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Jin Y, Wu J, Huang K, Liang Z. Heat-Killed Saccharomyces boulardii Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Restoring the Intestinal Barrier, Reducing Inflammation, and Modulating the Gut Microbiota. Nutrients 2024; 16:702. [PMID: 38474831 DOI: 10.3390/nu16050702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 03/14/2024] Open
Abstract
Ulcerative colitis (UC) is a global intestinal disease, and conventional therapeutic drugs often fail to meet the needs of patients. There is an urgent need to find efficient and affordable novel biological therapies. Saccharomyces boulardii has been widely used in food and pharmaceutical research due to its anti-inflammatory properties and gut health benefits. However, there is still a relatively limited comparison and evaluation of different forms of S. boulardii treatment for UC. This study aimed to compare the therapeutic effects of S. boulardii, heat-killed S. boulardii, and S. boulardii β-glucan on UC, to explore the potential of heat-killed S. boulardii as a new biological therapy. The results demonstrate that all three treatments were able to restore body weight, reduce the disease activity index (DAI), inhibit splenomegaly, shorten colon length, and alleviate histopathological damage to colonic epithelial tissues in DSS-induced colitis mice. The oral administration of S. boulardii, heat-killed S. boulardii, and S. boulardii β-glucan also increased the levels of tight junction proteins (Occludin and ZO-1), decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the serum, and suppressed the expressions of TNF-α, IL-1β, and IL-6 mRNA in the colon. In particular, in terms of gut microbiota, S. boulardii, heat-killed S. boulardii, and S. boulardii β-glucan exhibited varying degrees of modulation on DSS-induced dysbiosis. Among them, heat-killed S. boulardii maximally restored the composition, structure, and functionality of the intestinal microbiota to normal levels. In conclusion, heat-killed S. boulardii showed greater advantages over S. boulardii and S. boulardii β-glucan in the treatment of intestinal diseases, and it holds promise as an effective novel biological therapy for UC. This study is of great importance in improving the quality of life for UC patients and reducing the burden of the disease.
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Affiliation(s)
- Yuxin Jin
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Jingwei Wu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Kunlun Huang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Zhihong Liang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
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Crepaldi M, Maniero D, Massano A, Pavanato M, Barberio B, Savarino EV, Zingone F. Azathioprine monotherapy withdrawal in inflammatory bowel diseases: A retrospective mono-centric study. World J Gastroenterol 2023; 29:4334-4343. [PMID: 37545640 PMCID: PMC10401657 DOI: 10.3748/wjg.v29.i27.4334] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 06/04/2023] [Accepted: 07/03/2023] [Indexed: 07/13/2023] Open
Abstract
BACKGROUND There is no consensus on the recommended duration of and optimal time to stop azathioprine (AZA) therapy in inflammatory bowel disease (IBD). Determining the optimal duration and cessation time can help to balance the risks of long-term intake with the possibility of relapse after cessation.
AIM To describe the events following AZA cessation.
METHODS Retrospective analysis was performed to examine data from adult patients affected by IBD who were followed at the University of Padua and had started but then discontinued AZA between 1995 and 2022. Data on therapy duration, reasons for cessation, and type of relapse after cessation were collected. Cox regression models were used to estimate the risk of relapse in different subgroups.
RESULTS A total of 133 ulcerative colitis patients and 141 Crohn’s disease patients were included. Therapy with AZA was stopped in the 1st year in approximately 34% of patients but was continued for more than 10 years in approximately 10% of cases. AZA discontinuation was due to primary failure or disease relapse in 30% of patients and due to disease remission in 25.2% of patients. Most of the remaining cases stopped AZA therapy due to side effects (primarily clinical intolerance, cytopenia, and pancreatic disease). Patients who stopped AZA for clinical remission had an 83% lower risk of relapse during the observation time than other groups, with a relapse-free rate of 89% after 1 year and 79% after 2 years.
CONCLUSION AZA administration is effective and safe, but it requires careful monitoring for potential minor and major side effects. Only 10% of patients who achieved remission with AZA needed a new treatment within 1 year of drug interruption.
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Affiliation(s)
- Martina Crepaldi
- Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua 35128, Italy
| | - Daria Maniero
- Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua 35128, Italy
| | - Alessandro Massano
- Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua 35128, Italy
| | - Margherita Pavanato
- Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua 35128, Italy
| | - Brigida Barberio
- Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua 35128, Italy
| | | | - Fabiana Zingone
- Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua 35128, Italy
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Jorissen C, Verstockt B, Schils N, Sabino J, Ferrante M, Vermeire S. Long-term clinical outcome after thiopurine discontinuation in elderly IBD patients. Scand J Gastroenterol 2021; 56:1323-1327. [PMID: 34399630 DOI: 10.1080/00365521.2021.1965207] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Thiopurines - although used frequently in inflammatory bowel diseases (IBD) - carry a significant safety risk, particularly with prolonged use and/or in elderly patients. Stopping therapy, however, may trigger relapses. We assessed the long-term outcome of elderly IBD patients after discontinuation of thiopurine while in clinical remission. METHODS Electronic medical records from IBD patients >60 years whoever received thiopurine treatment were reviewed. Patients who stopped thiopurine after 60 years of age while in clinical and/or endoscopic remission were included. Long-term outcomes included duration of clinical remission, time to clinical relapse, and development of malignancy. RESULTS In total, 142 patients receiving thiopurines while they were >60 years were identified. Ninety-one patients stopped thiopurines at >60years while in clinical and/or endoscopic remission. After a median follow-up of 66 months, 28 (30.8%) developed a clinical relapse. The median duration of TP therapy in relapses was significantly shorter than in patients who remained in remission (median 45 vs. 103 months, respectively; p = .005). After relapse, 10 patients started a biological (36%) and seven received steroids (25%). Surgery was needed in 36% of patients (10/28). Overall, 26 malignancies developed. CONCLUSION Discontinuation of TP in elderly IBD patients in clinical and/or endoscopic remission results in sustained clinical remission in two-thirds of patients. Patients who flare can mostly be rescued with biologicals although one-third necessitate surgery. A significant proportion of patients developed malignancies under but also after thiopurines discontinuation, indicating that these patients necessitate a continued close follow-up. Decision-making in this vulnerable subgroup of patients remains difficult.
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Affiliation(s)
- C Jorissen
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - B Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Translational Research in Gastrointestinal Disorders - IBD, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - N Schils
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - J Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Translational Research in Gastrointestinal Disorders - IBD, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - M Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Translational Research in Gastrointestinal Disorders - IBD, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - S Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Translational Research in Gastrointestinal Disorders - IBD, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
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Chen YM, Deng JM, Wen Y, Chen B, Hou JT, Peng B, Zhang SJ, Mi H, Jiang QL, Wu XL, Liu FB, Chen XL. Modified Sijunzi decoction in the treatment of ulcerative colitis in the remission phase: study protocol for a series of N-of-1 double-blind, randomised controlled trials. Trials 2020; 21:396. [PMID: 32398112 PMCID: PMC7218572 DOI: 10.1186/s13063-020-04315-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 04/10/2020] [Indexed: 12/12/2022] Open
Abstract
Background Modified Sijunzi decoction (SJZD) has been used to treat ulcerative colitis (UC) in remission. However, more rigorous clinical trials are necessary to evaluate its effectiveness. Therefore, a series of single-case randomised controlled trials (N-of-1 trials) is proposed to compare the efficacy of modified SJZD with mesalazine for treating UC in remission. Methods This is a single-site, hospital-based, double-blind N-of-1 trial for 10 single subjects. Three cycles of N-of-1 trials are planned. There are two treatment periods in each cycle. Modified SJZD combined with mesalazine placebo or mesalazine combined with modified SJZD placebo will be randomised during each 8-week treatment period. There is no washout period in the study. Subjects will be selected by the researcher strictly in accordance with the inclusion and exclusion criteria. Discussion Paired t tests and mixed-effect models will be used to analyse the visual analogue scale (VAS) for clinical symptoms and the quality of life questionnaire responses. The findings will be interpreted with caution. We anticipate that the results will show that modified SJZD is effective for patients with UC in remission. Trial registration Chinese Clinical Trial Register, ID: ChiCTR1900024086. Registered on 24 June 2019.
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Affiliation(s)
- Yi-Ming Chen
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jie-Min Deng
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yi Wen
- The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Bin Chen
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiang-Tao Hou
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Bin Peng
- The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shi-Jing Zhang
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hong Mi
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qi-Long Jiang
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xia-Lin Wu
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Feng-Bin Liu
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
| | - Xin-Lin Chen
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
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Zhang B, Gulati A, Alipour O, Shao L. Relapse From Deep Remission After Therapeutic De-escalation in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis 2020; 14:1413-1423. [PMID: 32335670 PMCID: PMC7533897 DOI: 10.1093/ecco-jcc/jjaa087] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS We conducted a systematic review and meta-analysis evaluating the relapse rate after therapeutic de-escalation in inflammatory bowel disease [IBD] patients who achieved deep remission [DR]. METHODS We searched MEDLINE, EMBASE, and major gastroenterology conferences up to July 2019 for studies reporting relapse in adult patients with DR who subsequently underwent therapeutic de-escalation. Eligible studies defined DR as at least a combination of clinical remission and mucosal healing/endoscopic remission. The primary outcome was cumulative 1-year and 2-year relapse rates after therapeutic de-escalation. Secondary outcomes were relapse rates in ulcerative colitis [UC] and Crohn's disease [CD], relapse after anti-tumour necrosis factor-α [anti-TNFα] de-escalation, and the rate of disease response recapture following re-escalation. RESULTS Thirteen studies encompassing 837 patients were identified. The cumulative relapse rate after therapeutic de-escalation was 28.7% within 1 year [12 studies], and 38.4% within 2 years [eight studies]. Relapse rates within 1 year and 2 years were comparable between UC [five studies; 25.4% and 37.4%] and CD [seven studies; 34.1% and 39.9%]. Ten studies reported de-escalation of anti-TNFα, of which 29.8% patients relapsed within 1 year and 41.4% within 2 years. Response recapture following re-escalation [eight studies] was 75.4%. CONCLUSIONS Despite achieving deep remission, therapeutic de-escalation in this patient population is associated with significant relapse risk within 1 year and 2 years. This risk is more pronounced in patients requiring anti-TNFα for management, likely because of more severe disease. Similar rates of relapse were reported among UC and CD within these time periods. These findings suggest that combined clinical and endoscopic remission should not be an impetus to consider therapeutic de-escalation.
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Affiliation(s)
- Bing Zhang
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, CA, USA
| | - Alakh Gulati
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
| | - Omeed Alipour
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
| | - Ling Shao
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
- Corresponding author: Ling Shao, MD PhD, Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of the University of Southern California, 2011 Zonal Avenue, HMR 101, Los Angeles, CA 90033, USA, Tel.: 323-442-0248; fax: 323-442-5425;
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Iborra M, Beltrán B, Fernández-Clotet A, Gutiérrez A, Antolín B, Huguet JM, De Francisco R, Merino O, Carpio D, García-López S, Mesonero F, Navarro P, Ferreiro-Iglesias R, Carbajo AY, Rivero M, Gisbert JP, Piñero-Pérez MC, Monfort D, Bujanda L, García-Sepulcre MF, Martín-Cardona A, Cañete F, Taxonera C, Domènech E, Nos P. Real-world short-term effectiveness of ustekinumab in 305 patients with Crohn's disease: results from the ENEIDA registry. Aliment Pharmacol Ther 2019; 50:278-288. [PMID: 31222872 DOI: 10.1111/apt.15371] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 04/30/2019] [Accepted: 05/22/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (<250 µg/g) in 46% and 54% of the patients at weeks 8 and 14 respectively. CRP returned to normal (<3 mg/L) in the 35% and 41% of the patients at week 8 and 14 respectively. AEs were recorded in 38, and 40 patients were hospitalised. Intolerance to the most recent anti-TNF agent and fewer previous anti-TNF agents were associated with clinical remission at week 14. Endoscopic severity was associated with poor response. CONCLUSION This is the first study to show the real-world effectiveness and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - P Nos
- Valencia, Spain
- Madrid, Spain
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