Year 2023 / Volume 115 / Number 11
Review
“Out of the box” new therapeutic strategies for Crohn´s disease: moving beyond biologics

614-634

DOI: 10.17235/reed.2022.9010/2022

Ignacio Catalán-Serra, Petr Ricanek, Tore Grimstad,

Abstract
New treatment options beyond immunosuppression have emerged in recent years for patients with Crohn´s disease (CD), a chronic systemic condition affecting primarily the gut with great impact in the quality of life. The cause of CD is largely unknown, and a curative treatment is not yet available. In addition, despite the growing therapeutic armamentarium in recent years almost half of the patients don´t achieve a sustained response over time. Thus, new therapeutic strategies are urgently needed. In this review, we discuss the current state of promising new “out of the box” possibilities to control chronic inflammation beyond current pharmacological treatments, including: exclusive enteral nutrition, specific diets, cell therapies using T regs, hyperbaric oxygen, fecal microbiota transplantation, phage therapy, helminths, cannabis and vagal nerve stimulation. The exploration of original and novel therapeutic modalities is key to address their potential as main or complementary treatments in selected CD populations in order to increase efficacy, minimize side effects and improve quality of life of patients.
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References
1. Windsor JW, Kaplan GG. Evolving Epidemiology of IBD. Curr Gastroenterol Rep. 2019 ;21:40.
2. Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet 2012;380:1590–605.
3. Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn's disease. Lancet. 2017 ;389:1741-1755.
4. Greuter T, Vavricka SR. Extraintestinal manifestations in inflammatory bowel disease - epidemiology, genetics, and pathogenesis. Expert Rev Gastroenterol Hepatol. 2019;13:307-317.
5. Burisch J, Jess T, Martinato M, Lakatos PL. The burden of inflammatory bowel disease in Europe. Journal of Crohn’s and colitis. 2013;7:322.
6. Guan Q. A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. J Immunol Res. 2019 ;2019:7247238.
7. Chang JT. Pathophysiology of Inflammatory Bowel Diseases. N Engl J Med. 2020;31;383:2652-2664
8. Vinh DC, Behr MA. Crohn's as an immune deficiency: from apparent paradox to evolving paradigm. Expert Rev Clin Immunol. 2013 ;9:17-30.
9. Marks DJ, Rahman FZ, Sewell GW et al. Crohn's disease: an immune deficiency state. Clin Rev Allergy Immunol. 2010;38:20-31.
10. Schroder AL, Chami B, Liu Y et al. Neutrophil Extracellular Trap Density Increases With Increasing Histopathological Severity of Crohn's Disease. Inflamm Bowel Dis. 2022;28:586-598
11. Dharmasiri S, Garrido-Martin EM, Harris RJ et al. Human Intestinal Macrophages Are Involved in the Pathology of Both Ulcerative Colitis and Crohn Disease. Inflamm Bowel Dis. 2021 18;27:1641-1652.
12. Catalan-Serra I, Sandvik AK, Bruland T et al. Gammadelta T Cells in Crohn's Disease: A New Player in the Disease Pathogenesis? J Crohns Colitis. 2017;11:1135-1145.
13. Buisine MP, Desreumaux P, Debailleul V et al. Abnormalities in mucin gene expression in Crohn’s disease. Inflamm Bowel Dis 1999;5:24–32.
14. Zeissig S, Burgel N, Gunzel D, Richter J et al. Changes in expression and distribution of claudin 2, 5 and lead to discontinuous tight junctions and barrier dysfunction inactive Crohn’s disease. Gut. 2007;56:61–72..
15. Wehkamp J, Salzman NH, Porter E et al. Reduced Paneth cell a-defensins in ileal Crohn’s disease. Proc Natl Acad Sci U S A. 2005;102:18129–34. doi:10.1073/ pnas.0505256102. PMID:16330776.
16. Magro DO, Santos A, Guadagnini D et al. Remission in Crohn's disease is accompanied by alterations in the gut microbiota and mucins production. Sci Rep. 2019;9:13263.
17. Sokol H, Leducq V, Aschard H et al. Fungal microbiota dysbiosis in IBD. Gut. 2017 ;66:1039-1048.
18. Catalan-Serra I, Brenna Ø. Immunotherapy in inflammatory bowel disease: Novel and emerging treatments. Hum Vaccin Immunother. 2018;14: 2597-2611.
19. Torres J, Bonovas S, Doherty G et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis. 2020;14:4-22.
20. Reinink AR, Lee TC, Higgins PDR. Endoscopic mucosal healing predicts favorable clinical outcomes in inflammatory bowel disease: a meta-analysis. Inflamm Bowel Dis. 2016;22:1859-1869.
21. Cholapranee A, Hazlewood GS, Kaplan GG et al. Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn’s disease and ulcer- ative colitis controlled trials. Aliment Pharmacol Ther. 2017;45:1291-1302.
22. Picco MF, Farraye FA. Targeting Mucosal Healing in Crohn's Disease. Gastroenterol Hepatol (N Y). 2019;15:529-538.
23. Dulai PS, Jairath V, Zou G et al. Early Combined Immunosuppression May Be More Effective for Reducing Complications in Isolated Colonic- vs Ileal-Dominant Crohn Disease. Inflamm Bowel Dis. 2021;27:639-646.
24. de Sire R, Nardone OM, Testa A et al. Exclusive Enteral Nutrition in Adult Crohn's Disease: an Overview of Clinical Practice and Perceived Barriers. Clinical and experimental gastroenterology. 2021;14:493-501.
25. Rigaud D, Cosnes J, Le Quintrec Yet al. Controlled trial comparing two types of enteral nutrition in treatment of active Crohn's disease: elemental versus polymeric diet. Gut. 1991;32:1492-7.
26. Yamamoto T, Shimoyama T, Kuriyama M. Dietary and enteral interventions for Crohn's disease. Curr Opin Biotechnol. 2017;44:69-73.
27. Mitrev N, Huang H, Hannah B et al. Review of exclusive enteral therapy in adult Crohn's disease. BMJ Open Gastroenterol. 2021;8(1).
28. Narula N, Dhillon A, Zhang D et al. Enteral nutritional therapy for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2018;4:CD000542.
29. Gassull MA, Fernandez-Banares F, Cabre E et al. Fat composition may be a clue to explain the primary therapeutic effect of enteral nutrition in Crohn's disease: results of a double blind randomised multicentre European trial. Gut. 2002;51:164-8.
30. Yang Q, Gao X, Chen H et al. Efficacy of exclusive enteral nutrition in complicated Crohn's disease. Scand J Gastroenterol. 2017;52:995-1001.
31. Wall CL, Day AS, Gearry RB. Use of exclusive enteral nutrition in adults with Crohn's disease: a review. World J Gastroenterol. 2013;19:7652-60.
32. Lochs H, Steinhardt HJ, Klaus-Wentz B et al. Comparison of enteral nutrition and drug treatment in active Crohn's disease. Results of the European Cooperative Crohn's Disease Study. IV. Gastroenterology. 1991;101:881-8.
33. Cheifetz AS. Management of active Crohn disease. JAMA. 2013;309:2150-8.
34. Shariff S, Moran G, Grimes C et al. Current Use of EEN in Pre-Operative Optimisation in Crohn's Disease. Nutrients. 2021;13:4389.
35. Subramanian V, Saxena S, Kang JY et al. Preoperative steroid use and risk of postoperative complications in patients with inflammatory bowel disease undergoing abdominal surgery. Am J Gastroenterol. 2008;103:2373-81.
36. Brennan GT, Ha I, Hogan C et al. 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.
37. Ge X, Tang S, Yang X et al. The role of exclusive enteral nutrition in the preoperative optimization of laparoscopic surgery for patients with Crohn's disease: A cohort study. International journal of surgery. 2019;65:39-44.
38. Gordon-Dixon A, Gore-Rodney J, Hampal R et al. The role of exclusive enteral nutrition in the pre-operative optimisation of adult patients with Crohn's disease. A systematic review. Clin Nutr ESPEN. 2021;46:99-105.
39. Nguyen DL, Palmer LB, Nguyen ET et al. Specialized enteral nutrition therapy in Crohn's disease patients on maintenance infliximab therapy: a meta-analysis. Therap Adv Gastroenterol. 2015;8:168-75.
40. Hirai F, Takeda T, Takada Y et al. Efficacy of enteral nutrition in patients with Crohn's disease on maintenance anti-TNF-alpha antibody therapy: a meta-analysis. J Gastroenterol. 2020;55:133-41.
41. Hisamatsu T, Kunisaki R, Nakamura S et al. 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;16:494-8
42. Hirai F, Ishida T, Takeshima F et al. Effect of a concomitant elemental diet with maintenance anti-tumor necrosis factor-alpha antibody therapy in patients with Crohn's disease: A multicenter, prospective cohort study. J Gastroenterol Hepatol. 2019;34:132-9.
43. Halpin SJ, Ford AC. Prevalence of symptoms meeting criteria for irritable bowel syndrome in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2012;107:1474-82.
44. Marion-Letellier R, Amamou A, Savoye G, et al. Inflammatory Bowel Diseases and Food Additives: To Add Fuel on the Flames! Nutrients. 2019;11:1111.
45. Borsani B, De Santis R, Perico V, et al. The Role of Carrageenan in Inflammatory Bowel Diseases and Allergic Reactions: Where Do We Stand? Nutrients. 2021;13(10):3402.
46. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68(Suppl 3):s1-s106.
47. Bischoff SC, Escher J, Hébuterne X, et al. ESPEN practical guideline: Clinical Nutrition in inflammatory bowel disease. Clin Nutr. 2020;39(3):632-653.
48. Levine A, Wine E, Assa A et al. J. Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology. 2019;157:440-450.e8.
49. Pigneur B, Ruemmele FM. Nutritional interventions for the treatment of IBD: current evidence and controversies. Therap Adv Gastroenterol. 2019;12:1756284819890534.
50. Gu P, Feagins LA. Dining With Inflammatory Bowel Disease: A Review of the Literature on Diet in the Pathogenesis and Management of IBD. Inflamm Bowel Dis. 2020;26:181-191.
51. Sasson AN, Ananthakrishnan AN, Raman M. Diet in Treatment of Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2021;19:425-435.
52. Gerasimidis K, Godny L, Sigall-Boneh R, et al. Current recommendations on the role of diet in the aetiology and management of IBD. Frontline Gastroenterol. 2021;13:160-167.
53. Serrano-Moreno C, Brox-Torrecilla N, Arhip L, et al. Diets for inflammatory bowel disease: What do we know so far? Eur J Clin Nutr. 2022 Jan 22. Epub ahead of print.
54. Herfarth HH, Martin CF, Sandler RS, et al. Prevalence of a gluten-free diet and improvement of clinical symptoms in patients with inflammatory bowel diseases. Inflamm Bowel Dis. 2014;20:1194-7.
55. Aziz I, Branchi F, Pearson K, et al. A study evaluating the bidirectional relationship between inflammatory bowel disease and self-reported non-celiac gluten sensitivity. Inflamm Bowel Dis. 2015;21:847-53.
56. Limketkai BN, Sepulveda R, Hing T, et al. Prevalence and factors associated with gluten sensitivity in inflammatory bowel disease. Scand J Gastroenterol. 2018;53:147-151.
57. Schreiner P, Yilmaz B, Rossel JB, et al. Vegetarian or gluten-free diets in patients with inflammatory bowel disease are associated with lower psychological well-being and a different gut microbiota, but no beneficial effects on the course of the disease. United European Gastroenterol J. 2019;7:767-781.
58. Weaver KN, Herfarth H. Gluten-Free Diet in IBD: Time for a Recommendation? Mol Nutr Food Res. 2021;65(5):e1901274.
59. Szilagyi A, Galiatsatos P, Xue X. Systematic review and meta-analysis of lactose digestion, its impact on intolerance and nutritional effects of dairy food restriction in inflammatory bowel diseases. Nutr J. 2016;15:67.
60. Black CJ, Staudacher HM, Ford AC. Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis. Gut. 2021 Aug 10:gutjnl-2021-325214. Epub ahead of print.
61. Cox SR, Lindsay JO, Fromentin S, Stagg AJ, McCarthy NE, Galleron N, Ibraim SB, Roume H, Levenez F, Pons N, Maziers N, Lomer MC, Ehrlich SD, Irving PM, Whelan K. Effects of Low FODMAP Diet on Symptoms, Fecal Microbiome, and Markers of Inflammation in Patients With Quiescent Inflammatory Bowel Disease in a Randomized Trial. Gastroenterology. 2020 Jan;158:176-188.e7.
62. Gu B, Yu Z, Shi C, et al. Effects of low-FODMAP diet on irritable bowel symptoms in patients with quiescent inflammatory bowel disease: A protocol for a systematic review and meta-analysis. Medicine (Baltimore). 2022;101(11):e29088.
63. Haas SV, Haas MP. The treatment of celiac disease with the specific carbohydrate diet; report on 191 additional cases. Am J Gastroenterol. 1955;23:344-60.
64. Suskind DL, Wahbeh G, Gregory N, et al. Nutritional therapy in pediatric Crohn disease: the specific carbohydrate diet. J Pediatr Gastroenterol Nutr. 2014;58:87-91.
65. Kakodkar S, Farooqui AJ, Mikolaitis SL, et al. The Specific Carbohydrate Diet for Inflammatory Bowel Disease: A Case Series. J Acad Nutr Diet. 2015;115:1226-32.
66. Suskind DL, Wahbeh G, Cohen SA, et al. Patients Perceive Clinical Benefit with the Specific Carbohydrate Diet for Inflammatory Bowel Disease. Dig Dis Sci. 2016;61:3255-3260.
67. Lewis JD, Sandler RS, Brotherton C, et al. A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease. Gastroenterology. 2021;161:837-852.
68. Arjomand A, Suskind DL. Clinical and Histologic Remission in an Adult Crohn's Disease Patient Following the Specific Carbohydrate Diet and Its Impact on Healthcare Costs. Cureus. 2022;14(2):e22032.
69. Ajabnoor SM, Thorpe G, Abdelhamid A, et al. Long-term effects of increasing omega-3, omega-6 and total polyunsaturated fats on inflammatory bowel disease and markers of inflammation: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr. 2021;60:2293-2316.
70. Day AS, Davis R, Costello SP, et al. The Adequacy of Habitual Dietary Fiber Intake in Individuals With Inflammatory Bowel Disease: A Systematic Review. J Acad Nutr Diet. 2021;121:688-708.
71. Wedlake L, Slack N, Andreyev HJ, et al. Fiber in the treatment and maintenance of inflammatory bowel disease: a systematic review of randomized controlled trials. Inflamm Bowel Dis. 2014;20:576-86.
72. Trichopoulou A, Martínez-González MA, Tong TY, et al. Definitions and potential health benefits of the Mediterranean diet: views from experts around the world. BMC Med. 2014;12:112. doi: 10.1186/1741-7015-12-112.
73. Roncoroni L, Gori R, Elli L, et al. Nutrition in Patients with Inflammatory Bowel Diseases: A Narrative Review. Nutrients. 2022;14:751.
74. Chicco F, Magrì S, Cingolani A, et al. Multidimensional Impact of Mediterranean Diet on IBD Patients. Inflamm Bowel Dis. 2021;27:1-9.
75. Yang H, Feng R, Li T, et al. Systematic review with meta-analysis of partial enteral nutrition for the maintenance of remission in Crohn's disease. Nutr Res. 2020;81:7-18.
76. Sigall-Boneh R, Pfeffer-Gik T, Segal I, et al. 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;20:1353-60.
77. Ceballos D, Hernández-Camba A, Ramos L. Diet and microbiome in the beginning of the sequence of gut inflammation. World J Clin Cases 2021;9:11122-11147.
78. Szczubełek M, Pomorska K, Korólczyk-Kowalczyk M, et al. Effectiveness of Crohn's Disease Exclusion Diet for Induction of Remission in Crohn's Disease Adult Patients. Nutrients. 2021;13:4112.
79. Yanai H, Levine A, Hirsch A, et al. The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022;7:49-59.
80. Svolos V, Hansen R, Nichols B, et al. Treatment of Active Crohn's Disease with an Ordinary Food-based Diet That Replicates Exclusive Enteral Nutrition. Gastroenterology. 2019;156:1354-1367.
81. Fuss IJ, Neurath M, Boirivant M et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. Journal of immunology. 1996; 157:1261–1270.
82. Matsuoka K, Inoue N, Sato T et al. T-bet upregulation and subsequent interleukin 12 stimulation are essential for induction of Th1 mediated immunopathology in Crohn's disease. Gut. 2004; 53:1303–1308.
83. Leppkes M, Becker C, Ivanov II et al. RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F. Gastroenterology. 2009; 136:257–267.
84. Maul J, Loddenkemper C, Mundt P et al. Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology. 2005 Jun;128(7):1868-78. doi: 10.1053/j.gastro.2005.03.043.
85. Chen ML, Sundrud MS. Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2016;22: 1157-1167.
86. Sefik E, Geva-Zatorsky N, Oh S, Konnikova L et al. MUCOSAL IMMUNOLOGY. Individual intestinal symbionts induce a distinct population of RORγ⁺ regulatory T cells. Science. 2015;349:993-7.
87. Ohnmacht C, Park JH, Cording S et al. MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORγt⁺ T cells. Science. 2015;349(6251):989-93.
88. Negi S, Saini S, Tandel N et al. Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice. Cells. 2021;10:1847
89. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003 Feb 14;299(5609):1057-61.
90. Cook L, Stahl M, Han X, Nazli A et al. Suppressive and Gut-Reparative Functions of Human Type 1 T Regulatory Cells. Gastroenterology. 2019 ;157:1584-1598.
91. Gad M, Brimnes J, Claesson MH. CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis. Clin Exp Immunol. 2003;131:34-40.
92. Read S, Malmström V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med. 2000 ;192:295-302.
93. Boschetti G, Kanjarawi R, Bardel E et al. Gut Inflammation in Mice Triggers Proliferation and Function of Mucosal Foxp3+ Regulatory T Cells but Impairs Their Conversion from CD4+ T Cells. J Crohns Colitis. 2017;11:105-117.
94. Maul J, Loddenkemper C, Mundt P, et al. Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology 2005;128:1868–78.
95. Fantini MC, Rizzo A, Fina D, et al . Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression. Gastroenterology 2009;136:1308–16.
96. Bluestone JA, Buckner JH, Fitch M et al. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015;7(315):315ra189.
97. Di Ianni M, Falzetti F, Carotti A, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 2011;117:3921–8.
98. Trzonkowski P, Bieniaszewska M, Juścińska J et al. First-In-Man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+CD25+CD127- T regulatory cells. Clin Immunol 2009;133:22–6.
99. Mathew JM, H-Voss J, LeFever A, et al . A phase I clinical trial with ex vivo expanded recipient regulatory T cells in living donor kidney transplants. Sci Rep 2018;8:7428
100. Gliwiński M, Iwaszkiewicz-Grześ D, Trzonkowski P. Cell-Based Therapies with T Regulatory Cells. BioDrugs. 2017;31:335-347.
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Catalán-Serra I, Ricanek P, Grimstad T. “Out of the box” new therapeutic strategies for Crohn´s disease: moving beyond biologics. 9010/2022


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Received: 15/06/2022

Accepted: 19/06/2022

Online First: 24/06/2022

Published: 13/11/2023

Article Online First time: 9 days

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