1
|
Yang Q, Kang Y, Tang W, Li M, Zhao C. Interplay of gut microbiota in Kawasaki disease: role of gut microbiota and potential treatment strategies. Future Microbiol 2025; 20:357-369. [PMID: 40013895 PMCID: PMC11938985 DOI: 10.1080/17460913.2025.2469432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 02/17/2025] [Indexed: 02/28/2025] Open
Abstract
Kawasaki disease (KD) is an acute systemic immune vasculitis with predominant involvement of the medium and small arteries. It mostly affects pediatric patients, representing the most common form of pediatric vasculitis in children less than 5 years old. Numerous diseases, especially those related to the immune system, have established links with the intestinal flora. Recent studies have investigated the intestinal flora changes throughout the management of KD. There was gut microbiota dysbiosis in pediatric KD at the acute phase, particularly the downregulation of short-chain fat acids-producing microbiota and the over-proliferation of opportunistic pathogens. The relationship between the response to therapies in individuals with KD and specific microbiota remains uncertain. Targeted microbial supplements and dietary regulation may serve as potential measures to alleviate KD complications and thus improve prognosis. This review provides an overview of the current understanding of the interplay of the gut microbiota and KD. Furthermore, it discusses the possibility of altering the gut microbiota to reinstate a healthy condition.
Collapse
Affiliation(s)
- Qing Yang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Yaqing Kang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Wei Tang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Meng Li
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Cuifen Zhao
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| |
Collapse
|
2
|
Silva BCD, Azevedo MFCD, Mello MKD, Macedo MRF, Caetano JS, Moraes ACDS, Pessoa FSRDP, Trevisan MADS, Imbrizi M. DIAGNOSIS AND TREATMENT OF MICROSCOPIC COLITIS: POSITION PAPER ON BEHALF OF THE BRAZILIAN FEDERATION OF GASTROENTEROLOGY. ARQUIVOS DE GASTROENTEROLOGIA 2024; 61:e24102. [PMID: 39776129 DOI: 10.1590/s0004-2803.24612024-102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 10/31/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Microscopic colitis (MC) is a chronic inflammatory condition of the colon, primarily characterized by watery diarrhea, with normal or near-normal endoscopic findings. It encompasses two main subtypes: lymphocytic colitis and collagenous colitis. OBJECTIVE This position paper from the Brazilian Federation of Gastroenterology aims to review current evidence on the diagnosis and management of MC in Brazil, emphasizing the need for standardization across the country's healthcare systems. METHODS A comprehensive review of the latest scientific literature, clinical guidelines, and consensus statements was performed, focusing on randomized clinical trials, meta-analyses, and cohort studies. The evidence was analyzed by a panel of gastroenterologists and pathologists specializing in MC. The recommendations were based on the consensus of the group, approved by the majority of the panel members. RESULTS Histological examination with biopsies from multiple segments of the colon remains essential for the accurate diagnosis of MC, as endoscopic findings are often non-specific. Budesonide is the first-line treatment for inducing remission in most patients. However, alternatives such as immunosuppressants and biologics are available for those who are refractory to or intolerant of budesonide. Non-pharmacological interventions, including dietary and lifestyle modifications, can complement medical treatment. The need for long-term follow-up is highlighted due to the high recurrence rates and the impact of MC on the quality of life. CONCLUSION Standardizing the diagnosis and treatment of MC in Brazil is crucial, given the significant regional disparities in healthcare access. This position paper provides evidence-based recommendations to optimize care and improve patient outcomes across diverse clinical settings in Brazil. Further research is needed to address the gaps in understanding the epidemiology and management of MC in underserved regions.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Marcello Imbrizi
- Universidade de Campinas, Departamento de Gastroenterologia, Campinas, SP, Brasil
| |
Collapse
|
3
|
Ding G, Yang X, Li Y, Wang Y, Du Y, Wang M, Ye R, Wang J, Zhang Y, Chen Y, Zhang Y. Gut microbiota regulates gut homeostasis, mucosal immunity and influences immune-related diseases. Mol Cell Biochem 2024:10.1007/s11010-024-05077-y. [PMID: 39060829 DOI: 10.1007/s11010-024-05077-y] [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: 03/25/2024] [Accepted: 07/20/2024] [Indexed: 07/28/2024]
Abstract
The intestinal microbiome constitutes a sophisticated and massive ecosystem pivotal for maintaining gastrointestinal equilibrium and mucosal immunity via diverse pathways. The gut microbiota is continuously reshaped by multiple environmental factors, thereby influencing overall wellbeing or predisposing individuals to disease state. Many observations reveal an altered microbiome composition in individuals with autoimmune conditions, coupled with shifts in metabolic profiles, which has spurred ongoing development of therapeutic interventions targeting the microbiome. This review delineates the microbial consortia of the intestine, their role in sustaining gastrointestinal stability, the association between the microbiome and immune-mediated pathologies, and therapeutic modalities focused on microbiome modulation. We emphasize the entire role of the intestinal microbiome in human health and recommend microbiome modulation as a viable strategy for disease prophylaxis and management. However, the application of gut microbiota modification for the treatment of immune-related diseases, such as fecal microbiota transplantation and probiotics, remain quite challenging. Therefore, more research is needed into the role and mechanisms of these therapeutics.
Collapse
Affiliation(s)
- Guoao Ding
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China
- Department of Life Science, Anhui University, Hefei, 230061, China
| | - Xuezhi Yang
- Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and Immune Medicine, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, 230032, China
| | - Ying Li
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China
| | - Ying Wang
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China
| | - Yujie Du
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China
| | - Meng Wang
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China
| | - Ruxin Ye
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China
| | - Jingjing Wang
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China
| | - Yongkang Zhang
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China
| | - Yajun Chen
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China
| | - Yan Zhang
- School of Biological and Food Engineering, Hefei Normal University, Hefei, 230061, China.
- Department of Life Science, Anhui University, Hefei, 230061, China.
- Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and Immune Medicine, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, 230032, China.
| |
Collapse
|
4
|
Malik A, Goyal H, Adler DG, Javaid S, Malik MI, Singh S, Nadir A, Abegunde AT. Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials. J Clin Gastroenterol 2024:00004836-990000000-00329. [PMID: 39042479 DOI: 10.1097/mcg.0000000000002025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 04/24/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND Microscopic colitis (MC) is an inflammatory bowel disease of autoimmune origin that causes chronic watery diarrhea. Medications, including budesonide, mesalamine, loperamide, cholestyramine, and bismuth subsalicylate, are first-line therapies. Meanwhile, azathioprine, 6-mercaptopurine, and methotrexate are indicated for refractory MC. OBJECTIVE We aim to assess the efficacy and safety of budesonide compared with mesalamine for induction of remission in MC patients. METHODS We searched the Cochrane Library, Scopus, Web of Science, and PubMed for relevant clinical trials comparing either mesalamine or budesonide with a control group. We included the following outcomes: clinical remission (3 or fewer stools/day), daily stool weight, daily stool frequency, number of patients with clinical response <50% in the disease activity, and daily stool consistency. Safety end points included: any adverse event, serious adverse events, any adverse event-related discontinuation, abdominal discomfort, constipation, flatulence, nausea, dizziness, headache, bronchitis, nasopharyngitis, and depression. We conducted a meta-analysis model using the generic inverse variance method and performed a subgroup analysis based on the intervention administered. RESULTS Nineteen randomized clinical trials were included. We found that after 6 weeks of follow-up, budesonide is associated with increased clinical remission rates compared with mesalamine [RR=2.46 (2.27, 2.67), and RR=2.24 (1.95, 2.57), respectively]. However, the test of subgroup difference revealed that the difference is not significant (P=0.25). After 8 weeks of follow-up, budesonide showed significantly higher clinical remission rates than mesalamine RR=2.29 (2.14, 2.45), and RR=1.7 (1.41, 2.05), respectively (P=0.003). Regarding the daily stool weight, patients in the budesonide group showed nonsignificant less stool weight [MD=-351.62 (-534.25, -168.99)] compared with mesalamine [MD=-104.3 (-372.34, 163.74)], P=0.14. However, daily stool frequency was significantly less in the budesonide group compared with mesalamine (P<0.001). Budesonide is associated with a significantly lower incidence of adverse events compared with mesalamine (P=0.002). Analysis of other safety endpoints was not significant between both groups. CONCLUSIONS Budesonide was found to be better than mesalamine in MC patients in terms of clinical remission rate, especially after 8 weeks of follow-up. Budesonide also showed less incidence of adverse events. There is an urgent need for randomized, double-blinded clinical trials to provide direct and reliable evidence.
Collapse
Affiliation(s)
- Adnan Malik
- Division of Gastroenterology, Mountain Vista Medical Center, Mesa, AZ
| | - Hemant Goyal
- Division of Gastroenterology, The Wright Center for Graduate Medical Education, Scranton, PA
| | - Douglas G Adler
- Advanced Therapeutic Endoscopy Centura Health, Porter Adventist Hospital Denver, CO
| | | | - Muhammad Imran Malik
- Department of Hematology specialty, Airedale General Hospital, West Yorkshire, England
| | - Shailendra Singh
- Division of Gastroenterology West Virginia University, Morgantown, WV
| | - Abdul Nadir
- Division of Gastroenterology, Mountain Vista Medical Center, Mesa, AZ
| | - Ayokunle T Abegunde
- Division of Gastroenterology and Nutrition, Loyola University Medical Center, Maywood, IL
| |
Collapse
|
5
|
Kumar A, Hiner G, Brookes MJ, Segal JP. Efficacy and safety of medical therapies in microscopic colitis: a systematic review and network meta-analysis. Therap Adv Gastroenterol 2023; 16:17562848231154319. [PMID: 36860692 PMCID: PMC9969448 DOI: 10.1177/17562848231154319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 01/13/2023] [Indexed: 03/03/2023] Open
Abstract
Background The mainstay of treatment for microscopic colitis (MC) is budesonide. However, the optimal formulation and dosage of budesonide to induce and maintain remission has not yet been clearly demonstrated. Objectives To compare the data for efficacy and safety of treatments to induce and maintain remission for MC. Design We conducted a meta-analysis of randomised controlled trials (RCTs) comparing treatment with each other or placebo for induction and maintenance of clinical and histological remission in MC. Data sources and methods We searched MEDLINE (1946 to May 2021), EMBASE and EMBASE Classis (1947 to May 2021), the Cochrane central register of controlled trials (Issue 2, May 2021) and conference proceedings between 2006 and 2020. Results were reported as pooled relative risks (RRs) with 95% confidence intervals (CIs) to summarise the effect of each comparison tested, with treatments ranked according to p score. Results We identified 15 RCTs in total for the treatment of MC. Entocort 9 mg ranked first for clinical (RR: 4.89, CI: 2.43-9.83; p score: 0.86) and histological (RR: 13.39, CI: 1.92-93.44; p score 0.94) induction of remission, whilst VSL#3 ranked second for clinical induction (RR: 5.30, CI: 0.68-41.39; p score 0.81). Budenofalk 6 mg/3 mg alternate day dosing ranked first for clinical maintenance of remission (RR: 3.68, CI: 0.08-159.92, p-score 0.65). Entocort and Budenofalk were associated with the greatest adverse events for induction and maintenance of clinical remission, respectively, although the overall withdrawal numbers for treatment versus placebo groups were 10.9% (22/201) and 10.5% (20/190), respectively. Conclusion Entocort 9 mg/day ranked first among the treatment options in inducing remission and Budenofalk 6 mg/3 mg alternate day dosing for maintaining remission in the treatment of MC. Moving forward, mechanistic studies exploring the differences between Entocort and Budenofalk would be valuable whilst future RCT studies are needed in non-corticosteroidal maintenance, particularly looking into immunomodulators, biologics and probiotics.
Collapse
Affiliation(s)
| | | | - Matthew J. Brookes
- Department of Gastroenterology, The Royal
Wolverhampton NHS Trust, Wolverhampton, UK,School of Medicine and Clinical Practice,
Faculty of Sciences and Engineering, University of Wolverhampton,
Wolverhampton, UK
| | - Jonathan P. Segal
- Department of Gastroenterology, Northern
Hospital, Epping, VIC, Australia
| |
Collapse
|
6
|
Tuteja AK, Talley NJ, Murtaugh MA, Loc-Carrillo CM, Stoddard GJ, Anderson GL. Randomized, Double-Blind Placebo-Controlled Trial to Assess the Effect of Probiotics on Irritable Bowel Syndrome in Veterans With Gulf War Illness. Fed Pract 2022; 39:410-417. [PMID: 36744017 PMCID: PMC9896367 DOI: 10.12788/fp.0322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Background Many veterans who served in Operation Desert Storm (August 1990 to March 1991) experienced a complex of symptoms of unknown etiology called Gulf War illness (GWI), which significantly impacts the health and quality of life (QOL) and may have contributed to irritable bowel syndrome (IBS). Methods We performed a prospective, double-blind placebocontrolled study to determine the efficacy of the multistrain De Simone Formulation probiotic containing 8 strains of bacteria on symptoms of IBS and GWI. Veterans of Operation Desert Storm who had IBS and ≥ 2 nonintestinal symptoms of GWI were included. The primary study endpoint was change in bowel symptom score. The secondary endpoints were mean change in symptoms, QOL, and extra-intestinal and posttraumatic stress disorder (PTSD) symptoms. Results A total of 101 Gulf War veterans with IBS and GWI were screened at the Veteran Affairs Medical Center in Salt Lake City, Utah. The study was completed by 53 veterans; 47 (89%) were male with a mean (SD) age of 55 (8) years. The probiotic did not improve IBS symptoms or other extra-intestinal symptoms common to IBS and GWI. Conclusions Our study did not demonstrate statistically significant improvement in IBS symptoms or QOL after treatment with the probiotic. We also did not find any improvement in symptoms of GWI or PTSD.
Collapse
Affiliation(s)
- Ashok K Tuteja
- George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah
- University of Utah, Salt Lake City
| | | | | | - Catherine M Loc-Carrillo
- George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah
- University of Utah, Salt Lake City
| | - Gregory J Stoddard
- George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah
- University of Utah, Salt Lake City
| | | |
Collapse
|
7
|
Lee H, Jung KB, Kwon O, Son YS, Choi E, Yu WD, Son N, Jeon JH, Jo H, Yang H, Son YR, Yun CS, Cho HS, Kim SK, Kim DS, Park DS, Son MY. Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice. Gut Microbes 2022; 14:2121580. [PMID: 36130031 PMCID: PMC9519030 DOI: 10.1080/19490976.2022.2121580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Little is known about the modulatory capacity of the microbiota in early intestinal development. We examined various intestinal models that respond to gut microbial metabolites based on human pluripotent stem cell-derived human intestinal organoids (hIOs): physiologically relevant in vitro fetal-like intestine, intestinal stem cell, and intestinal disease models. We found that a newly isolated Limosilactobacillus reuteri strain DS0384 accelerated maturation of the fetal intestine using 3D hIO with immature fetal characteristics. Comparative metabolomic profiling analysis revealed that the secreted metabolite N-carbamyl glutamic acid (NCG) is involved in the beneficial effect of DS0384 cell-free supernatants on the intestinal maturation of hIOs. Experiments in an intestinal stem cell spheroid model and hIO-based intestinal inflamed model revealed that the cell-free supernatant from DS0384 comprising NCG promoted intestinal stem cell proliferation and was important for intestinal protection against cytokine-induced intestinal epithelial injury. The probiotic properties of DS0384 were also evaluated, including acid and bile tolerance and ability to adhere to human intestinal cells. Seven-day oral administration of DS0384 and cell-free supernatant promoted the intestinal development of newborn mice. Moreover, NCG exerted a protective effect on experimental colitis in mice. These results suggest that DS0384 is a useful agent for probiotic applications and therapeutic treatment for disorders of early gut development and for preventing intestinal barrier dysfunction.
Collapse
Affiliation(s)
- Hana Lee
- Stem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Kwang Bo Jung
- Stem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Ohman Kwon
- Stem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Ye Seul Son
- Stem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Eunho Choi
- Stem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea,KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea
| | - Won Dong Yu
- Stem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea,KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea
| | - Naeun Son
- Stem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea,KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea
| | - Jun Hyoung Jeon
- Korean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of Korea
| | - Hana Jo
- Korean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of Korea
| | - Haneol Yang
- Korean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of Korea
| | - Yeong Rak Son
- Korean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of Korea
| | - Chan-Seok Yun
- Korean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of Korea
| | - Hyun-Soo Cho
- KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea,Digital Biotech Innovation Center, KRIBB, Daejeon, Republic of Korea
| | - Sang Kyu Kim
- Laboratory of Efficacy Research, Korea Ginseng Corp., Daejeon, Republic of Korea
| | - Dae-Soo Kim
- KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea,Digital Biotech Innovation Center, KRIBB, Daejeon, Republic of Korea
| | - Doo-Sang Park
- Korean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of Korea,Doo-Sang Park Korean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, 56212, Republic of Korea
| | - Mi-Young Son
- Stem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea,KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea,CONTACT Mi-Young Son Stem Cell Research Convergence Center, KRIBB, Daejeon, 34141, Republic of Korea
| |
Collapse
|
8
|
Khushal S, Oliva-Hemker M. Diagnosis and Management of Microscopic Colitis in Pediatric Patients. Paediatr Drugs 2022; 24:217-233. [PMID: 35501559 DOI: 10.1007/s40272-022-00504-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/27/2022] [Indexed: 11/27/2022]
Abstract
Microscopic colitis (MC) is an inflammatory disease of the colon, characterized by chronic watery diarrhea with distinguishing histologic findings despite normal endoscopic appearance of the colonic mucosa. MC is a common cause of diarrhea in older adults, though it has been infrequently reported in children and adolescents. As MC is rare in the pediatric population, and the clinical presentation is non-specific, increased awareness of this disease amongst pediatric clinicians and pathologists is essential for timely diagnosis, which requires performing colonoscopy with biopsy. The etiology of MC is incompletely understood, but current theories in pathogenesis inform management strategies. The goals of management in pediatric MC should be to achieve symptomatic improvement while minimizing adverse effects of treatment. Many patients who achieve clinical response have symptomatic recurrence after discontinuation of initial therapy, and may require maintenance medication therapy to sustain remission. This review aims to summarize the epidemiology and risk factors, clinical features, diagnosis, theories regarding pathogenesis, and suggested management approaches for MC in the pediatric population.
Collapse
Affiliation(s)
- Salina Khushal
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Maria Oliva-Hemker
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| |
Collapse
|
9
|
Liu CY, Cham CM, Chang EB. Epithelial wound healing in inflammatory bowel diseases: the next therapeutic frontier. Transl Res 2021; 236:35-51. [PMID: 34126257 PMCID: PMC8380699 DOI: 10.1016/j.trsl.2021.06.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/25/2021] [Accepted: 06/08/2021] [Indexed: 02/07/2023]
Abstract
Patients with one of the many chronic inflammatory disorders broadly classified as inflammatory bowel disease (IBD) now have a diverse set of immunomodulatory therapies at their disposal. Despite these recent medical advances, complete sustained remission of disease remains elusive for most patients. The full healing of the damaged intestinal mucosa is the primary goal of all therapies. Achieving this requires not just a reduction of the aberrant immunological response, but also wound healing of the epithelium. No currently approved therapy directly targets the epithelium. Epithelial repair is compromised in IBD and normally facilitates re-establishment of the homeostatic barrier between the host and the microbiome. In this review, we summarize the evidence that epithelial wound healing represents an important yet underdeveloped therapeutic modality for IBD. We highlight 3 general approaches that are promising for developing a new class of epithelium-targeted therapies: epithelial stem cells, cytokines, and microbiome engineering. We also provide a frank discussion of some of the challenges that must be overcome for epithelial repair to be therapeutically leveraged. A concerted approach by the field to develop new therapies targeting epithelial wound healing will offer patients a game-changing, complementary class of medications and could dramatically improve outcomes.
Collapse
Affiliation(s)
- Cambrian Y Liu
- Department of Medicine, The University of Chicago, Chicago, Illinois.
| | - Candace M Cham
- Department of Medicine, The University of Chicago, Chicago, Illinois
| | - Eugene B Chang
- Department of Medicine, The University of Chicago, Chicago, Illinois.
| |
Collapse
|
10
|
Miehlke S, Guagnozzi D, Zabana Y, Tontini GE, Kanstrup Fiehn A, Wildt S, Bohr J, Bonderup O, Bouma G, D'Amato M, Heiberg Engel PJ, Fernandez‐Banares F, Macaigne G, Hjortswang H, Hultgren‐Hörnquist E, Koulaouzidis A, Kupcinskas J, Landolfi S, Latella G, Lucendo A, Lyutakov I, Madisch A, Magro F, Marlicz W, Mihaly E, Munck LK, Ostvik A, Patai ÁV, Penchev P, Skonieczna‐Żydecka K, Verhaegh B, Münch A. European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations. United European Gastroenterol J 2021; 9:13-37. [PMID: 33619914 PMCID: PMC8259259 DOI: 10.1177/2050640620951905] [Citation(s) in RCA: 122] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/27/2020] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. METHODS Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. RESULTS These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. CONCLUSION These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.
Collapse
|
11
|
Abstract
PURPOSE OF REVIEW With the growing popularity and commercialization of probiotics, it is important to understand the implications of existing randomized controlled trials and their applicability in the clinical setting to treat luminal gastrointestinal diseases. RECENT FINDINGS Probiotics may be useful in the prevention of antibiotic-associated diarrhea, prevention of Clostridioides difficile infection and eradication of Helicobacter pylori. Some evidence supports the use of probiotics in the treatment of ulcerative colitis, prevention and treatment of pouchitis and irritable bowel syndrome. Caution has to be exercised in immunocompromised and critically ill individuals. New society guidelines do not encourage probiotic use in gastrointestinal disorders with the exception of premature infants to prevent necrotizing enterocolitis. SUMMARY Despite burgeoning body of literature and wide acceptance by the public, a thorough understanding of efficacy and safety of probiotics is lacking. Uniform dosage, standardized clinical end points, personalization based on host microbial profile and longer duration of follow-up on the research front may help in the future in appropriate positioning of probiotics in health and disease.
Collapse
Affiliation(s)
- Abbinaya Elangovan
- Department of Internal Medicine-Pediatrics, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Monika Fischer
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana, USA
| |
Collapse
|
12
|
Cheng FS, Pan D, Chang B, Jiang M, Sang LX. Probiotic mixture VSL#3: An overview of basic and clinical studies in chronic diseases. World J Clin Cases 2020; 8:1361-1384. [PMID: 32368530 PMCID: PMC7190945 DOI: 10.12998/wjcc.v8.i8.1361] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/27/2020] [Accepted: 04/08/2020] [Indexed: 02/05/2023] Open
Abstract
Probiotics are known as “live microorganisms” and have been proven to have a health effect on hosts at the proper dose. Recently, a kind of probiotic mixture including eight live bacterial strains, VSL#3, has attracted considerable attention for its combined effect. VSL#3 is the only probiotic considered as a kind of medical food; it mainly participates in the regulation of the intestinal barrier function, including improving tight junction protein function, balancing intestinal microbial composition, regulating immune-related cytokine expression and so on. The objective of this review is to discuss the treatment action and mechanism for the administration of VSL#3 in chronic diseases of animals and humans (including children). We found that VSL#3 has a therapeutic or preventive effect in various systemic diseases per a large number of studies, including digestive systemic diseases (gastrointestinal diseases and hepatic diseases), obesity and diabetes, allergic diseases, nervous systemic diseases, atherosclerosis, bone diseases, and female reproductive systemic diseases.
Collapse
Affiliation(s)
- Fang-Shu Cheng
- Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
- Class 85 of 101k, China Medical University, Shenyang 110004, Liaoning Province, China
| | - Dan Pan
- Department of Geriatrics, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Min Jiang
- Department of Gastroenterology, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| |
Collapse
|
13
|
Iheozor-Ejiofor Z, Kaur L, Gordon M, Baines PA, Sinopoulou V, Akobeng AK. Probiotics for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2020; 3:CD007443. [PMID: 32128794 PMCID: PMC7059960 DOI: 10.1002/14651858.cd007443.pub3] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Ulcerative colitis is an inflammatory condition affecting the colon, with an annual incidence of approximately 10 to 20 per 100,000 people. The majority of people with ulcerative colitis can be put into remission, leaving a group who do not respond to first- or second-line therapies. There is a significant proportion of people who experience adverse effects with current therapies. Consequently, new alternatives for the treatment of ulcerative colitis are constantly being sought. Probiotics are live microbial feed supplements that may beneficially affect the host by improving intestinal microbial balance, enhancing gut barrier function and improving local immune response. OBJECTIVES The primary objective was to determine the efficacy of probiotics compared to placebo, no treatment, or any other intervention for the maintenance of remission in people with ulcerative colitis. The secondary objective was to assess the occurrence of adverse events associated with the use of probiotics. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, and two other databases on 31 October 2019. We contacted authors of relevant studies and manufacturers of probiotics regarding ongoing or unpublished trials that may be relevant to the review, and we searched ClinicalTrials.gov. We also searched references of trials for any additional trials. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared probiotics against placebo or any other intervention, in both adults and children, for the maintenance of remission in ulcerative colitis were eligible for inclusion. Maintenance therapy had to be for a minimum of three months when remission has been established by any clinical, endoscopic,histological or radiological relapse as defined by study authors. DATA COLLECTION AND ANALYSIS Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE methodology. MAIN RESULTS In this review, we included 12 studies (1473 randomised participants) that met the inclusion criteria. Participants were mostly adults. The studies compared probiotics to placebo, probiotics to 5-aminosalicylic acid (5-ASA) and a combination of probiotics and 5-ASA to 5-ASA. The studies ranged in length from 12 to 52 weeks. The average age of participants was between 32 and 51, with a range between 18 and 88 years. Seven studies investigated a single bacterial strain, and five studies considered mixed preparations of multiple strains. The risk of bias was high in all except three studies due to selective reporting, incomplete outcome data and lack of blinding. This resulted in low- to very low-certainty of evidence. It is uncertain if there is any difference in occurrence of clinical relapse when probiotics are compared with placebo (RR 0.87, 95% CI 0.63 to 1.18; 4 studies, 361 participants; very low-certainty evidence (downgraded for risk of bias, imbalance in baseline characteristics and imprecision)). It is also uncertain whether probiotics lead to a difference in the number of people who maintain clinical remission compared with placebo (RR 1.16, 95% CI 0.98 to 1.37; 2 studies, 141 participants; very low-certainty evidence (downgraded for risk of bias, imbalance in baseline characteristics and imprecision)). When probiotics are compared with 5-ASA, there may be little or no difference in clinical relapse (RR 1.01, 95% CI 0.84 to 1.22; 2 studies, 452 participants; low-certainty evidence) and maintenance of clinical remission (RR 1.06, 95% CI 0.90 to 1.25; 1 study, 125 participants; low-certainty evidence). It is uncertain if there is any difference in clinical relapse when probiotics, combined with 5-ASA are compared with 5-ASA alone (RR 1.11, 95% CI 0.66 to 1.87; 2 studies, 242 participants; very low-certainty evidence (downgraded due to risk of bias and imprecision)). There may be little or no difference in maintenance of remission when probiotics, combined with 5-ASA, are compared with 5-ASA alone (RR 1.05, 95% CI 0.89 to 1.24; 1 study, 122 participants; low-certainty evidence). Where reported, most of the studies which compared probiotics with placebo recorded no serious adverse events or withdrawals due to adverse events. For the comparison of probiotics and 5-ASA, one trial reported 11/110 withdrawals due to adverse events with probiotics and 11/112 with 5-ASA (RR 1.02, 95% CI 0.46 to 2.25; 222 participants; very low-certainty evidence). Discontinuation of therapy was due to gastrointestinal symptoms. One study (24 participants) comparing probiotics combined with 5-ASA with 5-ASA alone, reported no withdrawals due to adverse events; and two studies reported two withdrawals in the probiotic arm, due to avascular necrosis of bilateral femoral head and pulmonary thromboembolism (RR 5.29, 95% CI 0.26 to 107.63; 127 participants; very low-certainty evidence). Health-related quality of life and need for additional therapy were reported infrequently. AUTHORS' CONCLUSIONS The effectiveness of probiotics for the maintenance of remission in ulcerative colitis remains unclear. This is due to low- to very low-certainty evidence from poorly conducted studies, which contribute limited amounts of data from a small number of participants. Future trials comparing probiotics with 5-ASA rather than placebo will better reflect conventional care given to people with ulcerative colitis. Appropriately powered studies with a minimum length of 12 months are needed.
Collapse
Affiliation(s)
- Zipporah Iheozor-Ejiofor
- University of Central Lancashire, School of Medicine, Harrington Building, Preston, Lancashire, UK
| | - Lakhbir Kaur
- University of Central Lancashire, School of Medicine, Harrington Building, Preston, Lancashire, UK
| | - Morris Gordon
- University of Central Lancashire, School of Medicine, Harrington Building, Preston, Lancashire, UK
- Blackpool Victoria Hospital, Families Division, Blackpool, UK
| | | | - Vasiliki Sinopoulou
- University of Central Lancashire, School of Medicine, Harrington Building, Preston, Lancashire, UK
| | | |
Collapse
|
14
|
Elangovan A, Allegretti JR, Fischer M. Microbiota modulation-based therapy for luminal GI disorders: current applications of probiotics and fecal microbiota transplantation. Expert Opin Biol Ther 2019; 19:1343-1355. [PMID: 31570017 DOI: 10.1080/14712598.2019.1673725] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Introduction: Alteration in the intestinal microbiota also termed as intestinal dysbiosis has been demonstrated in numerous gastrointestinal disorders linked to aberrant immune processes, acquisition of pathogenic organisms and often administration of antibiotics. Restoration of microbiota through probiotics and fecal microbiota transplantation (FMT) has gained tremendous popularity among researchers in the prevention and treatment of gastrointestinal diseases.Areas covered: In this review, studies testing the safety and efficacy of probiotics and FMT for the treatment of various infectious and inflammatory luminal gastrointestinal diseases are reviewed. Randomized control studies are given priority while important uncontrolled studies are also highlighted.Expert opinion: Probiotics have demonstrated efficacy in the prevention of antibiotic-associated diarrhea and in the eradication of Helicobacter pylori infection. Their utility in the primary and secondary prevention of Clostridioides difficile infection is debatable. The future of medicine should bring forth a personalized approach to probiotic use. FMT has revolutionized the treatment of recurrent CDI as well as severe and fulminant CDI. At the same time, it has galvanized gut microbiota research in the last decade. While FMT in ulcerative colitis appears promising, further studies on the durability and long-term safety are needed before it can be recommended in clinical practice.
Collapse
Affiliation(s)
- Abbinaya Elangovan
- Department of Medicine-Pediatrics, MetroHealth Medical Center/Case Western Reserve University, Cleveland, OH, USA
| | - Jessica R Allegretti
- Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA
| | - Monika Fischer
- Medicine, Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| |
Collapse
|
15
|
Shor J, Churrango G, Hosseini N, Marshall C. Management of microscopic colitis: challenges and solutions. Clin Exp Gastroenterol 2019; 12:111-120. [PMID: 30881078 PMCID: PMC6398419 DOI: 10.2147/ceg.s165047] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by nonbloody diarrhea in the setting of normal appearing colonic mucosa. MC has two main subtypes based on histopathologic features, collagenous colitis and lymphocytic colitis. Management of both subtypes is the same, with treatment goal of reducing the number of bowel movements and improving consistency. First-line treatment involves counseling the patient about decreasing their risk factors, like discontinuing smoking and avoiding medications with suspected association such as NSAIDs, proton pump inhibitor, ranitidine, and sertraline. Starting loperamide for immediate symptomatic relief is used as an adjunct to therapy with glucocorticoids. Budesonide is considered first-line treatment for MC given its favorable side effect profile and good efficacy, though relapse rates are high. Systemic glucocorticoids should be reserved to patients unable to take budesonide. In glucocorticoid refractory disease, medications that have been tried include cholestyramine, bismuth salicylate, antibiotics, probiotics, aminosalicylates, immunomodulators, and anti-tumor necrosis factor-alpha inhibitors. More research is needed for the creation of a systematic stepwise approach for relapsing and refractory disease.
Collapse
Affiliation(s)
- Julia Shor
- Department of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA,
| | - Gustavo Churrango
- Department of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA,
| | - Nooshin Hosseini
- Department of Gastroenterology, Mount Sinai Hospital, New York, NY, USA
| | - Christopher Marshall
- Department of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA,
| |
Collapse
|
16
|
van Hemert S, Skonieczna-Żydecka K, Loniewski I, Szredzki P, Marlicz W. Microscopic colitis-microbiome, barrier function and associated diseases. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:39. [PMID: 29610731 DOI: 10.21037/atm.2017.03.83] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Microscopic colitis (MC) is a chronic inflammatory bowel disease (IBD) with little in terms of endoscopic abnormalities and is frequently associated with other autoimmune diseases. The peak incidence of the disease is in middle aged or older populations, mostly females. The pathogenesis of MC is complex, multifactorial and poorly understood. Current concepts revolve around innate immunity or microbiome alterations as well as gut barrier dysfunction, all of which lead to the development of subtle inflammatory lesions in gut mucosa. The results of numerous basic and clinical studies involving molecular techniques as well as advanced endoscopic imaging revealed the important role of both intrinsic (e.g., hormonal) as well as extrinsic (e.g., NSAIDs and PPIs) factors in the modulation of gastrointestinal microbiome and MC pathogenesis. Capsule endoscopy as well confocal endomicroscopy imaging, alongside standard endoscopic techniques offer new tools in the evaluation of MC patients and allow their better stratification for novel treatment protocols based on modulation of gut microbiome and barrier function.
Collapse
Affiliation(s)
| | | | - Igor Loniewski
- Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Szczecin, Poland.,Sanprobi Sp. z o.o. Sp. K., Szczecin, Poland
| | - Piotr Szredzki
- Endoscopy Unit, Department of Surgery, Hospital Sędziszów Małopolski, Sędziszów Małopolski, Poland
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland
| |
Collapse
|
17
|
Chande N, Al Yatama N, Bhanji T, Nguyen TM, McDonald JWD, MacDonald JK. Interventions for treating lymphocytic colitis. Cochrane Database Syst Rev 2017; 7:CD006096. [PMID: 28702956 PMCID: PMC6483541 DOI: 10.1002/14651858.cd006096.pub4] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Lymphocytic colitis is a cause of chronic diarrhea. It is a subtype of microscopic colitis characterized by chronic, watery, non-bloody diarrhea and normal endoscopic and radiologic findings. The etiology of this disorder is unknown.Therapy is based mainly on case series and uncontrolled trials, or by extrapolation of data for treating collagenous colitis, a related disorder. This review is an update of a previously published Cochrane review. OBJECTIVES To evaluate the efficacy and safety of treatments for clinically active lymphocytic colitis. SEARCH METHODS The MEDLINE, PUBMED and EMBASE databases were searched from inception to 11 August 2016 to identify relevant papers. Manual searches from the references of included studies and relevant review articles were performed.Abstracts from major gastroenterological meetings were also searched to identify research submitted in abstract form only. The trial registry web site www.ClinicalTrials.gov was searched to identify registered but unpublished trials. Finally, the Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies. SELECTION CRITERIA Randomized controlled trials assessing medical therapy for patients with biopsy-proven lymphocytic colitis were considered for inclusion DATA COLLECTION AND ANALYSIS: Data was independently extracted by at least two authors. Any disagreements were resolved by consensus. Data were analyzed on an intention-to-treat (ITT) basis. The primary outcome was clinical response as defined by the included studies. Secondary outcome measures included histological response as defined by the included studies, quality of life as measured by a validated instrument and the occurrence of adverse events. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. Data were combined for analysis if they assessed the same treatments. Dichotomous data were combined using a pooled RR along with corresponding 95% CI. A fixed-effect model was used for the pooled analysis. MAIN RESULTS Five RCTs (149 participants) met the inclusion criteria. These studies assessed bismuth subsalicylate versus placebo, budesonide versus placebo, mesalazine versus mesalazine plus cholestyramine and beclometasone dipropionate versus mesalazine. The study which assessed mesalazine versus mesalazine plus cholestyramine and the study which assessed beclometasone dipropionate versus mesalazine were judged to be at high risk of bias due to lack of blinding. The study which compared bismuth subsalicylate versus us placebo was judged as low quality due to a very small sample size and limited data. The other 3 studies were judged to be at low risk of bias. Budesonide (9 mg/day for 6 to 8 weeks) was significantly more effective than placebo for induction of clinical and histological response. Clinical response was noted in 88% of budesonide patients compared to 38% of placebo patients (2 studies; 57 participants; RR 2.03, 95% CI 1.25 to 3.33; GRADE = low). Histological response was noted in 78% of budesonide patients compared to 33% of placebo patients (2 studies; 39 patients; RR 2.44, 95% CI 1.13 to 5.28; GRADE = low). Forty-one patients were enrolled in the study assessing mesalazine (2.4 g/day) versus mesalazine plus cholestyramine (4 g/day). Clinical response was noted in 85% of patients in the mesalazine group compared to 86% of patients in the mesalazine plus cholestyramine group (RR 0.99, 95% CI 0.77 to 1.28; GRADE = low). Five patients were enrolled in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks versus placebo). There were no differences in clinical (P=0.10) or histological responses (P=0.71) in patients treated with bismuth subsalicylate compared with placebo (GRADE = very low). Forty-six patients were enrolled in the trial studying beclometasone dipropionate (5 mg/day or 10 mg/day) versus mesalazine (2.4 g/day). There were no differences in clinical remission at 8 weeks (RR 0.97; 95% CI 0.75 to 1.24; GRADE = low) and 12 months of treatment (RR 1.29; 95% CI 0.40 to 4.18; GRADE = very low). Although patients receiving beclometasone dipropionate (84%) and mesalazine (86%) achieved clinical remission at 8 weeks, it was not maintained at 12 months (26% and 20%, respectively). Adverse events reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, hyperhidrosis and headache. Nausea and skin rash were reported as adverse events in the mesalazine study. Adverse events in the beclometasone dipropionate trial include nausea, sleepiness and change of mood. No adverse events were reported in the bismuth subsalicylate study. AUTHORS' CONCLUSIONS Low quality evidence suggests that budesonide may be effective for the treatment of active lymphocytic colitis. This benefit needs to be confirmed by a large placebo -controlled trial. Low quality evidence also suggests that mesalazine with or without cholestyramine and beclometasone dipropionate may be effective for the treatment of lymphocytic colitis, however this needs to be confirmed by large placebo-controlled studies. No conclusions can be made regarding bismuth subsalicylate due to the very small number of patients in the study, Further trials studying interventions for lymphocytic colitis are warranted.
Collapse
Affiliation(s)
- Nilesh Chande
- London Health Sciences Centre ‐ Victoria HospitalRoom E6‐321A800 Commissioners Road EastLondonONCanadaN6A 5W9
| | - Noor Al Yatama
- University of Western OntarioDepartment of MedicineLondonONCanada
| | - Tania Bhanji
- University of Western OntarioDepartment of MedicineLondonONCanada
| | - Tran M Nguyen
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanada
| | - John WD McDonald
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanada
| | - John K MacDonald
- University of Western OntarioDepartment of MedicineLondonONCanada
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanada
| | | |
Collapse
|
18
|
Kedia S, Rampal R, Paul J, Ahuja V. Gut microbiome diversity in acute infective and chronic inflammatory gastrointestinal diseases in North India. J Gastroenterol 2016; 51:660-71. [PMID: 26994772 DOI: 10.1007/s00535-016-1193-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 02/23/2016] [Indexed: 02/04/2023]
Abstract
The disease profile in the Indian population provides a unique opportunity for studying the host microbiome interaction in both infectious (amebiasis) and autoimmune diseases like inflammatory bowel disease (IBD) from a similar environment and genetic background. Analysis of fecal samples from untreated amebic liver abscess (ALA) patients, Entamoeba histolytica (Eh)-negative and -positive asymptomatic individuals, and pus samples from naive ALA patients revealed a significant reduction in Lactobacillus in asymptomatic individuals (Eh +ve) and ALA patients. Two anaerobic genera, namely Bacteroides and Peptostreptococcus, were detected in naive ALA pus samples. Analysis of fecal samples from amoebic colitis patients showed a significant decline in population of Bacteroides, Clostridium coccoides and leptum subgroup, Lactobacillus, Campylobacter, and Eubacterium, whereas a significant increase in Bifidobacterium was observed. Mucosa-associated bacterial flora analysis from IBD patients and healthy controls revealed a significant difference in concentration of bacteria among predominating and subdominating genera between ulcerative colitis (UC), Crohn's disease (CD) patients, and controls. In contrast to the mucosal studies, we found a significant increase in lactobacilli population in fecal samples of active UC patients. Another study revealed a significant decrease of Clostridium coccoides and leptum clusters in fecal samples of active UC patients along with decreased concentrations of fecal SCFAs, especially of n-butyrate, iso-butyrate, and acetate. We therefore found similar perturbations in gut microbiome in both infectious and autoimmune diseases, indicating inflammation to be the major driver for changes in gut microbiome.
Collapse
Affiliation(s)
- Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Ritika Rampal
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Jaishree Paul
- School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
| |
Collapse
|
19
|
Effects of a Multispecies Probiotic Mixture on Glycemic Control and Inflammatory Status in Women with Gestational Diabetes: A Randomized Controlled Clinical Trial. J Nutr Metab 2016; 2016:5190846. [PMID: 27429803 PMCID: PMC4939193 DOI: 10.1155/2016/5190846] [Citation(s) in RCA: 99] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 04/30/2016] [Accepted: 05/10/2016] [Indexed: 12/31/2022] Open
Abstract
Objective. This trial aims to examine the effects of a Probiotic Mixture (VSL#3) on glycemic status and inflammatory markers, in women with GDM. Materials and Methods. Over a period of 8 weeks, 82 women with gestational diabetes were randomly assigned to either an intervention group (n = 41) which were given VSL#3 capsule or to a control group which were given placebo capsule (n = 41). Fasting plasma glucose, homeostatic model assessment of insulin resistance, glycosylated hemoglobin, high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-6, Interferon gamma, and interleukin-10 were measured before and after the intervention. Results. After 8 wk of supplementation FPG, HbA1c, HOMA-IR, and insulin levels remained unchanged in the probiotic and placebo groups. The comparison between the two groups showed no significant differences with FPG and HbA1c, but there were significant differences in insulin levels and HOMA-IR (16.6 ± 5.9; 3.7 ± 1.5, resp.). Unlike the levels of IFN-g (19.21 ± 16.6), there was a significant decrease in levels of IL-6 (3.81 ± 0.7), TNF-α (3.10 ± 1.1), and hs-CRP (4927.4 ± 924.6). No significant increase was observed in IL-10 (3.11 ± 5.7) in the intervention group as compared with the control group. Conclusions. In women with GDM, supplementation with probiotics (VSL#3) may help to modulate some inflammatory markers and may have benefits on glycemic control.
Collapse
|