A recent study published in The American Journal of Clinical Nutrition investigated the hypothesis that higher gluten intake during early childhood may be associated with a higher risk of developing celiac disease autoimmunity (CDA) and celiac disease. They further evaluated dietary patterns independent of gluten for their relative contributions to CDA and celiac disease risk in children genetically predisposed to these conditions. Results from their large cohort, long-term study revealed that high vegetable fats and milk intake at age nine months was associated with reduced CDA risk. At age 24 months, high vegetable fats, juices, and wheat intake increased CDA risk, which was exuberated by low milk, meat, and oats consumption. These findings establish the association between diet and autoimmune risk in genetically susceptible children during the first two years of their lives.
Study: Associations of dietary patterns between age 9 and 24 months with risk of celiac disease autoimmunity and celiac disease among children at increased risk. Image Credit: Galigrafiya / Shutterstock
Celiac disease and diet
Celiac disease is a chronic autoimmune disorder characterized by an immune reaction to dietary gluten, resulting in damage to the small intestine's lining. Symptoms include diarrhea, bloating, fatigue, anemia, and, in severe cases, osteoporosis. Celiac disease is a common condition estimated to affect 1.4% of all humans globally. Research has identified the human leukocyte antigen (HLA)-DQ2 and DQ8 haplotypes as being strongly associated with the disease. However, this genetic predisposition accounts for only half of the overall disease risk, suggesting that environmental exposure (diet) plays a significant role in disease manifestation.
Studies on the association between dietary patterns (total dietary exposure) and subsequent health outcomes are superior to conventionally studied single food/nutrient investigations, as they help establish the synergistic effects between multiple nutrients. For example, western diets, composed of higher quantities of sugar, saturated fats, and ultra-processed foods alongside lower fiber intake, have been associated with enhanced risk of proinflammatory biomarkers and allergic risk compared to traditional diets rich in minimally processed foods and higher fruits and vegetables.
Recent research has identified high dietary exposure to pasta, potatoes, vegetables, and rice, alongside lower intake of sweetened beverages and refined cereals, as beneficial to children susceptible to celiac disease autoimmunity (CDA). However, this study included a small cohort, was short-term, and has yet to be verified by follow-up research, necessitating a comprehensive analysis of the dietary patterns responsible for CDA risk and those that may confer resistance against the condition.
About the study
In the present study, researchers aimed to investigate the associations between early childhood (9 to 24 months) dietary patterns that impacted CDA and celiac disease risk in children genetically predisposed to these conditions. Participants were enrolled from the Environmental Determinants of Diabetes in the Young (TEDDY) cohort, across the United States (US), Sweden, Germany, and Finland. TEDDY comprises 8,676 children genetically susceptible to type 1 diabetes, of which 6,677 were recruited into the present study, with the remaining excluded due to a lack of dietary data or clinical celiac disease screening.
Three-day food records were used to assess daily dietary intake. These composite records were collected at 9, 12, 18, and 24 months of age and, during analysis, were disaggregated and recategorized into one of 27 food cohorts based on the preexisting TEDDY database. A total of 22,410 records were collected for this study.
The radiobinding assay was used to assess tissue transglutaminase autoantibodies (tTGAs) as a proxy for celiac disease prevalence. Screening was first conducted at 24 months of age, with follow-up screening every subsequent three months. In children positive for CDA at 24 months, routine blood samples collected as a part of the TEDDY methodology were analyzed to identify the first instance of seropositivity.
"CDA was defined as tTGA-positive in 2 consecutive samples at least 3 mo apart. Celiac disease was defined as either having a small intestine biopsy showing a Marsh score ≥2 or in children who did not undergo an intestinal biopsy, having a mean tTGA concentration ≥100 U/L in 2 consecutive samples."
Statistical analyses involved using principle component analysis (PCA) to evaluate dietary patterns of children at months 9, 12, 18, and 24. Food groups were coded as predictors and dietary patterns as components, with the exploratory analyses attempting to resolve predictors that explained maximum variation in the observed data. Individual adherence scores were calculated for each child to estimate their dietary intake in relation to their identified dietary pattern.
Finally, Cox proportional hazards regression was employed to elucidate associations between dietary adherence (for each age period) and CDA/celiac disease risk. Regression models were corrected for risk factors previously reported as being associated with CDA. These association analyses were only carried out for individuals with complete genetic, clinical, and dietary data.
This study revealed that dietary patterns during the first 24 months of a child's life significantly increased their risk of contracting CDA or celiac disease. The associations elucidated were independent of their quanta of gluten intake, suggesting that additional dietary factors following weaning may contribute to CDA and celiac disease in children.
The 'Vegetable fats and Milk' dietary pattern at nine months of age was associated with reduced CDA risk, even after adjusting for overall gluten intake. Children from the US and Finland showed the most robust adherence to this dietary pattern. Surprisingly, vegetable fats (alongside wheat consumption) at 18 and 24 months resulted in increased CDA risk, though this association was weaker than that at nine months.
The dietary pattern 'Meat, Rice and GF grains' depicted reduced risk of celiac disease at age 18 months. Similar to results from the CDA analyses, at 24 months, 'Vegetable fats and Milk' dietary patterns showed a direct positive association with increased celiac disease risk.
"The dietary pattern "Wheat and Vegetable fats" at age 24 mo was associated with increased risk of both study outcomes, and the gluten intake from this pattern further attenuated the association. This was in line with an Italian study in which a more Western-like diet with higher intakes of wheat and juice and lower intakes of legumes and milk in the second year of life were demonstrated in children later diagnosed with celiac disease."
Contrasting previous studies, the present research was unable to confirm the hypothesis that Western diet and lifestyle significantly increase CDA and celiac disease risk, while "prudent" diets comprising high oats, rice, meat, and potatoes reduce this association. Research has identified higher maternal (proxy for offspring intake) fiber intakes, especially from fruits, as reducing celiac disease risk.
In the present study, researchers aimed to investigate the associations between early-life dietary patterns and CDA or celiac disease risk in a large cohort (TEDDY), long-term (24 months) analysis. Their findings reveal that adherence to specific dietary regimes during the first two years of life can significantly alter CDA/celiac disease risk, independent of gluten intake. Significantly, wheat, juice, vegetable fats, and processed meats were associated with higher CDA and celiac disease risk. This association was exuberated by low milk, oats, meat, and legume consumption during the second year of a child's life.
"Although gluten intake is critical in affecting risk of celiac disease in early childhood, nongluten dietary factors should also be considered, and more research is needed to further define these associations in children at genetic risk."
- Hård af Segerstad, E. M., Mramba, L. K., Liu, X., Uusitalo, U., Yang, J., Norris, J., Virtanen, S. M., Liu, E., Kurppa, K., Koletzko, S., Ziegler, A. G., Toppari, J., Rewers, M., Akolkar, B., Krischer, J. P., Aronsson, C. A., & Agardh, D. (2023). Associations of dietary patterns between age 9 and 24 months with risk of celiac disease autoimmunity and celiac disease among children at increased risk. The American Journal of Clinical Nutrition, DOI – https://doi.org/10.1016/j.ajcnut.2023.08.009, https://www.sciencedirect.com/science/article/pii/S0002916523660794