Gluten Introduction and Development of Celiac Disease

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Celiac disease remains one of the most common autoimmune diseases, affecting approximately 1% of the population in the United States. Celiac disease is genetic; having a first degree relative with it means you are about ten times more likely to develop the disease. However, almost one third of the U.S. population has the genetic components of the disease, indicating that there are other factors involved with the development of the disease. A common hypothesis for one of these factors is the time of introduction of gluten into the diet as an infant. Previous studies have suggested that the risk of developing celiac disease is decreased if gluten is introduced into the diet around the time of 4-6 months. This hypothesis primarily resulted from the 1980’s epidemic of celiac disease in Sweden. Two research groups tested out this potential window of opportunity in an effort to better understand why celiac disease develops in some children but not in others.

Both studies were published by the New England Journal of Medicine on October 2, 2014. The first was titled “Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children,” and had contributions from 19 authors, including Dr. Alessio Fasano, one of the members of Celiac Disease Foundation’s Medical Advisory Board. The second article, “Randomized Feeding Intervention in Infants at High Risk for Celiac Disease” had 33 contributing authors.

The first article took several hundred infants with a high risk for developing celiac disease based on their genetics and family history, and divided them into two groups. The first group received gluten in their diet starting at six months, while the second group had gluten introduction delayed until 12 months. The primary outcome measured in the experiment was the incidence rate of celiac disease in the children, measured at multiple years of age.

The authors found that there was no significant increase in risk of developing celiac disease in either group after five years had passed. Children in group A (the group that had gluten introduced at six months) initially had a higher rate of celiac disease, but it leveled out as time went on in the experiment. The only factor that was associated with developing celiac disease was having two copies of the HLA-DQ2 allele.

The second group of researchers took a different approach to the problem. Instead of separating the children by diet, the authors exposed certain children to small amounts of gluten between the ages of four and six months, while other children were given a placebo. The experimental group was given 100 mg of gluten daily for eight weeks. The primary outcome again was the development of celiac disease later in life. Over 1,300 children were initially selected, but after exclusions and dropouts, the experimental group included 475 children, while the placebo group contained 469. At the end of the study, 80 children were diagnosed with celiac disease.

Once again, the authors found no protective effect resulting from the introduction of gluten in the hypothesized window of opportunity at 4-6 months of age. Both the experimental and placebo groups had similar incidence rates of celiac disease. Interestingly, when the researchers categorized the children by gender, there was a difference between the experimental and placebo group for girls. The authors suggest that this may simply be due to chance, as there were more girls with the higher risk genotype in the placebo group.

The group also recorded data on breastfeeding and found no link between breastfeeding and developing celiac disease. Breastfeeding, exclusively or supplementary, did not increase the risk of developing celiac disease, nor offer any protection from it.

This study was randomized, double-blinded, and placebo-controlled, and showed no association, negative or positive, between gluten introduction into the diet, and developing celiac disease. This finding agrees with the previous experiment mentioned in this article, and together, these studies present strong evidence against the hypothesis of a potential protective effect caused by introducing gluten in the suggested window of opportunity at 4-6 months. Though these papers did not find an answer to why certain genetically susceptible people develop celiac disease and others do not, they still progress the search for a cure.