. Ninety-six patients with CD in need of MRE examination and mid-gut tubing (prepared for fecal microbiota transplantation and/or enteral nutrition), aged ≥ 14 years, will be included. Patients will be randomized 1:1 into either bowel preparation by oral administering (oral group) or bowel preparation through mid-gut transendoscopic enteral tubing (TET) (tubing group). The primary outcome measures are: (1) degree of discomfort before/during/after bowel preparation for MRE using a visual 5-grade scale (1 = few, 5 = very severe); and (2) grade of bowel distention evaluated by a 5-grade scale (1 = 0-20% segmental distention, 2 = 20-40% distention, 3 = 40-60% distention, 4 = 60-80% distention, 5 = 80-100% distention). The secondary outcome measure is the accuracy of lesion detection through MRE confirmed by colonoscopy which is evaluated by a 5-point scale. DISCUSSION The outcome of this study is expected to provide a novel effective clinical protocol of bowel preparation for MRE in patients with CD. We hope to highlight the concept of physician-patient satisfaction based on different methods of bowel preparation for MRE. TRIAL REGISTRATION ClinicalTrials.gov, NCT03541733 . Registered on 30 May 2018.
Collapse
Affiliation(s)
- Min Dai
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011 China
| | - Ting Zhang
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011 China
| | - Qianqian Li
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011 China
| | - Bota Cui
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011 China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011 China
| | - Liyuan Xiang
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011 China
| | - Xiao Ding
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011 China
| | - Rong Rong
- Department of Gastroenterology, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000 China
| | - Jianling Bai
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211100 China
| | - Jianguo Zhu
- Department of Radiology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011 China
| | - Faming Zhang
- Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011 China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011 China
- Division of Gastroenterology, Sir Run Run Shaw Hospital, Nanjing Medical University, Nanjing, 211166 China
| |
Collapse
|
|
40
|
Li P, Zhang T, Xiao Y, Tian L, Cui B, Ji G, Liu YY, Zhang F. Timing for the second fecal microbiota transplantation to maintain the long-term benefit from the first treatment for Crohn's disease. Appl Microbiol Biotechnol 2019; 103:349-360. [PMID: 30357440 PMCID: PMC6311185 DOI: 10.1007/s00253-018-9447-x] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 10/01/2018] [Accepted: 10/03/2018] [Indexed: 12/14/2022]
Abstract
Increasing evidence has shown that fecal microbiota transplantation (FMT) could be a promising treatment option for Crohn's disease (CD). However, the frequency of FMT for CD treatment remains unclear. This study aimed to evaluate the optimal timing for administering the second course of FMT to maintain the long-term clinical effects from the first FMT for patients with CD. Sixty-nine patients with active CD who underwent FMT twice and benefited from the first FMT were enrolled in this study. Clinical response, stool microbiota, and urine metabolome of patients were assessed during the follow-up. The median time of maintaining clinical response to the first FMT in total 69 patients was 125 days (IQR, 82.5-225.5). The time of maintaining clinical response to the second FMT in 56 of 69 patients was 176.5 days (IQR, 98.5-280). The fecal microbiota composition of each patient post the first FMT was closer to that of his/her donor. Compared to that of the baseline, patients prior to the second course of FMT showed significant differences in urinary metabolic profiles characterized by increased indoxyl sulfate, 4-hydroxyphenylacetate, creatinine, dimethylamine, glycylproline, hippurate, and trimethylamine oxide (TMAO). This study demonstrated that patients with CD could be administered the second course of FMT less than 4 months after the first FMT for maintaining the clinical benefits from the first FMT. This was supported by the host-microbial metabolism changes in patients with active CD. Trial registration: ClinicalTrials.gov , NCT01793831. Registered 18 February 2013. https://clinicaltrials.gov/ct2/show/NCT01793831?term=NCT01793831&rank=1.
Collapse
Affiliation(s)
- Pan Li
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Ting Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Yandong Xiao
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
- Science and Technology on Information Systems Engineering Laboratory, National University of Defense Technology, Changsha, 410073, China
| | - Liang Tian
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
- Department of Physics, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Guozhong Ji
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China
| | - Yang-Yu Liu
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
- Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
| | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 210011, China.
| |
Collapse
|
|
41
|
Zhang F, Cui B, He X, Nie Y, Wu K, Fan D. Microbiota transplantation: concept, methodology and strategy for its modernization. Protein Cell 2018; 9:462-473. [PMID: 29691757 DOI: 10.1007/s13238-018-0541] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 04/08/2018] [Indexed: 05/25/2023] Open
Abstract
Fecal microbiota transplantation (FMT) has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut-brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step-up FMT strategy based on literature and state experts' perspectives.
Collapse
Affiliation(s)
- Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 211166, China.
- Division of Microbiotherapy, Sir Run Run Shaw Hospital, Nanjing Medical University, Nanjing, 211166, China.
| | - Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 211166, China
| | - Xingxiang He
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China
| | - Yuqiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China
| | - Kaichun Wu
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
- National Clinical Research Center for Digestive Diseases, Xi'an, 710032, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
- National Clinical Research Center for Digestive Diseases, Xi'an, 710032, China
| |
Collapse
|
|
42
|
Zhang F, Cui B, He X, Nie Y, Wu K, Fan D. Microbiota transplantation: concept, methodology and strategy for its modernization. Protein Cell 2018; 9:462-473. [PMID: 29691757 PMCID: PMC5960466 DOI: 10.1007/s13238-018-0541-8] [Citation(s) in RCA: 168] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 04/08/2018] [Indexed: 02/06/2023] Open
Abstract
Fecal microbiota transplantation (FMT) has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut-brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step-up FMT strategy based on literature and state experts' perspectives.
Collapse
Affiliation(s)
- Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 211166, China.
- Division of Microbiotherapy, Sir Run Run Shaw Hospital, Nanjing Medical University, Nanjing, 211166, China.
| | - Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, 211166, China
| | - Xingxiang He
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China
| | - Yuqiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China
| | - Kaichun Wu
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
- National Clinical Research Center for Digestive Diseases, Xi'an, 710032, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
- National Clinical Research Center for Digestive Diseases, Xi'an, 710032, China
| |
Collapse
|