title: The opioid effects of gluten exorphins: asymptomatic celiac disease.
abstract: Gluten-containing cereals are a main food staple present in the daily human diet, including wheat, barley, and rye. Gluten intake is associated with the development of celiac disease (CD) and related disorders such as diabetes mellitus type I, depression, and schizophrenia. However, until now, there is no consent about the possible deleterious effects of gluten intake because of often failing symptoms even in persons with proven CD. Asymptomatic CD (ACD) is present in the majority of affected patients and is characterized by the absence of classical gluten-intolerance signs, such as diarrhea, bloating, and abdominal pain. Nevertheless, these individuals very often develop diseases that can be related with gluten intake. Gluten can be degraded into several morphine-like substances, named gluten exorphins. These compounds have proven opioid effects and could mask the deleterious effects of gluten protein on gastrointestinal lining and function. Here we describe a putative mechanism, explaining how gluten could "mask" its own toxicity by exorphins that are produced through gluten protein digestion.
authors.affiliation: Natura Foundation, Edisonstraat 66, 3281 NC, Numansdorp, Netherlands. cpni.pruimboom@icloud.com.|Department of Laboratory Medicine, University Medical Center Groningen (UMCG), University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, Netherlands. cpni.pruimboom@icloud.com.
authors.forename: Leo
authors.initials: L
authors.lastname: Pruimboom
authors.affiliation: Natura Foundation, Edisonstraat 66, 3281 NC, Numansdorp, Netherlands. karin.de-punder@charite.de.|Institute of Medical Psychology, Charité University Medicine Berlin, Hufelandweg 14, 10117, Berlin, Germany. karin.de-punder@charite.de.
authors.forename: Karin
authors.initials: K
authors.lastname: de Punder
mesh_terms: D000818:Animals; D058070:Asymptomatic Diseases; D002446:Celiac Disease / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D004063:Digestion; D002523:Edible Grain / Q000009:adverse effects* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D005772:Gastrointestinal Transit; D005983:Glutens / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018847:Opioid Peptides / Q000009:adverse effects* / Q000378:metabolism; D010455:Peptides / Q000009:adverse effects* / Q000378:metabolism; D059748:Proteolysis; D012720:Severity of Illness Index
chemical_list: D018847:Opioid Peptides; D010455:Peptides; C019178:exorphins; D005983:Glutens
references.citation: Eur J Gastroenterol Hepatol. 2011 Mar;23(3):238-44
references.pmid: 21304317
references.citation: Adv Exp Med Biol. 2000;477:67-87
references.pmid: 10849732
references.citation: Actas Dermosifiliogr. 2014 Jun;105(5):469-82
references.pmid: 23664252
references.citation: Arq Gastroenterol. 2013 Jul-Sep;50(3):231-5
references.pmid: 24322197
references.citation: J Neurosci. 2011 Mar 2;31(9):3459-69
references.pmid: 21368058
references.citation: Physiol Behav. 2003 Oct;80(1):123-34
references.pmid: 14568317
references.citation: Neurol Sci. 2013 Dec;34(12):2199-204
references.pmid: 23615718
references.citation: BMC Med Genet. 2011 Sep 28;12:126
references.pmid: 21951915
references.citation: Ann Intern Med. 2012 Feb 21;156(4):309-11
references.pmid: 22351716
references.citation: Med Hypotheses. 2014 Mar;82(3):326-34
references.pmid: 24472865
references.citation: Pharmacol Biochem Behav. 2015 Jul;134:70-8
references.pmid: 25661529
references.citation: Hematol Rep. 2014 Dec 09;6(4):5612
references.pmid: 25568762
references.citation: Gastroenterol Res Pract. 2012;2012:952753
references.pmid: 22693492
references.citation: Am J Clin Nutr. 2006 Feb;83(2):211-20
references.pmid: 16469977
references.citation: J Med Chem. 2015 Feb 12;58(3):1390-9
references.pmid: 25588142
references.citation: Scand J Gastroenterol. 1998 Aug;33(8):817-21
references.pmid: 9754728
references.citation: Acta Neurol Scand. 2013 Jan;127(1):19-25
references.pmid: 22494246
references.citation: Gastroenterology. 2010 Jul;139(1):112-9
references.pmid: 20398668
references.citation: Clin Sci (Lond). 2005 Apr;108(4):277-92
references.pmid: 15584901
references.citation: Clin Chim Acta. 2015 Jun 15;446:237-40
references.pmid: 25944768
references.citation: Eur J Endocrinol. 2014 Sep;171(3):353-62
references.pmid: 24935932
references.citation: J Pediatr Gastroenterol Nutr. 2007 Jul;45(1):65-70
references.pmid: 17592366
references.citation: Clin Exp Allergy. 2008 Nov;38(11):1712-26
references.pmid: 18823308
references.citation: Hypertension. 2009 Sep;54(3):468-70
references.pmid: 19581503
references.citation: Acta Paediatr. 2015 Feb;104(2):185-91
references.pmid: 25283799
references.citation: Life Sci. 1995;57(7):729-34
references.pmid: 7637543
references.citation: Gastroenterol Hepatol (N Y). 2010 Dec;6(12):772-7
references.pmid: 21301631
references.citation: Pharm Res. 2012 Jan;29(1):306-18
references.pmid: 21830140
references.citation: Rev Med Suisse. 2010 Jan 13;6(231):28-31
references.pmid: 20196430
references.citation: Protein Sci. 2004 Jan;13(1):145-54
references.pmid: 14691230
references.citation: Clin Exp Rheumatol. 2014 Jan-Feb;32(1):137-42
references.pmid: 24447910
references.citation: Eur Rev Med Pharmacol Sci. 2013 May;17(9):1167-73
references.pmid: 23690185
references.citation: Semin Immunopathol. 2012 Jul;34(4):523-40
references.pmid: 22535446
references.citation: Regul Pept. 1999 Nov 30;85(1):9-24
references.pmid: 10588446
references.citation: Curr Pharm Des. 2003;9(16):1331-44
references.pmid: 12769741
references.citation: Am J Physiol Gastrointest Liver Physiol. 2002 Oct;283(4):G996-G1003
references.pmid: 12223360
references.citation: J Neurol Neurosurg Psychiatry. 2012 Dec;83(12):1216-21
references.pmid: 22906616
references.citation: Curr Med Chem. 1999 Apr;6(4):311-27
references.pmid: 10101215
references.citation: Cell. 2007 Dec 14;131(6):1034-6
references.pmid: 18083091
references.citation: Dermatol Clin. 2007 Oct;25(4):563-75, ix
references.pmid: 17903615
references.citation: Neurogastroenterol Motil. 2010 Nov;22(11):1191-200, e315
references.pmid: 20584260
references.citation: Clin Gastroenterol Hepatol. 2015 Sep;13(9):1604-12.e3
references.pmid: 25701700
references.citation: Arch Biochem Biophys. 1988 Nov 1;266(2):369-76
references.pmid: 2461166
references.citation: Methods Enzymol. 2012;502:241-71
references.pmid: 22208988
references.citation: Med Monatsschr Pharm. 2013 Oct;36(10):369-80; quiz 381-2
references.pmid: 24266248
references.citation: Jpn J Pharmacol. 2000 Nov;84(3):259-65
references.pmid: 11138726
references.citation: Eur Heart J. 2015 Jan 21;36(4):195
references.pmid: 25756143
references.citation: N Engl J Med. 2012 Dec 20;367(25):2419-26
references.pmid: 23252527
references.citation: Psychoneuroendocrinology. 1997 Feb;22(2):65-78
references.pmid: 9149329
references.citation: Plant J. 2015 Jun;82(5):794-805
references.pmid: 25864460
references.citation: Eur J Pharmacol. 1996 Oct 24;314(1-2):27-32
references.pmid: 8957215
references.citation: World J Gastroenterol. 2006 Feb 14;12(6):843-52
references.pmid: 16521210
references.citation: Diabetes Metab Res Rev. 2014 Jul;30(5):354-71
references.pmid: 24989141
references.citation: Dtsch Med Wochenschr. 2014 Oct;139(42):2123-6
references.pmid: 25289919
references.citation: ScientificWorldJournal. 2012;2012:837416
references.pmid: 22629212
references.citation: Cell. 2007 Dec 14;131(6):1164-78
references.pmid: 18083105
references.citation: Biomed Res Int. 2014;2014:368703
references.pmid: 25140306
references.citation: Clin Exp Allergy. 2007 May;37(5):631-50
references.pmid: 17456211
references.citation: Horm Res Paediatr. 2014;81(5):309-13
references.pmid: 24603159
references.citation: Neurobiol Dis. 2012 Dec;48(3):447-53
references.pmid: 22801085
references.citation: Am J Gastroenterol. 2011 Mar;106(3):508-14; quiz 515
references.pmid: 21224837
references.citation: Scand J Gastroenterol. 2014 Jan;49(1):52-8
references.pmid: 24164443
references.citation: Pediatr Dermatol. 2014 Jul-Aug;31(4):483-8
references.pmid: 24831884
references.citation: Nutr Neurosci. 2002 Sep;5(4):251-61
references.pmid: 12168688
references.citation: Einstein (Sao Paulo). 2014 Apr;12(2):251-3
references.pmid: 25003936
references.citation: Clin Rev Allergy Immunol. 2012 Jun;42(3):279-87
references.pmid: 21181303
references.citation: Life Sci. 2002 Oct 4;71(20):2383-90
references.pmid: 12231399
references.citation: FASEB J. 1995 Jun;9(9):736-44
references.pmid: 7601338
references.citation: J Nutr Biochem. 2014 Oct;25(10):1011-8
references.pmid: 25018147
references.citation: Am J Gastroenterol. 2012 Oct;107(10):1538-44; quiz 1537, 1545
references.pmid: 22850429
references.citation: Microbes Infect. 2010 Jun;12(6):421-7
references.pmid: 20178858
references.citation: J Intern Med. 2011 Jun;269(6):582-90
references.pmid: 21481018
references.citation: Biochim Biophys Acta. 1991 Jan 29;1076(2):314-6
references.pmid: 1671823
references.citation: Curr Med Chem. 2005;12(8):971-98
references.pmid: 15853709
references.citation: Science. 2002 Sep 27;297(5590):2275-9
references.pmid: 12351792
references.citation: Seizure. 2015 Feb;25:181-3
references.pmid: 25457448
references.citation: Hum Psychopharmacol. 2007 Dec;22(8):567-73
references.pmid: 17768771
references.citation: Compr Rev Food Sci Food Saf. 2013 Jul;12(4):364-380
references.pmid: 33412684
references.citation: J Leukoc Biol. 2006 Jul;80(1):1-15
references.pmid: 16698940
references.citation: Diabet Med. 2014 Dec;31(12):e33-6
references.pmid: 24805141
references.citation: Diabetes Care. 2012 Aug;35(8):e60
references.pmid: 22826453
references.citation: Nat Med. 1997 Jul;3(7):797-801
references.pmid: 9212111
references.citation: Gut Pathog. 2011 Jan 31;3(1):1
references.pmid: 21281494
references.citation: World J Clin Cases. 2015 Mar 16;3(3):275-84
references.pmid: 25789300
references.citation: Schizophr Res. 2012 Sep;140(1-3):262-3
references.pmid: 22771303
references.citation: Scand J Gastroenterol. 2014 Jan;49(1):43-51
references.pmid: 24256141
references.citation: BMC Med. 2013 Aug 28;11:188
references.pmid: 23981538
references.citation: Dig Dis. 2015;33(2):147-154
references.pmid: 25925916