{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T20:42:17Z","timestamp":1773434537795,"version":"3.50.1"},"reference-count":131,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T00:00:00Z","timestamp":1454025600000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation\u2010mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.<\/jats:p>","DOI":"10.1038\/cti.2015.47","type":"journal-article","created":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T08:37:38Z","timestamp":1454056658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease"],"prefix":"10.1002","volume":"5","author":[{"given":"Yaron","family":"Ilan","sequence":"first","affiliation":[{"name":"Gastroenterology and Liver Units, Department of Medicine, Hebrew University\u2010Hadassah Medical Center Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,1,29]]},"reference":[{"key":"e_1_2_21_2_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i1.6"},{"key":"e_1_2_21_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.24.021605.090650"},{"key":"e_1_2_21_4_2","first-page":"551","article-title":"Contribution of immunoglobulin\u2010secreting cells in the murine small intestine to the total 'background' immunoglobulin production","volume":"62","author":"van der Heijden PJ","year":"1987","journal-title":"Immunology"},{"key":"e_1_2_21_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021639"},{"key":"e_1_2_21_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.10.013"},{"key":"e_1_2_21_7_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114512005223"},{"key":"e_1_2_21_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00280.x"},{"key":"e_1_2_21_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.6824"},{"key":"e_1_2_21_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-33778-4_1"},{"key":"e_1_2_21_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/17402520600876804"},{"key":"e_1_2_21_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161209787846784"},{"key":"e_1_2_21_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2009.06.018"},{"key":"e_1_2_21_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.974"},{"key":"e_1_2_21_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.09.005"},{"key":"e_1_2_21_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908771107"},{"key":"e_1_2_21_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/2040622315579621"},{"key":"e_1_2_21_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/2040622315579063"},{"key":"e_1_2_21_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/gou087"},{"key":"e_1_2_21_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2013.01.007"},{"key":"e_1_2_21_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00488"},{"key":"e_1_2_21_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343782"},{"key":"e_1_2_21_23_2","first-page":"1329","article-title":"The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis","volume":"19","author":"Magrone T","year":"2013","journal-title":"Curr Pharm Des"},{"key":"e_1_2_21_24_2","doi-asserted-by":"publisher","DOI":"10.1159\/000354685"},{"key":"e_1_2_21_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12181"},{"key":"e_1_2_21_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-013-0929-4"},{"key":"e_1_2_21_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00301"},{"key":"e_1_2_21_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000358156"},{"key":"e_1_2_21_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12182"},{"key":"e_1_2_21_30_2","first-page":"1099","article-title":"Epithelial transport in inflammatory bowel diseases","volume":"20","author":"Ghishan FK","year":"2014","journal-title":"Inflamm Bowel Dis"},{"key":"e_1_2_21_31_2","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2015.13.1.11"},{"key":"e_1_2_21_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303955"},{"key":"e_1_2_21_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0b013e31828dcac7"},{"key":"e_1_2_21_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0821-4"},{"key":"e_1_2_21_35_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39134"},{"key":"e_1_2_21_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21247"},{"key":"e_1_2_21_37_2","doi-asserted-by":"publisher","DOI":"10.1556\/EuJMI.1.2011.1.5"},{"key":"e_1_2_21_38_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i33.3761"},{"key":"e_1_2_21_39_2","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.2014010088"},{"key":"e_1_2_21_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.99"},{"key":"e_1_2_21_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.06.042"},{"key":"e_1_2_21_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.09.012"},{"key":"e_1_2_21_43_2","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0b013e318280b1e3"},{"key":"e_1_2_21_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290334"},{"key":"e_1_2_21_45_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.095497"},{"key":"e_1_2_21_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2000.01935.x"},{"key":"e_1_2_21_47_2","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/S0022-3565(24)29616-6","article-title":"Amelioration of immune\u2010mediated experimental colitis: tolerance induction in the presence of preexisting immunity and surrogate antigen bystander effect","volume":"297","author":"Gotsman I","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_21_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2004.0935.x"},{"key":"e_1_2_21_49_2","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2015.13.2.105"},{"key":"e_1_2_21_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2011.04.003"},{"key":"e_1_2_21_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344205"},{"key":"e_1_2_21_52_2","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0b013e31829ed7df"},{"key":"e_1_2_21_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxs113"},{"key":"e_1_2_21_54_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132657"},{"key":"e_1_2_21_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2013.09.002"},{"key":"e_1_2_21_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.60"},{"key":"e_1_2_21_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2011.01.012"},{"key":"e_1_2_21_58_2","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0b013e318281f5a3"},{"key":"e_1_2_21_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12171"},{"key":"e_1_2_21_60_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i12.3255"},{"key":"e_1_2_21_61_2","first-page":"928461","article-title":"Role of Th17 Cells in the Pathogenesis of Human IBD","author":"Galvez J","year":"2014","journal-title":"ISRN Inflamm"},{"key":"e_1_2_21_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.04.003"},{"key":"e_1_2_21_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2014.03.012"},{"key":"e_1_2_21_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12192"},{"key":"e_1_2_21_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/1757-4749-5-23"},{"key":"e_1_2_21_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2013.10.002"},{"key":"e_1_2_21_67_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.01.060"},{"key":"e_1_2_21_68_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i10.1493"},{"key":"e_1_2_21_69_2","doi-asserted-by":"publisher","DOI":"10.1159\/000324281"},{"key":"e_1_2_21_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.11.008"},{"key":"e_1_2_21_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.07.001"},{"key":"e_1_2_21_72_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72330"},{"key":"e_1_2_21_73_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21332"},{"key":"e_1_2_21_74_2","first-page":"8751","article-title":"Escherichia coli\u2010host macrophage interactions in the pathogenesis of inflammatory bowel disease","volume":"20","author":"Tawfik A","year":"2014","journal-title":"World J Gastroenterol"},{"key":"e_1_2_21_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.02.028"},{"key":"e_1_2_21_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.07.001"},{"key":"e_1_2_21_77_2","doi-asserted-by":"publisher","DOI":"10.1159\/000338136"},{"key":"e_1_2_21_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2014.08.006"},{"key":"e_1_2_21_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.10.013"},{"key":"e_1_2_21_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/gou036"},{"key":"e_1_2_21_81_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e32836410a4"},{"key":"e_1_2_21_82_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26494"},{"key":"e_1_2_21_83_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26702"},{"key":"e_1_2_21_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10208"},{"key":"e_1_2_21_85_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i20.3105"},{"key":"e_1_2_21_86_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00441.x"},{"key":"e_1_2_21_87_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i18.5685"},{"key":"e_1_2_21_88_2","first-page":"12","article-title":"Efect of short\u2010term oral administration of a mixture of autologous proteins extracted from the colon of patients with Crohn's disease: a memory effect of oral tolerance induction","volume":"2","author":"Israeli ED","year":"2015","journal-title":"J Gastroenterol Hepatol"},{"key":"e_1_2_21_89_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945011796150343"},{"key":"e_1_2_21_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2011.12.003"},{"key":"e_1_2_21_91_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.06.002"},{"key":"e_1_2_21_92_2","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-200012110-00010"},{"key":"e_1_2_21_93_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.18144"},{"key":"e_1_2_21_94_2","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000197"},{"key":"e_1_2_21_95_2","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12640"},{"key":"e_1_2_21_96_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1000"},{"key":"e_1_2_21_97_2","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2012.9.372"},{"key":"e_1_2_21_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.02.009"},{"key":"e_1_2_21_99_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.03.049"},{"key":"e_1_2_21_100_2","first-page":"w13711","article-title":"Combination therapies in the context of anti\u2010CD3 antibodies for the treatment of autoimmune diseases","volume":"142","author":"Dean Y","year":"2012","journal-title":"Swiss Med Wkly"},{"key":"e_1_2_21_101_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01017.x"},{"key":"e_1_2_21_102_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2008.07.027"},{"key":"e_1_2_21_103_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1408"},{"key":"e_1_2_21_104_2","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1632"},{"key":"e_1_2_21_105_2","doi-asserted-by":"publisher","DOI":"10.1177\/0961203308100511"},{"key":"e_1_2_21_106_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.9.6038"},{"key":"e_1_2_21_107_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.07.019"},{"key":"e_1_2_21_108_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-009-9323-7"},{"key":"e_1_2_21_109_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0160-6"},{"key":"e_1_2_21_110_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2011.04511.x"},{"key":"e_1_2_21_111_2","first-page":"163A","article-title":"Alleviation of insulin resistance and liver damage by oral administration of etec colostrums is mediated by increased GLP\u20101, adiponectin serum levels and tregs: results of a phase I\/II clinical trial in NASH","volume":"52","author":"Mizrahi MLG","year":"2010","journal-title":"Hepatology"},{"key":"e_1_2_21_112_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-015-0388-x"},{"key":"e_1_2_21_113_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2009.42"},{"key":"e_1_2_21_114_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(88)90271-7"},{"key":"e_1_2_21_115_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00105.2005"},{"key":"e_1_2_21_116_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.104950"},{"key":"e_1_2_21_117_2","first-page":"151","article-title":"beta\u2010glycosphingolipids ameliorated non\u2010alcoholic steatohepatitis in the Psammomys obesus model","volume":"7","author":"Zigmond E","year":"2014","journal-title":"J Inflamm Res"},{"key":"e_1_2_21_118_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90634.2008"},{"issue":"204","key":"e_1_2_21_119_2","first-page":"200A","article-title":"Treatment of insulin rsistance and non\u2010alcoholic steatohepatitis by administration of beta glucosylceramide controlled trial","volume":"50","author":"Lalazar GZE","year":"2009","journal-title":"Hepatology"},{"key":"e_1_2_21_120_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-014-0258-9"},{"key":"e_1_2_21_121_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.106"},{"key":"e_1_2_21_122_2","doi-asserted-by":"publisher","DOI":"10.1177\/03946320140270S102"},{"key":"e_1_2_21_123_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00393-012-1114-5"},{"key":"e_1_2_21_124_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00382-2"},{"key":"e_1_2_21_125_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(14)63276-5"},{"key":"e_1_2_21_126_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830180903197498"},{"key":"e_1_2_21_127_2","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1236"},{"key":"e_1_2_21_128_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.116"},{"key":"e_1_2_21_129_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2015.01.012"},{"key":"e_1_2_21_130_2","first-page":"76","article-title":"Probiotic\u2010induced changes in the intestinal epithelium: implications in gastrointestinal disease","volume":"30","author":"Ramakrishna BS","year":"2009","journal-title":"Trop Gastroenterol"},{"key":"e_1_2_21_131_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20602"},{"key":"e_1_2_21_132_2","first-page":"919","article-title":"Probiotics, prebiotics and symbiotics in inflammatory bowel diseases: state\u2010of\u2010the\u2010art and new insights","volume":"27","author":"Sinagra E","year":"2013","journal-title":"J Biol Regul Homeost Agents"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/cti.2015.47","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T07:52:57Z","timestamp":1748764377000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1038\/cti.2015.47"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1]]},"references-count":131,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1038\/cti.2015.47"],"URL":"https:\/\/doi.org\/10.1038\/cti.2015.47","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1]]},"assertion":[{"value":"2015-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e60"}}