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Celiac.com 03/11/2019 - Many researchers believe that intestinal microbiota play a key role in the development of celiac disease. Since gut microbiota are strongly influenced by systemic antibiotics, especially in early life, the role of antibiotics in the development of celiac disease comes into question. Do antibiotics in infancy influence celiac disease rates later on? The team’s observational nationwide register-based cohort study included all children born in Denmark from 1995 through 2012, and Norway from 2004 through 2012. They followed the children born in Denmark until May 8, 2015 and the children born in Norway until December 31, 2013. In all, they gathered medical data on more than 1.7 million children, including 3,346 with a diagnosis of celiac disease. Any patient who received a dispensed systemic antibiotic in the first year of life was defined as having been exposed to systemic antibiotics. In both the Danish and in the Norwegian groups, infants exposed to systemic antibiotics in the first year of life had higher rates of celiac disease than those with no exposure. The team found that the relationship between an increasing number of dispensed antibiotics and the risk of celiac disease was dose-dependent. That is, more antibiotics correlated to higher celiac rates of celiac disease, and vice versa. The data did not single out any one antibiotic, or narrow the age window within the first year of life. Rates were similar for infants who had been hospitalized versus those who had not. This study was both large and comprehensive. The findings provide more evidence that childhood exposure to systemic antibiotics in the first year of life may be a risk factor for later celiac disease. Read more at Gastroenterology The research team included Stine Dydensborg Sander, MD, PhD, Anne-Marie Nybo Andersen, MD, PhD, Joseph A. Murray, MD, Øystein Karlstad, MSci, PhD, Steffen Husby, MD, DMSci, and Ketil Størdal, MD, PhD. They are variously affiliated with the Hans Christian Andersen Children’s Hospital, Odense University Hospital, Denmark, the Department of Clinical Research, University of Southern Denmark, Denmark, the Department of Public Health, University of Copenhagen, Denmark, the Division of Gastroenterology and Hepatology, Mayo Clinic, USA, the Department of Non-Communicable Diseases, Norwegian Institute of Public Health, Norway, and the Department of Pediatrics, Ostfold Hospital Trust, Norway.
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Celiac.com 10/12/2012 - What is the relationship between breastfeeding, the age of gluten introduction and rates of celiac disease? A number of studies have shown that increased breastfeeding may provide some protection against celiac disease. However, one study found no change in the overall prevalence of celiac disease in breastfed infants compared to controls, suggesting that breastfeeding may only delay the presentation of the disease but, does not prevent it. Other studies show no significant difference in the prevalence of celiac disease between breastfed and non-breastfed patients. Data from the Swedish celiac disease epidemic suggest a 3% prevalence of celiac disease in the children born during the epidemic. An analysis by Ivarsson et al. of children born during the epidemic, found that children under 2 years of age had a lower risk of celiac disease if they were still being breastfed when dietary gluten was introduced (odds ratio 0.59, 95, with a confidence interval 0.42–0.83). Children who continued breastfeeding after gluten was introduced to their diet showed a further decrease in the risk for celiac disease (OR 0.36, 95% CI 0.26–0.51). A meta-analysis that included the Ivarsson data, showed celiac disease risk was significantly lower in infants who were breastfed at the time of gluten introduction (pooled OR 0.48, 95% CI 0.40–0.59), compared to infants who were not breastfed at the time of first gluten exposure. A later study, by Akobeng and others, estimated that breastfeeding all babies in the UK at the time of gluten introduction, would prevent 2500 cases of celiac disease every year. The best data currently available on celiac disease and the age of gluten introduction comes from a prospective study by Norris et al. The study followed 1560 children in Denver between 1994 and 2004. This study showed that children exposed to gluten in the first 3 months of life had a fivefold increased risk of having celiac disease than children exposed to gluten between 4 and 6 months of age, while children exposed to gluten at 7 months old or later had an almost twofold increased risk compared with those exposed at 4 to 6 months (hazard ratio 1.87, 95% CI 0.97–3.60). When the analysis was limited to biopsy-diagnosed celiac disease, the hazard ratio was 23.97 (95% CI 4.55–115.9) for children exposed to gluten during the first 3 months of life compared to the 4–6 months exposure group, and 3.98 (95% CI 1.18–13.46) in the group exposed at 7 months or later What remains unclear, is whether breastfeeding and the age of introduction of gliadin prevent celiac disease or merely delay its onset. To clarify the relationship between breastfeeding, the age at which gluten is introduced into the diet, and celiac disease, the EU has funded a prospective study, called PREVENTCD, FP6, in 10 European centers. The PREVENTCD study recruited pregnant women with a family history of celiac disease, and determined HLA4 of the newborn at birth. By the end of December 2010, researchers had recruited a total of 1345 children at birth and enrolled 986 with positive HLA DQ status. Researchers instructed mothers to breastfeed for 6 months, if possible. Beginning at the age of 4 months, the researchers placed the infants into randomized study groups, and fed them 100 mg of gliadin or a non-gliadin placebo every day. The full data won't be available until all children reach the age of 3 years of age, but the researchers hope that the study will offer definitive answers on the relationship between breastfeeding and the age of gluten introduction and rates of celiac disease. Until new information become available, the ESPGHAN Committee on Nutrition recommendations remain in effect. This recommendations state that gluten should be introduced to infants no earlier than 4 months of age, and no later than 7 months, and that the introduction should be gluten be made while the infant is still being breastfed. This information was compiled by researcher R. Shamir of the Institute for Pediatric Gastroenterology, Nutrition and Liver Diseases, at the Schneider Children's Medical Center of Israel, Petah Tikva, affiliated with Sackler Faculty of Medicine, Tel Aviv University in Ramat Aviv, Israel. Source: Isr Med Assoc J. 2012 Jan;14(1):50-2.
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. 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. 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. 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. 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. Prior to that, a paper published on Celiac.com 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 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:  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  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  Vitamin D Preserves the Intestinal Mucosal Barrier Roy S. Jamron https://www.celiac.com/articles/21476/  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  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/  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  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  Are Commensal Bacteria with a Taste for Gluten the Missing Link in the Pathogenesis of Celiac Disease? Roy S. Jamron https://www.celiac.com/articles/779/