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Dryden GW, Dryden SM. Synergistic Benefits of Dietary Strategies in the Management of IBD. Curr Gastroenterol Rep 2025; 27:8. [PMID: 39702516 DOI: 10.1007/s11894-024-00949-1] [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: 10/08/2024] [Indexed: 12/21/2024]
Abstract
PURPOSE OF REVIEW Inflammatory bowel disease (IBD) patients commonly inquire about the role of diet in the onset and management of their disease process. This review sought to assess the impact of the inflammatory bowel diseases on the nutritional state of patients and evaluate the evidence supporting nutritional interventions as therapy. RECENT FINDINGS The role of nutrition has evolved from one of deficient nutrient and calorie replacement alone into a proactive therapeutic for treating active inflammatory disease symptoms. The realization that initiating total parenteral nutrition (TPN) in place of oral take could improve disease symptoms provided the first indication that food intake played a causative role in the IBD. The evolution of TPN to enteral nutrition improved tolerance and reduced side effects but clouded the role of oral intake in the pathophysiology of IBD. Advanced understanding of the role of the microbiota in IBD combined with recognition of the influence of nutrients on microbial composition have ushered in a new era of food as therapy. The role of nutrition in IBD has evolved significantly over the past 30-40 years. From complete elimination of oral intake to the carefully curated menu intended to mold the intestinal microbiota to a non-inflammatory milieu has revolutionized the approach to dietary intervention. Additional studies are warranted to optimize dietary intervention strategies.
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Affiliation(s)
- Gerald W Dryden
- Department of Medicine, University of Louisville, 505 S. Hancock Street, Room 519, Louisville, KY, 40202, USA.
| | - Sara M Dryden
- Department of Anesthesiology, University of North Carolina, N2198 UNC Hospitals, CB# 7010, Chapel Hill, NC, 27599, USA
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Geesala R, Gongloor P, Recharla N, Shi XZ. Mechanisms of Action of Exclusive Enteral Nutrition and Other Nutritional Therapies in Crohn's Disease. Nutrients 2024; 16:3581. [PMID: 39519414 PMCID: PMC11547457 DOI: 10.3390/nu16213581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/18/2024] [Accepted: 10/19/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by transmural inflammation and intestinal fibrosis involving mostly the small intestine and colon. The pathogenic mechanisms of CD remain incompletely understood and cures are unavailable. Current medical therapies are aimed at inducing prolonged remission. Most of the medical therapies such as corticosteroids have substantial adverse effects. Consequently, many dietary therapies have been explored for the management of CD. Up to now, exclusive enteral nutrition (EEN) has been considered the only established dietary treatment for IBD, especially CD. In this article, we aim to give a concise review about the current therapeutic options and challenges in the management of CD and aim to compare the efficacy of EEN with other dietary therapies and update on the possible mechanisms of the benefits of EEN and other nutritional therapies. METHODS We searched the literature up to August 2024 through PubMed, Web of Science, and other sources using search terms such as EEN, nutritional therapy, IBD, Crohn's disease, ulcerative colitis. Clinical studies in patients and preclinical studies in rodent models of IBD were included in the summary of the therapeutic benefits. RESULTS AND CONCLUSIONS EEN involves oral or nasogastric tube feeding of a complete liquid diet with exclusion of normal foods for a defined period (usually 6 to 8 weeks). EEN treatment is demonstrated to have anti-inflammatory and healing effects in CD through various potential pathways, including altering gut bacteria and their metabolites, restoring the barrier function, direct anti-inflammatory action, and indirect anti-inflammatory action by eliminating mechanical stress in the bowel. However, efficacy of other nutritional therapies is not well established in CD, and mechanisms of action are largely unknown.
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Affiliation(s)
- Ramasatyaveni Geesala
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA; (R.G.); (N.R.)
| | - Pratik Gongloor
- John Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA;
| | - Neeraja Recharla
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA; (R.G.); (N.R.)
| | - Xuan-Zheng Shi
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA; (R.G.); (N.R.)
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Nasser J, Mehravar S, Pimentel M, Lim J, Mathur R, Boustany A, Rezaie A. Elemental Diet as a Therapeutic Modality: A Comprehensive Review. Dig Dis Sci 2024; 69:3344-3360. [PMID: 39001958 PMCID: PMC11415405 DOI: 10.1007/s10620-024-08543-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 06/21/2024] [Indexed: 07/15/2024]
Abstract
Elemental diets have been employed for the management of various diseases for over 50 years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn's disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.
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Affiliation(s)
- Jason Nasser
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, 700 N. San Vicente Blvd, Suite G271, West Hollywood, CA, 90069, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA
| | - Sepideh Mehravar
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, 700 N. San Vicente Blvd, Suite G271, West Hollywood, CA, 90069, USA
| | - Mark Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, 700 N. San Vicente Blvd, Suite G271, West Hollywood, CA, 90069, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA
| | - Jane Lim
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, 700 N. San Vicente Blvd, Suite G271, West Hollywood, CA, 90069, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA
| | - Ruchi Mathur
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, 700 N. San Vicente Blvd, Suite G271, West Hollywood, CA, 90069, USA
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA
| | - Antoine Boustany
- Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Ali Rezaie
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, 700 N. San Vicente Blvd, Suite G271, West Hollywood, CA, 90069, USA.
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA.
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Otley A, Day AS, Zachos M. Nutritional Management of Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:355-383. [DOI: 10.1007/978-3-031-14744-9_27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Schwärzler J, Mayr L, Vich Vila A, Grabherr F, Niederreiter L, Philipp M, Grander C, Meyer M, Jukic A, Tröger S, Enrich B, Przysiecki N, Tschurtschenthaler M, Sommer F, Kronberger I, Koch J, Hilbe R, Hess MW, Oberhuber G, Sprung S, Ran Q, Koch R, Effenberger M, Kaneider NC, Wieser V, Keller MA, Weersma RK, Aden K, Rosenstiel P, Blumberg RS, Kaser A, Tilg H, Adolph TE. PUFA-Induced Metabolic Enteritis as a Fuel for Crohn's Disease. Gastroenterology 2022; 162:1690-1704. [PMID: 35031299 DOI: 10.1053/j.gastro.2022.01.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 12/16/2021] [Accepted: 01/04/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Crohn's disease (CD) globally emerges with Westernization of lifestyle and nutritional habits. However, a specific dietary constituent that comprehensively evokes gut inflammation in human inflammatory bowel diseases remains elusive. We aimed to delineate how increased intake of polyunsaturated fatty acids (PUFAs) in a Western diet, known to impart risk for developing CD, affects gut inflammation and disease course. We hypothesized that the unfolded protein response and antioxidative activity of glutathione peroxidase 4 (GPX4), which are compromised in human CD epithelium, compensates for metabolic perturbation evoked by dietary PUFAs. METHODS We phenotyped and mechanistically dissected enteritis evoked by a PUFA-enriched Western diet in 2 mouse models exhibiting endoplasmic reticulum (ER) stress consequent to intestinal epithelial cell (IEC)-specific deletion of X-box binding protein 1 (Xbp1) or Gpx4. We translated the findings to human CD epithelial organoids and correlated PUFA intake, as estimated by a dietary questionnaire or stool metabolomics, with clinical disease course in 2 independent CD cohorts. RESULTS PUFA excess in a Western diet potently induced ER stress, driving enteritis in Xbp1-/-IEC and Gpx4+/-IEC mice. ω-3 and ω-6 PUFAs activated the epithelial endoplasmic reticulum sensor inositol-requiring enzyme 1α (IRE1α) by toll-like receptor 2 (TLR2) sensing of oxidation-specific epitopes. TLR2-controlled IRE1α activity governed PUFA-induced chemokine production and enteritis. In active human CD, ω-3 and ω-6 PUFAs instigated epithelial chemokine expression, and patients displayed a compatible inflammatory stress signature in the serum. Estimated PUFA intake correlated with clinical and biochemical disease activity in a cohort of 160 CD patients, which was similarly demonstrable in an independent metabolomic stool analysis from 199 CD patients. CONCLUSIONS We provide evidence for the concept of PUFA-induced metabolic gut inflammation which may worsen the course of human CD. Our findings provide a basis for targeted nutritional therapy.
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Affiliation(s)
- Julian Schwärzler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Lisa Mayr
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Arnau Vich Vila
- Department of Gastroenterology and Hepatology, University of Groningen and Groningen University Medical Center, Groningen, the Netherlands
| | - Felix Grabherr
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Lukas Niederreiter
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Maureen Philipp
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Christoph Grander
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Moritz Meyer
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Almina Jukic
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Simone Tröger
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Barbara Enrich
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Nicole Przysiecki
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus Tschurtschenthaler
- Institute for Experimental Cancer Therapy, Center for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Felix Sommer
- Institute of Clinical Molecular Biology, Christian Albrecht University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany
| | - Irmgard Kronberger
- Department of Visceral, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Jakob Koch
- Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria
| | - Richard Hilbe
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria
| | - Michael W Hess
- Institute of Histology and Embryology, Medical University of Innsbruck, Innsbruck, Austria
| | - Georg Oberhuber
- INNPATH, Innsbruck Medical University Hospital, Innsbruck, Austria
| | - Susanne Sprung
- Department of Pathology, Medical University of Innsbruck, Innsbruck, Austria
| | - Qitao Ran
- Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, Texas
| | - Robert Koch
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Maria Effenberger
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Nicole C Kaneider
- Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Verena Wieser
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus A Keller
- Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen and Groningen University Medical Center, Groningen, the Netherlands
| | - Konrad Aden
- Institute of Clinical Molecular Biology, Christian Albrecht University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany
| | - Philip Rosenstiel
- Institute of Clinical Molecular Biology, Christian Albrecht University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany
| | - Richard S Blumberg
- Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Arthur Kaser
- Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Timon E Adolph
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
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Ramaswamy PK. Exclusive enteral nutrition with oral polymeric diet helps in inducing clinical and biochemical remission in adults with active Crohn's Disease. JPEN J Parenter Enteral Nutr 2021; 46:423-432. [PMID: 34618355 DOI: 10.1002/jpen.2273] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND AND AIMS Exclusive enteral nutrition (EEN) is not routinely used as induction therapy for adults with active Crohn's Disease (CD). The aim of this study was to assess the effectiveness of EEN with oral polymeric formula as an adjunct for inducing clinical and biochemical remission in adults with active CD. METHODS We performed a retrospective analysis of data from January 2018 to September 2019 on all patients with active CD who commenced EEN. Primary endpoint was clinical remission (CDAI ≤150) or response (100-point decrease in CDAI) at 8 weeks. Secondary endpoint was achievement of biochemical remission (CRP ≤5 mg/L or faeces calprotectin ≤150 mcg/g) at 8 weeks in those whose baseline values were elevated. We also aimed to identify predictors of response to EEN therapy. RESULTS Sixty-six patients commenced EEN, 53/66 (80.3%) completed the prescribed EEN course. At 8 weeks, 42/66 (63.6%) patients achieved primary endpoint and secondary endpoint was achieved in 30/53 (56.6%) of patients. Patients receiving EEN for ≥ 6 weeks achieved primary (72% vs 47.8%, OR 2.8, p = 0.047, CI 0.97 -8.16) and secondary endpoint (67.6% vs 36.8%, OR 3.58, p = 0.035, CI 1.1- 11.63) more frequently when compared with patients who received EEN for <6 weeks. Nine patients reported adverse effects (4 nausea,3 diarrhoea,1 constipation and 1 abdominal pain), none of whom ceased therapy. CONCLUSION Polymeric EEN is well tolerated, safe and effective in inducing clinical and biochemical remission in adults with active CD. EEN duration of ≥ 6 weeks has better outcomes. This article is protected by copyright. All rights reserved.
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Affiliation(s)
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- Department of Digestive Health, Gold Coast University Hospital.,Department of Nutrition and Food Services, Gold Coast University Hospital.,Faculty of Health Sciences and Medicine, Bond University
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Mitrev N, Huang H, Hannah B, Kariyawasam VC. Review of exclusive enteral therapy in adult Crohn's disease. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000745. [PMID: 34580154 PMCID: PMC8477235 DOI: 10.1136/bmjgast-2021-000745] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/07/2021] [Indexed: 12/14/2022] Open
Abstract
Background Exclusive enteral nutrition (EEN) is a potentially effective but underused therapy for Crohn’s disease (CD) in adults. It is first-line induction treatment for paediatric patients but remains a second-line or third-line therapy in adults. Objective To analyse the evidence for EEN in adult patients with CD, and summarise this in a narrative review. Methods In April/May 2020 and July 2021, a literature search was performed using the Medical Subject Headings (MeSH) terms: ‘Crohn’s disease’, ‘CD’, ‘inflammatory bowel disease’, ‘IBD’, ‘exclusive enteral nutrition’, ‘enteral nutrition’, ‘EEN’, in PubMed, Scopus, Cochrane. Additional studies were obtained from references of search result articles as well as general reading. Studies with adult patients with CD treated with EEN were selected. 79 articles of relevance were found. Where data in adults were lacking, data from paediatric studies as extrapolated with care. Results EEN in adult patients been shown to improve clinical, biomarker, endoscopic and radiologic measures of disease activity. EEN avoids the potential adverse effects of recurrent corticosteroids for induction such as metabolic derangements and opportunistic infections. EEN has also demonstrated benefits among adult patients with fistulising and stricturing CD. It may avoid surgery in such patients. Preoperative EEN has also been shown to reduce postoperative complications and recurrence. There appears to be benefits in combing EEN with antitumour necrosis factor agents, however, benefits of combination therapy with other biologics are less clear. A major drawback of EEN therapy in adults has been poor compliance. More palatable polymeric formulations improved patient education and dietitian support may overcome this. Evidence in adults is limited to small studies, often with suboptimal control arms and lack of blinding. Larger scale studies with improved study design are needed to confirm these beneficial effects. Conclusion Despite limitations in evidence EEN should be considered in treating adults with CD.
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Affiliation(s)
- Nikola Mitrev
- Department of Gastroenterology, Blacktown Hospital, Blacktown, New South Wales, Australia.,Western Sydney University Blacktown Mount Druitt Medical School, Blacktown, New South Wales, Australia
| | - Hin Huang
- Western Sydney University Blacktown Mount Druitt Medical School, Blacktown, New South Wales, Australia
| | - Barbara Hannah
- Department of Gastroenterology, Blacktown Hospital, Blacktown, New South Wales, Australia
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Caio G, Lungaro L, Caputo F, Zoli E, Giancola F, Chiarioni G, De Giorgio R, Zoli G. Nutritional Treatment in Crohn's Disease. Nutrients 2021; 13:nu13051628. [PMID: 34066229 PMCID: PMC8151495 DOI: 10.3390/nu13051628] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/04/2021] [Accepted: 05/06/2021] [Indexed: 12/12/2022] Open
Abstract
Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) which can affect any part of the whole gastrointestinal tract (from mouth to anus). Malnutrition affects 65-75% of CD patients, and it is now well acknowledged that diet is of paramount importance in the management of the disease. In this review, we would like to highlight the most recent findings in the field of nutrition for the treatment of CD. Our analysis will cover a wide range of topics, from the well-established diets to the new nutritional theories, along with the recent progress in emerging research fields, such as nutrigenomics.
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Affiliation(s)
- Giacomo Caio
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.L.); (F.C.); (E.Z.); (F.G.); (R.D.G.)
- Center for the Study and Treatment of Chronic Inflammatory Intestinal Diseases (IBD) and Gastroenterological Manifestations of Rare Diseases, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
- Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital-Harvard Medical School, Boston, MA 02114, USA
- Correspondence: (G.C.); (G.Z.); Tel.: +39-0532-236823 (G.C.); +39-051-6838307 (G.Z.)
| | - Lisa Lungaro
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.L.); (F.C.); (E.Z.); (F.G.); (R.D.G.)
- Department of Internal Medicine, Santissima Annunziata Hospital, Cento (Ferrara), University of Ferrara, 44042 Ferrara, Italy
| | - Fabio Caputo
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.L.); (F.C.); (E.Z.); (F.G.); (R.D.G.)
- Center for the Study and Treatment of Chronic Inflammatory Intestinal Diseases (IBD) and Gastroenterological Manifestations of Rare Diseases, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
- Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
- Department of Internal Medicine, Santissima Annunziata Hospital, Cento (Ferrara), University of Ferrara, 44042 Ferrara, Italy
| | - Eleonora Zoli
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.L.); (F.C.); (E.Z.); (F.G.); (R.D.G.)
- Department of Internal Medicine, Santissima Annunziata Hospital, Cento (Ferrara), University of Ferrara, 44042 Ferrara, Italy
| | - Fiorella Giancola
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.L.); (F.C.); (E.Z.); (F.G.); (R.D.G.)
| | - Giuseppe Chiarioni
- Division of Gastroenterology of the University of Verona, A.O.U.I. Verona, 37126 Verona, Italy;
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7080, USA
| | - Roberto De Giorgio
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.L.); (F.C.); (E.Z.); (F.G.); (R.D.G.)
- Center for the Study and Treatment of Chronic Inflammatory Intestinal Diseases (IBD) and Gastroenterological Manifestations of Rare Diseases, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
- Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
| | - Giorgio Zoli
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.L.); (F.C.); (E.Z.); (F.G.); (R.D.G.)
- Center for the Study and Treatment of Chronic Inflammatory Intestinal Diseases (IBD) and Gastroenterological Manifestations of Rare Diseases, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
- Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
- Department of Internal Medicine, Santissima Annunziata Hospital, Cento (Ferrara), University of Ferrara, 44042 Ferrara, Italy
- Correspondence: (G.C.); (G.Z.); Tel.: +39-0532-236823 (G.C.); +39-051-6838307 (G.Z.)
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Herrador-López M, Martín-Masot R, Navas-López VM. EEN Yesterday and Today … CDED Today and Tomorrow. Nutrients 2020; 12:nu12123793. [PMID: 33322060 PMCID: PMC7764146 DOI: 10.3390/nu12123793] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/04/2020] [Accepted: 12/08/2020] [Indexed: 12/11/2022] Open
Abstract
The treatment of Pediatric Crohn’s Disease (CD) requires attention both to achieve mucosal healing and to optimize growth, while also maintaining proper bone health. Exclusive Enteral Nutrition (EEN) is recommended as first-line treatment in luminal CD. The therapeutic mechanisms of EEN are being discovered by advances in the study of the gut microbiota. Although the total exclusion of a normal diet during the time of EEN continues to be of high importance, new modalities of dietary treatment suggest a successful future for the nutritional management of CD. In this sense, Crohn’s Disease Exclusion Diet (CDED) is a long-term strategy, it apparently acts on the mechanisms that influence the appearance of inflammation (reducing dietary exposure to products negatively affecting the microbiota), but does so using specific available whole foods to achieve this goal, increases the time of clinical remission and promotes healthy lifestyle habits. The development of CDED, which partly minimizes the problems of EEN, has enabled a turnaround in the treatment of pediatric CD. This review highlights the role of enteral nutrition in the treatment of Crohn’s disease with special emphasis on newer dietary modalities such as CDED.
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Mayr L, Grabherr F, Schwärzler J, Reitmeier I, Sommer F, Gehmacher T, Niederreiter L, He GW, Ruder B, Kunz KTR, Tymoszuk P, Hilbe R, Haschka D, Feistritzer C, Gerner RR, Enrich B, Przysiecki N, Seifert M, Keller MA, Oberhuber G, Sprung S, Ran Q, Koch R, Effenberger M, Tancevski I, Zoller H, Moschen AR, Weiss G, Becker C, Rosenstiel P, Kaser A, Tilg H, Adolph TE. Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease. Nat Commun 2020; 11:1775. [PMID: 32286299 PMCID: PMC7156516 DOI: 10.1038/s41467-020-15646-6] [Citation(s) in RCA: 166] [Impact Index Per Article: 33.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 03/23/2020] [Indexed: 12/19/2022] Open
Abstract
The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn’s disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD. Dietary lipids are linked to the development of inflammatory bowel diseases through unclear mechanisms. Here, the authors report that dietary polyunsaturated fatty acids trigger intestinal inflammation resembling aspects of Crohn’s disease, which is restricted by glutathione peroxidase 4 in the intestinal epithelium.
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Affiliation(s)
- Lisa Mayr
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Felix Grabherr
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Julian Schwärzler
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Isabelle Reitmeier
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Felix Sommer
- Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany
| | - Thomas Gehmacher
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Lukas Niederreiter
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Gui-Wei He
- Department of Medicine 1, Gastroenterology, Pneumology and Endocrinology, University Medical Center Erlangen, Erlangen, Germany
| | - Barbara Ruder
- Department of Medicine 1, Gastroenterology, Pneumology and Endocrinology, University Medical Center Erlangen, Erlangen, Germany
| | - Kai T R Kunz
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Piotr Tymoszuk
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria
| | - Richard Hilbe
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Innsbruck, Austria
| | - David Haschka
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria
| | - Clemens Feistritzer
- Department of Internal Medicine V, Haematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria
| | - Romana R Gerner
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Barbara Enrich
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Nicole Przysiecki
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Mucosal Immunology, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus Seifert
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus A Keller
- Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria
| | - Georg Oberhuber
- Pathology Department of Innsbruck Medical University Hospital, Innsbruck, Austria
| | - Susanne Sprung
- Department of Pathology, Medical University of Innsbruck, Innsbruck, Austria
| | - Qitao Ran
- Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, Texas, USA
| | - Robert Koch
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Maria Effenberger
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Ivan Tancevski
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria
| | - Heinz Zoller
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Alexander R Moschen
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Mucosal Immunology, Medical University of Innsbruck, Innsbruck, Austria
| | - Günter Weiss
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Innsbruck, Austria
| | - Christoph Becker
- Department of Medicine 1, Gastroenterology, Pneumology and Endocrinology, University Medical Center Erlangen, Erlangen, Germany
| | - Philip Rosenstiel
- Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany
| | - Arthur Kaser
- Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Timon E Adolph
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria.
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11
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Yao JY, Jiang Y, Ke J, Lu Y, Hu J, Zhi M. Development of a prognostic model for one-year surgery risk in Crohn’s disease patients: A retrospective study. World J Gastroenterol 2020; 26:524-534. [PMID: 32089628 PMCID: PMC7015715 DOI: 10.3748/wjg.v26.i5.524] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 01/06/2020] [Accepted: 01/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Accelerated therapeutic treatment should be considered in patients with progressive Crohn’s disease (CD) to prevent complications as well as surgery. Therefore, screening for risk factors and predicting the need for early surgery are of great importance in clinical practice.
AIM To establish a model to predict CD-related early surgery.
METHODS This was a retrospective study collecting data from CD patients diagnosed at our inflammatory bowel disease center from January 1, 2012 to December 31, 2016. All data were randomly stratified into a training set and a testing set at a ratio of 8:2. Multivariable logistic regression analysis was conducted with receiver operating characteristic curves constructed and areas under the curve calculated. This model was further validated with calibration and discrimination estimated. A nomogram was finally developed.
RESULTS A total of 1002 eligible patients were enrolled with a mean follow-up period of 53.54 ± 13.10 mo. In total, 24.25% of patients received intestinal surgery within 1 year after diagnosis due to complications or disease relapse. Disease behavior (B2: OR [odds ratio] = 6.693, P < 0.001; B3: OR = 14.405, P < 0.001), smoking (OR = 4.135, P < 0.001), body mass index (OR = 0.873, P < 0.001) and C-reactive protein (OR = 1.022, P = 0.001) at diagnosis, previous perianal (OR = 9.483, P < 0.001) or intestinal surgery (OR = 8.887, P < 0.001), maximum bowel wall thickness (OR = 1.965, P < 0.001), use of biologics (OR = 0.264, P < 0.001), and exclusive enteral nutrition (OR = 0.089, P < 0.001) were identified as independent significant factors associated with early intestinal surgery. A prognostic model was established and further validated. The receiver operating characteristic curves and calculated areas under the curves (94.7%) confirmed an ideal predictive ability of this model with a sensitivity of 75.92% and specificity of 95.81%. A nomogram was developed to simplify the use of the predictive model in clinical practice.
CONCLUSION This prognostic model can effectively predict 1-year risk of CD-related intestinal surgery, which will assist in screening progressive CD patients and tailoring therapeutic management.
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Affiliation(s)
- Jia-Yin Yao
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Yi Jiang
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Jia Ke
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Yi Lu
- Department of Anesthesiology, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou 510130, Guangdong Province, China
| | - Jun Hu
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Min Zhi
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
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12
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Di Caro S, Fragkos KC, Keetarut K, Koo HF, Sebepos-Rogers G, Saravanapavan H, Barragry J, Rogers J, Mehta SJ, Rahman F. Enteral Nutrition in Adult Crohn's Disease: Toward a Paradigm Shift. Nutrients 2019; 11:E2222. [PMID: 31540038 PMCID: PMC6770416 DOI: 10.3390/nu11092222] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 09/05/2019] [Accepted: 09/08/2019] [Indexed: 02/06/2023] Open
Abstract
Medical and surgical treatments for Crohn's disease are associated with toxic effects. Medical therapy aims for mucosal healing and is achievable with biologics, immunosuppressive therapy, and specialised enteral nutrition, but not with corticosteroids. Sustained remission remains a therapeutic challenge. Enteral nutrition, containing macro- and micro-nutrients, is nutritionally complete, and is provided in powder or liquid form. Enteral nutrition is a low-risk and minimally invasive therapy. It is well-established and recommended as first line induction therapy in paediatric Crohn's disease with remission rates of up to 80%. Other than in Japan, enteral nutrition is not routinely used in the adult population among Western countries, mainly due to unpalatable formulations which lead to poor compliance. This study aims to offer a comprehensive review of available enteral nutrition formulations and the literature supporting the use and mechanisms of action of enteral nutrition in adult Crohn's disease patients, in order to support clinicians in real world decision-making when offering/accepting treatment. The mechanisms of actions of enteral feed, including their impact on the gut microbiome, were explored. Barriers to the use of enteral nutrition, such as compliance and the route of administration, were considered. All available enteral preparations have been comprehensively described as a practical guide for clinical use. Likewise, guidelines are reported and discussed.
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Affiliation(s)
- Simona Di Caro
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Konstantinos C Fragkos
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Katie Keetarut
- Department of Dietetics, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Hui Fen Koo
- UCL Medical School, 74 Huntley Street, Bloomsbury, London WC1E 6DE, UK.
| | - Gregory Sebepos-Rogers
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Hajeena Saravanapavan
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - John Barragry
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Jennifer Rogers
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Shameer J Mehta
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Farooq Rahman
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
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13
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Mack DR, Benchimol EI, Critch J, deBruyn J, Tse F, Moayyedi P, Church P, Deslandres C, El-Matary W, Huynh H, Jantchou P, Lawrence S, Otley A, Sherlock M, Walters T, Kappelman MD, Sadowski D, Marshall JK, Griffiths A. Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn's Disease. J Can Assoc Gastroenterol 2019; 2:e35-e63. [PMID: 31294379 PMCID: PMC6619414 DOI: 10.1093/jcag/gwz018] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND & AIMS We aim to provide guidance for medical treatment of luminal Crohn's disease in children. METHODS We performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn's disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them. RESULTS The consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation. CONCLUSIONS Evidence-based medical treatment of Crohn's disease in children is recommended, with thorough ongoing assessments to define treatment success.
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Affiliation(s)
- David R Mack
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
- Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
| | - Eric I Benchimol
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
- Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Jeff Critch
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Faculty of Medicine, Memorial University, St John's, Newfoundland and Labrador, Canada
| | - Jennifer deBruyn
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Section of Pediatric Gastroenterology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada
| | - Frances Tse
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Paul Moayyedi
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Peter Church
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Colette Deslandres
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Centre Hospitalier Universitaire, Sainte-Justine, Montréal, Quebec, Canada
| | - Wael El-Matary
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Section of Pediatric Gastroenterology, Department of Pediatrics, Health Sciences Centre, Winnipeg, Manitoba, Canada
| | - Hien Huynh
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Department of Pediatrics (Gastroenterology), Stollery Children's Hospital, Edmonton, Alberta, Canada
| | - Prévost Jantchou
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Centre Hospitalier Universitaire, Sainte-Justine, Montréal, Quebec, Canada
| | - Sally Lawrence
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Anthony Otley
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Division of Gastroenterology and Nutrition, IWK Health Centre, Halifax, Nova Scotia, Canada
| | - Mary Sherlock
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- Division of Pediatric Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | - Thomas Walters
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Michael D Kappelman
- Division of Pediatric Gastroenterology, University of North Carolina, Hospital-Children's Specialty Clinic, Chapel Hill, North Carolina
| | - Dan Sadowski
- Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Alberta, Canada
| | - John K Marshall
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Anne Griffiths
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
- IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
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14
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Mack DR, Benchimol EI, Critch J, deBruyn J, Tse F, Moayyedi P, Church P, Deslandres C, El-Matary W, Huynh H, Jantchou P, Lawrence S, Otley A, Sherlock M, Walters T, Kappelman MD, Sadowski D, Marshall JK, Griffiths A. Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn's Disease. Gastroenterology 2019; 157:320-348. [PMID: 31320109 DOI: 10.1053/j.gastro.2019.03.022] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 02/28/2019] [Accepted: 03/02/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS We aim to provide guidance for medical treatment of luminal Crohn's disease in children. METHODS We performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn's disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them. RESULTS The consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation. CONCLUSIONS Evidence-based medical treatment of Crohn's disease in children is recommended, with thorough ongoing assessments to define treatment success.
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Affiliation(s)
- David R Mack
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada; Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada
| | - Eric I Benchimol
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada; Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Jeff Critch
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Faculty of Medicine, Memorial University, St John's, Newfoundland and Labrador, Canada
| | - Jennifer deBruyn
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Section of Pediatric Gastroenterology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada
| | - Frances Tse
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Paul Moayyedi
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Peter Church
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Colette Deslandres
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Centre Hospitalier Universitaire, Sainte-Justine, Montréal, Quebec, Canada
| | - Wael El-Matary
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Section of Pediatric Gastroenterology, Department of Pediatrics, Health Sciences Centre, Winnipeg, Manitoba, Canada
| | - Hien Huynh
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Department of Pediatrics (Gastroenterology), Stollery Children's Hospital, Edmonton, Alberta, Canada
| | - Prévost Jantchou
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Centre Hospitalier Universitaire, Sainte-Justine, Montréal, Quebec, Canada
| | - Sally Lawrence
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Anthony Otley
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Division of Gastroenterology and Nutrition, IWK Health Centre, Halifax, Nova Scotia, Canada
| | - Mary Sherlock
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; Division of Pediatric Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | - Thomas Walters
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Michael D Kappelman
- Division of Pediatric Gastroenterology, University of North Carolina, Hospital-Children's Specialty Clinic, Chapel Hill, North Carolina
| | - Dan Sadowski
- Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Alberta, Canada
| | - John K Marshall
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Anne Griffiths
- Ch.I.L.D. Foundation Canadian Children IBD Network, Vancouver, British Columbia, Canada; IBD Centre, Department of Paediatrics, SickKids Hospital, University of Toronto, Toronto, Ontario, Canada.
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15
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A Review of Dietary Therapy for IBD and a Vision for the Future. Nutrients 2019; 11:nu11050947. [PMID: 31035465 PMCID: PMC6566428 DOI: 10.3390/nu11050947] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Revised: 04/23/2019] [Accepted: 04/24/2019] [Indexed: 12/18/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract. The rising incidence of IBD has been associated with urbanization and shifts toward a Westernized diet. The intestinal microbiome has been a focus of disease pathogenesis and also therapeutic intervention. Dietary therapy for IBD has been well-studied with exclusive enteral nutrition, a formula-based diet with the exclusion of foods. In addition, interest in food-based exclusion diets has been increasing, with patients and families leading the charge. Challenges with dietary therapy for IBD include the lack of understanding of a detailed mechanistic pathway to explain the impact of diet on IBD pathogenesis and the difficult nature of designing and implementing dietary clinical trials. Epidemiological studies have demonstrated associations and intervention studies have demonstrated efficacy, but specific dietary targets remain as hypotheses at present. Current IBD therapy focuses on suppression of the immune system, yet the incomplete efficacy of present drugs suggests that other therapies must be developed and employed. Dietary interventions, with known ability to modulate the intestinal microbiome, are a unique opportunity to improve outcomes in IBD. Dietary intervention trials are challenging, and capturing both broad dietary patterns as well as exposure to individual food compounds is important. With increasing patient interest and preliminary research in dietary therapy indicating efficacy, it is imperative to further advance the science of utilizing diet in IBD, as well as to support patients by proactively addressing diet within their care plan.
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Chronic Inflammatory Diseases: Are We Ready for Microbiota-based Dietary Intervention? Cell Mol Gastroenterol Hepatol 2019; 8:61-71. [PMID: 30836147 PMCID: PMC6517864 DOI: 10.1016/j.jcmgh.2019.02.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 02/22/2019] [Accepted: 02/22/2019] [Indexed: 12/12/2022]
Abstract
The last 15 years have witnessed the emergence of a new field of research that focuses on the roles played by the intestinal microbiota in health and disease. This research field has produced accumulating evidence indicating that dysregulation of host-microbiota interactions contributes to a range of chronic inflammatory diseases, including inflammatory bowel diseases, colorectal cancer, and metabolic syndrome. Although dysregulation of the microbiota can take complex forms, in some cases, specific bacterial species that can drive specific clinical outcomes have been identified. Among the numerous factors influencing the intestinal microbiota composition, diet is a central actor, wherein numerous dietary factors can beneficially or detrimentally impact the host/microbiota relationship. This review will highlight recent literature that has advanced understanding of microbiota-diet-disease interplay, with a central focus on the following question: Are we ready to use intestinal microbiota composition-based personalized dietary interventions to treat chronic inflammatory diseases?
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Wharton S, Raiber L, Serodio KJ, Lee J, Christensen RA. Medications that cause weight gain and alternatives in Canada: a narrative review. Diabetes Metab Syndr Obes 2018; 11:427-438. [PMID: 30174450 PMCID: PMC6109660 DOI: 10.2147/dmso.s171365] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The cause of the obesity epidemic is multifactorial, but may, in part, be related to medication-induced weight gain. While clinicians may strive to do their best to select pharmacotherapy(ies) that has the least negative impact on weight, the literature regarding the weight effects of medication is often limited and devoid of alternative therapies. RESULTS Antipsychotics, antidepressants, antihyperglycemics, antihypertensives and corticosteroids all contain medications that were associated with significant weight gain. However, there are several medication alternatives within the majority of these classes associated with weight neutral or even weight loss effects. Further, while not all of the classes of medication examined in this review have weight-favorable alternatives, there exist many other tools to mitigate weight gain associated with medication use, such as changes in dosing, medication delivery or the use of adjunctive therapies. CONCLUSION Medication-induced weight gain can be frustrating for both the patient and the clinician. As the use of pharmaceuticals continues to increase, it is pertinent for clinicians to consider the weight effects of medications prior to prescribing or in the course of treatment. In the case where it is not feasible to make changes to medication, adjunctive therapies should be considered.
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Affiliation(s)
- Sean Wharton
- The Wharton Medical Clinic, Toronto, Canada,
- School of Kinesiology and Health Science, York University, Toronto, Canada
| | | | | | - Jasmine Lee
- The Wharton Medical Clinic, Toronto, Canada,
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Akobeng AK, Zhang D, Gordon M, MacDonald JK. Enteral nutrition for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2018; 8:CD005984. [PMID: 30098021 PMCID: PMC6513617 DOI: 10.1002/14651858.cd005984.pub3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Prevention of relapse is a major issue in the management of quiescent Crohn's disease (CD). Current therapies (e.g. methotrexate, biologics, 6-mercaptopurine and azathioprine) may be effective for maintaining remission in CD, but these drugs may cause significant adverse events. Interventions that are effective and safe for maintenance of remission in CD are desirable. OBJECTIVES The primary objectives were to evaluate the efficacy and safety of enteral nutrition for the maintenance of remission in CD and to assess the impact of formula composition on effectiveness. SEARCH METHODS We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register and clinicaltrials.gov from inception to 27 July 2018. We also searched references of retrieved studies and reviews. SELECTION CRITERIA Randomised controlled trials (RCTs) including participants of any age with quiescent CD were considered for inclusion. Studies that compared enteral nutrition with no intervention, placebo or any other intervention were selected for review. DATA COLLECTION AND ANALYSIS Two authors independently screened studies for inclusion, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was clinical or endoscopic relapse as defined by the primary studies. Secondary outcomes included anthropometric measures (i.e. height and weight), quality of life (QoL), adverse events, serious adverse events and withdrawal due to adverse events. We calculated the risk ratio and 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference and 95% CI. A random-effects model was used for the statistical analysis. We used the GRADE criteria to assess the overall certainty of the evidence supporting the primary outcome and selected secondary outcomes. MAIN RESULTS Four RCTs (262 adult participants) met the inclusion criteria. One study (N = 33) compared an elemental diet to a non-elemental (polymeric) diet. One study (N = 51) compared a half elemental diet to a regular free diet. Another study (N = 95) compared an elemental diet to 6-mercaptopurine (6-MP) or a no treatment control group. One study (N= 83) compared a polymeric diet to mesalamine. Two studies were rated as high risk of bias due to lack of blinding or incomplete outcome data. The other two studies were judged to have an unclear risk of bias. The studies were not pooled due to differences in control interventions and the way outcomes were assessed.The effect of an elemental diet compared to a polymeric diet on remission rates or withdrawal due to adverse events is uncertain. Fifty-eight per cent (11/19) of participants in the elemental diet group relapsed at 12 months compared to 57% (8/14) of participants in the polymeric diet group (RR 1.01, 95% CI 0.56 to 1.84; very low certainty evidence). Thirty-two per cent (6/19) of participants in the elemental diet group were intolerant to the enteral nutritional formula because of taste or smell and were withdrawn from the study in the first 2 weeks compared to zero participants (0/14) in the polymeric diet group (RR 9.75, 95% CI 0.59 to 159.93; low certainty evidence). Anthropometric measures, QoL, adverse events and serious adverse events were not reported as outcomes.The effect of an elemental diet (half of total daily calorie requirements) compared to a normal free diet on relapse rates is uncertain. Thirty-five per cent (9/26) of participants in the elemental diet group relapsed at 12 months compared to 64% (16/25) of participants in the free diet group (RR 0.54, 95% CI 0.30 to 0.99; very low certainty evidence). No adverse events were reported. This study reported no differences in weight change between the two diet groups. Height and QoL were not reported as outcomes.The effect of an elemental diet compared to 6-MP on relapse rates or adverse events is uncertain. Thirty-eight per cent (12/32) of participants in the elemental diet group relapsed at 12 months compared to 23% (7/30) of participants in the 6-MP group (RR 1.61; 95% CI 0.73 to 3.53; very low certainty evidence). Three per cent (1/32) of participants in the elemental diet group had an adverse event compared to 13% (4/30) of participants in the 6-MP group (RR 0.23, 95% CI 0.03 to 1.98; low certainty evidence). Adverse events in the elemental diet group included surgery due to worsening CD. Adverse events in the 6-MP group included liver injury (n = 2), hair loss (n = 1) and surgery due to an abscess (n = 1). No serious adverse events or withdrawals due to adverse events were reported. Weight, height and QoL were not reported as outcomesThe effect of a polymeric diet compared to mesalamine on relapse rates and weight is uncertain. Forty-two per cent (18/43) of participants in the polymeric diet group relapsed at 6 months compared to 55% (22/40) of participants in the mesalamine group (RR 0.76; 95% CI 0.49 to 1.19; low certainty evidence). The mean difference in weight gain over the study period was 1.9 kg higher in the polymeric diet group compared to mesalamine (95% CI -4.62 to 8.42; low certainty evidence). Two participants in the polymeric diet group experienced nausea and four had diarrhoea. It is unclear if any participants in the mesalamine group had an adverse event. Height, QoL, serious adverse events and withdrawal due to adverse events were not reported as outcomes. AUTHORS' CONCLUSIONS The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn. More research is needed to determine the efficacy and safety of using enteral nutrition as maintenance therapy in CD. Currently, there are four ongoing studies (estimated enrolment of 280 participants). This review will be updated when the results of these studies are available.
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Affiliation(s)
| | - Dongni Zhang
- University of Western OntarioSchulich School of Medicine & DentistryLondonONCanada
| | - Morris Gordon
- University of Central LancashireSchool of MedicinePrestonLancashireUK
| | - John K MacDonald
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
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Wall CL, Gearry RB, Day AS. Treatment of Active Crohn's Disease with Exclusive and Partial Enteral Nutrition: A Pilot Study in Adults. Inflamm Intest Dis 2018; 2:219-227. [PMID: 30221149 PMCID: PMC6135224 DOI: 10.1159/000489630] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 04/26/2018] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND AND AIM Enteral nutrition (EN) is not commonly used for the treatment of adults with active Crohn's disease (CD), despite patient interest in nutrition-based alternatives to corticosteroids and evidence of efficacy in paediatric CD. The aim of this study was to assess the impact of 2 different EN regimens on disease symptoms, nutrition and inflammatory markers in young adults with active CD. METHODS A prospective non-randomized pilot study of adults aged 16-40 years with active CD on endoscopy or imaging was undertaken. Patients were sequentially recruited to use 2 weeks of exclusive EN (EEN) followed by either 6 weeks of EEN or partial EN (PEN) with usual diet. Assessments of disease symptoms, nutrition and inflammatory markers were undertaken at baseline and throughout the treatment. RESULTS Thirty-eight patients with active disease were recruited. Thirty-two (84$) patients completed 2 weeks of EEN and had significant improvements in disease symptoms (p = 0.003), serum c-reactive protein (CRP; p = 0.005), insulin-like growth factor-1 (p = 0.006) and faecal calprotectin (FC; p = 0.028). During the following 6 weeks, 21 patients continued EEN (14 [67$] completed treatment) and 11 patients used PEN (9 [82$] completed treatment). Initial improvements in symptoms, CRP and nutrition markers were sustained over the next 6 weeks on both treatments. FC non-significantly increased in 5 out of 9 patients who used PEN and at week 8 FC was greater than 500 µg/g in 9 out of 14 and 7 out of 9 patients who used exclusive or PEN respectively. There was no significant difference in clinical outcomes between the 2 groups at week 8. CONCLUSION Two weeks of EEN significantly improved disease symptoms, nutrition and inflammatory markers. Further treatment with exclusive or PEN maintained initial improvements.
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Affiliation(s)
- Catherine L. Wall
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Richard B. Gearry
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Andrew S. Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
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Narula N, Dhillon A, Zhang D, Sherlock ME, Tondeur M, Zachos M. Enteral nutritional therapy for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2018; 4:CD000542. [PMID: 29607496 PMCID: PMC6494406 DOI: 10.1002/14651858.cd000542.pub3] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Corticosteroids are often preferred over enteral nutrition (EN) as induction therapy for Crohn's disease (CD). Prior meta-analyses suggest that corticosteroids are superior to EN for induction of remission in CD. Treatment failures in EN trials are often due to poor compliance, with dropouts frequently due to poor acceptance of a nasogastric tube and unpalatable formulations. This systematic review is an update of a previously published Cochrane review. OBJECTIVES To evaluate the effectiveness and safety of exclusive EN as primary therapy to induce remission in CD and to examine the importance of formula composition on effectiveness. SEARCH METHODS We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2017. We also searched references of retrieved articles and conference abstracts. SELECTION CRITERIA Randomized controlled trials involving patients with active CD were considered for inclusion. Studies comparing one type of EN to another type of EN or conventional corticosteroids were selected for review. DATA COLLECTION AND ANALYSIS Data were extracted independently by at least two authors. The primary outcome was clinical remission. Secondary outcomes included adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. We performed intention-to-treat and per-protocol analyses for the primary outcome. Heterogeneity was explored using the Chi2 and I2 statistics. The studies were separated into two comparisons: one EN formulation compared to another EN formulation and EN compared to corticosteroids. Subgroup analyses were based on formula composition and age. Sensitivity analyses included abstract publications and poor quality studies. We used the Cochrane risk of bias tool to assess study quality. We used the GRADE criteria to assess the overall quality of the evidence supporting the primary outcome and selected secondary outcomes. MAIN RESULTS Twenty-seven studies (1,011 participants) were included. Three studies were rated as low risk of bias. Seven studies were rated as high risk of bias and 17 were rated as unclear risk of bias due to insufficient information. Seventeen trials compared different formulations of EN, 13 studies compared one or more elemental formulas to a non-elemental formula, three studies compared EN diets of similar protein composition but different fat composition, and one study compared non-elemental diets differing in glutamine enrichment. Meta-analysis of 11 trials (378 participants) demonstrated no difference in remission rates. Sixty-four per cent (134/210) of patients in the elemental group achieved remission compared to 62% (105/168) of patients in the non-elemental group (RR 1.02, 95% CI 0.88 to 1.18; GRADE very low quality). A per-protocol analysis (346 participants) produced similar results (RR 1.04, 95% CI 0.91 to 1.18). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no differences in remission rates. An analysis of 7 trials including 209 patients treated with EN formulas of differing fat content (low fat: < 20 g/1000 kCal versus high fat: > 20 g/1000 kCal) demonstrated no difference in remission rates (RR 1.03; 95% CI 0.85 to 1.26). Very low fat content (< 3 g/1000 kCal) and very low long chain triglycerides demonstrated higher remission rates than higher content EN formulas. There was no difference between elemental and non-elemental diets in adverse event rates (RR 1.00, 95% CI 0.63 to 1.60; GRADE very low quality), or withdrawals due to adverse events (RR 1.29, 95% CI 0.80 to 2.09; GRADE very low quality). Common adverse events included nausea, vomiting, diarrhea and bloating.Ten trials compared EN to steroid therapy. Meta-analysis of eight trials (223 participants) demonstrated no difference in remission rates between EN and steroids. Fifty per cent (111/223) of patients in the EN group achieved remission compared to 72% (133/186) of patients in the steroid group (RR 0.77, 95% CI 0.58 to 1.03; GRADE very low quality). Subgroup analysis by age showed a difference in remission rates for adults but not for children. In adults 45% (87/194) of EN patients achieved remission compared to 73% (116/158) of steroid patients (RR 0.65, 95% CI 0.52 to 0.82; GRADE very low quality). In children, 83% (24/29) of EN patients achieved remission compared to 61% (17/28) of steroid patients (RR 1.35, 95% CI 0.92 to 1.97; GRADE very low quality). A per-protocol analysis produced similar results (RR 0.93, 95% CI 0.75 to 1.14). The per-protocol subgroup analysis showed a difference in remission rates for both adults (RR 0.82, 95% CI 0.70 to 0.95) and children (RR 1.43, 95% CI 1.03 to 1.97). There was no difference in adverse event rates (RR 1.39, 95% CI 0.62 to 3.11; GRADE very low quality). However, patients on EN were more likely to withdraw due to adverse events than those on steroid therapy (RR 2.95, 95% CI 1.02 to 8.48; GRADE very low quality). Common adverse events reported in the EN group included heartburn, flatulence, diarrhea and vomiting, and for steroid therapy acne, moon facies, hyperglycemia, muscle weakness and hypoglycemia. The most common reason for withdrawal was inability to tolerate the EN diet. AUTHORS' CONCLUSIONS Very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD. Protein composition does not appear to influence the effectiveness of EN for the treatment of active CD. EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient adherence with this therapy.
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Affiliation(s)
- Neeraj Narula
- McMaster UniversityDivision of Gastroenterology1280 Main Street WestHamiltonONCanadaL8S 4K1
| | - Amit Dhillon
- Northern Ontario School of MedicineDepartment of Internal MedicineSudburyONCanada
| | - Dongni Zhang
- University of Western OntarioSchulich School of Medicine & DentistryLondonONCanada
| | - Mary E Sherlock
- McMaster Children's HospitalDivision of Gastroenterology & NutritionHamilton Health Sciences1280 Main Street WestHamiltonONCanada
| | - Melody Tondeur
- The Hospital for Sick ChildrenCentre for Global Child Health525 University AveTorontoONCanadaM5G 2L3
| | - Mary Zachos
- McMaster Children’s HospitalDivision of Gastroenterology & Nutrition1280 Main St. WestHamiltonONCanadaL8S 4K1
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Parenteral Nutrition–Dependent Patient With a History of Crohn's Disease Complicated by Central Line–Associated Bloodstream Infections. TOP CLIN NUTR 2018. [DOI: 10.1097/tin.0000000000000137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Agalioti T, Villablanca EJ, Huber S, Gagliani N. T H17 cell plasticity: The role of dendritic cells and molecular mechanisms. J Autoimmun 2018; 87:50-60. [PMID: 29371049 DOI: 10.1016/j.jaut.2017.12.003] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 12/03/2017] [Indexed: 01/18/2023]
Abstract
Upon interaction with dendritic cells (DCs), naïve CD4 T cells differentiate into distinct subsets and orchestrate the development of a physiological immune response. When uncontrolled by cellular and molecular mechanisms, CD4 T cells can also lead to immune mediated inflammatory diseases (IMIDs). Initially, these distinct CD4 T-cell subsets were defined according to the expression of a limited number of cytokines. Later it was revealed that CD4 T cells can acquire much more complex functional phenotypes than previously thought. Experimental data showed that the CD4 T-cell subset TH17 can secrete IFN-γ and IL-4, which are signature molecules of other T-cell subsets. Furthermore, some TH17 cells can also explore an anti-inflammatory fate and participate in the resolution of the immune response. A more flexible theory has therefore evolved with the scope to better represent the plastic biology of CD4 T cells. In this context, several aspects still remain unclear. The goal of this review is to discuss the role of extrinsic and intrinsic cellular and molecular mechanisms, which can drive the plasticity of TH17 cells. In particular, we will outline the role of DCs and the function of transcriptional factors in shaping the fate of TH17 cells towards either a pathogenic or a regulatory phenotype. Finally, we will discuss whether TH17 cell plasticity could be a target for new therapies for IMIDs. We indeed envision that when the cellular and molecular mechanisms controlling TH17 plasticity are known, new therapies, which aim to reset the immune system, will be developed. This will be achieved by either selectively depleting only the pathogenic TH17 cells or, if possible, re converting these cells from pathogenic to regulatory. This will overcome the challenge posed by the immune suppressive side effects caused by the current therapies, which impair the function of CD4 cells or delete all of them, to the detriment of the patient.
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Affiliation(s)
- Theodora Agalioti
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Eduardo J Villablanca
- Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, 17176 Stockholm, Sweden
| | - Samuel Huber
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Nicola Gagliani
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; I. Department of Medicine, University Medical Center Hamburg-Eppendorf Hamburg-Eppendorf, 20246 Hamburg, Germany; Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, 17176 Stockholm, Sweden.
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Ajabnoor SM, Forbes A. Effect of fat composition in enteral nutrition for Crohn's disease in adults: A systematic review. Clin Nutr 2017; 38:90-99. [PMID: 29310893 DOI: 10.1016/j.clnu.2017.12.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 11/10/2017] [Accepted: 12/20/2017] [Indexed: 01/16/2023]
Abstract
BACKGROUND & AIMS The role of enteral nutrition (EN) fat composition in regulating inflammation in Crohn's disease (CD) is not clear. There is, moreover, insufficient evidence to guide the choice of EN in CD with any confidence. We have reanalysed the findings of previous studies in a systematic review focussing on the relationship between EN fat content and remission rates (RR). METHODS A systematic search with no language restriction was undertaken in Medline and Embase databases supplemented by a manual search in the reference lists of identified studies. The selection criteria were: clinical trial, exclusive EN, adults and CD. Data on the type of EN, its fat composition, achieved RR, and study design were extracted. An established assessment tool was used to assess the quality of the studies. RESULTS A total of 29 clinical trials are included in this review. The quality of the studies was highly variable. No fewer than 27 formulations of enteral feed were identified including 4 elemental and 23 non-elemental preparations. There was a positive correlation between the total n-6 fatty acid content and response rates, which was significant when expressed as the ratio between n-6 and n-3 fatty acids (r = 0.378, p = 0.018). A non-significant positive trend was founded (r = 0.072; p = 0.643) between medium chain triglycerides (MCT) delivery as a percentage of the total energy provision and RR. While a non-significant negative trend was reported for the delivery of monounsaturated fatty acids (MUFA) (r = -0.23, p = 0.13). A qualitative advantage to regimens based on safflower oil suggest that optimised therapeutic approaches are within reach.
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Affiliation(s)
- Sarah M Ajabnoor
- Norwich Medical School, University of East Anglia, Norwich Research Park, UK; Clinical Nutrition Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Saudi Arabia
| | - Alastair Forbes
- Norwich Medical School, University of East Anglia, Norwich Research Park, UK.
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Vora R, Puntis JW. Dietary Treatment for Crohn’s Disease—Old Therapy, New Insights. EXPLORATORY RESEARCH AND HYPOTHESIS IN MEDICINE 2017; 2:1-8. [DOI: 10.14218/erhm.2017.00026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Souza AL, Fiorini Aguiar SL, Gonçalves Miranda MC, Lemos L, Freitas Guimaraes MA, Reis DS, Vieira Barros PA, Veloso ES, Carvalho TG, Ribeiro FM, Ferreira E, Cara DC, Gomes-Santos AC, Faria AMC. Consumption of Diet Containing Free Amino Acids Exacerbates Colitis in Mice. Front Immunol 2017; 8:1587. [PMID: 29209321 PMCID: PMC5701921 DOI: 10.3389/fimmu.2017.01587] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 11/03/2017] [Indexed: 12/25/2022] Open
Abstract
Dietary proteins can influence the maturation of the immune system, particularly the gut-associated lymphoid tissue, when consumed from weaning to adulthood. Moreover, replacement of dietary proteins by amino acids at weaning has been shown to impair the generation of regulatory T cells in the gut as well as immune activities such as protective response to infection, induction of oral and nasal tolerance as well as allergic responses. Polymeric and elemental diets are used in the clinical practice, but the specific role of intact proteins and free amino acids during the intestinal inflammation are not known. It is plausible that these two dietary nitrogen sources would yield distinct immunological outcomes since proteins are recognized by the immune system as antigens and amino acids do not bind to antigen-recognition receptors but instead to intracellular receptors such as mammalian target of rapamycin (mTOR). In this study, our aim was to evaluate the effects of consumption of an amino acid-containing diet (AA diet) versus a control protein-containing diet in adult mice at steady state and during colitis development. We showed that consumption of a AA diet by adult mature mice lead to various immunological changes including decrease in the production of serum IgG as well as increase in the levels of IL-6, IL-17A, TGF-β, and IL-10 in the small and large intestines. It also led to changes in the intestinal morphology, to increase in intestinal permeability, in the number of total and activated CD4+ T cells in the small intestine as well as in the frequency of proliferating cells in the colon. Moreover, consumption of AA diet during and prior to development of dextran sodium sulfate-induced colitis exacerbated gut inflammation. Administration of rapamycin during AA diet consumption prevented colitis exacerbation suggesting that mTOR activation was involved in the effects triggered by the AA diet. Therefore, our study suggests that different outcomes can result from the use of diets containing either intact proteins or free amino acids such as elemental, semielemental, and polymeric diets during intestinal inflammation. These results may contribute to the design of nutritional therapeutic intervention for inflammatory bowel diseases.
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Affiliation(s)
- Adna Luciana Souza
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.,Centro das Ciências Biológicas e da Saúde, Universidade Federal do Oeste da Bahia, Barreiras, Brazil
| | - Sarah Leão Fiorini Aguiar
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Luisa Lemos
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Daniela Silva Reis
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Emerson Soares Veloso
- Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Fabiola Mara Ribeiro
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Enio Ferreira
- Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Denise Carmona Cara
- Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Ana Cristina Gomes-Santos
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.,Centro Universitário UNA, Belo Horizonte, Brazil
| | - Ana Maria Caetano Faria
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Witkowski M, Witkowski M, Gagliani N, Huber S. Recipe for IBD: can we use food to control inflammatory bowel disease? Semin Immunopathol 2017; 40:145-156. [PMID: 29124320 PMCID: PMC5809523 DOI: 10.1007/s00281-017-0658-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 10/18/2017] [Indexed: 02/07/2023]
Abstract
The mucosal immune system and the microbiota in the intestinal tract have recently been shown to play a key role in the pathogenesis of inflammatory bowel disease (IBD). Both of these can be influenced by food. Thus, we propose dietary intervention as a therapeutic option for IBD. In this review, we discuss the interaction of the intestinal mucosal immune system and the intestinal microbiota in the context of IBD. In addition, we discuss the impact of food components on immune responses in IBD. Finally, we address the current evidence of how this interaction (i.e., immune system-microbiota) can be modulated by food components, pre/probiotics, and fecal microbiota transplantation (FMT) and how these approaches can support intestinal homeostasis. By gathering the vast amount of literature available on the impact of food on IBD, we aim to distinguish between scientifically sound data and theories, which have not been included in this review.
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Affiliation(s)
- Mario Witkowski
- Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany
| | - Marco Witkowski
- Department of Internal Medicine and Cardiology, Campus Benjamin Franklin, Charité - Universitätsmedizin, Berlin, Germany
| | - Nicola Gagliani
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institute, 17176 , Stockholm, Sweden
| | - Samuel Huber
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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The use of oral corticosteroids in inflammatory bowel diseases in Italy: An IG-IBD survey. Dig Liver Dis 2017; 49:1092-1097. [PMID: 28801181 DOI: 10.1016/j.dld.2017.07.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Revised: 07/06/2017] [Accepted: 07/13/2017] [Indexed: 12/11/2022]
Abstract
AIM To evaluate how Italian gastroenterologists use corticosteroids in clinical practice for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). MATERIAL AND METHODS All members of the Italian Group for Inflammatory Bowel Disease (IG-IBD) were invited to fill in a web-based questionnaire. RESULTS 131/448 (29.2%) members completed the survey. In mild-to-moderate UC and CD relapses, low-bioavailability steroids (LBS) are first-line therapy for 37% and 42% of clinicians, respectively. In case of failure, immediate step-up to biologics or immunosuppressants is considered by 23% and 29%. Regarding conventional corticosteroids (CCS), a fixed starting dose is prescribed by 50%, and a weight-based dose by 22%. Tapering is started after 7-10days by 41% and after 14days by 32%. The preferred tapering schedule is 5mg/week. In case of CCS failure, 47% switch to parenteral steroids before considering shifting to different drug classes. In case of symptoms recurrence during tapering, 14% re-increase the dose and try tapering again. Before prescribing steroids, 72% do not prescribe any specific evaluation whereas during treatment some evaluation is performed by 85%. Vitamin D and calcium supplements are routinely prescribed along with steroids by 38%. CONCLUSIONS Several discrepancies and some deviation from the available guidelines were recorded among Italian gastroenterologists regarding corticosteroids use in IBD patients.
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Yang Q, Gao X, Chen H, Li M, Wu X, Zhi M, Lan P, Hu P. Efficacy of exclusive enteral nutrition in complicated Crohn's disease. Scand J Gastroenterol 2017; 52:995-1001. [PMID: 28598298 DOI: 10.1080/00365521.2017.1335770] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM To investigate the efficacy of exclusive enteral nutrition (EEN) in induction of remission in adult active Crohn's disease (CD) complicated with intestinal fistula/abdominal abscess or inflammatory intestinal stricture. METHOD Patients diagnosed with active CD with complications were recruited between July 2013 and July 2015. Patients were offered EEN for 12 weeks. Patients with abscess received antibiotic treatment with or without percutaneous drainage. Clinical variables were recorded (ClinicalTrials.gov Identifier: NCT02887287). RESULTS Forty-one patients with CD and with intestinal fistula/abdominal abscess or inflammatory intestinal stricture aged 18-60 years, were included. Ten patients were accompanied with stenosis and 33 with intestinal fistula/abscess. After 12 weeks of EEN, the Crohn's disease activity index significantly decreased (223.43 ± 65.5 vs. 106.77 ± 42.73, p ≤ .001), and 80.5% of patients achieved full clinical remission totally. Fistula closure after EEN was observed in 75% of patients with entero-cutaneous fistula. In patients with stenosis, 20% had no response to EEN and were transferred for surgery. Partial remission and full remission were observed in 20% and 60% of patients after 12 weeks of EEN, respectively. Intra-abdominal abscess resolved in 76% of patients. Seventeen patients who had mucosal ulcers underwent colonoscopy before and after EEN, 47% achieved mucosal healing after the treatment. The inflammatory index of patients significantly decreased (p ≤ .01), nutritional parameters increased (p ≤ .01) and the European Nutritional Risk Screening (2002) decreased (p ≤ .01). CONCLUSION EEN is effective in inducing early clinical remission, mucosal healing, promoting fistula closure and reducing the size of abscess in adult CD patients with complications.
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Affiliation(s)
- Qingfan Yang
- a Department of Gastroenterology , The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China.,b Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases , the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
| | - Xiang Gao
- a Department of Gastroenterology , The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China.,b Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases , the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
| | - Huiping Chen
- a Department of Gastroenterology , The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China.,b Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases , the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
| | - Miao Li
- a Department of Gastroenterology , The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China.,b Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases , the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
| | - Xiaojian Wu
- a Department of Gastroenterology , The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China.,b Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases , the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
| | - Min Zhi
- a Department of Gastroenterology , The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China.,b Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases , the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
| | - Ping Lan
- a Department of Gastroenterology , The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China.,b Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases , the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
| | - Pinjin Hu
- a Department of Gastroenterology , The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou , PR China.,b Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases , the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , PR China
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Heerasing N, Thompson B, Hendy P, Heap GA, Walker G, Bethune R, Mansfield S, Calvert C, Kennedy NA, Ahmad T, Goodhand JR. Exclusive enteral nutrition provides an effective bridge to safer interval elective surgery for adults with Crohn's disease. Aliment Pharmacol Ther 2017; 45:660-669. [PMID: 28105752 DOI: 10.1111/apt.13934] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Revised: 11/20/2016] [Accepted: 12/18/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Few studies have reported the systematic use of exclusive enteral nutrition in the perioperative setting. AIM To test the hypothesis that exclusive enteral nutrition provides a safe and effective bridge to surgery and reduces post-operative complications, in adult patients with Crohn's disease requiring urgent surgery for stricturing or penetrating complications. METHODS Patients treated with exclusive enteral nutrition prior to surgery were each matched with two control patients for disease behaviour, type of surgery, age at diagnosis and disease duration. Data on disease phenotype, nutritional status, operative course and post-operative complications were obtained. RESULTS Twenty-five per cent [13/51] patients treated with exclusive enteral nutrition avoided surgery. Exclusive enteral nutrition had no effect on pre-operative weight, but it significantly reduced serum CRP [median at baseline 36 (interquartile range, IQR: 13-91] vs. pre-operation 8 (4-31) mg/L, P = 0.02]. The median (IQR) length of surgery was shorter in patients pre-optimised with exclusive enteral nutrition than controls [3.0 (2.5-3.5) vs. 3.5 (3.0-4.0) hours respectively, P < 0.001]. Multivariable logistic regression analysis confirmed that going straight-to-surgery compared exclusive enteral nutrition pre-optimisation was associated with a ninefold increase in the incidence of post-operative abscess and/or anastomotic leak [OR 9.1; 95% CI (1.2-71.2), P = 0.04]. CONCLUSIONS Exclusive enteral nutrition frequently down-stages the need for surgery in patients presenting with stricturing or penetrating complications of Crohn's disease; it is associated with a reduction in systemic inflammation, operative times and the incidence of post-operative abscess or anastomotic leak. Further trials are needed to elucidate how exclusive enteral nutrition may improve operative outcomes.
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Affiliation(s)
- N Heerasing
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - B Thompson
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - P Hendy
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - G A Heap
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - G Walker
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - R Bethune
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - S Mansfield
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - C Calvert
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - N A Kennedy
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - T Ahmad
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - J R Goodhand
- Exeter IBD group, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
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Ciampa BP, Reyes Ramos E, Borum M, Doman DB. The Emerging Therapeutic Role of Medical Foods for Gastrointestinal Disorders. Gastroenterol Hepatol (N Y) 2017; 13:104-115. [PMID: 28450817 PMCID: PMC5402682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
In addition to drugs approved by the US Food and Drug Administration (FDA) that treat, cure, or mitigate disease, medical foods are a tool to help manage chronic conditions and diseases. A medical food, according to the FDA, is a food that is developed to be eaten or administered enterally under the guidance of a physician and that is meant for the specific dietary management of a condition or disease for which distinctive nutritional requirements, based upon known scientific principles, are established by medical evaluation. A variety of medical foods exist to help manage a wide range of medical conditions, from Alzheimer disease to HIV-associated enteropathy. EnteraGam contains serum-derived bovine immunoglobulin/protein isolate, which has been studied extensively in diarrhea-predominant irritable bowel syndrome, inflammatory bowel disease (IBD), and HIV-associated enteropathy. VSL#3 is a probiotic that is used in pouchitis for patients with ulcerative colitis as well as irritable bowel syndrome. Modulen IBD is a whole-protein, sole-nutrition formulation used to manage the active phase of Crohn's disease. Vivonex is an elemental diet that is used in a variety of diseases associated with severe gastrointestinal dysfunction. Medical foods are safe and must have proven efficacy in helping to manage a variety of gastrointestinal conditions and diseases. These therapies represent tools that can be used prior or in addition to traditional medical therapies. This article discusses the history and development of medical foods under the FDA and concentrates specifically on medical foods used to help manage diseases of the gastrointestinal tract.
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Affiliation(s)
- Brian P Ciampa
- Dr Ciampa and Dr Reyes Ramos are gastroenterology fellows in the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center and are affiliated with Medical Faculty Associates, both in Washington, DC. Dr Borum is a professor of medicine at George Washington University School of Medicine in Washington, DC; director of the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center; and is affiliated with Medical Faculty Associates. Dr Doman is a clinical professor of medicine at George Washington University School of Medicine
| | - Emmanuel Reyes Ramos
- Dr Ciampa and Dr Reyes Ramos are gastroenterology fellows in the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center and are affiliated with Medical Faculty Associates, both in Washington, DC. Dr Borum is a professor of medicine at George Washington University School of Medicine in Washington, DC; director of the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center; and is affiliated with Medical Faculty Associates. Dr Doman is a clinical professor of medicine at George Washington University School of Medicine
| | - Marie Borum
- Dr Ciampa and Dr Reyes Ramos are gastroenterology fellows in the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center and are affiliated with Medical Faculty Associates, both in Washington, DC. Dr Borum is a professor of medicine at George Washington University School of Medicine in Washington, DC; director of the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center; and is affiliated with Medical Faculty Associates. Dr Doman is a clinical professor of medicine at George Washington University School of Medicine
| | - David B Doman
- Dr Ciampa and Dr Reyes Ramos are gastroenterology fellows in the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center and are affiliated with Medical Faculty Associates, both in Washington, DC. Dr Borum is a professor of medicine at George Washington University School of Medicine in Washington, DC; director of the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center; and is affiliated with Medical Faculty Associates. Dr Doman is a clinical professor of medicine at George Washington University School of Medicine
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Charlebois A, Rosenfeld G, Bressler B. The Impact of Dietary Interventions on the Symptoms of Inflammatory Bowel Disease: A Systematic Review. Crit Rev Food Sci Nutr 2017; 56:1370-8. [PMID: 25569442 DOI: 10.1080/10408398.2012.760515] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Diet may be a successful part of the treatment plan for improving outcome in patients with inflammatory bowel disease (IBD). This study aimed to systematically review all published clinical trials evaluating the effects of a regular diet on symptoms of IBD. Three medical databases were searched for clinical trials evaluating an intervention that involved dietary manipulation using a regular diet on adults with IBD whose symptoms were objectively measured before and after the intervention. The most common types of regular diet interventions that we observed in the literature fell into the following three categories: low residue/low fiber diets, exclusion diets, or other specific diets. Of all included studies, the few that were of higher quality and that observed a statistically significant improvement in symptoms in the diet group compared to the control group fell under the exclusion diet group or the other specific diet group. We were able to identify several high quality clinical trials evaluating dietary manipulations on symptoms of IBD. Exclusion diets and the low FODMAP diet are two areas identified in this review that show promise for having therapeutic benefits for patients with IBD.
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Affiliation(s)
- Ashley Charlebois
- a Department of Medicine , Division of Gastroenterology, University of British Columbia , Vancouver , British Columbia , Canada
| | - Greg Rosenfeld
- b Division of Gastroenterology, Department of Medicine, St. Paul's Hospital , University of British Columbia , Vancouver , Canada
| | - Brian Bressler
- b Division of Gastroenterology, Department of Medicine, St. Paul's Hospital , University of British Columbia , Vancouver , Canada
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Otley AR, Day AS, Zachos M. Nutritional Management of Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2017:333-356. [DOI: 10.1007/978-3-319-49215-5_27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Beattie RM. Enteral Nutrition as Primary Therapy in Childhood Crohn's Disease: Control of Intestinal Inflammation and Anabolic Response. JPEN J Parenter Enteral Nutr 2016; 29:S151-5; discussion S155-9, S184-8. [PMID: 15980277 DOI: 10.1177/01486071050290s4s151] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Crohn's disease in childhood is a chronic relapsing and remitting condition that can significantly impact normal growth and development. This influences choice of both initial and ongoing management. The goal of therapy is to induce and maintain remission with minimal side effects. Enteral nutrition is effective in active disease and will induce disease remission in most cases avoiding corticosteroid use. The high frequency of relapse means additional immunosuppressive therapies are usually required but nutrition remains a key priority as part of the subsequent management strategy.
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Affiliation(s)
- Robert M Beattie
- Pediatric Medical Unit, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
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Vindigni SM, Zisman TL, Suskind DL, Damman CJ. The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions. Therap Adv Gastroenterol 2016; 9:606-25. [PMID: 27366227 PMCID: PMC4913337 DOI: 10.1177/1756283x16644242] [Citation(s) in RCA: 140] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We discuss the tripartite pathophysiological circuit of inflammatory bowel disease (IBD), involving the intestinal microbiota, barrier function, and immune system. Dysfunction in each of these physiological components (dysbiosis, leaky gut, and inflammation) contributes in a mutually interdependent manner to IBD onset and exacerbation. Genetic and environmental risk factors lead to disruption of gut homeostasis: genetic risks predominantly affect the immune system, environmental risks predominantly affect the microbiota, and both affect barrier function. Multiple genetic and environmental 'hits' are likely necessary to establish and exacerbate disease. Most conventional IBD therapies currently target only one component of the pathophysiological circuit, inflammation; however, many patients with IBD do not respond to immune-modulating therapies. Hope lies in new classes of therapies that target the microbiota and barrier function.
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Affiliation(s)
- Stephen M. Vindigni
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Timothy L. Zisman
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - David L. Suskind
- Department of Pediatrics, Seattle Children’s Hospital and University of Washington, Seattle, WA, USA
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Low fat-containing elemental formula is effective for postoperative recovery and potentially useful for preventing chyle leak during postoperative early enteral nutrition after esophagectomy. Clin Nutr 2016; 35:1423-1428. [PMID: 27071696 DOI: 10.1016/j.clnu.2016.03.018] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Revised: 03/08/2016] [Accepted: 03/23/2016] [Indexed: 01/18/2023]
Abstract
BACKGROUND AND AIMS Transthoracic esophagectomy using 3-field lymphadenectomy (TTE-3FL) for esophageal cancer is one of the most aggressive gastrointestinal surgeries. Early enteral nutrition (EN) for TTE-3FL patients is useful and valid for early recovery; however, EN using a fat-containing formula risks inducing chyle leak. In the present study, we retrospectively examined esophageal cancer patients treated byTTE-3FL and administered postoperative EN to elucidate the validity of lowering the fat levels in elemental formulas to prevent postoperative chyle leak and improve postoperative recovery. METHODS A total of 74 patients who received TTE-3FL for esophageal cancer were retrospectively examined. Patients were classified into two groups according to the type of postoperative EN: Group LF patients received a low-fat elemental formula, and Group F patients received a standard fat-containing polymeric formula. The following clinical factors were compared between the groups: EN start day, maximum EN calories administered, duration of respirator use, length of ICU stay, incidence of postoperative infectious complications, use of parenteral nutrition (PN), and incidence of postoperative chyle leak. RESULTS Patients in Group LF were started on EN significantly earlier after surgery and they consumed significantly higher maximum EN calories compared to Group F patients (P < 0.01). Duration of respirator use and length of ICU stay were also significantly shorter, and TPN was used significantly less in Group LF compared to Group F (P < 0.05). Postoperative chyle leak was observed in six patients in total (8.1%); five patients in Group F and one patient in Group LF, although there was no significant difference in frequency of chyle leak per patient between Group LF and Group F. CONCLUSIONS Early EN using low-fat elemental formula after esophagectomy with three-field lymphadenectomy was safe and valid for postoperative recovery and potentially useful in preventing chyle leak.
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Martin TD, Chan SSM, Hart AR. Environmental factors in the relapse and recurrence of inflammatory bowel disease: a review of the literature. Dig Dis Sci 2015; 60:1396-405. [PMID: 25407806 DOI: 10.1007/s10620-014-3437-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Accepted: 11/11/2014] [Indexed: 02/08/2023]
Abstract
INTRODUCTION The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability. RESULTS The clinical epidemiological data consistently reports positive associations between smoking and relapses in CD, and inverse ones with UC. For NSAIDs and estrogens, the epidemiological findings are inconsistent, although general antibiotic use was associated with a reduced risk of relapse in CD. High levels of stress were positively associated with relapse, although psychological interventions did not have therapeutic benefits. The limited work on diet has reported sulphur-containing foods are positively associated with relapse in UC, but there is no work in CD. Ecological data reported positive correlations between air pollution levels and IBD hospitalisations. CONCLUSIONS In the future, to clarify this area, more clinical epidemiological work is required where detailed drug types and doses, and complete dietary intakes are measured, in specific forms of IBD. Such work could provide guidance to both patients and doctors to help maintain remission.
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Affiliation(s)
- Thomas D Martin
- Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK,
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Abstract
The current general interest in the use of food choice or diet in maintaining good health and in preventing and treating disease also applies to patients with IBD, who often follow poor or nutritionally challenging dietary plans. Unfortunately, dietary advice plays only a minor part in published guidelines for management of IBD, which sends a message that diet is not of great importance. However, a considerable evidence base supports a focused and serious attention to nutrition and diet in patients with IBD. In this Review, a step-wise approach in the evaluation and management of these patients is proposed. First, dietary intake and eating habits as well as current nutritional state should be documented, and corrective measures instituted. Secondly, dietary strategies as primary or adjunctive therapy for the reduction of inflammation and/or prevention of relapse of IBD should be seriously contemplated. Thirdly, use of diet to improve symptoms or lessen the effects of complications should be considered. Finally, dietary advice regarding disease prevention should be discussed when relevant. An increasing need exists for applying improved methodologies into establishing the value of current and new ways of using food choice as a therapeutic and preventive tool in IBD.
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The role of enteral nutrition in patients with inflammatory bowel disease: current aspects. BIOMED RESEARCH INTERNATIONAL 2015; 2015:197167. [PMID: 25793189 PMCID: PMC4352452 DOI: 10.1155/2015/197167] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Accepted: 10/13/2014] [Indexed: 12/15/2022]
Abstract
Enteral nutrition (EN) is considered to be of great importance in patients with inflammatory bowel disease (IBD) and nutritional problems. This comprehensive review is aiming to provide the reader with an update on the role of EN in IBD patients. EN can reduce Crohn's disease (CD) activity and maintain remission in both adults and children. Nutritional support using liquid formulas should be considered for CD patients and in serious cases of ulcerative colitis (UC), especially for those who may require prolonged cycles of corticosteroids. Given that the ultimate goal in the treatment of CD is mucosal healing, this advantage of EN over corticosteroid treatment is valuable in therapeutic decision-making. EN is indicated in active CD, in cases of steroid intolerance, in patient's refusal of steroids, in combination with steroids in undernourished individuals, and in patients with an inflammatory stenosis of the small intestine. No differences between the efficiency of elemental diets and nonelemental formulas have been noticed. EN must be the first choice compared to TPN. EN has a restricted value in the treatment of patients with large bowel CD. In conclusion, it seems important not to underestimate the role of nutrition as supportive care in patients with IBD.
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Wall CL, Gearry RB, Day AS. Polymeric formula is more palatable than elemental formula to adults with Crohn's disease. ACTA ACUST UNITED AC 2014. [DOI: 10.1016/j.clnme.2014.08.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Fischer M, Zopf Y, Elm C, Pechmann G, Hahn EG, Schwab D, Kornhuber J, Thuerauf NJ. Subjective and objective olfactory abnormalities in Crohn's disease. Chem Senses 2014; 39:529-38. [PMID: 24862958 DOI: 10.1093/chemse/bju022] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
The pathogenesis of Crohn's disease (CD) is still unknown, but the involvement of the olfactory system in CD appears possible. No study to date has systematically assessed the olfactory function in CD patients. We investigated the olfactory function in CD patients in active (n = 31) and inactive disease (n = 27) and in a control group of age- and sex-matched healthy subjects (n = 35). Subjective olfactory testing was applied using the Sniffin' Sticks test. For olfactory testing, olfactory event-related potentials (OERPs) were obtained with a 4-channel olfactometer using phenyl ethyl alcohol (PEA) and hydrogen sulfide (H(2)S). Carbon dioxide (CO(2)) was employed as control stimulus, and chemosomatosensory event-related potentials (CSSERPs) were registered. Results of the Sniffin' Sticks test revealed significantly different olfactory hedonic judgment with increased olfactory hedonic estimates for pleasant odorants in CD patients in active disease compared with healthy subjects. A statistical trend was found toward lower olfactory thresholds in CD patients. In objective olfactory testing, CD patients showed lower amplitudes of OERPs and CSSERPs. Additionally, OERPs showed significantly shorter N1- and P2 latencies following stimulation of the right nostril with H(2)S in CD patients in inactive disease compared with controls. Our study demonstrates specific abnormalities of olfactory perception in CD patients.
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Affiliation(s)
- Marie Fischer
- Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany and
| | - Yurdagül Zopf
- Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany
| | - Cornelia Elm
- Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany and
| | - Georg Pechmann
- Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany and
| | - Eckhart G Hahn
- Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany
| | - Dieter Schwab
- Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany
| | - Johannes Kornhuber
- Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany and
| | - Norbert Joachim Thuerauf
- Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany and
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Lee J, Allen R, Ashley S, Becker S, Cummins P, Gbadamosi A, Gooding O, Huston J, Le Couteur J, O'Sullivan D, Wilson S, Lomer MCE. British Dietetic Association evidence-based guidelines for the dietary management of Crohn's disease in adults. J Hum Nutr Diet 2013; 27:207-18. [PMID: 24313460 DOI: 10.1111/jhn.12176] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Crohn's disease is a debilitating chronic inflammatory bowel disease. Appropriate use of diet and nutritional therapy is integral to the overall management strategy of Crohn's disease. The aim was to develop evidence-based guidelines on the dietary management of Crohn's disease in adults. METHODS Questions relating to the dietary management of Crohn's disease were developed. These included the roles of enteral nutrition to induce remission, food re-introduction diets to structure food re-introduction and maintain remission, and dietary management of stricturing disease, as well as whether probiotics or prebiotics induce or maintain remission. A comprehensive literature search was conducted and relevant studies from January 1985 to November 2009 were identified using the electronic database search engines CINAHL, Cochrane Library, EMBASE, MEDLINE, Scopus and Web of Science. Evidence statements, recommendations, practical considerations and research recommendations were developed. RESULTS Fifteen research papers were critically appraised and the evidence formed the basis of these guidelines. Although corticosteroids appear to be more effective, enteral nutrition (elemental or non-elemental) can be offered as an alternative option to induce disease remission. After a course of enteral nutrition, food re-introduction diets may be useful to structure food re-introduction and help maintain disease remission. Dietary fibre is contraindicated in the presence of strictures as a result of the risk of mechanical obstruction. The use of probiotics and prebiotics is not currently supported. CONCLUSIONS As an alternative to corticosteroids, evidence supports enteral nutrition to induce disease remission. Food re-introduction diets provide structure to food re-introduction and help maintain disease remission. These guidelines aim to reduce variation in clinical practice.
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Affiliation(s)
- J Lee
- Department of Nutrition and Dietetics, Addenbrookes, Cambridge, UK
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Enteral nutrition in Crohn's disease: an underused therapy. Gastroenterol Res Pract 2013; 2013:482108. [PMID: 24382954 PMCID: PMC3870077 DOI: 10.1155/2013/482108] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Revised: 11/08/2013] [Accepted: 11/08/2013] [Indexed: 12/13/2022] Open
Abstract
This paper reviews the literature on the history, efficacy, and putative mechanism of action of enteral nutrition for inflammatory bowel disease in both paediatric and adult patients. It also analyses the reasoning behind the low popularity of exclusive enteral nutrition in clinical practice despite the benefits and safety profile.
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Wall CL, Day AS, Gearry RB. Use of exclusive enteral nutrition in adults with Crohn’s disease: A review. World J Gastroenterol 2013; 19:7652-7660. [PMID: 24282355 PMCID: PMC3837264 DOI: 10.3748/wjg.v19.i43.7652] [Citation(s) in RCA: 117] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Revised: 08/08/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
Exclusive enteral nutrition (EEN) is well-established as a first line therapy instead of corticosteroid (CS) therapy to treat active Crohn’s disease (CD) in children. It also has been shown to have benefits over and above induction of disease remission in paediatric populations. However, other than in Japanese populations, this intervention is not routinely utilised in adults. To investigate potential reasons for variation in response between adult studies of EEN and CS therapy. The Ovid database was searched over a 6-mo period. Articles directly comparing EEN and CS therapy in adults were included. Eleven articles were identified. EEN therapy remission rates varied considerably. Poor compliance with EEN therapy due to unpalatable formula was an issue in half of the studies. Remission rates of studies that only included patients with previously untreated/new CD were higher than studies including patients with both existing and new disease. There was limited evidence to determine if disease location, duration of disease or age of diagnosis affected EEN therapy outcomes. There is some evidence to support the use of EEN as a treatment option for a select group of adults, namely those motivated to adhere to an EEN regimen and possibly those newly diagnosed with CD. In addition, the use of more palatable formulas could improve treatment compliance.
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Guo Z, Wu R, Zhu W, Gong J, Zhang W, Li Y, Gu L, Li N, Li J. Effect of exclusive enteral nutrition on health-related quality of life for adults with active Crohn's disease. Nutr Clin Pract 2013; 28:499-505. [PMID: 23851180 DOI: 10.1177/0884533613487218] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Exclusive enteral nutrition (EEN) is an effective and safe remission induction treatment for Crohn's disease in adults. Its influence on adults' health-related quality of life remains unknown. The aim of this study was to determine the effect of EEN on health-related quality of life in adults with active Crohn's disease. MATERIALS AND METHODS Patients recruited were treated with a polymeric enteral feed that was taken orally in the daytime and via a self-intubated nasogastric tube at night for 4 weeks. Prospective evaluation of disease activity (Crohn's Disease Activity Index, CDAI) and health-related quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ) were performed at enrollment and after 4 weeks of treatment. Patients' feelings about EEN were also investigated through 2 questions. RESULTS Thirteen patients were treated with 4-week EEN. They had a significant improvement in total IBDQ score (P < .001) and all IBDQ dimensions: bowel symptoms (P < .001), systemic symptoms (P < .001), social function (P = .003), and emotional status (P < .001), with 11 patients (84.6%) achieving clinical remission after treatment. In addition, 8 patients (61.5%) expressed their willingness to receive this 4-week EEN treatment again to induce remission if the disease relapsed. The IBDQ correlated significantly with the CDAI at 4 weeks. CONCLUSIONS A 4-week treatment of EEN improves health-related quality of life significantly in adults with active Crohn's disease and was acceptable by most patients.
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Affiliation(s)
- Zhen Guo
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China
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Exclusive elemental diet impacts on the gastrointestinal microbiota and improves symptoms in patients with chronic pouchitis. J Crohns Colitis 2013; 7:460-6. [PMID: 22857825 DOI: 10.1016/j.crohns.2012.07.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Revised: 06/24/2012] [Accepted: 07/08/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Treatment resistant chronic pouchitis causes significant morbidity. Elemental diet is effective treatment for Crohn's disease. Since pouchitis shares some similarities to Crohn's disease we hypothesised that elemental diet may be an effective treatment. METHOD Seven pouchitis patients (with ulcerative colitis) were studied. All had active pouchitis with a pouch disease activity index (PDAI) ≥7. Exclusion criteria were recent NSAIDs, antibiotics or probiotics. Sufficient elemental diet to achieve energy requirements was provided. Flexible-pouchoscopy was performed, and the Cleveland Global Quality of Life score (CGQoL), Pouch Disease Activity Index (PDAI) and BMI were recorded at baseline and following 28 days of elemental diet. Faecal samples were also collected at these time points and analysed for major bacterial groups using culture independent fluorescence in situ hybridisation. Data were analysed using Wilcoxon's signed-rank test. RESULTS Following 28 days of exclusive elemental diet, median stool frequency decreased from 12 to 6 per day (p=0.028), median clinical PDAI decreased from 4 to 1 (p=0.039). There was no significant difference in quality of life scores or PDAI before and following treatment. There was a trend towards an increase in the concentration of Clostridium coccoides-Eubacterium rectale (median 7.9 to 8.5 log₁₀/g, p=0.08) following exclusive elemental diet. CONCLUSION Treatment with four weeks elemental diet appeared to improve the symptoms of chronic pouchitis in some patients but is not an effective strategy for inducing remission. Although a potential symptom modifier, elemental diet cannot be recommended for the routine treatment of active pouchitis.
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Changes of faecal microbiota in patients with Crohn's disease treated with an elemental diet and total parenteral nutrition. Dig Liver Dis 2012; 44:736-42. [PMID: 22622202 DOI: 10.1016/j.dld.2012.04.014] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2011] [Revised: 04/17/2012] [Accepted: 04/19/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intestinal microbiota contributes to the pathogenesis of Crohn's disease. Elemental diet and total parenteral nutrition are effective therapies for Crohn's disease; however, changes of microbiota as a result of both treatments have not been fully elucidated. AIM To elucidate changes of faecal microbiota in Crohn's disease patients treated with elemental diet and total parenteral nutrition. METHODS Stool samples were collected from 33 active Crohn's disease patients and 17 healthy subjects, and recollected after elemental diet (8 patients) and total parenteral nutrition (9 patients). Terminal restriction fragment length polymorphism analysis of bacterial 16srDNA was performed to evaluate the whole microbiota. Specific quantitative PCR was then used to determine populations of predominant bacterial groups. RESULTS In Crohn's disease patients, the number of terminal restriction fragments, which reflects bacterial species, was significantly lower. Populations of total bacteria and Bifidobacterium were significantly lower and the ratio of Enterococcus was higher. The number of terminal restriction fragments was significantly decreased after total parenteral nutrition, but not after elemental diet. Population of Bacteroides fragilis significantly decreased after elemental diet, while population of Enterococcus significantly increased after total parenteral nutrition. CONCLUSION Faecal microbiota in Crohn's disease patients was markedly different from healthy subjects. Species diversity was reduced by total parenteral nutrition, but not by elemental diet.
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Kurzweil V, Tarangelo A, Oliver PM. Gastrointestinal microbiota do not significantly contribute to T cell activation or GI inflammation in Ndfip1-cKO mice. PLoS One 2012; 7:e34478. [PMID: 22506022 PMCID: PMC3323617 DOI: 10.1371/journal.pone.0034478] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2012] [Accepted: 03/05/2012] [Indexed: 11/18/2022] Open
Abstract
The bacteria inhabiting the mammalian gastrointestinal (GI) tract play a vital role in normal digestion and immune function. In a healthy host, the immune system is tolerant to gut bacteria and does not mount an effector response to bacteria-derived antigens. Loss of tolerance to intestinal microflora has been associated with inflammatory bowel disease (IBD) in both mice and humans. Mice lacking Ndfip1, an adaptor protein for E3 ubiquitin ligases of the Nedd4-family, in T cells (Ndfip1-cKO) develop a disease resembling IBD. Inflammation in these mice is characterized by increased activation of peripheral T cells, infiltration of eosinophils into the GI tract, and epithelial hypertrophy in the esophagus. We hypothesized that this intestinal inflammation in Ndfip1-cKO mice is caused by a loss of T-cell tolerance to bacterial antigens. Here, we show that treatment of Ndfip1-cKO mice with broad-spectrum antibiotics drastically reduced bacterial load in stool but had little effect on T-cell activation and did not affect eosinophil infiltration into the GI tract or epithelial hypertrophy in the esophagus. Thus, inflammation in Ndfip1-cKO mice is not caused by a loss of tolerance to intestinal microbiota. Rather, T cell activation and eosinophilia may instead be triggered by other environmental antigens.
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Affiliation(s)
- Vanessa Kurzweil
- Cell and Molecular Biology Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Amy Tarangelo
- Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Paula M. Oliver
- Children's Hospital of Philadelphia and Department of Pathology and Lab Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- * E-mail:
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Grogan JL, Casson DH, Terry A, Burdge GC, El-Matary W, Dalzell AM. Enteral feeding therapy for newly diagnosed pediatric Crohn's disease: a double-blind randomized controlled trial with two years follow-up. Inflamm Bowel Dis 2012; 18:246-53. [PMID: 21425210 DOI: 10.1002/ibd.21690] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2010] [Accepted: 01/19/2011] [Indexed: 12/16/2022]
Abstract
BACKGROUND This study compared the efficacy of an elemental formula (EF) to a polymeric formula (PF) in inducing remission for pediatric Crohn's disease (CD). METHODS Newly diagnosed CD children were randomized to EF or PF for 6 weeks. Change in the Pediatric Crohn's Disease Activity Index (PCDAI), fecal calprotectin, and plasma fatty acids were measured at 0 and 6 weeks. Patients were followed up for 2 years. Time and treatment choice for first relapse were documented. RESULTS Thirty-four children completed the study; EF: 15 (7 M, 8 F), PF: 19 (13 M, 6 F). The mean age was (years) EF: 12.6, PF: 11.7. Ninety-three percent of children (14/15) achieved remission in the EF group and 79% (15/19) in the PF group. One-third of patients maintained remission for 2 years. Mean time to relapse (days); EF: 183 (63-286), PF: 162 (53-301). Most children who relapsed used feed as a treatment for that relapse (EF: 9/10 and PF: 8/13). With PF, an increase of eicosapentanoic acid (EPA) and alpha linolenic acid was found with a reciprocal decrease in arachidonic acid (AA). With EF, AA and EPA levels were reduced with a significant decrease in docosahexaenoic acid. Fecal calprotectin measurements decreased significantly but did not normalize at the end of week 6. CONCLUSIONS There was no significant difference between EF and PF in inducing remission. One-third of children maintained remission. Changes in plasma polyunsaturated fatty acid status were subtle and may be relevant; however, further evaluation is recommended.
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Affiliation(s)
- Joanne L Grogan
- Dietetic Department, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
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Gionchetti P, Calabrese C, Tambasco R, Brugnera R, Straforini G, Liguori G, Fornarini GS, Riso D, Campieri M, Rizzello F. Role of conventional therapies in the era of biological treatment in Crohn’s disease. World J Gastroenterol 2011; 17:1797-806. [PMID: 21528051 PMCID: PMC3080713 DOI: 10.3748/wjg.v17.i14.1797] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2010] [Revised: 07/12/2010] [Accepted: 07/19/2010] [Indexed: 02/06/2023] Open
Abstract
Outstanding progress regarding the pathophysiology of Crohn’s disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentrates on the results of randomized, placebo-controlled trials, and meta-analyses when available, that provide the highest degree of evidence. Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase. The advent of biological drugs has opened new therapeutic horizons for treating CD, modifying the treatment goals. However, the large majority of patients with CD will be managed through conventional therapy, even if they are a prelude to biological therapy.
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