Celiac Disease & Gluten-free Diet Information at Celiac.com - http://www.celiac.com
Do Vitamin D Deficiency, Gut Bacteria, and Gluten Combine in Infancy to Cause Celiac Disease?
http://www.celiac.com/articles/21605/1/Do-Vitamin-D-Deficiency-Gut-Bacteria-and-Gluten-Combine-in-Infancy-to-Cause-Celiac-Disease/Page1.html
Roy Jamron
Roy S. Jamron holds a B.S. in Physics from the University of Michigan and an M.S. in Engineering Applied Science from the University of California at Davis, and independently investigates the latest research on celiac disease and related disorders. 
By Roy Jamron
Published on 06/16/2008
 
Do vitamin D deficiency, gut bacteria, and timing of gluten introduction during infancy all combine to initiate the onset of celiac disease? Two recent papers raise the potential that this indeed may be the case. One paper finds that when transgenic mice expressing the human DQ8 heterodimer (a mouse model of celiac disease) are mucosally immunized with gluten co-administered with Lactobacillus casei bacteria, the mice exhibit an enhanced and increased immune response to gluten compared to the administration of gluten alone. A second paper finds that vitamin D receptors expressed by intestinal epithelial cells are involved in the suppression of bacteria-induced intestinal inflammation in a study which involved use of germ-free mice and knockout mice lacking vitamin D receptors exposed to both friendly and pathogenic strains of gut bacteria. Pathogenic bacteria caused increased expression of vitamin D receptors in epithelial cells. Friendly bacteria did not.

This article appeared in the Summer 2008 edition of Celiac.com's Scott-Free Newsletter.

Celiac.com 06/16/2008 - Do vitamin D deficiency, gut bacteria, and timing of gluten introduction during infancy all combine to initiate the onset of celiac disease? Two recent papers raise the potential that this indeed may be the case. One paper finds that when transgenic mice expressing the human DQ8 heterodimer (a mouse model of celiac disease) are mucosally immunized with gluten co-administered with Lactobacillus casei bacteria, the mice exhibit an enhanced and increased immune response to gluten compared to the administration of gluten alone.[1] A second paper finds that vitamin D receptors expressed by intestinal epithelial cells are involved in the suppression of bacteria-induced intestinal inflammation in a study which involved use of germ-free mice and knockout mice lacking vitamin D receptors exposed to both friendly and pathogenic strains of gut bacteria.[2] Pathogenic bacteria caused increased expression of vitamin D receptors in epithelial cells. Friendly bacteria did not.

If one considers these two papers together, one notices: (1) Certain species of gut bacteria may work in conjunction with gluten to cause an increased immune response which initiates celiac disease; (2) The presence of an adequate level of vitamin D may suppress the immune response to those same gut bacteria in such a way as to reduce or eliminate the enhanced immune response to gluten caused by those gut bacteria, thus preventing the onset of celiac disease.

Vitamin D has recently been demonstrated to play a role in preserving the intestinal mucosal barrier. A Swedish study found children born in the summer, likely introduced to gluten during winter months with minimal sunlight, have a higher incidence of celiac disease strongly suggesting a relationship to vitamin D deficiency.[3] Recent studies found vitamin D supplementation in infancy and living in world regions with high ultraviolet B irradiance both result in a lower incidence of type 1 diabetes, an autoimmune disease closely linked to celiac disease.[4][5]

Gut bacteria have long been suspected as having some role in the pathogenesis of celiac disease. In 2004, a study found rod-shaped bacteria attached to the small intestinal epithelium of some untreated and treated children with celiac disease, but not to the epithelium of healthy controls.[6][7] Prior to that, a paper published on Celiac.com[8] first proposed that celiac disease might be initiated by a T cell immune response to "undigested" gluten peptides found inside of pathogenic gut bacteria which have "ingested" short chains of gluten peptides resistant to breakdown. The immune system would have no way of determining that the "ingested" gluten peptides were not a part of the pathogenic bacteria and, thus, gluten would be treated as though it were a pathogenic bacteria. The new paper cited above[1] certainly gives credence to this theory.

Celiac disease begins in infancy. Studies consistently find the incidence of celiac disease in children is the same (approximately 1%) as in adults. The incidence does not increase throughout life, meaning, celiac disease starts early in life. Further, in identical twins, one twin may get celiac disease, and the other twin may never experience celiac disease during an entire lifetime. Something other than genetics differs early on in the childhood development of the twins which initiates celiac disease. Differences in vitamin D levels and the makeup of gut bacteria in the twins offers a reasonable explanation as to why one twin gets celiac disease and the other does not. Early childhood illnesses and antibiotics could also affect vitamin D level and gut bacteria makeup. Pregnant and nursing mothers also need to maintain high levels of vitamin D for healthy babies.

Sources:

[1] Immunol Lett. 2008 May 22.
Adjuvant effect of Lactobacillus casei in a mouse model of gluten sensitivity.
D'Arienzo R, Maurano F, Luongo D, Mazzarella G, Stefanile R, Troncone R, Auricchio S, Ricca E, David C, Rossi M.
http://dx.doi.org/10.1016/j.imlet.2008.04.006

[2] The FASEB Journal. 2008;22:320.10. Meeting Abstracts - April 2008.
Bacterial Regulation of Vitamin D Receptor in Intestinal Epithelial Inflammation
Jun Sun, Anne P. Liao, Rick Y. Xia, Juan Kong, Yan Chun Li and Balfour Sartor
http://www.fasebj.org/cgi/content/meeting_abstract/22/1_MeetingAbstracts/320.10

[3] Vitamin D Preserves the Intestinal Mucosal Barrier
Roy S. Jamron
http://www.celiac.com/articles/21476/

[4] Arch Dis Child. 2008 Jun;93(6):512-7. Epub 2008 Mar 13.
Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis.
Zipitis CS, Akobeng AK.
http://adc.bmj.com/cgi/content/full/93/6/512

[5] Diabetologia. 2008 Jun 12. [Epub ahead of print]
The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide.
Mohr SB, Garland CF, Gorham ED, Garland FC.
http://www.springerlink.com/content/32jx3635884xt112/

[6] Am J Gastroenterol. 2004 May;99(5):905-6.
A role for bacteria in celiac disease?
Sollid LM, Gray GM.
http://dx.doi.org/10.1111/j.1572-0241.2004.04158.x

[7] Am J Gastroenterol. 2004 May;99(5):894-904.
Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease.
Forsberg G, Fahlgren A, Hörstedt P, Hammarström S, Hernell O, Hammarström ML.
http://dx.doi.org/10.1111/j.1572-0241.2004.04157.x

[8] Are Commensal Bacteria with a Taste for Gluten the Missing Link in the Pathogenesis of Celiac Disease?
Roy S. Jamron
http://www.celiac.com/articles/779/