Significance of nutritional treatment for patients with inflammatory bowel disease in the era of biologics

Significance of nutritional treatment for patients with inflammatory bowel disease in the era of biologics

Yoshihiro Yokoyama, Tomoya Iida, Hiroshi Nakase

Department of Gastroenterology and Hepatology, Sapporo Medical University, School of Medicine, Minami 1-jo Nishi 17-chome, Chuo-ku, Sapporo, Hokkaido, 060-8556, Japan, Phone: +81-11-611-2111 Fax: +81-11-611-2282

Open Journal of Gastroenterology and Hepatology

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease (CD), is a chronic gastrointestinal tract inflammatory disorder. Although its etiology remains unknown, it has been reported that nutrition is involved in the onset of IBD. Patients with IBD often experience malnutrition due to malabsorption and increased energy requirements. Malnutrition is a serious issue for patients with IBD, especially in young people. Growth retardation characterized by delayed skeletal maturation and onset of puberty is a representative complication. In addition, immunosuppression, osteoporosis, and sarcopenia are important issues. Functional foods and diets have been known to alleviate gastrointestinal inflammation by modulating inflammatory cytokines. Furthermore, appropriate nutritional treatment has been reported to be effective on the induction and maintenance of remission in patients with IBD, especially with CD. Conversely, there are negative reports regarding the efficacy of nutritional therapy in patients with IBD. Recently, various new therapeutic agents such as biologics have emerged as key drugs in IBD treatment. In this new era, the efficacy of nutritional treatment, including combination therapy with biologics, should be reconsidered to improve the quality of life in patients with IBD. In this review, the nutritional treatment for patients with IBD is reviewed, and the latest evidence is provided.

Supported by Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare of Japan (Investigation and Research for intractable Inflammatory Bowel Disease), and Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) Grant Number JP17J02428 (to T.I.) and JP18H02799 (to H.N.). The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Keywords: Inflammatory bowel disease; ulcerative colitis; Crohn’s disease; nutrition; biologics

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How to cite this article:
Yoshihiro Yokoyama, Tomoya Iida, Hiroshi Nakase.Significance of nutritional treatment for patients with inflammatory bowel disease in the era of biologics.Open Journal of Gastroenterology and Hepatology, 2019, 2:20. DOI: 10.28933/ojgh-2019-10-3106


1. Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol 2014; 20: 91-99. PMID: 24415861 DOI: 10.3748/wjg.v20.i1.91]
2. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007; 448: 427-434 [PMID: 17653185 DOI: 10.1038/nature06005]
3. Sanderson IR. Growth problems in children with IBD. Nat Rev Gastroenterol Hepatol 2014; 11: 601-610 [PMID: 24957008 DOI: 10.1038/nrgastro.2014.102]
4. Cholapranee A, Hazlewood, GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn’s disease and ulcerative colitis controlled trials. Aliment Pharmacol Ther 2017; 45: 1291-1302 [PMID: 28326566 DOI: 10.1111/apt.14030]
5. Lee D, Albenberg L, Compher C, Baldassano R, Piccoli D, Lewis JD, Wu GD. Diet in the pathogenesis and treatment of inflammatory bowel diseases. Gastroenterology 2015; 148: 1087-1106 [PMID: 25597840 DOI: 10.1053/j.gastro.2015.01.007]
6. Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol 2015; 12: 720-727 [PMID: 26323879 DOI: 10.1038/nrgastro.2015.150]
7. Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 2015; 12: 205-217 [PMID: 25732745 DOI: 10.1038/nrgastro.2015.34]
8. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 2001; 411: 603-606 [PMID: 11385577 DOI: 10.1038/35079114]
9. Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med 2016; 375: 2369-2379 [PMID: 27974040 DOI: 10.1056/NEJMra1600266]
10. Brestoff JR, Artis D. Commensal bacteria at the interface of host metabolism and the immune system. Nat Immunol 2013; 14: 676-684 [PMID: 23778795 DOI: 10.1038/ni.2640]
11. Yao CK, Muir JG, Gibson PR. Review article: insights into colonic protein fermentation, its modulation and potential health implications. Aliment Pharmacol Ther 2016; 43: 181-196 [PMID: 26527169 DOI: 10.1111/apt.13456]
12. Wang D, Dubois RN. Eicosanoids and cancer. Nat Rev Cancer 2010; 10: 181-193 [PMID: 20168319 DOI: 10.1038/nrc2809]
13. Coeffier M, Marion-Letellier R, Dechelotte P. Potential for amino acids supplementation during inflammatory bowel diseases. Inflamm Bowel Dis 2010; 16: 518-524 [PMID: 19572337 DOI: 10.1002/ibd.21017]
14. Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004; 80: 1717s-1720s [PMID: 15585793 DOI: 10.1093/ajcn/80.6.1717S]
15. Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, Pudl NA, Kitamoto S, Terrapon N, Muller A, Young VB, Henrissat B, Wilmes P, Stappenbeck TS, Nunez G, Martens EC. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell 2016; 167: 1339-1353. e21 [PMID: 27863247 DOI: 10.1016/j.cell.2016.10.043]
16. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 2009; 139: 485-498 [PMID: 19836068 DOI: 10.1016/j.cell.2009.09.033]
17. Piechota-Polanczyk A, Fichna J. Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases. Naunyn Schmiedebergs Arch Pharmacol 2014; 387: 605-620 [PMID: 24798211 DOI: 10.1007/s00210-014-0985-1]
18. Lissner D, Schumann M, Batra A, Kredel LI, Kuhl AA, Erben U, May C, Schulzke JD, Siegmund B. Monocyte and M1 Macrophage-induced Barrier Defect Contributes to Chronic Intestinal Inflammation in IBD. Inflamm Bowel Dis 2015; 21: 1297-1305 [PMID: 25901973 DOI: 10.1097/mib.0000000000000384]
19. Rubio CA, Langner C, Schmidt PT. Partial to complete abrogation of the subepithelial macrophage barrier against the gut microbiota in patients with ulcerative colitis and Crohn’s colitis. Histopathology 2018; 72: 580-587 [PMID: 29023984 DOI: 10.1111/his.13417]
20. Matsuoka K, Kanai T. The gut microbiota and inflammatory bowel disease. Semin Immunopathol 2015; 37: 47-55 [PMID: 25420450 DOI: 10.1007/s00281-014-0454-4]
21. Thibault R, Blachier F, Darcy-Vrillon B, de Coppet P, Bourreille A, Segain JP. Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: a transport deficiency. Inflamm Bowel Dis 2010; 16: 684-695 [PMID: 19774643 DOI: 10.1002/ibd.21108]
22. Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology 2008; 134: 577-594 [PMID: 18242222 DOI: 10.1053/j.gastro.2007.11.059]
23. Gerasimidis K, McGrogan P, Edwards CA. The aetiology and impact of malnutrition in paediatric inflammatory bowel disease. J Hum Nutr Diet 2011; 24: 313-326 [PMID: 21564345 DOI: 10.1111/j.1365-277X.2011.01171.x]
24. Motil KJ, Grand RJ, Davis-Kraft L, Ferlic LL, Smith, EO. Growth failure in children with inflammatory bowel disease: a prospective study. Gastroenterology 1993; 105: 681-691 [PMID: 8359640]
25. Murawska N, Fabisiak A, Fichna J. Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment. Inflamm Bowel Dis 2016; 22: 1198-1208 [PMID: 26818422 DOI: 10.1097/mib.0000000000000648]
26. Eriksson C, Henriksson I, Brus O, Zhulina Y, Nyhlin N, Tysk C, Montgomery S, Halfvarson J. Incidence, prevalence and clinical outcome of anaemia in inflammatory bowel disease: a population-based cohort study. Aliment Pharmacol Ther 2018; 48: 638-645 [PMID: 30069892 DOI: 10.1111/apt.14920]
27. Nielsen OH, Ainsworth M, Coskun M, Weiss G. Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease: A Systematic Review. Medicine (Baltimore). 2015; 94: e963 [PMID: 26061331 DOI: 10.1097/md.0000000000000963]
28. Pan Y, Liu Y, Guo H, Jabir MS, Liu X, Cui W, Li D. Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis. Nutrients 2017; 9: pii: E382 [PMID: 28406440 DOI: 10.3390/nu9040382]
29. Hyams JS, Wyzga N, Kreutzer DL, Justinich CJ, Gronowicz GA. Alterations in bone metabolism in children with inflammatory bowel disease: An in vitro study. J Pediatr Gastroenterol Nutr 1997; 24: 289-295 [PMID: 9138175 DOI: 10.1097/00005176-199703000-00011]
30. Walther F, Fusch C, Radke M, Beckert S, Findeisen A. Osteoporosis in pediatric patients suffering from chronic inflammatory bowel disease with and without steroid treatment. J Pediatr Gastroenterol Nutr 2006; 43: 42-51 [PMID: 16819376 DOI: 10.1097/01.mpg.0000228105.91240.80]
31. Ezzat Y, Hamdy K. The frequency of low bone mineral density and its associated risk factors in patients with inflammatory bowel diseases. Int J Rheum Dis 2010; 13: 259-265 [PMID: 20704624 DOI: 10.1111/j.1756-185X.2010.01542.x]
32. Wada Y, Hisamatsu T, Naganuma M, Matsuoka K, Okamoto S, Inoue N, Yajima T, Kouyama K, Iwao Y, Ogata H, Hibi H, Abe T, Kanai T. Risk factors for decreased bone mineral density in inflammatory bowel disease: A cross-sectional study. Clin Nutr 2015; 34: 1202-1209 [PMID: 25618799 DOI: 10.1016/j.clnu.2015.01.003]
33. Adams DW, Gurwara S, Silver HJ, Horst SN, Beaulieu DB, Schwartz DA, Seidner DL. Sarcopenia Is Common in Overweight Patients with Inflammatory Bowel Disease and May Predict Need for Surgery. Inflamm Bowel Dis 2017; 23: 1182-1186 [PMID: 28410342 DOI: 10.1097/MIB.0000000000001128]
34. Mager DR, Carroll MW, Wine E, Siminoski K, MacDonald K, Kluthe CL, Medvedev P, Chen M, Wu J, Turner JM, Huynh HQ. Vitamin D status and risk for sarcopenia in youth with inflammatory bowel diseases. Eur J Clin Nutr 2018; 72: 623-626 [PMID: 29391593 DOI: 10.1038/s41430-018-0105-2]
35. Bamba S, Sasaki M, Takaoka A, Takahashi K, Imaeda H, Nishida A, Inatomi O, Sugimoto M, Andoh A. Sarcopenia is a predictive factor for intestinal resection in admitted patients with Crohn’s disease. Plos One 2017; 12: e0180036 [PMID: 28644887 DOI: 10.1371/journal.pone.0180036]
36. Pedersen M, Cromwell J, Nau P. Sarcopenia is a Predictor of Surgical Morbidity in Inflammatory Bowel Disease. Inflamm Bowel Dis 2017; 23: 1867-1872 [PMID: 28604415 DOI: 10.1097/MIB.0000000000001166]
37. Bryant RV, Ooi S, Schultz CG, Goess C, Grafton R, Hughes J, Lim A, Bartholomeusz FD, Andrews JM. Low muscle mass and sarcopenia: common and predictive of osteopenia in inflammatory bowel disease. Aliment Pharmacol Ther 2015; 41: 895-906 [PMID: 25753216 DOI: 10.1111/apt.13156]
38. Holt DQ, Varma P, Strauss BJG, Rajadurai AS, Moore GT. Low muscle mass at initiation of anti-TNF therapy for inflammatory bowel disease is associated with early treatment failure: a retrospective analysis. Eur J Clin Nutr 2017; 71: 773-777 [PMID: 28225051 DOI: 10.1038/ejcn.2017.10]
39. Fabisiak N, Fabisiak A, Watala C, Fichna J. Fat-soluble Vitamin Deficiencies and Inflammatory Bowel Disease: Systematic Review and Meta-Analysis. J Clin Gastroenterol 2017; 51: 878-889 [PMID: 28858940 DOI: 10.1097/mcg.0000000000000911]
40. Ananthakrishnan AN, Khalili H, Higuchi LM, Bao Y, Korzenik JR, Giovannucci EL, Richter JM, Fuchs CS, Chan AT. Higher Predicted Vitamin D Status Is Associated With Reduced Risk of Crohn’s Disease. Gastroenterology 2012; 142: 482-489 [PMID: 22155183 DOI: 10.1053/j.gastro.2011.11.040]
41. Garg M, Hendy P, Ding JN, Shaw S, Hold G, Hart A. The Effect of Vitamin D on Intestinal Inflammation and Faecal Microbiota in Patients with Ulcerative Colitis. J Crohns Colitis 2018; 12: 963-972 [PMID: 29726893 DOI: 10.1093/ecco-jcc/jjy052]
42. Vagianos K, Bector S, McConnell J, Bernstein CN. Nutrition assessment of patients with inflammatory bowel disease. J Parenter Enteral Nutr 2007; 31: 311-319 [PMID: 17595441 DOI: 10.1177/0148607107031004311]
43. Siva S, Rubin DT, Gulotta G, Wroblewski K, Pekow J. Zinc Deficiency is Associated with Poor Clinical Outcomes in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2017; 23: 152-157 [PMID: 27930412 DOI: 10.1097/MIB.0000000000000989]
44. Ruemmele FM, Veres G, Kolho KL, Griffiths A, Levine A, Escher JC, Amil Dias J, Barabino A, Braegger CP, Bronsky J, Buderus S, Martin-de-Carpi J, De Ridder L, Fagerberg UL, Hugot JP, Kierkus J, Kolacek S, Koletzko S, Lionetti P, Miele E, Navas Lopez VM, Paerregaard A, Russell RK, Serban DE, Shaoul R, Van Rheenen P, Veereman G, Weiss B, Wilson D, Dignass A, Eliakim A, Winter H, Turner D. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis 2014; 8: 1179-1207 [PMID: 24909831 DOI: 10.1016/j.crohns.2014.04.005]
45. Kleinman RE, Baldassano RN, Caplan A, Griffiths AM, Heyman MB, Issenman RM, Lake AM, Motil KJ, Seidman E, Udall JN. Nutrition support for pediatric patients with inflammatory bowel disease: a clinical report of the North American Society for Pediatric Gastroenterology, Hepatology And Nutrition. J Pediatr Gastroenterol Nutr 2004; 39: 15-27 [PMID: 15187775]
46. Day AS, Burgess L. Exclusive enteral nutrition and induction of remission of active Crohn’s disease in children. Expert Rev Clin Immunol 2013; 9: 375-383 [PMID: 23557272 DOI: 10.1586/eci.13.12]
47. Harries AD, Jones LA, Danis V, Fifield R, Heatley RV, Newcombe RG, Rhodes J. Controlled trial of supplemented oral nutrition in Crohn’s disease. Lancet 1983; 1: 887-890 [PMID: 6132218]
48. O’Morain C, Segal AW, Levi AJ. Elemental diet as primary treatment of acute Crohn’s disease: a controlled trial. Br Med J (Clin Res Ed). 1984; 288: 1859-1862 [PMID: 1441790]
49. Giaffer MH, North G, Holdsworth CD. Controlled trial of polymeric versus elemental diet in treatment of active Crohn’s disease. Lancet 1990; 335: 816-819 [PMID: 1969560]
50. Lochs H, Steinhardt HJ, Klaus-Wentz B, Zeitz M, Vogelsang H, Sommer H, Fleig WE, Bauer P, Schirrmeister J, Malchow H. Comparison of enteral nutrition and drug treatment in active Crohn’s disease. Results of the European Cooperative Crohn’s Disease Study. IV. Gastroenterology 1991; 101: 881-888 [PMID: 1679736]
51. Rigaud D, Cosnes J, Le Quintrec Y, Rene E, Gendre JP, Mignon M. Controlled trial comparing two types of enteral nutrition in treatment of active Crohn’s disease: elemental versus polymeric diet. Gut 1991; 32: 1492-1497 [PMID: 1773955]
52. Lindor KD, Fleming CR, Burnes JU, Nelson JK, Ilstrup DM. A randomized prospective trial comparing a defined formula diet, corticosteroids, and a defined formula diet plus corticosteroids in active Crohn’s disease. Mayo Clin Proc 1992; 67: 328-333 [PMID: 1548947]
53. Gonzalez-Huix F, Fernandez-Banares F, Esteve-Comas M, Abad-Lacruz A, Cabre E, Acero D, Figa M, Guilera M, Humbert P, de Leon R. Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis. Am J Gastroenterol 1993; 88: 227-232 [PMID: 8424426]
54. Gorard DA, Hunt JB, Payne-James JJ, Palmer KR, Rees RG, Clark ML, Farthing MJ, Misiewicz JJ, Silk DB. Initial response and subsequent course of Crohn’s disease treated with elemental diet or prednisolone. Gut 1993; 34: 1198-1202 [PMID: 8406153]
55. Fernandez-Banares F, Cabre E, Esteve-Comas M, Gassull MA. How effective is enteral nutrition in inducing clinical remission in active Crohn’s disease? A meta-analysis of the randomized clinical trials. JPEN J Parenter Enteral Nutr 1995; 19: 356-364 [PMID: 8577011 DOI: 10.1177/0148607195019005356]
56. Griffiths AM, Ohlsson A, Sherman PM, Sutherland LR. Meta-analysis of enteral nutrition as a primary treatment of active Crohn’s disease. Gastroenterology 1995; 108: 1056-1067 [PMID: 7698572]
57. Zoli G, Care M, Parazza M, Spano C, Biagi PL, Bernardi M, Gasbarrini G. A randomized controlled study comparing elemental diet and steroid treatment in Crohn’s disease. Aliment Pharmacol Ther 1997; 11: 735-740 [PMID: 9305483]
58. Heuschkel RB, Menache CC, Megerian JT, Baird AE. Enteral nutrition and corticosteroids in the treatment of acute Crohn’s disease in children. J Pediatr Gastroenterol Nutr 2000; 31: 8-15 [PMID: 10896064]
59. Verma S, Brown S, Kirkwood B, Giaffer MH. Polymeric versus elemental diet as primary treatment in active Crohn’s disease: a randomized, double-blind trial. Am J Gastroenterol 2000; 95: 735-739 [PMID: 10719270 DOI: 10.1111/j.1572-0241.2000.01527.x]
60. Ludvigsson JF, Krantz M, Bodin L, Stenhammar L, Linquist B. Elemental versus polymeric enteral nutrition in paediatric Crohn’s disease: a multicentre randomized controlled trial. Acta Paediatr 2004; 93: 327-335 [PMID: 15124834]
61. Grover Z, Muir R, Lewindon P. Exclusive enteral nutrition induces early clinical, mucosal and transmural remission in paediatric Crohn’s disease. J Gastroenterol 2014; 49: 638-645 [PMID: 23636735 DOI: 10.1007/s00535-013-0815-0]
62. Sigall-Boneh R, Pfeffer-Gik T, Segal I, Zangen T, Boaz M, Levine A. Partial enteral nutrition with a Crohn’s disease exclusion diet is effective for induction of remission in children and young adults with Crohn’s disease. Inflamm Bowel Dis 2014; 20: 1353-1360 [PMID: 24983973 DOI: 10.1097/mib.0000000000000110]
63. Swaminath A, Feathers A, Ananthakrishnan AN, Falzon L, Li FS. Systematic review with meta-analysis: enteral nutrition therapy for the induction of remission in paediatric Crohn’s disease. Aliment Pharmacol Ther 2017; 46: 645-656 [PMID: 28815649 DOI: 10.1111/apt.14253]
64. 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]
65. Luo Y, Yu J, Lou J, Fang Y, Chen J. Exclusive Enteral Nutrition versus Infliximab in Inducing Therapy of Pediatric Crohn’s Disease. Gastroenterol Res Pract 2017; 2017: 6595048 [PMID: 28928769 DOI: 10.1155/2017/6595048]
66. Connors J, Basseri S, Grant A, Giffin N, Mahdi G, Noble A, Rashid M, Otley A, Van Limbergen J. Exclusive Enteral Nutrition Therapy in Paediatric Crohn’s Disease Results in Long-term Avoidance of Corticosteroids: Results of a Propensity-score Matched Cohort Analysis. J Crohns Colitis 2017; 11: 1063-1070 [PMID: 28575325 DOI: 10.1093/ecco-jcc/jjx060]
67. 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 DOI: 10.1002/14651858.CD000542.pub3]
68. Wilschanski M, Sherman P, Pencharz P, Davis L, Corey M, Griffiths A. Supplementary enteral nutrition maintains remission in paediatric Crohn’s disease. Gut 1996; 38: 543-548 [PMID: 8707085]
69. Esaki M, Matsumoto T, Nakamura S, Yada S, Fujisawa K, Jo Y, Iida M. Factors affecting recurrence in patients with Crohn’s disease under nutritional therapy. Dis Colon Rectum 2006; 49: S68-74 [PMID: 17106818 DOI: 10.1007/s10350-006-0692-1]
70. Takagi S, Utsunomiya K, Kuriyama S, Yokoyama H, Takahashi S, Iwabuchi M, Takahashi H, Kinouchi Y, Hiwatashi N, Funayama Y, Sasaki I, Tsuji I, Shimosegawa T. Effectiveness of an ‘half elemental diet’ as maintenance therapy for Crohn’s disease: A randomized-controlled trial. Aliment Pharmacol Ther 2006; 24: 1333-1340 [PMID: 17059514 DOI: 10.1111/j.1365-2036.2006.03120.x]
71. Yamamoto T, Nakahigashi M, Umegae S, Matsumoto K. Enteral nutrition for the maintenance of remission in Crohn’s disease: a systematic review. Eur J Gastroenterol Hepatol 2010; 22: 1-8 [PMID: 19707151 DOI: 10.1097/MEG.0b013e32832c788c]
72. Hanai H, Iida T, Takeuchi K, Arai H, Arai O, Abe J, Tanaka T, Maruyama Y, Ikeya K, Sugimoto K, Nakamura T, Nakamura K, Watanabe F. Nutritional therapy versus 6-mercaptopurine as maintenance therapy in patients with Crohn’s disease. Dig Liver Dis 2012; 44: 649-654 [PMID: 22542605 DOI: 10.1016/j.dld.2012.03.007]
73. Duncan H, Buchanan E, Cardigan T, Garrick V, Curtis L, McGrogan P, Barclay A, Russell RK. A retrospective study showing maintenance treatment options for paediatric CD in the first year following diagnosis after induction of remission with EEN: supplemental enteral nutrition is better than nothing! BMC Gastroenterol 2014; 14: 50 [PMID: 24645851 DOI: 10.1186/1471-230x-14-50]
74. Grover Z, Lewindon P. Two-Year Outcomes After Exclusive Enteral Nutrition Induction Are Superior to Corticosteroids in Pediatric Crohn’s Disease Treated Early with Thiopurines. Dig Dis Sci 2015; 60: 3069-3074 [PMID: 26038093 DOI: 10.1007/s10620-015-3722-9]
75. Kang Y, Kim S, Kim SY, Koh H. Effect of short-term partial enteral nutrition on the treatment of younger patients with severe Crohn’s disease. Gut Liver 2015; 9: 87-93 [PMID: 25170058 DOI: 10.5009/gnl13345]
76. El-Matary W, Otley A, Critch J, Abou-Setta AM. Enteral Feeding Therapy for Maintaining Remission in Crohn’s Disease: A Systematic Review. JPEN J Parenter Enteral Nutr 2017; 41: 550-561 [PMID: 26645668 DOI: 10.1177/0148607115621051]
77. 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 DOI: 10.1002/14651858.CD005984.pub3]
78. Ikeuchi H, Yamamura T, Nakano H, Kosaka T, Shimoyama T, Fukuda Y. Efficacy of nutritional therapy for perforating and non-perforating Crohn’s disease. Hepatogastroenterology 2004; 51: 1050-1052 [PMID: 15239244]
79. Yamamoto T, Nakahigashi M, Umegae S, Kitagawa T, Matsumoto K. Impact of long-term enteral nutrition on clinical and endoscopic recurrence after resection for Crohn’s disease: A prospective, non-randomized, parallel, controlled study. Aliment Pharmacol Ther 2007; 25: 67-72 [PMID: 17229221 DOI: 10.1111/j.1365-2036.2006.03158.x]
80. Wang H, Zuo L, Zhao J, Dong J, Li Y, Gu L, Gong J, Liu Q, Zhu W. Impact of Preoperative Exclusive Enteral Nutrition on Postoperative Complications and Recurrence After Bowel Resection in Patients with Active Crohn’s Disease. World J Surg 2016; 40: 1993-2000 [PMID: 26940580 DOI: 10.1007/s00268-016-3488-z]
81. Brennan GT, Ha I, Hogan C, Nguyen E, Jamal MM, Bechtold ML, Nguyen DL. Does preoperative enteral or parenteral nutrition reduce postoperative complications in Crohn’s disease patients: a meta-analysis. Eur J Gastroenterol Hepatol 2018; 30: 997-1002 [PMID: 29738326 DOI: 10.1097/meg.0000000000001162]
82. Klaassen J, Zapata R, Mella JG, Aguayo G, Alvarado D, Espinosa O, Maiz A, Zuniga A, Quintana C. Enteral nutrition in severe ulcerative colitis. Digestive tolerance and nutritional efficiency. Rev Med Chil 1998; 126: 899-904 [PMID: 9830740]
83. Pithadia AB, Jain S. Treatment of inflammatory bowel disease. Pharmacol Rep 2011; 63: 629-642 [PMID: 21857074]
84. Ito K, Chung KF, Adcock IM. Update on glucocorticoid action and resistance. J Allergy Clin Immunol 2006; 117: 522-543 [PMID: 16522450 DOI: 10.1016/j.jaci.2006.01.032]
85. Ispas-Szabo P, Friciu MM, Nguyen P, Dumoulin Y, Mateescu MA. Novel self-assembled mesalamine-sucralfate complexes: preparation, characterization, and formulation aspects. Drug Dev Ind Pharm 2016; 42: 1183-1193 [PMID: 26574144 DOI: 10.3109/03639045.2015.1118493]
86. Derkx B, Taminiau J, Radema S, Stronkhorst A, Wortel C, Tytgat G, Vandeventer S. TUMOR-NECROSIS-FACTOR ANTIBODY TREATMENT IN CROHNS-DISEASE. Lancet 1993; 342: 173-174 [PMID: 8101267 DOI: 10.1016/0140-6736(93)91375-v]
87. Suzuki Y, Motoya S, Hanai H, Matsumoto T, Hibi T, Robinson AM, Mostafa NM, Chao JD, Arora V, Camez A, Thakkar RB, Watanabe M. Efficacy and safety of adalimumab in Japanese patients with moderately to severely active ulcerative colitis. J Gastroenterol 2014; 49: 283-294 [PMID: 24363029 DOI: 10.1007/s00535-013-0922-y]
88. Sandborn WJ, Feagan BG, Marano C, Zhang HY, Strauss R, Johanns J, Adedokun OJ, Guzzo C, Colombel JF, Reinisch W, Gibson PR, Collins J, Jarnerot G, Hibi T, Rutgeerts P, Pursuit-Sc Study Grp. Subcutaneous Golimumab Induces Clinical Response and Remission in Patients With Moderate-to-Severe Ulcerative Colitis. Gastroenterology 2014; 146: 85-95 [PMID: 23735746 DOI: 10.1053/j.gastro.2013.05.048]
89. Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, Blank MA, Johanns J, Gao LL, Miao Y, Adedokun OJ, Sands BE, Hanauer SB, Vermeire S, Targan S, Ghosh S, de Villiers WJ, Colombel JF, Tulassay Z, Seidler U, Salzberg BA, Desreumaux P, Lee SD, Loftus EVJ, Dieleman LA, Katz S, Rutgeerts P. Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med 2016; 375: 1946-1960 [PMID: 27959607 DOI: 10.1056/NEJMoa1602773]
90. Gordon FH, Lai CWY, Hamilton MI, Allison MC, Srivastava ED, Fouweather MG, Donoghue S, Greenlees C, Subhani J, Amlot PL, Pounder RE. A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha 4 integrin in active Crohn’s disease. Gastroenterology 2001; 121: 268-274 [PMID: 11487536]
91. Sandborn WJ, Su C, Sands BE, D’Haens GR, Vermeire S, Schreiber S, Danase S, Feagan BG, Reinisch W, Niezychowski W, Friedman G, Lawendy N, Yu D, Woodworth D, Mukherjee A, Zhang H, Healey P, Panes J. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2017; 376: 1723-1736 [PMID: 28467869 DOI: 10.1056/NEJMoa1606910]
92. Matsumoto T, Iida M, Kohgo Y, Imamura A, Kusugami K, Nakano H, Fujiyama Y, Matsu T, Hibi T. Therapeutic efficacy of infliximab on active Crohn’s disease under nutritional therapy. Scand J Gastroenterol 2005; 40: 1423-1430 [PMID: 16316890 DOI: 10.1080/00365520510023639]
93. Tanaka T, Takahama K, Kimura T, Mizuno T, Nagasaka M, Iwata K, Nakano H, Muramatsu M, Takazoe M. Effect of concurrent elemental diet on infliximab treatment for Crohn’s disease. J Gastroenterol Hepatol 2006; 21: 1143-1149 [PMID: 16824066 DOI: 10.1111/j.1440-1746.2006.04317.x]
94. Yamamoto T, Nakahigashi M, Umegae S, Matsumoto K. Prospective clinical trial: enteral nutrition during maintenance infliximab in Crohn’s disease. J Gastroenterol 2010; 45: 24-29 [PMID: 19798465 DOI: 10.1007/s00535-009-0136-5]
95. Sazuka S, Katsuno T, Nakagawa T, Saito M, Saito K, Matsumura T, Arai M, Sato T, Yokosuka O. Concomitant use of enteral nutrition therapy is associated with sustained response to infliximab in patients with Crohn’s disease. Eur J Clin Nutr 2012; 66: 1219-1223 [PMID: 23010687 DOI: 10.1038/ejcn.2012.120]
96. Hirai F, Ishihara H, Yada S, Esaki M, Ohwan T, Nozaki R, Ashizuka S, Inatsu H, Ohi H, Aoyagi K, Mizuta Y, Matsumoto T, Matsui T. Effectiveness of concomitant enteral nutrition therapy and infliximab for maintenance treatment of Crohn’s disease in adults. Dig Dis Sci 2013; 58: 1329-1334 [PMID: 22926500 DOI: 10.1007/s10620-012-2374-2]
97. Kamata N, Oshitani N, Watanabe K, Hosomi S, Noguchi A, Yukawa T, Yamagami H, Shiba M, Tanigawa T, Watanabe T, Tominaga K, Fujiwara Y, Arakawa T. Efficacy of concomitant elemental diet therapy in scheduled infliximab therapy in patients with Crohn’s disease to prevent loss of response. Dig Dis Sci 2015; 60: 1382-1388 [PMID: 25532505 DOI: 10.1007/s10620-014-3493-8]
98. Nguyen DL, Palmer LB, Nguyen ET, McClave SA, Martindale RG, Bechtold ML. Specialized enteral nutrition therapy in Crohn’s disease patients on maintenance infliximab therapy: a meta-analysis. Therap Adv Gastroenterol 2015; 8: 168-175 [PMID: 26136834 DOI: 10.1177/1756283X15578607]
99. Sugita N, Watanabe K, Kamata N, Yukawa T, Otani K, Hosomi S, Nagami Y, Tanaka F, Taira K, Yamagami H, Tanigawa T, Shiba M, Watanabe T, Tominaga K Kabata D, Shintani A, Arakawa T, Fujiwara Y. Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn’s disease. J Gastroenterol Hepatol 2018; 33: 631-637 [PMID: 28857255 DOI: 10.1111/jgh.13969]
100. Hisamatsu T, Kunisaki R, Nakamura S, Tsujikawa T, Hirai F, Nakase H, Watanabe K, Yokoyama K, Nagahori M, Kanai T, Naganuma M, Michimae H, Andoh A, Yamada A, Yokoyama T, Kamata N, Tanaka S, Suzuki Y, Hibi T, Watanabe M. Effect of elemental diet combined with infliximab dose escalation in patients with Crohn’s disease with loss of response to infliximab: CERISIER trial. Intest Res 2018; 16: 494-498 [PMID: 30090050 DOI: 10.5217/ir.2018.16.3.494]
101. Triantafillidis JK, Papalois AE. The role of total parenteral nutrition in inflammatory bowel disease: current aspects. Scand J Gastroenterol 2014; 49: 3-14 [PMID: 24354966 DOI: 10.3109/00365521.2013.860557]
102. Dickinson RJ, Ashton MG, Axon AT, Smith RC, Yeung CK, Hill GL. Controlled trial of intravenous hyperalimentation and total bowel rest as an adjunct to the routine therapy of acute colitis. Gastroenterology 1980; 79: 1199-1204 [PMID: 6777233]
103. Muller JM, Keller HW, Erasmi H, Pichlmaier H. Total parenteral nutrition as the sole therapy in Crohn’s disease-a prospective study. Br J Surg 1983; 70: 40-43 [PMID: 6402050]
104. Ostro MJ, Greenberg GR, Jeejeebhoy KN. Total parenteral nutrition and complete bowel rest in the management of Crohn’s disease. J Parenter Enteral Nutr 1985; 9: 280-287 [PMID: 3925172 DOI: 10.1177/0148607185009003280]
105. McIntyre PB, Powell-Tuck J, Wood SR, Lennard-Jones JE, Lerebours E, Hecketsweiler P, Galmiche JP, Colin R. Controlled trial of bowel rest in the treatment of severe acute colitis. Gut 1986; 27: 481-485 [PMID: 3084344]
106. Greenberg GR, Fleming CR, Jeejeebhoy KN, Rosenberg IH, Sales D, Tremaine WJ. Controlled trial of bowel rest and nutritional support in the management of Crohn’s disease. Gut 1988; 29: 1309-1315 [PMID: 3143625]
107. Duerksen DR, Nehra V, Bistrian BR, Blackburn GL. Appropriate nutritional support in acute and complicated Crohn’s disease. Nutrition 1998; 14: 462-465 [PMID: 9614313]
108. Richman E, Rhodes JM. Review article: evidence-based dietary advice for patients with inflammatory bowel disease. Aliment Pharmacol Ther 2013; 38: 1156-1171 [PMID: 24102340 DOI: 10.1111/apt.12500]
109. Egberg MD, Galanko JA, Barnes EL, Kappelman MD. Thrombotic and Infectious Risks of Parenteral Nutrition in Hospitalized Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis 2019; 25: 601-609 [PMID 30304444 DOI: 10.1093/ibd/izy298]
110. Scaioli E, Liverani E, Belluzzi A. The Imbalance between n-6/n-3 Polyunsaturated Fatty Acids and Inflammatory Bowel Disease: A Comprehensive Review and Future Therapeutic Perspectives. Int J Mol Sci 2017; 18: pii: E2619 [PMID: 29206211 DOI: 10.3390/ijms18122619]
111. Goncalves P, Araujo JR, Di Santo JP. A Cross-Talk Between Microbiota-Derived Short-Chain Fatty Acids and the Host Mucosal Immune System Regulates Intestinal Homeostasis and Inflammatory Bowel Disease. Inflamm Bowel Dis 2018; 24: 558-572 [PMID: 29462379 DOI: 10.1093/ibd/izx029]
112. Scaioli E, Sartini A, Bellanova M, Campieri M, Festi D, Bazzoli F, Belluzzi A. Eicosapentaenoic Acid Reduces Fecal Levels of Calprotectin and Prevents Relapse in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol 2018; 16: 1268-1275 [PMID: 29391271 DOI: 10.1016/j.cgh.2018.01.036]
113. Sitkin S, Pokrotnieks J. Alterations in Polyunsaturated Fatty Acid Metabolism and Reduced Serum Eicosadienoic Acid Level in Ulcerative Colitis: Is There a Place for Metabolomic Fatty Acid Biomarkers in IBD? Dig Dis Sci 2018; 63: 2480-2481 [PMID: 29987625 DOI: 10.1007/s10620-018-5182-5]
114. Ananthakrishnan AN, Khalili H, Song MY, Higuchi LM, Lochhead P, Richter JM, Chan AT. Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3:n6 Intake and Risk of Ulcerative Colitis: A Prospective Cohort Study. Inflamm Bowel Dis 2017; 23: 1898-1904 [PMID: 28991856 DOI: 10.1097/MIB.0000000000001236]
115. Barnes EL, Nestor M, Onyewadume L, de Silva PS, Korzenik JR, DREAM Investigators. High Dietary Intake of Specific Fatty Acids Increases Risk of Flares in Patients With Ulcerative Colitis in Remission During Treatment With Aminosalicylates. Clin Gastroenterol Hepatol 2017; 15: 1390-1396 [PMID: 28110099 DOI: 10.1016/j.cgh.2016.12.036]
116. Feagan BG, Sandborn WJ, Mittmann U, Bar-Meir S, D’Haens G, Bradette M, Cohen A, Dallaire C, Ponich TP, McDonald JW, Hebuterne X, Pare P, Klvana P, Niv Y, Ardizzone S, Alexeeva O, Rostom A, Kiudelis G, Spleiss J, Gilgen D, Vandervoort MK, Wong CJ, Zou GY, Donner A, Rutgeerts P. Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials. JAMA 2008; 299: 1690-1697 [PMID: 18398081 DOI: 10.1001/jama.299.14.1690]
117. Turner D, Zlotkin SH, Shah PS, Griffiths AM. Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev 2009; 1: CD006320 [PMID: 19160277 DOI: 10.1002/14651858.CD006320.pub3]
118. Ameho CK, Adjei AA, Harrison EK, Takeshita K, Morioka T, Arakaki Y, Ito E, Suzuki I, Kulkarni AD, Kawajiri A, Yamamoto S. Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis. Gut 1997; 41: 487-493 [PMID: 9391247]
119. Vicario M, Amat C, Rivero M, Moreto M, Pelegri C. Dietary glutamine affects mucosal functions in rats with mild DSS-induced colitis. J Nutr 2007; 137: 1931-1937 [PMID: 17634266 DOI: 10.1093/jn/137.8.1931]
120. Andou A, Hisamatsu T, Okamoto S, Chinen H, Kamada N, Kobayashi T, Hashimoto M, Okutsu T, Shimbo K, Takeda T, Matsumoto H, Sato A, Ohtsu H, Suzuki M, Hibi T. Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages. Gastroenterology 2009; 136: 564-574. e2 [PMID: 19027739 DOI: 10.1053/j.gastro.2008.09.062]
121. Tsune I, Ikejima K, Hirose M, Yoshikawa M, Enomoto N, Takei Y, Sato N. Dietary glycine prevents chemical-induced experimental colitis in the rat. Gastroenterology 2003; 125: 775-785 [PMID: 12949723]
122. Gibson PR, Shepherd SJ. Personal view: food for thought-western lifestyle and susceptibility to Crohn’s disease. The FODMAP hypothesis. Aliment Pharmacol Ther 2005; 21: 1399-1409 [PMID: 15948806 DOI: 10.1111/j.1365-2036.2005.02506.x]
123. Gearry RB, Irving PM, Barrett JS, Nathan DM, Shepherd SJ, Gibson PR. Reduction of dietary poorly absorbed short-chain carbohydrates (FODMAPs) improves abdominal symptoms in patients with inflammatory bowel disease-a pilot study. J Crohns Colitis 2009; 3: 8-14 [PMID: 21172242 DOI: 10.1016/j.crohns.2008.09.004]
124. Barrett JS, Gearry RB, Muir JG, Irving PM, Rose R, Rosella O, Haines ML, Shepherd SJ, Gibson PR. Dietary poorly absorbed, short-chain carbohydrates increase delivery of water and fermentable substrates to the proximal colon. Aliment Pharmacol Ther 2010; 31: 874-882 [PMID: 20102355 DOI: 10.1111/j.1365-2036.2010.04237.x]
125. Shepherd SJ, Parker FC, Muir JG, Gibson PR. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol Hepatol 2008; 6: 765-771 [PMID: 18456565 DOI: 10.1016/j.cgh.2008.02.058]
126. Pedersen N, Ankersen DV, Felding M, Wachmann H, Vegh Z, Molzen L, Burisch J, Andersen JR, Munkholm P. Low-FODMAP diet reduces irritable bowel symptoms in patients with inflammatory bowel disease. World J Gastroenterol 2017; 23: 3356-3366 [PMID: 28566897 DOI: 10.3748/wjg.v23.i18.3356]
127. Ghouri YA, Richards DM, Rahimi EF, Krill JT, Jelinek KA, DuPont AW. Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease. Clin Exp Gastroenterol 2014; 7: 473-487 [PMID: 25525379 DOI: 10.2147/ceg.s27530]
128. Mitsuyama K, Saiki T, Kanauchi O, Iwanaga T, Tomiyasu N, Nishiyama T, Tateishi H, Shirachi A, Ide M, Suzuki A, Noguchi K, Ikeda H, Toyonaga A, Sata M. Treatment of ulcerative colitis with germinated barley foodstuff feeding: a pilot study. Aliment Pharmacol Ther 1998; 12: 1225-1230 [PMID: 9882030]
129. Heaton KW, Thornton JR, Emmett PM. Treatment of Crohn’s disease with an unrefined-carbohydrate, fibre-rich diet. Br Med J 1979; 2: 764-766 [PMID: 519185]
130. Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, de Silva P, Korzenik JR, Fuchs CS, Willett WC, Richter JM, Chan AT. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology 2013; 145: 970-977 [PMID: 23912083 DOI: 10.1053/j.gastro.2013.07.050]
131. Levenstein S, Prantera C, Luzi C, D’Ubaldi A. Low residue or normal diet in Crohn’s disease: a prospective controlled study in Italian patients. Gut 1985; 26: 989-993 [PMID: 2996991]
132. Curro D, Ianiro G, Pecere S, Bibbo S, Cammarota G. Probiotics, fibre and herbal medicinal products for functional and inflammatory bowel disorders. Br J Pharmacol 2017; 174: 1426-1449 [PMID: 27696378 DOI: 10.1111/bph.13632]
133. Srutkova D, Schwarzer M, Hudcovic T, Zakostelska Z, Drab V, Spanova A, Rittich B, Kozakova H, Schabussova I. Bifidobacterium longum CCM 7952 Promotes Epithelial Barrier Function and Prevents Acute DSS-Induced Colitis in Strictly Strain-Specific Manner. PLoS One 2015; 10: e0134050 [PMID: 26218526 DOI: 10.1371/journal.pone.0134050]
134. Ganji-Arjenaki M, Rafieian-Kopaei M. Probiotics are a good choice in remission of inflammatory bowel diseases: A meta-analysis and systematic review. J Cell Physiol 2018; 233: 2091-2103 [PMID: 28294322 DOI: 10.1002/jcp.25911]
135. Derwa Y, Gracie DJ, Hamlin PJ, Ford AC. Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease. Aliment Pharmacol Ther 2017; 46: 389-400 [PMID: 28653751 DOI: 10.1111/apt.14203]
136. Tursi A, Brandimarte G, Papa A, Giglio A, Elisei W, Giorgetti GM, Forti G, Morini S, Hassan C, Pistoia MA, Modeo ME, Rodino S, D’Amico T, Sebkova L, Sacca N, Di Guilio E, Luzza F, Imeneo M, Larussa T, Di Rosa S, Annese V, Danase S, Gasbarrini A. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol 2010; 105: 2218-2227 [PMID: 20517305 DOI: 10.1038/ajg.2010.218]
137. Takeda Y, Nakase H, Namba K, Inoue S, Ueno S, Uza N, Chiba, T. Upregulation of T-bet and tight junction molecules by Bifidobactrium longum improves colonic inflammation of ulcerative colitis. Inflamm Bowel Dis 2009; 15: 1617-1618 [PMID: 19161180 DOI: 10.1002/ibd.20861]
138. Tamaki H, Nakase H, Inoue S, Kawanami C, Itani T, Ohana M, Kusaka T, Uose S, Hisatsune H, Tojo M, Noda T, Arasawa S, Izuta M, Kubo A, Ogawa C, Matsunaka T, Shibatouge M. Efficacy of probiotic treatment with Bifidobacterium longum 536 for induction of remission in active ulcerative colitis: A randomized, double-blinded, placebo-controlled multicenter trial. Dig Endosc 2016; 28: 67-74 [PMID: 26418574 DOI: 10.1111/den.12553]

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