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Szilagyi A, Wyse J, Abdulezer J. Dietary Relationships between Obesity and Inflammatory Bowel Diseases: A Narrative Review of Diets Which May Promote Both Diseases. Curr Gastroenterol Rep 2025; 27:29. [PMID: 40304971 PMCID: PMC12043785 DOI: 10.1007/s11894-025-00980-w] [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] [Accepted: 04/14/2025] [Indexed: 05/02/2025]
Abstract
PURPOSE OF REVIEW The pandemic of obesity preceded global spread of Inflammatory Bowel diseases by almost 2 decades. A pathogenic relationship has been described between obesity and inflammatory bowel diseases, but Crohn`s disease may be selectively impacted. The role of diet in pathogenesis has also gained significant support in the last few decades. This review explores dietary relationships to account for epidemiological observations. Quantifiable indices for diets have been described including a glycemic index, inflammatory indices and levels of food processing. Meta-analyses have been published which examine each for effects on obesity and co-morbidities as well as Crohn's disease and ulcerative colitis. This review suggests that ultra-processed foods provide the best link between obesity and Crohn's disease explaining epidemiological observations. However, the other 2 types of dietary indices likely contribute to ulcerative colitis as well as to co-morbidities related to both obesity and inflammatory bowel diseases. The term ultra-processed foods cover a large number of additives and extensive work is needed to define individual or combined harmful effects. Furthermore, the interactions among the 3 main indices need clarification in order to precisely apply therapeutic diets to both diseases (obesity and inflammatory bowel disease).
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Affiliation(s)
- Andrew Szilagyi
- Division of Gastroenterology, Department of Medicine, Jewish General Hospital, McGill University School of Medicine, 3755 Cote St Catherine Rd, Montreal, Quebec, H3 T 1E2, Canada.
- ELNA Medical Center Decarie ELNA Medical Group, 6900 Decarie Blvd, Côte Saint-Luc, Canada.
| | - Jonathan Wyse
- Division of Gastroenterology, Department of Medicine, Jewish General Hospital, McGill University School of Medicine, 3755 Cote St Catherine Rd, Montreal, Quebec, H3 T 1E2, Canada
| | - Jennifer Abdulezer
- Independent researcher at Jewish General Hospital for This Work, Montreal, Canada
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2
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Quigley EMM, Shanahan F. Probiotics in Health Care: A Critical Appraisal. Annu Rev Med 2025; 76:129-141. [PMID: 39527719 DOI: 10.1146/annurev-med-042423-042315] [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] [Indexed: 11/16/2024]
Abstract
Consumption of probiotic products continues to increase, perhaps driven by an interest in gut health. However, the field is filled with controversy, inconsistencies, misuse of terminology, and poor communication. While the probiotic concept is biologically plausible and in some cases mechanistically well established, extrapolation of preclinical results to humans has seldom been proven in well-conducted clinical trials. With noteworthy exceptions, clinical guidance has often been derived not from large, adequately powered clinical trials but rather from comparisons of disparate, small studies with insufficient power to identify the optimal strain. The separation of probiotics from live biotherapeutic products has brought some clarity from a regulatory perspective, but in both cases, consumers should expect scientific rigor and strong supporting evidence for health claims.
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Affiliation(s)
- Eamonn M M Quigley
- Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA
| | - Fergus Shanahan
- Department of Medicine and Alimentary Pharmabiotic Centre, Microbiome Ireland, University College Cork, National University of Ireland, Cork, Ireland;
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3
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Sulaimany S, Farahmandi K, Mafakheri A. Computational prediction of new therapeutic effects of probiotics. Sci Rep 2024; 14:11932. [PMID: 38789535 PMCID: PMC11126595 DOI: 10.1038/s41598-024-62796-4] [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: 12/12/2023] [Accepted: 05/21/2024] [Indexed: 05/26/2024] Open
Abstract
Probiotics are living microorganisms that provide health benefits to their hosts, potentially aiding in the treatment or prevention of various diseases, including diarrhea, irritable bowel syndrome, ulcerative colitis, and Crohn's disease. Motivated by successful applications of link prediction in medical and biological networks, we applied link prediction to the probiotic-disease network to identify unreported relations. Using data from the Probio database and International Classification of Diseases-10th Revision (ICD-10) resources, we constructed a bipartite graph focused on the relationship between probiotics and diseases. We applied customized link prediction algorithms for this bipartite network, including common neighbors, Jaccard coefficient, and Adamic/Adar ranking formulas. We evaluated the results using Area under the Curve (AUC) and precision metrics. Our analysis revealed that common neighbors outperformed the other methods, with an AUC of 0.96 and precision of 0.6, indicating that basic formulas can predict at least six out of ten probable relations correctly. To support our findings, we conducted an exact search of the top 20 predictions and found six confirming papers on Google Scholar and Science Direct. Evidence suggests that Lactobacillus jensenii may provide prophylactic and therapeutic benefits for gastrointestinal diseases and that Lactobacillus acidophilus may have potential activity against urologic and female genital illnesses. Further investigation of other predictions through additional preclinical and clinical studies is recommended. Future research may focus on deploying more powerful link prediction algorithms to achieve better and more accurate results.
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Affiliation(s)
- Sadegh Sulaimany
- Social and Biological Network Analysis Laboratory (SBNA), Department of Computer Engineering, University of Kurdistan, Sanandaj, Iran.
| | - Kajal Farahmandi
- Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
| | - Aso Mafakheri
- Social and Biological Network Analysis Laboratory (SBNA), Department of Computer Engineering, University of Kurdistan, Sanandaj, Iran
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4
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Shaheen WA, Quraishi MN, Iqbal TH. Gut microbiome and autoimmune disorders. Clin Exp Immunol 2022; 209:161-174. [PMID: 35652460 DOI: 10.1093/cei/uxac057] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 04/29/2022] [Accepted: 05/30/2022] [Indexed: 12/13/2022] Open
Abstract
Autoimmune diseases have long been known to share a common pathogenesis involving a dysregulated immune system with failure to recognize self from non-self antigens. This immune dysregulation is now increasingly understood to be induced by environmental triggers in genetically predisposed individuals. Although several external environmental triggers have been defined in different autoimmune diseases, much attention is being paid to the role of the internal micro-environment occupied by the microbiome which was once termed "the forgotten organ". In this regard, the gut microbiome, serving as an intermediary between some of those external environmental effectors and the immune system helps programming of the immune system to be tolerant to innocent external and self antigens. However, in the presence of perturbed gut microbiota (dysbiosis), the immune system could be erroneously directed in favor of pro-inflammatory pathways to instigate different autoimmune processes. An accumulating body of evidence, including both experimental and human studies (observational and interventional) points to a role of gut microbiome in different autoimmune diseases. Such evidence could provide a rationale for gut microbiome manipulation with therapeutic and even preventative intents in patients with established or predisposed to autoimmune diseases respectively. Perturbations of the gut microbiome have been delineated in some immune mediated diseases, IBD in particular. However, such patterns of disturbance (microbiome signatures) and related pathogenetic roles of the gut microbiome are context dependent and cannot be generalized in the same exact way to other autoimmune disorders and the contribution of gut microbiome to different disease phenotypes has to be precisely defined. In this review, we revise the evidence for a role of gut microbiome in various autoimmune diseases and possible mechanisms mediating such a role.
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Affiliation(s)
- Walaa Abdelaty Shaheen
- University of Birmingham Microbiome Treatment Center, Birmingham, UK.,Institute of Cancer and Genomic Sciences, University of Birmingham, UK.,Gastroenterology Department, Menoufia University, Egypt
| | - Mohammed Nabil Quraishi
- University of Birmingham Microbiome Treatment Center, Birmingham, UK.,Institute of Cancer and Genomic Sciences, University of Birmingham, UK.,University Hospitals of Birmingham NHS Foundation Trust, Birmingham, UK
| | - Tariq H Iqbal
- University of Birmingham Microbiome Treatment Center, Birmingham, UK.,Institute of Microbiology and Infection, University of Birmingham, UK.,University Hospitals of Birmingham NHS Foundation Trust, Birmingham, UK
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5
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Dempsey E, Corr SC. Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives. Front Immunol 2022; 13:840245. [PMID: 35464397 PMCID: PMC9019120 DOI: 10.3389/fimmu.2022.840245] [Citation(s) in RCA: 196] [Impact Index Per Article: 65.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 03/15/2022] [Indexed: 11/13/2022] Open
Abstract
In recent decades, probiotic bacteria have become increasingly popular as a result of mounting scientific evidence to indicate their beneficial role in modulating human health. Although there is strong evidence associating various Lactobacillus probiotics to various health benefits, further research is needed, in particular to determine the various mechanisms by which probiotics may exert these effects and indeed to gauge inter-individual value one can expect from consuming these products. One must take into consideration the differences in individual and combination strains, and conditions which create difficulty in making direct comparisons. The aim of this paper is to review the current understanding of the means by which Lactobacillus species stand to benefit our gastrointestinal health.
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Affiliation(s)
- Elaine Dempsey
- Trinity Biomedical Science Institute, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.,Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland
| | - Sinéad C Corr
- Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland.,APC Microbiome Ireland, University College Cork, Cork, Ireland
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6
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Hedin CR, McCarthy NE, Louis P, Farquharson FM, McCartney S, Stagg AJ, Lindsay JO, Whelan K. Prebiotic fructans have greater impact on luminal microbiology and CD3+ T cells in healthy siblings than patients with Crohn's disease: A pilot study investigating the potential for primary prevention of inflammatory bowel disease. Clin Nutr 2021; 40:5009-5019. [PMID: 34364241 DOI: 10.1016/j.clnu.2021.05.033] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 05/28/2021] [Accepted: 05/29/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Siblings of people with Crohn's disease (CD) share aspects of the disease phenotype (raised faecal calprotectin, altered microbiota), which are markers of risk for their own development of CD. The aim was to determine whether supplementation with prebiotic oligofructose/inulin induces a prebiotic response and impacts the risk phenotype in CD patients and siblings. METHODS Patients with inactive CD (n = 19, CD activity index <150) and 12 of their unaffected siblings (with calprotectin >50 μg/g) ingested oligofructose/inulin (15 g/day) for three weeks. Faecal microbiota (qPCR), intestinal permeability (lactulose-rhamnose test), blood T cells (flow-cytometry) and calprotectin (ELISA) were measured at baseline and follow-up. RESULTS Following oligofructose/inulin, calprotectin did not significantly change in patients (baseline mean 537 SD 535 μg/g; follow-up mean 974 SD 1318 μg/g, p = 0.08) or siblings (baseline mean 73 SD 90 μg/g: follow up mean 58 SD 72 μg/g, p = 0.62). Faecal Bifidobacteria and Bifidobacterium longum increased in patients and siblings; Bifidobacterium adolescentis and Roseburia spp. increased only in siblings. Compared with patients, siblings had a greater magnitude change in Bifidobacteria (+14.6% vs +0.4%, p = 0.028), B. adolescentis (+1.1% vs 0.0% p = 0.006) and Roseburia spp. (+1.5% vs -0.1% p = 0.004). Intestinal permeability decreased significantly in patients after oligofructose/inulin to a level that was similar to siblings. Blood T cell abundance reduced in siblings but not patients following oligofructose/inulin. CONCLUSIONS Oligofructose/inulin supplementation did not significantly impact calprotectin, but the prebiotic effect was more marked in healthy siblings compared with patients with inactive CD and was associated with alterations in other CD risk markers. Future research should focus on dietary intervention, including with prebiotics, in the primary prevention of CD.
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Affiliation(s)
- Charlotte R Hedin
- King's College London, Department of Nutritional Sciences, London, UK; Queen Mary University of London, Blizard Institute, Centre for Immunobiology, London, UK
| | - Neil E McCarthy
- Queen Mary University of London, Blizard Institute, Centre for Immunobiology, London, UK
| | - Petra Louis
- Rowett Institute, University of Aberdeen, Microbiology Group, Gut Health Theme, Aberdeen, UK
| | - Freda M Farquharson
- Rowett Institute, University of Aberdeen, Microbiology Group, Gut Health Theme, Aberdeen, UK
| | - Sara McCartney
- University College Hospitals NHS Foundation Trust, Department for Gastroenterology and Clinical Nutrition, London, UK
| | - Andrew J Stagg
- Queen Mary University of London, Blizard Institute, Centre for Immunobiology, London, UK
| | - James O Lindsay
- Queen Mary University of London, Blizard Institute, Centre for Immunobiology, London, UK; Barts Health NHS Trust, Royal London Hospital, Department of Gastroenterology, London, UK
| | - Kevin Whelan
- King's College London, Department of Nutritional Sciences, London, UK.
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Shafiee NH, Manaf ZA, Mokhtar NM, Raja Ali RA. Anti-inflammatory diet and inflammatory bowel disease: what clinicians and patients should know? Intest Res 2021; 19:171-185. [PMID: 33525858 PMCID: PMC8100370 DOI: 10.5217/ir.2020.00035] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 12/03/2020] [Accepted: 12/03/2020] [Indexed: 12/22/2022] Open
Abstract
Current treatment for inflammatory bowel disease (IBD) includes the application of anti-inflammatory agents for the induction and remission of IBD. However, prolonged use of anti-inflammatory agents can exert adverse effects on patients. Recently, formulated dietary approach in treating IBD patients is utilized to improve clinical activity scores. An alteration of gastrointestinal microbiota through dietary therapy was found to reduce IBD and is recognized as a promising therapeutic strategy for IBD. One of the recommended formulated diets is an anti-inflammatory diet (AID) that restricts the intake of carbohydrates with modified fatty acids. This diet also contains probiotics and prebiotics that can promote balanced intestinal microbiota composition. However, scientific evidences are limited to support this specific dietary regime in maintaining the remission and prevention relapse of IBD. Therefore, this review aimed to summarize available data from various studies to evaluate the AID diet effectiveness which will be useful for clinicians to manage their IBD patients by application of improved dietary therapy.
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Affiliation(s)
- Nor Hamizah Shafiee
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Zahara Abdul Manaf
- Dietetics Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Norfilza M. Mokhtar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Raja Affendi Raja Ali
- GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- Gastroenterology Unit, Department of Medicine, UKM Medical Centre, Kuala Lumpur, Malaysia
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8
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Liang H, Luo Z, Miao Z, Shen X, Li M, Zhang X, Chen J, Ze X, Chen Q, He F. Lactobacilli and bifidobacteria derived from infant intestines may activate macrophages and lead to different IL-10 secretion. Biosci Biotechnol Biochem 2020; 84:2558-2568. [PMID: 32862788 DOI: 10.1080/09168451.2020.1811948] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In this study, three strains of lactobacilli and bifidobacteria originally isolated from healthy infants, were tested for their abilities to activate RAW264.7 cells. Gene expression and cytokine production of interleukin-10 (IL-10) of RAW264.7 cells were evaluated. The activation of extracellular regulated protein kinases 1/2 (ERK1/2), p38, and nuclear factor-κB (NK-κB) were also assessed. These results suggest lactobacilli and bifidobacteria in infants may promote production of IL-10 in macrophages, conferring a protective effect in hosts suffering from inflammation. Dimerization of TLR2 and MyD88 and subsequent phosphorylation of the key downstream signaling molecules, such as MAPKs and NK-κB, may be one of the key underlying mechanisms of activation of macrophages by these microbes. Bifidobacteria and lactobacilli induced macrophages to secrete IL-10 in a different manner, which may relate to their abilities to activate key signaling pathways mediated by TLR2 and MyD88.
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Affiliation(s)
- Huijing Liang
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University , Chengdu, China
| | - Zihao Luo
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University , Chengdu, China
| | - Zhonghua Miao
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University , Chengdu, China
| | - Xi Shen
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University , Chengdu, China
| | - Ming Li
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University , Chengdu, China
| | - Xuguang Zhang
- Nutrition and Health Research Centre, By-Health Co., Ltd , Guangzhou, China
| | - Jiehua Chen
- Nutrition and Health Research Centre, By-Health Co., Ltd , Guangzhou, China
| | - Xiaolei Ze
- Nutrition and Health Research Centre, By-Health Co., Ltd , Guangzhou, China
| | - Qiwei Chen
- Department of Pathogenic Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University , Chengdu, China
| | - Fang He
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University , Chengdu, China
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9
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Yue B, Yu ZL, Lv C, Geng XL, Wang ZT, Dou W. Regulation of the intestinal microbiota: An emerging therapeutic strategy for inflammatory bowel disease. World J Gastroenterol 2020; 26:4378-4393. [PMID: 32874052 PMCID: PMC7438192 DOI: 10.3748/wjg.v26.i30.4378] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 07/02/2020] [Accepted: 07/04/2020] [Indexed: 02/06/2023] Open
Abstract
The rapid development of metagenomics, metabolomics, and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease (IBD). Multiple microorganisms play a role in intestinal health; these include bacteria, fungi, and viruses that exist in a dynamic balance to maintain mucosal homeostasis. Perturbations in the intestinal microbiota disrupt mucosal homeostasis and are closely related to IBD in humans and colitis in mice. Therefore, preventing or correcting the imbalance of microbiota may serve as a novel prevention or treatment strategy for IBD. We review the most recent evidence for direct or indirect interventions targeting intestinal microbiota for treatment of IBD in order to overcome the current limitations of IBD therapies and shed light on personalized treatment options.
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Affiliation(s)
- Bei Yue
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Zhi-Lun Yu
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Cheng Lv
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiao-Long Geng
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Zheng-Tao Wang
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Wei Dou
- The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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10
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Lu R, Shang M, Zhang YG, Jiao Y, Xia Y, Garrett S, Bakke D, Bäuerl C, Martinez GP, Kim CH, Kang SM, Sun J. Lactic Acid Bacteria Isolated From Korean Kimchi Activate the Vitamin D Receptor-autophagy Signaling Pathways. Inflamm Bowel Dis 2020; 26:1199-1211. [PMID: 32170938 PMCID: PMC7365811 DOI: 10.1093/ibd/izaa049] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Probiotic lactic acid bacteria (LAB) have been used in the anti-inflammation and anti-infection process of various diseases, including inflammatory bowel disease (IBD). Vitamin D receptor (VDR) plays an essential role in pathogenesis of IBD and infectious diseases. Previous studies have demonstrated that the human VDR gene is a key host factor to shape gut microbiome. Furthermore, intestinal epithelial VDR conditional knockout (VDRΔIEC) leads to dysbiosis. Low expressions of VDR is associated with impaired autophagy, accompanied by a reduction of ATG16L1 and LC3B. The purpose of this study is to investigate probiotic effects and mechanism in modulating the VDR-autophagy pathways. METHODS Five LAB strains were isolated from Korean kimchi. Conditional medium (CM) from these strains was used to treat a human cell line HCT116 or intestinal organoids to measure the expression of VDR and autophagy. Mouse embryonic fibroblast (MEF) cells with or without VDR were used to investigate the dependence on the VDR signaling. To test the role of LAB in anti-inflammation, VDR+/+ organoids were treated with 121-CM before infection with Salmonella enterica serovar Enteritidis. In vivo, the role of LAB in regulating VDR-autophagy signaling was examined using LAB 121-CM orally administrated to VDRLoxp and VDRΔIEC mice. RESULTS The LAB-CM-treated groups showed higher mRNA expression of VDR and its target genes cathelicidin compared with the control group. LAB treatment also enhanced expressions of Beclin-1 and ATG16L1 and changed the ratio of LC3B I and II, indicating the activation of autophagic responses. Furthermore, 121-CM treatment before Salmonella enterica serovar Enteritidis infection dramatically increased VDR and ATG16L1 and inhibited the inflammation. Administration of 121-CM to VDRLoxp and VDRΔIEC mice for 12 and 24 hours resulted in an increase of VDR and LC3B II:I ratio. Furthermore, we identified that probiotic proteins P40 and P75 in the LAB-CM contributed to the anti-inflammatory function by increasing VDR. CONCLUSIONS Probiotic LAB exert anti-inflammation activity and induces autophagy. These effects depend on the VDR expression. Our data highlight the beneficial effects of these 5 LAB strains isolated from food in anti-infection and anti-inflammation.
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Affiliation(s)
- Rong Lu
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Mei Shang
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Yong-Guo Zhang
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Yang Jiao
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Yinglin Xia
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Shari Garrett
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Danika Bakke
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Christine Bäuerl
- Lactic Acid Bacteria Laboratory, Department of Biotechnology, Instituto de Agroquimicay Tecnologia de Alimentos, Spanish National Research Council (C.S.I.C.), Valencia, Spain
| | - Gaspar Perez Martinez
- Lactic Acid Bacteria Laboratory, Department of Biotechnology, Instituto de Agroquimicay Tecnologia de Alimentos, Spanish National Research Council (C.S.I.C.), Valencia, Spain
| | - Cheol-Hyun Kim
- Animal Resource Science, Dankook University, Chungnam, Korea
| | - Sang-Moo Kang
- Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA
| | - Jun Sun
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA,UIC Cancer Center, Chicago, Illinois, USA,Address correspondence to: Jun Sun, PhD, AGAF, FAPS, Professor, Division of Gastroenterology and Hepatology Department of Medicine, University of Illinois at Chicago 840 S. Wood Street, Room 704 CSB, MC716 Chicago, IL, 60612, USA. E-mail:
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11
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Glassner KL, Abraham BP, Quigley EMM. The microbiome and inflammatory bowel disease. J Allergy Clin Immunol 2020; 145:16-27. [PMID: 31910984 DOI: 10.1016/j.jaci.2019.11.003] [Citation(s) in RCA: 522] [Impact Index Per Article: 104.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/06/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic immune-mediated disease affecting the gastrointestinal tract. IBD consists of 2 subtypes: ulcerative colitis and Crohn disease. IBD is thought to develop as a result of interactions between environmental, microbial, and immune-mediated factors in a genetically susceptible host. Of late, the potential role of the microbiome in the development, progression, and treatment of IBD has been a subject of considerable interest and enquiry. Indeed, studies in human subjects have shown that the gut microbiome is different in patients with IBD compared with that in healthy control subjects. Other evidence in support of a fundamental role for the microbiome in patients with IBD includes identification of mutations in genes involved in microbiome-immune interactions among patients with IBD and epidemiologic observations implicating such microbiota-modulating risk factors as antibiotic use, cigarette smoking, levels of sanitation, and diet in the pathogenesis of IBD. Consequently, there has been much interest in the possible benefits of microbiome-modulating interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in the treatment of IBD. In this review we will discuss the role of the gut microbiome in patients with IBD; our focus will be on human studies.
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Affiliation(s)
- Kerri L Glassner
- Fondren IBD Program, Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Tex.
| | - Bincy P Abraham
- Fondren IBD Program, Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Tex
| | - Eamonn M M Quigley
- Fondren IBD Program, Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Tex
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12
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Tarasiuk A, Eibl G. Nutritional Support and Probiotics as a Potential Treatment of IBD. Curr Drug Targets 2020; 21:1417-1427. [PMID: 32364071 DOI: 10.2174/1389450121666200504075519] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 02/04/2020] [Accepted: 04/02/2020] [Indexed: 01/12/2023]
Abstract
The pathogenesis of inflammatory bowel disease (IBD) remains unknown. However, there is growing evidence that the increase in the overall incidence of IBD relates to the improvement of sanitary and hygienic conditions of the society leading to lower exposure to both bacterial and parasitic infections. IBD is incurable and characterized by alternating periods of exacerbation and remission of symptoms. Therefore, the main goal of treatment strategies in IBD patients is the most effective maintenance of clinical and endoscopic remission, which does allow patients to function normally for a significant part of life. Taking into account the evidence from different areas, there is a strong rationale supporting the concept that bacteria are important in gut inflammation and that probiotic bacteria may modulate the host-microbe interaction in a way that is directly beneficial to IBD patients along with nutritional support. In this review, we focus on the potential role of gastrointestinal microbiota in the pathogenesis of IBD and the possible value of probiotics, prebiotics, and symbiotics as well as nutritional support in the treatment of IBD.
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Affiliation(s)
- Aleksandra Tarasiuk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Guido Eibl
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
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Yılmaz İ, Dolar ME, Özpınar H. Effect of administering kefir on the changes in fecal microbiota and symptoms of inflammatory bowel disease: A randomized controlled trial. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:242-253. [PMID: 30662004 DOI: 10.5152/tjg.2018.18227] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND/AIMS Kefir is a kind of fermented probiotic dairy product. The objective of the present study was to investigate the effects of kefir consumption on the fecal microflora and symptoms of patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS Kefir was serially diluted and inoculated into de Man, Rogosa, and Sharpe agar and incubated at 37°C for 48 to 72 h under anaerobic conditions. This was a single-center, prospective, open-label randomized controlled trial. Forty-five patients with IBD were classified into two groups: 25 for treatment and 20 for control. A 400 mL/day kefir was administered to the patients for 4 weeks day and night. Their stool Lactobacillus, Lactobacillus kefiri, content was quantitated by real-time quantitative polymerase chain reaction before and after consumption. Abdominal pain, bloating, stool frequency, stool consistency, and feeling good scores were recorded in diaries daily by the patients. RESULTS A 5×107 CFU/mL count of lactic acid bacteria colony forming units was found in a kefir sample as the total average count. Lactobacillus bacterial load of feces of all subjects in the treatment group was between 104 and 109 CFU/g, and the first and last measurements were statistically significant (p=0.001 in ulcerative colitis and p=0.005 in Crohn's disease (CD)). The L. kefiri bacterial load in the stool of 17 subjects was measured as between 104 and 106 CFU/g. For patients with CD, there was a significant decrease in erythrocyte sedimentation rate and C-reactive protein, whereas hemoglobin increased, and for the last 2 weeks, bloating scores were significantly reduced (p=0.012), and feeling good scores increased (p=0.032). CONCLUSION According to our data, kefir consumption may modulate gut microbiota, and regular consumption of kefir may improve the patient's quality of life in the short term.
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Affiliation(s)
- İlkay Yılmaz
- Department of Food Engineering, İstanbul Aydın University, İstanbul, Turkey
| | - M Enver Dolar
- Department of Internal Medicine and Gastroenterology, Uludağ University School of Medicine, Bursa, Turkey
| | - Haydar Özpınar
- Graduate School of Health Sciences, Istanbul Gedik University, İstanbul, Turkey
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14
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Panaccione R, Steinhart AH, Bressler B, Khanna R, Marshall JK, Targownik L, Afif W, Bitton A, Borgaonkar M, Chauhan U, Halloran B, Jones J, Kennedy E, Leontiadis GI, Loftus EV, Meddings J, Moayyedi P, Murthy S, Plamondon S, Rosenfeld G, Schwartz D, Seow CH, Williams C, Bernstein CN. Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease. Clin Gastroenterol Hepatol 2019; 17:1680-1713. [PMID: 30853616 DOI: 10.1016/j.cgh.2019.02.043] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 02/21/2019] [Accepted: 02/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. METHODS We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. RESULTS The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. CONCLUSIONS Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.
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Affiliation(s)
- Remo Panaccione
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
| | - A Hillary Steinhart
- Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Brian Bressler
- Department of Medicine, Division of Gastroenterology, St Paul's Hospital, Vancouver, British Columbia, Canada
| | - Reena Khanna
- Department of Medicine, University of Western Ontario, London, Ontario, Canada
| | - John K Marshall
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Laura Targownik
- Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Waqqas Afif
- Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Alain Bitton
- Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Mark Borgaonkar
- Faculty of Medicine, Memorial University, St John's, Newfoundland, Canada
| | - Usha Chauhan
- Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Brendan Halloran
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - Jennifer Jones
- Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Erin Kennedy
- Division of General Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Grigorios I Leontiadis
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Jonathan Meddings
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Paul Moayyedi
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Sanjay Murthy
- Division of Gastroenterology, University of Ottawa, Ottawa, Ontario, Canada
| | - Sophie Plamondon
- Department of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada
| | - Greg Rosenfeld
- Division of Gastroenterology, Pacific Gastroenterology Associates, Vancouver, British Columbia, Canada
| | - David Schwartz
- Inflammatory Bowel Disease Center, Vanderbilt University, Nashville, Tennessee
| | - Cynthia H Seow
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | | | - Charles N Bernstein
- Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada
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Amiri M, Navabi J, Shokoohinia Y, Heydarpour F, Bahrami G, Behbood L, Derakhshandeh P, Momtaz S, Farzaei MH. Efficacy and safety of a standardized extract from Achillea wilhelmsii C. Koch in patients with ulcerative colitis: A randomized double blind placebo-controlled clinical trial. Complement Ther Med 2019; 45:262-268. [PMID: 31331572 DOI: 10.1016/j.ctim.2019.05.001] [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] [Received: 12/05/2018] [Revised: 03/26/2019] [Accepted: 05/01/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Using Achillea wilhelmsii as a dietary supplement for gastrointestinal disorders is common in Persian traditional medicine. Its anti-inflammatory, anti-spasmodic and antibacterial properties have been proven by different in vitro and in vivo studies, yet it has not been evaluated in a controlled clinical trial. AIM This study intended to evaluate the efficacy and safety of A. wilhelmsii in patients with mild to moderate active ulcerative colitis in a randomized, double-blinded, placebo-controlled clinical trial. The hydroalcoholic extract of A. wilhelmsii was standardized based on caffeic acid. METHODS Forty-nine patients were randomly received A. wilhelmsii capsules or placebo, twice daily for 4 weeks in a 1:1 ratio. The disease activity index (DAI) (Partial Mayo Score), haemoglobin, platelet count, erythrocyte sedimentation rate (ESR) and serum level of C-reactive protein (CRP) were measured at the entry and the end of the treatment. To standardize the extract, caffeic acid was detected and measured in the plant extract using high performance liquid chromatography (HPLC). RESULTS Of 49 patients who entered the trial, 40 patients completed the study. In both treatment and placebo groups, significant reductions were observed in stool frequency, rectal bleeding, physician global assessment and partial mayo score. There was no significant difference in stool frequency (P = 0.176), rectal bleeding (P = 0.523), physician global assessment (P = 0.341) and partial mayo score (P = 1) in the treatment versus the placebo groups. Laboratory variables including hemoglobin, platelet count, ESR and CRP showed no significant difference between the treatment and the placebo group. Of all participants, only one patient in the treatment group complained about skin rash (grade 1 based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0). CONCLUSION Oral administration of A. wilhelmsii powder for 4 weeks did not create a clinical response more than placebo. It seemed to be safe in UC patients. Further studies are obligatory to evaluate the therapeutic potential of A. wilhelmsii in the form of extract in UC patients.
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Affiliation(s)
- Mahtab Amiri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Jafar Navabi
- Department of Internal Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Yalda Shokoohinia
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Fatemeh Heydarpour
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gholamreza Bahrami
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Leila Behbood
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | | | - Saeideh Momtaz
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran; Toxicology and Diseases Group, the Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Akinshina AI, Smirnova DV, Zagainova AV, Makarov VV, Yudin SM. Prospects of Using Microbiota Correction Methods in the Treatment of Inflammatory Bowel Disease. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2019; 29:12-22. [DOI: 10.22416/1382-4376-2019-29-2-12-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Aim. The present article examines key methods of microbiota correction (antibiotic therapy; pro-, pre- and metabiotic therapy; faecal microbiota transplantation) used in treating inflammatory bowel disease, as well as compares the clinical trial results of these methods.Key findings. Inflammatory bowel disease (IBD) is an umbrella term used to describe a group of chronic diseases of unknown aetiology. In the past, bacteriological methods based on the isolation of a pure bacterial culture were used to determine the microbiota composition. However, such methods did not provide complete information on the microbiota composition. In recent years, preference has been given to more accurate and faster molecular genetic methods allowing a more detailed study of the key mechanisms by which microbiota affects the intestine in Crohn’s disease (CD) and ulcerative colitis (UC), as well as of the effect of microbial metabolites on their pathogenesis. The article provides an overview of main microbiota metabolites and their role in regulating the intestinal barrier function. One of the current issues consists in the development of personalised approaches to therapy and remission maintenance in IBD, including via methods for correcting the microbial composition: probiotic, prebiotic and metabiotic therapy, as well as faecal microbiota transplantation.Conclusion. The use of probiotics, prebiotics, and metabiotics can enhance the effectiveness of therapeutic regimens and significantly improve the quality of life of patients with chronic IBD. The use of antibiotics and faecal microbiota transplantation in treating IBD is the subject of extensive discussion and debate. The safety of these methods has not been confirmed so far; therefore, it is vital to continue studying their influence on the clinical condition of patients.
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Affiliation(s)
- A. I. Akinshina
- Centre for Strategic Planning and Management of Biomedical Health Risks
| | - D. V. Smirnova
- Centre for Strategic Planning and Management of Biomedical Health Risks
| | - A. V. Zagainova
- Centre for Strategic Planning and Management of Biomedical Health Risks
| | - V. V. Makarov
- Centre for Strategic Planning and Management of Biomedical Health Risks
| | - S. M. Yudin
- Centre for Strategic Planning and Management of Biomedical Health Risks
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A randomised, double-blind, placebo-controlled trial of a multi-strain probiotic in patients with asymptomatic ulcerative colitis and Crohn's disease. Inflammopharmacology 2019; 27:465-473. [PMID: 31054010 PMCID: PMC6554453 DOI: 10.1007/s10787-019-00595-4] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 04/03/2019] [Indexed: 01/01/2023]
Abstract
Background There is considerable interest in the possible importance of the gut microflora in the pathophysiology of the inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD). Probiotics offer a potential adjuvant treatment in these patients by modifying the intestinal milieu, but reports of their efficacy are conflicting. Aims To assess the efficacy of a multi-strain probiotic (Symprove™, Symprove Ltd, Farnham, United Kingdom) in quality of life issues and intestinal inflammation in patients with asymptomatic UC and CD. Methods A single-centre, randomised, double-blind, placebo-controlled trial of adult patients with asymptomatic IBD. Patients received 4 weeks of treatment with the probiotic or placebo (1 ml/kg/day). The primary efficacy measure was the difference in change in the IBD Quality of Life Questionnaire results (QOL) between probiotic vs. placebo at week 4. Secondary outcome measures included analyses of the change in laboratory findings, including faecal calprotectin (FCAL). Results Over 500 patients were recruited to the study and 81 and 61 patients with UC and CD, respectively were randomised and completed the study. There were no significant differences in IBD-QOL scores between placebo and the probiotic groups. Similarly, there were no significant changes observed in the laboratory data. However, the differences in FCAL between patients with UC before and after probiotics versus placebo approached statistical significance with a p value of 0.076. Post-hoc analyses showed that the FCAL levels were significantly (p < 0.015) reduced in the UC patients receiving the probiotic as opposed to placebo. No significant changes were seen in CD. No serious adverse events were observed. Conclusion This multi-strain probiotic is associated with decreased intestinal inflammation in patients with UC, but not in CD and is well tolerated. Further research is required to see if the probiotic reduces the incidence of clinical relapses in asymptomatic IBD patients.
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18
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Jeong DY, Kim S, Son MJ, Son CY, Kim JY, Kronbichler A, Lee KH, Shin JI. Induction and maintenance treatment of inflammatory bowel disease: A comprehensive review. Autoimmun Rev 2019; 18:439-454. [PMID: 30844556 DOI: 10.1016/j.autrev.2019.03.002] [Citation(s) in RCA: 148] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) are the two major types of inflammatory bowel disease (IBD). We conducted a comprehensive review of meta-analyses to summarize the reported effectiveness of different drugs for IBD. We performed a literature search and a total of 110 meta-analyses from 66 articles were summarized and re-analyzed (62 in UC and 48 in CD). In summary, 5-ASA was more effective than placebo in both induction and maintenance treatment of UC, but there were conflicting results on the effect of 5-ASA on the induction treatment or relapse of CD. The use of immunomodulatory agents in the induction or maintenance phase of UC and CD using immunomodulators appeared to be more effective than placebo, but the results were impacted by small number of patients, discordant results with the largest study and risk of biases. Anti-TNF-α and anti-integrin therapeutic antibodies in both, induction and maintenance, showed a better efficacy than placebo in a large proportion of patients analyzed. Other agents, such as probiotics, antibiotics, omega-3, were shown to be more effective than placebo, but the same issues arose as stated above with the use of immunomodulatory agents. In conclusion, we performed a comprehensive review of meta-analysis on comparative efficacy of pharmacotherapy used in the management of IBD. Our review will augment our understanding of the treatment of UC and CD by providing a guideline for interpreting the statistically significant findings and discusses the optimal choice for IBD treatment.
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Affiliation(s)
- Dong Yeon Jeong
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Kim
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea; Pediatric Gastroenterology, Hepatology and Nutrition, Yonsei University College of Medicine, Severance Pediatric IBD Research Group, Severance Children's Hospital, Seoul 03722, Republic of Korea
| | - Min Ji Son
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | - Jong Yeob Kim
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Andreas Kronbichler
- Department of Internal Medicine IV, Medical University Innsbruck, Innsbruck, Austria
| | - Keum Hwa Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Gut-brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease. Acta Neuropsychiatr 2018; 30:275-296. [PMID: 28270247 DOI: 10.1017/neu.2017.3] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
UNLABELLED IntroductionInflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder characterised by inflammation of the gastrointestinal tract. There is a growing consensus that IBD is associated with anxiety- and depression-related symptoms. Psychological symptoms appear to be more prevalent during active disease states with no difference in prevalence between Crohn's disease and ulcerative colitis. Behavioural disturbances including anxiety- and depression-like symptoms have also been observed in animal models of IBD. RESULTS The likely mechanisms underlying the association are discussed with particular reference to communication between the gut and brain. The close bidirectional relationship known as the gut-brain axis includes neural, hormonal and immune communication links. Evidence is provided for a number of interacting factors including activation of the inflammatory response system in the brain, the hypothalamic-pituitary-adrenal axis, and brain areas implicated in altered behaviours, changes in blood brain barrier integrity, and an emerging role for gut microbiota and response to probiotics in IBD.DiscussionThe impact of psychological stress in models of IBD remains somewhat conflicted, however, it is weighted in favour of stress or early stressful life events as risk factors in the development of IBD, stress-induced exacerbation of inflammation and relapse. CONCLUSION It is recommended that patients with IBD be screened for psychological disturbance and treated accordingly as intervention can improve quality of life and may reduce relapse rates.
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Panaccione R, Steinhart AH, Bressler B, Khanna R, Marshall JK, Targownik L, Afif W, Bitton A, Borgaonkar M, Chauhan U, Halloran B, Jones J, Kennedy E, Leontiadis GI, Loftus EV, Meddings J, Moayyedi P, Murthy S, Plamondon S, Rosenfeld G, Schwartz D, Seow CH, Williams C, Bernstein CN. Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease. J Can Assoc Gastroenterol 2018; 2:e1-e34. [PMID: 31294378 PMCID: PMC6619415 DOI: 10.1093/jcag/gwz019] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background & Aims Crohn’s disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. Methods We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. Results The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Conclusions Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.
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Affiliation(s)
- Remo Panaccione
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - A Hillary Steinhart
- Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Brian Bressler
- Department of Medicine, Division of Gastroenterology, St Paul's Hospital, Vancouver, British Columbia, Canada
| | - Reena Khanna
- Department of Medicine, University of Western Ontario, London, Ontario, Canada
| | - John K Marshall
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Laura Targownik
- Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Waqqas Afif
- Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Alain Bitton
- Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Mark Borgaonkar
- Faculty of Medicine, Memorial University, St John's, Newfoundland, Canada
| | - Usha Chauhan
- Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Brendan Halloran
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - Jennifer Jones
- Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Erin Kennedy
- Division of General Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Grigorios I Leontiadis
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Jonathan Meddings
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Paul Moayyedi
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Sanjay Murthy
- Division of Gastroenterology, University of Ottawa, Ottawa, Ontario, Canada
| | - Sophie Plamondon
- Department of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada
| | - Greg Rosenfeld
- Division of Gastroenterology, Pacific Gastroenterology Associates, Vancouver, British Columbia, Canada
| | - David Schwartz
- Inflammatory Bowel Disease Center, Vanderbilt University, Nashville, Tennessee
| | - Cynthia H Seow
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | | | - Charles N Bernstein
- Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada
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21
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Schäffler H, Herlemann DP, Klinitzke P, Berlin P, Kreikemeyer B, Jaster R, Lamprecht G. Vitamin D administration leads to a shift of the intestinal bacterial composition in Crohn's disease patients, but not in healthy controls. J Dig Dis 2018; 19:225-234. [PMID: 29573237 DOI: 10.1111/1751-2980.12591] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Revised: 03/09/2018] [Accepted: 03/14/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Dysbiosis is a common feature in the pathogenesis of inflammatory bowel diseases (IBD). Environmental factors, such as vitamin D deficiency, seem to play a role in the intestinal inflammation of IBD. The aim of this study was to investigate whether vitamin D administration has an impact on the bacterial composition in Crohn's disease (CD) compared to healthy controls (HC). METHODS A prospective, longitudinal, controlled interventional analysis was conducted in seven patients with CD in clinical remission and 10 HC to investigate the effect of orally administrated vitamin D on the intestinal bacterial composition using 16S ribosomal RNA gene amplicon sequencing. Clinical parameters were assessed. RESULTS In contrast to HC, microbial communities of CD patients changed significantly during early vitamin D administration. However, a further increase in vitamin D level was associated with a reversal of this effect and additionally with a decrease in the bacterial richness in the CD microbiome. Specific species with a high abundancy were found during vitamin D administration in CD, but not in HC; the abundancy of Alistipes, Barnesiella, unclassified Porphyromonadaceae (both Actinobacteria), Roseburia, Anaerotruncus, Subdoligranulum and an unclassified Ruminococaceae (all Firmicutes) increased significantly after 1-week vitamin D administration in CD. CONCLUSIONS Vitamin D has a specific influence on the bacterial communities in CD, but not in HC. Administration of vitamin D may have a positive effect in CD by modulating the intestinal bacterial composition and also by increasing the abundance of potential beneficial bacterial strains.
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Affiliation(s)
- Holger Schäffler
- Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany
| | - Daniel Pr Herlemann
- Leibniz-Institut für Ostseeforschung Warnemünde (IOW), Biological Oceanography, Rostock, Germany.,Estonian University of Life Sciences, Center of Limnology, Elva, Estonia
| | - Paul Klinitzke
- Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany
| | - Peggy Berlin
- Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany
| | - Bernd Kreikemeyer
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center, Rostock, Germany
| | - Robert Jaster
- Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany
| | - Georg Lamprecht
- Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany
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Limketkai BN, Wolf A, Parian AM. Nutritional Interventions in the Patient with Inflammatory Bowel Disease. Gastroenterol Clin North Am 2018; 47:155-177. [PMID: 29413010 DOI: 10.1016/j.gtc.2017.09.007] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nutritional strategies have been explored as primary or adjunct therapies for inflammatory bowel disease (IBD). Exclusive enteral nutrition is effective for the induction of remission in Crohn disease and is recommended as a first-line therapy for children. Dietary strategies focus on adjusting the ratio of consumed nutrients that are proinflammatory or antiinflammatory. Treatments with dietary supplements focus on the antiinflammatory effects of the individual supplements (eg, curcumin, omega-3 fatty acids, vitamin D) or their positive effects on the intestinal microbiome (eg, prebiotics, probiotics). This article discusses the role of diets and dietary supplements in the treatment of IBD.
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Affiliation(s)
- Berkeley N Limketkai
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Alway M211, Stanford, CA 94305, USA.
| | - Andrea Wolf
- Department of Clinical Nutrition, Stanford Health Care, Stanford, 300 Pasteur Drive, Palo Alto, CA 94305, USA
| | - Alyssa M Parian
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD 21287, USA
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Abstract
With the advent of the scientific realization that the microbiota of the gastrointestinal tract was more than the cells that exist in the body, the full importance of prebiotics and probiotics has come forth. The importance has been stressed and is available in the new textbook entitled, "The Microbiota in Gastrointestinal Pathophysiology: Implication for Human Health, Prebiotics, Probiotics and Dysbiosis." There is enough evidence now published in the literature so that the scientific world now believes that prebiotics and probiotics are important in gastrointestinal disease.
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Affiliation(s)
- Martin H Floch
- Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, 1089 LMP, New Haven, CT 06850, USA.
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24
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Miyoshi J, Qiao Y, Chang EB. The role of the intestinal microbiota in the pathogenesis and treatment of inflammatory bowel diseases. SEMINARS IN COLON AND RECTAL SURGERY 2018. [DOI: 10.1053/j.scrs.2017.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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25
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Abstract
The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity.
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Affiliation(s)
- Jose C Clemente
- Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Julia Manasson
- Department of Medicine, Division of Rheumatology, New York University School of Medicine and Hospital for Joint Diseases, New York, NY 10003, USA
| | - Jose U Scher
- Department of Medicine, Division of Rheumatology, New York University School of Medicine and Hospital for Joint Diseases, New York, NY 10003, USA
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27
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Abstract
Evidence indicates that the gut microbiota and/or interactions between the microbiota and the host immune system are involved in the pathogenesis of inflammatory bowel disease (IBD). Strategies that target the microbiota have emerged as potential therapies and, of these, probiotics have gained the greatest attention. Data derived from animal models of IBD have revealed the potential of several bacterial strains to modify the natural history of IBD. However, thought there is some evidence for efficacy in ulcerative colitis and in pouchitis, in particular, there has been little indication that probiotics exert any benefit in Crohn disease. More targeted approaches involving live bacteria, genetically modified bacteria, and bacterial products are now being evaluated.
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Affiliation(s)
- Bincy P Abraham
- Fondren Inflammatory Bowel Disease Program, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Weill Cornell Medical College, 6550 Fannin Street, SM 1201, Houston, TX 77030, USA; Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Weill Cornell Medical College, 6550 Fannin Street, SM 1201, Houston, TX 77030, USA
| | - Eamonn M M Quigley
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Weill Cornell Medical College, 6550 Fannin Street, SM 1201, Houston, TX 77030, USA.
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28
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Shen Z, Zhu C, Quan Y, Yuan W, Wu S, Yang Z, Luo W, Tan B, Wang X. Update on intestinal microbiota in Crohn's disease 2017: Mechanisms, clinical application, adverse reactions, and outlook. J Gastroenterol Hepatol 2017; 32:1804-1812. [PMID: 28677158 DOI: 10.1111/jgh.13861] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 06/30/2017] [Indexed: 12/17/2022]
Abstract
The pathogenesis of Crohn's disease (CD) is complex, and it is thought to be associated with the environment, immune, hereditary, microbe, and other factors. If the balance between the host and the intestinal microbes in CD patients was broken, immune-inflammatory response of susceptible individuals might be triggered. Probiotics could improve the intestinal microbial flora balance and treat human effectively. There are several new mechanisms that might explain the role of probiotics. Fecal microbiota transplantation (FMT) is becoming more and more attractive in treating a large amount of digestive system diseases that are related to the dysbiosis of intestinal microbiota. FMT has been widely used in recurrent Clostridium difficile infection. More and more attention has been paid on the clinical application of FMT in CD, while the exact mechanism is still a mystery. So in this review, we explore the mechanism, clinical application, and adverse reactions of intestinal microbiota in CD so that we can use the tool to cure more diseases. Enteric microbiota leads to new therapeutic strategies for CD.
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Affiliation(s)
- 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
| | - 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
| | - 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
| | - 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
| | - 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
| | - 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
| | - Weiwei Luo
- Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Bei Tan
- 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
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29
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Zoumpopoulou G, Tsakalidou E, Thomas L. An Overview of Probiotic Research. PROBIOTIC DAIRY PRODUCTS 2017:293-357. [DOI: 10.1002/9781119214137.ch8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Derwa Y, Gracie DJ, Hamlin PJ, Ford AC. Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease. Aliment Pharmacol Ther 2017; 46:389-400. [PMID: 28653751 DOI: 10.1111/apt.14203] [Citation(s) in RCA: 254] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Revised: 05/23/2017] [Accepted: 06/04/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. AIM To perform a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. METHODS MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). RESULTS The search identified 12 253 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86; 95% CI=0.68-1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74; 95% CI=0.63-0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR=1.02; 95% CI=0.85-1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission. CONCLUSIONS VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.
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Affiliation(s)
- Y Derwa
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
| | - D J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
| | - P J Hamlin
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - A C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
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31
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Shang M, Sun J. Vitamin D/VDR, Probiotics, and Gastrointestinal Diseases. Curr Med Chem 2017; 24:876-887. [PMID: 27915988 DOI: 10.2174/0929867323666161202150008] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 10/17/2016] [Accepted: 10/18/2016] [Indexed: 12/14/2022]
Abstract
Vitamin D is an important factor in regulating inflammation, immune responses, and carcinoma inhibition via action of its receptor, vitamin D receptor (VDR). Recent studies have demonstrated the role of vitamin D/VDR in regulating host-bacterial interactions. Probiotics are beneficial bacteria with the power of supporting or favoring life on the host. In the current review, we will discuss the recent progress on the roles of vitamin D/VDR in gut microbiome and inflammation. We will summarize evidence of probiotics in modulating vitamin D/VDR and balancing gut microbiota in health and gastrointestinal diseases. Moreover, we will review the clinical application of probiotics in prevention and therapy of IBD or colon cancer. Despite of the gains, there remain several barriers to advocate broad use of probiotics in clinical therapy. We will also discuss the limits and future direction in scientific understanding of probiotics, vitamin D/VDR, and host responses.
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Affiliation(s)
- Mei Shang
- Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou. China
| | - Jun Sun
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, 840 S Wood Street, Room 704 CSB, Chicago, IL, 60612. United States
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32
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Currò D, Ianiro G, Pecere S, Bibbò S, Cammarota G. Probiotics, fibre and herbal medicinal products for functional and inflammatory bowel disorders. Br J Pharmacol 2017; 174:1426-1449. [PMID: 27696378 PMCID: PMC5429330 DOI: 10.1111/bph.13632] [Citation(s) in RCA: 109] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 08/11/2016] [Accepted: 09/13/2016] [Indexed: 12/11/2022] Open
Abstract
Functional bowel disorders (FBD), mainly irritable bowel syndrome (IBS) and functional constipation (FC, also called chronic idiopathic constipation), are very common worldwide. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, although less common, has a strong impact on patients' quality of life, as well as being highly expensive for our healthcare. A definite cure for those disorders is still yet to come. Over the years, several therapeutic approaches complementary or alternative to traditional pharmacological treatments, including probiotics, prebiotics, synbiotics, fibre and herbal medicinal products, have been investigated for the management of both groups of diseases. However, most available studies are biased by several drawbacks, including small samples and poor methodological quality. Probiotics, in particular Saccharomyces boulardii and Lactobacilli (among which Lactobacillus rhamnosus), synbiotics, psyllium, and some herbal medicinal products, primarily peppermint oil, seem to be effective in ameliorating IBS symptoms. Synbiotics and fibre seem to be beneficial in FC patients. The probiotic combination VSL#3 may be effective in inducing remission in patients with mild-to-moderate ulcerative colitis, in whom Escherichia coli Nissle 1917 seems to be as effective as mesalamine in maintaining remission. No definite conclusions can be drawn as to the efficacy of fibre and herbal medicinal products in IBD patients due to the low number of studies and the lack of randomized controlled trials that replicate the results obtained in the individual studies conducted so far. Thus, further, well-designed studies are needed to address the real role of these therapeutic options in the management of both FBD and IBD. LINKED ARTICLES This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
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Affiliation(s)
- Diego Currò
- Institute of PharmacologySchool of Medicine, Catholic University of the Sacred HeartL.go F. Vito 100168RomeItaly
| | - Gianluca Ianiro
- Department of Internal MedicineSchool of Medicine, Catholic University of the Sacred HeartL.go F. Vito 100168RomeItaly
| | - Silvia Pecere
- Department of Internal MedicineSchool of Medicine, Catholic University of the Sacred HeartL.go F. Vito 100168RomeItaly
| | - Stefano Bibbò
- Department of Clinical and Experimental MedicineUniversity of SassariV.le S. Pietro, 807100SassariItaly
| | - Giovanni Cammarota
- Department of Internal MedicineSchool of Medicine, Catholic University of the Sacred HeartL.go F. Vito 100168RomeItaly
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33
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Ganji-Arjenaki M, Rafieian-Kopaei M. Probiotics are a good choice in remission of inflammatory bowel diseases: A meta analysis and systematic review. J Cell Physiol 2017; 233:2091-2103. [PMID: 28294322 DOI: 10.1002/jcp.25911] [Citation(s) in RCA: 217] [Impact Index Per Article: 27.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 03/13/2017] [Indexed: 02/06/2023]
Abstract
Altered gut bacteria and bacterial metabolic pathways are two important factors in initiation and progression of inflammatory bowel disease (IBD). However, efficacy of probiotics in remission of patients with IBD has not been characterized. This study was performed on the studies that specifically assessed the efficacy of probiotics in attaining clinical response on patients with various types of IBD. The efficacy of variant species of probiotics in different conditions and the influence of study quality in outcomes of randomized controlled trials (RCTs) were also assessed. The RCTs were collected by searching in MEDLINE Web of Science and Google scholar. Then all studies were abstracted in abstraction form and the outcomes were analyzed with fixed-effect and mixed-effect models for assessment of efficacy of variant species of probiotics in subgroups of IBDs. Analysis of 9 trials showed that probiotics had not significant effect on Crohn's disease (CD) (p = 0.07) but analysis of 3 trials in children with IBD revealed a significant advantage (p < 0.01). Analysis of 18 trials revealed that probiotics in patients with Ulcerative colitis (UC) in different conditions have significant effects (p = 0.007). VSL#3 probiotics in patients with UC had significant effect (p < 0.01). Combination of Lactobacillus probiotic, prebiotics had significant effect (p = 0.03) only in patients with UC. Combination of Saccharomyces boulardii, Lactobacillus, and VSL#3 probiotics in CD had also a trend for efficiency (p = 0.057). In children with IBD, the combination of Lactobacillus with VSL#3 probiotics had significant effect (p < 0.01). Probiotics are beneficial in IBD, especially the combination ones in UC.
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34
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Roy U, Jessani LG, Rudramurthy SM, Gopalakrishnan R, Dutta S, Chakravarty C, Jillwin J, Chakrabarti A. Seven cases of Saccharomyces fungaemia related to use of probiotics. Mycoses 2017; 60:375-380. [PMID: 28133894 DOI: 10.1111/myc.12604] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 12/15/2016] [Accepted: 01/06/2017] [Indexed: 11/28/2022]
Abstract
Probiotics are increasingly used in critically ill patients without enough safety data. The aim of the present study was to determine the association of probiotics with Saccharomyces cerevisiae fungaemia. Seven patients with S. cerevisiae fungaemia were reported at two hospitals in India between July 2014 and September 2015. Detailed clinical history of patients was recorded. Besides the seven patient isolates, three probiotics sachets used in those patients and five unrelated clinical isolates were used for association study by Fluorescent amplified fragment length polymorphism (FAFLP). Antifungal susceptibility testing was performed by broth microdilution technique of CLSI (M27-A3) and interpreted according to CLSI (M27S4). Two patients were premature neonates and five were adults. They were admitted in intensive care unit and were on probiotics containing S. boulardii (except one adult patient). FAFLP analysis showed 96.4-99.7% similarity between blood and corresponding probiotic isolates. Of the three AFLP types (group I, II, II) identified, all the probiotic isolates clustered in group I (major cluster) including majority of the blood isolates. The isolates were susceptible to all antifungal agents tested. Five patients, who could be evaluated, responded promptly to echinocandins or voriconazole. As the prescription of probiotic containing S. boulardii in critically ill patient's leads to the fungaemia, we recommend avoiding this probiotic in those patients.
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Affiliation(s)
| | | | - Shivaprakash M Rudramurthy
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Soma Dutta
- Apollo Gleneagles Hospitals, Kolkata, India
| | | | - Joseph Jillwin
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arunaloke Chakrabarti
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Dong J, Teng G, Wei T, Gao W, Wang H. Methodological Quality Assessment of Meta-Analyses and Systematic Reviews of Probiotics in Inflammatory Bowel Disease and Pouchitis. PLoS One 2016; 11:e0168785. [PMID: 28005973 PMCID: PMC5179087 DOI: 10.1371/journal.pone.0168785] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Accepted: 12/06/2016] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Probiotics are widely used for the induction and maintenance of remission in inflammatory bowel disease (IBD) and pouchitis. There are a large number of meta-analyses (MAs)/ systematic reviews (SRs) on this subject, the methodological quality of which has not been evaluated. OBJECTIVES This study aimed to evaluate the methodological quality of and summarize the evidence obtained from MAs/SRs of probiotic treatments for IBD and pouchitis patients. METHODS The PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases were searched to identify Chinese and English language MAs/SRs of the use of probiotics for IBD and pouchitis. The Assessment of Multiple Systematic Reviews (AMSTAR) scale was used to assess the methodological quality of the studies. RESULTS A total of 36 MAs/SRs were evaluated. The AMSTAR scores of the included studies ranged from 1 to 10, and the average score was 5.81. According to the Canadian Agency for Drugs and Technologies in Health, 4 articles were classified as high quality, 24 articles were classified as moderate quality, and 8 articles were classified as low quality. Most of the MAs/SRs suggested that probiotics had potential benefits for patients with ulcerative colitis (UC), but failed to show effectiveness in the induction and maintenance of remission in Crohn's disease (CD). The probiotic preparation VSL#3 may play a beneficial role in pouchitis. CONCLUSION The overall methodological quality of the current MAs/SRs in the field of probiotics for IBD and pouchitis was found to be low to moderate. More MAs/SRs of high quality are required to support using probiotics to treat IBD and pouchitis.
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Affiliation(s)
- Jinpei Dong
- Department of Gastroenterology, Peking University First Hospital, Peking University, Beijing, China
| | - Guigen Teng
- Department of Gastroenterology, Peking University First Hospital, Peking University, Beijing, China
| | - Tiantong Wei
- Department of Gastroenterology, Peking University First Hospital, Peking University, Beijing, China
| | - Wen Gao
- Department of Gastroenterology, Peking University First Hospital, Peking University, Beijing, China
| | - Huahong Wang
- Department of Gastroenterology, Peking University First Hospital, Peking University, Beijing, China
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36
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Qiao YQ, Cai CW, Ran ZH. Therapeutic modulation of gut microbiota in inflammatory bowel disease: More questions to be answered. J Dig Dis 2016; 17:800-810. [PMID: 27743467 DOI: 10.1111/1751-2980.12422] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 10/12/2016] [Indexed: 02/06/2023]
Abstract
Patients with inflammatory bowel disease (IBD) exhibit impaired control of the microbiome in the gut, and 'dysbiosis' is commonly observed. Western diet is a risk factor for the development of IBD, but it may have different effects on gut microbiota between IBD and non-IBD individuals. Exclusive enteral nutrition (EEN) can induce remission in pediatric Crohn's disease with a decrease in gut microbial diversity. Although there are some theoretical benefits, actual treatment effects of prebiotics and probiotics in IBD vary. High-quality studies have shown that VSL#3 (a high-potency probiotic medical food containing eight different strains) exhibits benefits in treating ulcerative colitis, and gut microbial diversity is reduced after treated with VSL#3 in animal models. The effect of fecal microbiome transplantation on IBD is controversial. Increasing microbial diversity compared with impaired handling of bacteria presents a dilemma. Antibiotics are the strongest factors in the reduction of microbiome ecological diversity. Some antibiotics may help to induce remission of the disease. Microbiome alteration has been suggested to be an intrinsic property of IBD and a potential predictor in diagnosis and prognosis. However, the effects of therapeutic modulations are variable; thus, more questions remain to be answered.
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Affiliation(s)
- Yu Qi Qiao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
| | - Chen Wen Cai
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
| | - Zhi Hua Ran
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
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Abstract
Inflammatory bowel diseases (IBD) are chronic immune disorders of unclear aetiology. Dietary deficiencies may be a potential pathogenic factor in their development. Patients often take food supplements without knowledge of any evidence base. We have therefore assessed the evidence for food supplementation in the management of IBD. A PubMed search was performed for the terms Inflammatory bowel disease; nutritional deficiencies; dietary supplements; curcumin; green tea; vitamin D/other vitamins; folic acid; iron; zinc; probiotics; andrographis paniculata; and boswellia serrate. PubMed was used to search for all relevant articles published between January 1975 and September 2015. Curcumin supplementation has been reported to be effective in reducing the symptoms and the inflammatory indices in IBD patients. Similar results have been observed for green tea; however, pertinent studies are limited. Vitamin D supplementation may help to increase bone mineral density in IBD patients and to reduce disease activity. IBD patients with ileal resections higher than 20 cm may develop vitamin B12 deficiency that requires parenteral supplementation. There is no current evidence to support fat-soluble vitamin supplementation in IBD patients. Zinc and iron should be supplemented in selected cases. Probiotics (VSL#3) may reduce disease activity in IBD patients with pouchitis. Complementary and alternative medicines are used by IBD patients and some studies have shown promising results. In summary, attention to dietary factors such as curcumin, green tea and vitamins, including vitamins D and B12, appears to be beneficial and, if necessary, supplementation may be appropriate.
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38
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Butel M, Waligora‐Dupriet A. Probiotics and prebiotics. THE HUMAN MICROBIOTA AND CHRONIC DISEASE 2016:467-481. [DOI: 10.1002/9781118982907.ch30] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Gallo A, Passaro G, Gasbarrini A, Landolfi R, Montalto M. Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate. World J Gastroenterol 2016; 22:7186-202. [PMID: 27621567 PMCID: PMC4997632 DOI: 10.3748/wjg.v22.i32.7186] [Citation(s) in RCA: 77] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Revised: 06/23/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, PubMed was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn's disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.
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Abstract
The intestinal microbiota has important metabolic and host-protective functions. Conversely to these beneficial functions, the intestinal microbiota is thought to play a central role in the etiopathogenesis of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), a chronic inflammation of the gut mucosa. Genetic screens and studies in experimental mouse models have clearly demonstrated that IBD can develop due to excessive translocation of bacteria into the bowel wall or dysregulated handling of bacteria in genetically susceptible hosts. In healthy individuals, the microbiota is efficiently separated from the mucosal immune system of the gut by the gut barrier, a single layer of highly specialized epithelial cells, some of which are equipped with innate immune functions to prevent or control access of bacterial antigens to the mucosal immune cells. It is currently unclear whether the composition of the microbial flora or individual bacterial strains or pathogens induces or supports the pathogenesis of IBD. Further research will be necessary to carefully dissect the contribution of individual bacterial species to this disease and to ascertain whether specific modulation of the intestinal microbiome may represent a valuable further option for future therapeutic strategies.
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Affiliation(s)
- Christoph Becker
- Christoph Becker, PhD, is associated professor, Markus F. Neurath, MD, is director, and Stefan Wirtz, PhD, is senior scientist at the Department of Medicine 1 at the Friedrich-Alexander University Erlangen-Nuremberg in Erlangen, Germany
| | - Markus F Neurath
- Christoph Becker, PhD, is associated professor, Markus F. Neurath, MD, is director, and Stefan Wirtz, PhD, is senior scientist at the Department of Medicine 1 at the Friedrich-Alexander University Erlangen-Nuremberg in Erlangen, Germany
| | - Stefan Wirtz
- Christoph Becker, PhD, is associated professor, Markus F. Neurath, MD, is director, and Stefan Wirtz, PhD, is senior scientist at the Department of Medicine 1 at the Friedrich-Alexander University Erlangen-Nuremberg in Erlangen, Germany
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41
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Basson A. Nutrition management in the adult patient with Crohn’s disease. SOUTH AFRICAN JOURNAL OF CLINICAL NUTRITION 2016. [DOI: 10.1080/16070658.2012.11734423] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Lichtenstein L, Avni-Biron I, Ben-Bassat O. Probiotics and prebiotics in Crohn's disease therapies. Best Pract Res Clin Gastroenterol 2016; 30:81-8. [PMID: 27048899 DOI: 10.1016/j.bpg.2016.02.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Revised: 01/29/2016] [Accepted: 02/02/2016] [Indexed: 02/06/2023]
Abstract
Therapeutic manipulation of gut microbiota has proven valuable in the management of ulcerative colitis and pouchitis. Despite some similarities among the various inflammatory bowel conditions, the probiotics investigated thus far seem to confer little benefit in Crohn's disease. In this review, we aim to bring together the evidence available on the clinical effect of probiotics and prebioltics in Crohn's disease patients, and to clarify the place of probiotic treatment in current Crohn's therapeutic regimens.
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Affiliation(s)
- Lev Lichtenstein
- Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel.
| | - Irit Avni-Biron
- Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
| | - Ofer Ben-Bassat
- Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
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Rastegarpanah M, Malekzadeh R, Vahedi H, Mohammadi M, Elahi E, Chaharmahali M, Safarnavadeh T, Abdollahi M. A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis. Chin J Integr Med 2015; 21:902-906. [PMID: 22528757 DOI: 10.1007/s11655-012-1026-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2011] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To evaluate the clinical efficacy of silymarin in ulcerative colitis (UC) patients. METHODS A randomized double blinded placebo-controlled clinical trial was conducted in 80 UC patients whose disease had been documented and were in remission state between September 2009 and October 2010. Patients were assigned to silymarin group (42 cases) and placebo group (38 cases) using a random number table. Either silymarin (140 mg) or placebo (lactose mono-hydrate, corn starch magnesium stearate) tablets were given once daily for 6 months along with their standard therapy. The efficacies were assessed by disease activity index (DAI), frequency difference of the disease flare-up, and paraclinical data. RESULTS Ten patients (4 in the silymarin group due to nausea and 6 in the placebo group due to disease flare-up and abdominal pain) discontinued the study. An improvement in hemoglobin level (11.8±1.6 g/dL vs. 13.4±1.2 g/dL,P<0.05) and erythrocyte sedimentation rate (23.7±11.5 mm/h vs.10.8±3.2 mm/h,P<0.05) was observed in the silymarin group but not in the placebo group. DAI significantly decreased in the silymarin group and reached from 11.3±3.5 to 10.7±2.8 (P<0.05). Thirty-five out of 38 patients in the silymarin group were in complete remission with no flare-up after 6 months as compared to 21 out of 32 patients in the placebo group (P=0.5000). CONCLUSION Silymarin as a natural supplement may be used in UC patients to maintain remission.
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Affiliation(s)
- Mansoor Rastegarpanah
- Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Homayoun Vahedi
- Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Elham Elahi
- Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Meghedi Chaharmahali
- Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Tahereh Safarnavadeh
- Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
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44
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Antioxidant therapy for treatment of inflammatory bowel disease: Does it work? Redox Biol 2015; 6:617-639. [PMID: 26520808 PMCID: PMC4637335 DOI: 10.1016/j.redox.2015.10.006] [Citation(s) in RCA: 266] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 10/18/2015] [Accepted: 10/20/2015] [Indexed: 12/13/2022] Open
Abstract
Oxidative stress (OS) is considered as one of the etiologic factors involved in several signals and symptoms of inflammatory bowel diseases (IBD) that include diarrhea, toxic megacolon and abdominal pain. This systematic review discusses approaches, challenges and perspectives into the use of nontraditional antioxidant therapy on IBD, including natural and synthetic compounds in both human and animal models. One hundred and thirty four papers were identified, of which only four were evaluated in humans. Some of the challenges identified in this review can shed light on this fact: lack of standardization of OS biomarkers, absence of safety data and clinical trials for the chemicals and biological molecules, as well as the fact that most of the compounds were not repeatedly tested in several situations, including acute and chronic colitis. This review hopes to stimulate researchers to become more involved in this fruitful area, to warrant investigation of novel, alternative and efficacious antioxidant-based therapies.
Major biomarkers used for evaluation of antioxidant therapy were MPO, TBARS/MDA and glutathione levels. Challenges were identified for the yet poor use of antioxidant therapy in IBD. This review stimulates the investigation of alternative and efficacious antioxidant therapies.
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Scientific evidence for health effects attributed to the consumption of probiotics and prebiotics: an update for current perspectives and future challenges. Br J Nutr 2015; 114:1993-2015. [PMID: 26443321 DOI: 10.1017/s0007114515003864] [Citation(s) in RCA: 111] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Probiotics and prebiotics, mainly commercialised as food ingredients and also as supplements, are considered highly profitable niche markets. However, in recent years, the food industry has suffered from a series of health claim restrictions on probiotics and prebiotics in many parts of the world, including those made by the European Food Safety Authority. Therefore, we reviewed the core benefits of probiotic and prebiotic consumption on health. A number of studies have examined the prevention and/or management of intestinal infections, respiratory tract infections, CVD, osteoporosis, urogenital infections, cavities, periodontal disease and halitosis, allergic reactions, inflammatory bowel disease and irritable bowel syndrome and Helicobacter pylori gastric infections. In fact, a deeper understanding of the mechanisms involved in human microbiota and immune system modulation by probiotics and prebiotics relies on continuous efforts to establish suitable biomarkers of health and diseases risk factors for the design of clinical trials required for health claim approval. In spite of the promising results, the performance of large, long-term, well-planned, well-aligned clinical studies is crucial to provide more reliability and a more solid basis for the outcomes achieved and to support the potential use of probiotics and prebiotics in clinical practice.
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46
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Wu S, Yoon S, Zhang YG, Lu R, Xia Y, Wan J, Petrof EO, Claud EC, Chen D, Sun J. Vitamin D receptor pathway is required for probiotic protection in colitis. Am J Physiol Gastrointest Liver Physiol 2015; 309:G341-9. [PMID: 26159695 PMCID: PMC4556945 DOI: 10.1152/ajpgi.00105.2015] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 06/26/2015] [Indexed: 02/08/2023]
Abstract
Low expression of vitamin D receptor (VDR) and dysfunction of vitamin D/VDR signaling are reported in patients with inflammatory bowel disease (IBD); therefore, restoration of VDR function to control inflammation in IBD is desirable. Probiotics have been used in the treatment of IBD. However, the role of probiotics in the modulation of VDR signaling to effectively reduce inflammation is unknown. We identified a novel role of probiotics in activating VDR activity, thus inhibiting inflammation, using cell models and VDR knockout mice. We found that the probiotics Lactobacillus rhamnosus strain GG (LGG) and Lactobacillus plantarum (LP) increased VDR protein expression in both mouse and human intestinal epithelial cells. Using the VDR luciferase reporter vector, we detected increased transcriptional activity of VDR after probiotic treatment. Probiotics increased the expression of the VDR target genes, such as antimicrobial peptide cathelicidin, at the transcriptional level. Furthermore, the role of probiotics in regulating VDR signaling was tested in vivo using a Salmonella-colitis model in VDR knockout mice. Probiotic treatment conferred physiological and histologic protection from Salmonella-induced colitis in VDR(+/+) mice, whereas probiotics had no effects in the VDR(-/-) mice. Probiotic treatment also enhanced numbers of Paneth cells, which secrete AMPs for host defense. These data indicate that the VDR pathway is required for probiotic protection in colitis. Understanding how probiotics enhance VDR signaling and inhibit inflammation will allow probiotics to be used effectively, resulting in innovative approaches to the prevention and treatment of chronic inflammation.
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Affiliation(s)
- Shaoping Wu
- 1Department of Biochemistry, Rush University, Chicago, Illinois;
| | - Sonia Yoon
- 2Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York;
| | - Yong-Guo Zhang
- 1Department of Biochemistry, Rush University, Chicago, Illinois;
| | - Rong Lu
- 1Department of Biochemistry, Rush University, Chicago, Illinois;
| | - Yinglin Xia
- 3Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York;
| | - Jiandi Wan
- 4Microsystems Engineering, Rochester Institute of Technology, Rochester, New York;
| | - Elaine O. Petrof
- 5Department of Medicine, Gastrointestinal Diseases Research Unit and Division of Infectious Diseases, Queen's University, Kingston, Ontario, Canada; and
| | - Erika C. Claud
- 6Departments of Pediatrics and Medicine, The University of Chicago Medical Center, Chicago, Illinois
| | - Di Chen
- 1Department of Biochemistry, Rush University, Chicago, Illinois;
| | - Jun Sun
- Department of Biochemistry, Rush University, Chicago, Illinois;
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47
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Srutkova D, Schwarzer M, Hudcovic T, Zakostelska Z, Drab V, Spanova A, Rittich B, Kozakova H, Schabussova I. Bifidobacterium longum CCM 7952 Promotes Epithelial Barrier Function and Prevents Acute DSS-Induced Colitis in Strictly Strain-Specific Manner. PLoS One 2015. [PMID: 26218526 PMCID: PMC4517903 DOI: 10.1371/journal.pone.0134050] [Citation(s) in RCA: 134] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Reduced microbial diversity has been associated with inflammatory bowel disease (IBD) and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis. METHODS Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952) and CCDM 372 (Bl 372) were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS)-induced colitis was used to compare their beneficial effects in vivo. RESULTS The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum. CONCLUSIONS We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD.
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Affiliation(s)
- Dagmar Srutkova
- Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Novy Hradek, Czech Republic
| | - Martin Schwarzer
- Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Novy Hradek, Czech Republic
| | - Tomas Hudcovic
- Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Novy Hradek, Czech Republic
| | - Zuzana Zakostelska
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Czech Republic
| | - Vladimir Drab
- Dairy Research Institute Ltd., Prague, Czech Republic
| | - Alena Spanova
- Brno University of Technology, Faculty of Chemistry, Brno, Czech Republic
| | - Bohuslav Rittich
- Brno University of Technology, Faculty of Chemistry, Brno, Czech Republic
| | - Hana Kozakova
- Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Novy Hradek, Czech Republic
- * E-mail:
| | - Irma Schabussova
- Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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48
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Parian AM, Limketkai BN, Shah ND, Mullin GE. Nutraceutical Supplements for Inflammatory Bowel Disease. Nutr Clin Pract 2015; 30:551-8. [PMID: 26024677 DOI: 10.1177/0884533615586598] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Alyssa M Parian
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Berkeley N Limketkai
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Palo Alto, California
| | - Neha D Shah
- Digestive Health Center, Stanford Health Care, Palo Alto, California
| | - Gerard E Mullin
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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49
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Patel R, DuPont HL. New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Clin Infect Dis 2015; 60 Suppl 2:S108-21. [PMID: 25922396 PMCID: PMC4490231 DOI: 10.1093/cid/civ177] [Citation(s) in RCA: 170] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota has a significant role in human health and disease. Dysbiosis of the intestinal ecosystem contributes to the development of certain illnesses that can be reversed by favorable alterations by probiotics. The published literature was reviewed to identify scientific data showing a relationship between imbalance of gut bacteria and development of diseases that can be improved by biologic products. The medical conditions vary from infectious and antibiotic-associated diarrhea to obesity to chronic neurologic disorders. A number of controlled clinical trials have been performed to show important biologic effects in a number of these conditions through administration of prebiotics, probiotics, and synbiotics. Controlled clinical trials have identified a limited number of prebiotics, probiotic strains, and synbiotics that favorably prevent or improve the symptoms of various disorders including inflammatory bowel disease, irritable bowel syndrome, infectious and antibiotic-associated diarrhea, diabetes, nonalcoholic fatty liver disease, necrotizing enterocolitis in very low birth weight infants, and hepatic encephalopathy. Studies have shown that probiotics alter gut flora and lead to elaboration of flora metabolites that influence health through 1 of 3 general mechanisms: direct antimicrobial effects, enhancement of mucosal barrier integrity, and immune modulation. Restoring the balance of intestinal flora by introducing probiotics for disease prevention and treatment could be beneficial to human health. It is also clear that significant differences exist between different probiotic species. Metagenomics and metatranscriptomics together with bioinformatics have allowed us to study the cross-talk between the gut microbiota and the host, furthering insight into the next generation of biologic products.
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Affiliation(s)
| | - Herbert L. DuPont
- University of Texas School of Public Health
- Baylor St Luke's Medical Center
- Baylor College of Medicine, Houston, Texas
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50
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Intestinales Mikrobiom und chronisch-entzündliche Darmerkrankungen: Feindschaft oder Freundschaft? GASTROENTEROLOGE 2015. [DOI: 10.1007/s11377-014-0963-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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