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Celiac disease

People with celiac disease react to gluten, which is found in wheat, rye, spelt and barley. Villus atrophy in the small intestine is one of the most significant findings in celiac disease, rendering the patient with a poor absorptive capacity. The vast majority of celiac patients produce antibodies to tissue transglutaminase and have either the gene variant HLA-DQ-2 or HLA-DQ-8. However, these gene variants are much more common than the occurence of celiac disease. Thus, there must be additional factors that can explain why celiac disease develops. 1)

Epidemiology

After birth, an infant's environment shifts from a sterile space to one colonized by bacteria. Almost immediately, microbial products and live bacteria can be seen, but only in a part of the baby's intestine. The arrival of solid food several months later establishes a complex bacterial flora throughout the entire bowel. The composition of the flora has been shown to vary significantly depending on whether the birth was vaginal or cesarean.

“Differences in the microbial flora and impaired priming of the enteric epithelial surface in individuals who are born by cesarean delivery might therefore contribute to inflammatory conditions of the intestinal mucosa later in life,” write lead author Evalotte Decker, from the Department of Pediatrics, Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Germany, and colleagues. “Indeed, the rate of cesarean delivery as well as the incidence of [inflammatory bowel disease] and celiac disease have increased in recent decades.”

Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children.

Abstract OBJECTIVES: The aim of this study was to analyze a possible association between cesarean delivery and enteric inflammatory diseases in children.

METHODS: A retrospective, multicenter, case-control study that included 1950 children was performed in cooperation with 26 university and 16 nonacademic children's hospitals. Information on intestinal disease manifestation, together with mode of delivery and gestational age at birth, postnatal complications, and breastfeeding, was collected by the attending physician from children and their parents who were visiting a gastrointestinal outpatient clinic for Crohn disease (CD; 516 cases), ulcerative colitis (250 cases), celiac disease (157 cases), and other gastrointestinal diseases (165 cases) and control subjects who were visiting ophthalmologic, orthodontic, and dental outpatient clinics (862 cases).

RESULTS: Whereas the rate of cesarean delivery of children with Crohn disease or ulcerative colitis was similar to that of control subjects, a significantly enhanced likelihood of being born by cesarean delivery was found in children with celiac disease compared with control subjects (odds ratio: 1.8 [95% confidence interval: 1.13-2.88]; P = .014).

CONCLUSIONS: The mode of delivery and associated alterations in the development of the enteric homeostasis during the neonatal period might influence the incidence of celiac disease. 2)

The emerging data on viral and bacterial microbe-host interactions and their alterations in celiac disease provides a plausible mechanism linking environmental risk and disease development. 3)

Celiac and D metabolite levels

Some patients with celiac disease have low/normal 25D but elevated 1,25D apparently related to celiac. 4)

Our patient had hypocalcemia caused by celiac disease and values for serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. that were normal and elevated, respectively. Correction was demonstrated after dietary gluten withdrawal. 5)

Calcium and vitamin D supplement intake may increase arterial stiffness in systemic lupus erythematosus patients. 6)

7)

Evidence of infectious cause

“The finding of rod-shaped bacteria attached to the small intestinal epithelium of some untreated and treated celiac-disease patients, but not to the epithelium of healthy controls, ignites the notion that bacteria may be involved in the pathogenesis of celiac disease.” Am J Gastroenterol. 2004 May;99(5):905-6. A role for bacteria in celiac disease? Sollid LM, Gray GM 8)

“As presence of Campylobacter jejuni in other diseases with antigangliosides antibody formation has been established, we propose the possible role of Campylobacter jejuni in development of CD in association with other genetic and environmental factors by the mechanism that molecular mimicry of gangliosides-like epitopes common to both lipo-polysacharide coats of certain strains of Campylobacter jejuni and gangliosides in cell structure of gastrointestinal mucosa may cause an autoimmune response and consequently lead to atrophy and degeneration of mucosa possibly by apoptosis.” World J Gastroenterol. 2007 Sep 21;13(35):4784-5. Can Campylobacter jejuni play a role in development of celiac disease? Sabayan B, Foroughinia F, Imanieh MH 9)

Specific duodenal and faecal bacterial groups are associated with paediatric celiac disease.10)

Lymphocytic gastritis and celiac disease in indian children: evidence of a positive relation.11)

Autoantibodies involved in celiac disease are not specific, as infection may increase levels of anti-transglutaminase antibodies. These antibodies are not detectable once the infection is gone.12)

recent research

Could a common virus trigger coeliac disease in some children? Tye-Din JA et al, Norway February 2019

study in humans supports a role for infection with reovirus, a seemingly innocuous virus, in triggering the development of CeD 13) 14)

Findings suggest that neither olmesartan nor other ARBs were associated with diarrhea among patients undergoing endoscopy. The spruelike enteropathy recently associated with olmesartan is likely a rare adverse effect and milder presentations are unlikely. 15)

In 2015 I saw that 6 individuals in the USA were suing maker of Benicar. (presumably for bowel immunopathology caused by cytokines). Somewhere else I found that 1.9 million individuals are currently taking Olmesartan Medoxomil. 6 in 1.9 million ? Seems pretty rare to me. (Editor)

Gluten in “gluten-free” manufactured foods in Australia: a cross-sectional study. 16) PMID 30404591

2018 data show that OLM is an Nrf2 activator, NFkB inhibitor and apoptosis inhibitor in an experimental model of ulcerative colitis. Overall, the study indicates that OLM shows promise as a potential therapy for the treatment of human inflammatory bowel diseases. 17)

Research associated with J Tye-Din 18) , 19) , 20) , 21) , 22) , 23) , 24)

===== Notes and comments =====

Tye-Din JA has pub. review PMID 30519552 AND news 16/2/19 thenewdaily says new study suggests virus

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World J Gastroenterol. 2007 Sep 21;13(35):4784-5. Can Campylobacter jejuni play a role in development of celiac disease? A hypothesis. Sabayan B, Foroughinia F, Imanieh MH. Abstract Celiac disease (CD) is an entropathy with malabsortive condition in which an allergic reaction to the cereal grain-protein (gluten) causes small intestine mucosal injury. CD is a multifactorial disorder in which both genetic and environmental factors contribute to the disease development. Mechanisms have been described to explain the pathology of CD. T cells specific for multiple gluten peptides are found in virtually all patients. Generation of such a broad T cell response may be a prerequisite for disease development. CD is associated with multiple extraintestinal presentations, including neurological deficits. Recent studies have shown a significant correlation between anti-ganglioside antibodies and neurological disorders in patients with underlying CD. Gangliosides are glycosphingolipids which are abundant in nervous system and in other tissues including gastrointestinal tract. It is not known what triggers the release of anti-ganglioside antibodies in people with gluten sensitivity. But, the mechanism is likely to involve the intestinal immune system response to ingested gliadin, a component of wheat gluten. Studies showed that mechanisms different from gluten exposure may be implicated in antibody formation, and other environmental factors may also exist. In addition, considering the fact that genetic predisposition dysregulating mucosal immune responses in the presence of certain environmental triggers like gastrointestinal infections may be strong etiological factors for developing chronic intestinal inflammation including CD, the hypothesis raised in our mind that antiganglioside antibody formation in CD may play a role not only in development of neurological complications in celiac patients, but also in development of CD itself. As presence of Campylobacter jejuni in other diseases with antigangliosides antibody formation has been established, we propose the possible role of Campylobacter jejuni in development of CD in association with other genetic and environmental factors by the mechanism that molecular mimicry of gangliosides-like epitopes common to both lipo-polysacharide coats of certain strains of Campylobacter jejuni and gangliosides in cell structure of gastrointestinal mucosa may cause an autoimmune response and consequently lead to atrophy and degeneration of mucosa possibly by apoptosis.

PMID: 17729402

Am J Gastroenterol. 2004 May;99(5):905-6. A role for bacteria in celiac disease? Sollid LM, Gray GM. Abstract The finding of rod-shaped bacteria attached to the small intestinal epithelium of some untreated and treated celiac-disease patients, but not to the epithelium of healthy controls, ignites the notion that bacteria may be involved in the pathogenesis of celiac disease. This editorial discusses this possibility in relation to the current understanding of the molecular basis of this disorder.

Comment on Am J Gastroenterol. 2004 May;99(5):894-904. PMID: 15128358

Am J Gastroenterol. 2011 Mar;106(3):548-9. Celiac disease increases the risk of Toxoplasma gondii infection in a large cohort of pregnant women. Rostami Nejad M, Rostami K, Cheraghipour K, Nazemalhosseini Mojarad E, Volta U, Al Dulaimi D, Zali MR. PMID: 21378773 [PubMed - indexed for MEDLINE]

keepiing authors of Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease

  Romain Bouziat1,2,*, Reinhard Hinterleitner1,2,*, Judy J. Brown3,4,*, Jennifer E. Stencel-Baerenwald3,4, Mine Ikizler4,5, 

as link will likely break (news media) ===== References =====

1)
Garrote JA, Gómez-González E, Bernardo D, Arranz E, Chirdo F. Celiac disease pathogenesis: the proinflammatory cytokine network. J Pediatr Gastroenterol Nutr. 2008 Aug;47 Suppl 1:S27-32. doi: 10.1097/MPG.0b013e3181818fb9.
[PMID: 18667914] [DOI: 10.1097/MPG.0b013e3181818fb9]
2)
Decker E, Engelmann G, Findeisen A, Gerner P, Laass M, Ney D, Posovszky C, Hoy L, Hornef MW. Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children. Pediatrics. 2010 Jun;125(6):e1433-40. doi: 10.1542/peds.2009-2260. Epub 2010 May 17.
[PMID: 20478942] [DOI: 10.1542/peds.2009-2260]
3)
Tye-Din JA, Galipeau HJ, Agardh D. Celiac Disease: A Review of Current Concepts in Pathogenesis, Prevention, and Novel Therapies. Front Pediatr. 2018 Nov 21;6:350. doi: 10.3389/fped.2018.00350. eCollection 2018.
[PMID: 30519552] [PMCID: 6258800] [DOI: 10.3389/fped.2018.00350]
4)
Rakover Y, Hager H, Nussinson E, Luboshitzky R. Celiac disease as a cause of transient hypocalcemia and hypovitaminosis D in a 13 year-old girl. J Pediatr Endocrinol. 1994 Jan-Mar;7(1):53-5. doi: 10.1515/jpem.1994.7.1.53.
[PMID: 8186825] [DOI: 10.1515/jpem.1994.7.1.53]
5)
Rickels MR, Mandel SJ. Celiac disease manifesting as isolated hypocalcemia. Endocr Pract. 2004 May-Jun;10(3):203-7. doi: 10.4158/ep.10.3.203.
[PMID: 15310538] [DOI: 10.4158/ep.10.3.203]
6)
Mellor-Pita S, Tutor-Ureta P, Rosado S, Alkadi K, Granado F, Jimenez-Ortiz C, Castejon R. Calcium and vitamin D supplement intake may increase arterial stiffness in systemic lupus erythematosus patients. Clin Rheumatol. 2019 Apr;38(4):1177-1186. doi: 10.1007/s10067-018-04416-x. Epub 2019 Jan 9.
[PMID: 30628012] [DOI: 10.1007/s10067-018-04416-x]
7) , 18) , 20) , 21) , 24)
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8)
Sollid LM, Gray GM. A role for bacteria in celiac disease?. Am J Gastroenterol. 2004 May;99(5):905-6. doi: 10.1111/j.1572-0241.2004.04158.x.
[PMID: 15128358] [DOI: 10.1111/j.1572-0241.2004.04158.x]
9)
Sabayan B, Foroughinia F, Imanieh M. Can Campylobacter jejuni play a role in development of celiac disease? A hypothesis. World J Gastroenterol. 2007 Sep 21;13(35):4784-5. doi: 10.3748/wjg.v13.i35.4784.
[PMID: 17729402] [PMCID: 4611202] [DOI: 10.3748/wjg.v13.i35.4784]
10)
Collado MC, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease. J Clin Pathol. 2009 Mar;62(3):264-9. doi: 10.1136/jcp.2008.061366. Epub 2008 Nov 7.
[PMID: 18996905] [DOI: 10.1136/jcp.2008.061366]
11)
Prasad KK, Thapa BR, Lal S, Sharma AK, Nain CK, Singh K. Lymphocytic gastritis and celiac disease in indian children: evidence of a positive relation. J Pediatr Gastroenterol Nutr. 2008 Nov;47(5):568-72. doi: 10.1097/mpg.0b013e31816232a7.
[PMID: 18979579] [DOI: 10.1097/mpg.0b013e31816232a7]
12)
Ferrara F, Quaglia S, Caputo I, Esposito C, Lepretti M, Pastore S, Giorgi R, Martelossi S, Dal Molin G, Di Toro N, Ventura A, Not T. Anti-transglutaminase antibodies in non-coeliac children suffering from infectious diseases. Clin Exp Immunol. 2010 Feb;159(2):217-23. doi: 10.1111/j.1365-2249.2009.04054.x. Epub 2009 Nov 12.
[PMID: 19912255] [PMCID: 2810390] [DOI: 10.1111/j.1365-2249.2009.04054.x]
13)
Bouziat R, Hinterleitner R, Brown JJ, Stencel-Baerenwald JE, Ikizler M, Mayassi T, Meisel M, Kim SM, Discepolo V, Pruijssers AJ, Ernest JD, Iskarpatyoti JA, Costes LMM, Lawrence I, Palanski BA, Varma M, Zurenski MA, Khomandiak S, McAllister N, Aravamudhan P, Boehme KW, Hu F, Samsom JN, Reinecker H, Kupfer SS, Guandalini S, Semrad CE, Abadie V, Khosla C, Barreiro LB, Xavier RJ, Ng A, Dermody TS, Jabri B. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science. 2017 Apr 7;356(6333):44-50. doi: 10.1126/science.aah5298.
[PMID: 28386004] [PMCID: 5506690] [DOI: 10.1126/science.aah5298]
14)
Kim SM, Mayassi T, Jabri B. Innate immunity: actuating the gears of celiac disease pathogenesis. Best Pract Res Clin Gastroenterol. 2015 Jun;29(3):425-35. doi: 10.1016/j.bpg.2015.05.001. Epub 2015 May 11.
[PMID: 26060107] [PMCID: 4465077] [DOI: 10.1016/j.bpg.2015.05.001]
15)
Greywoode R, Braunstein ED, Arguelles-Grande C, Green PHR, Lebwohl B. Olmesartan, other antihypertensives, and chronic diarrhea among patients undergoing endoscopic procedures: a case-control study. Mayo Clin Proc. 2014 Sep;89(9):1239-43. doi: 10.1016/j.mayocp.2014.05.012. Epub 2014 Jul 11.
[PMID: 25023670] [PMCID: 4157109] [DOI: 10.1016/j.mayocp.2014.05.012]
16)
Halmos EP, Clarke D, Pizzey C, Tye-Din JA. Gluten in "gluten-free" manufactured foods in Australia: a cross-sectional study. Med J Aust. 2018 Nov 19;209(10):448-449. doi: 10.5694/mja18.00457. Epub 2018 Nov 12.
[PMID: 30404591] [DOI: 10.5694/mja18.00457]
17)
Saber S, Khalil RM, Abdo WS, Nassif D, El-Ahwany E. Olmesartan ameliorates chemically-induced ulcerative colitis in rats via modulating NFκB and Nrf-2/HO-1 signaling crosstalk. Toxicol Appl Pharmacol. 2019 Feb 1;364:120-132. doi: 10.1016/j.taap.2018.12.020. Epub 2018 Dec 27.
[PMID: 30594690] [DOI: 10.1016/j.taap.2018.12.020]
19)
Henderson KN, Tye-Din JA, Reid HH, Chen Z, Borg NA, Beissbarth T, Tatham A, Mannering SI, Purcell AW, Dudek NL, van Heel DA, McCluskey J, Rossjohn J, Anderson RP. A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease. Immunity. 2007 Jul;27(1):23-34. doi: 10.1016/j.immuni.2007.05.015. Epub 2007 Jul 12.
[PMID: 17629515] [DOI: 10.1016/j.immuni.2007.05.015]
22)
Anderson RP, Henry MJ, Taylor R, Duncan EL, Danoy P, Costa MJ, Addison K, Tye-Din JA, Kotowicz MA, Knight RE, Pollock W, Nicholson GC, Toh B, Brown MA, Pasco JA. A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways. BMC Med. 2013 Aug 28;11:188. doi: 10.1186/1741-7015-11-188.
[PMID: 23981538] [PMCID: 3765645] [DOI: 10.1186/1741-7015-11-188]
23)
Anderson RP, van Heel DA, Tye-Din JA, Barnardo M, Salio M, Jewell DP, Hill AVS. T cells in peripheral blood after gluten challenge in coeliac disease. Gut. 2005 Sep;54(9):1217-23. doi: 10.1136/gut.2004.059998.
[PMID: 16099789] [PMCID: 1774637] [DOI: 10.1136/gut.2004.059998]
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