Endotoxin, Food Allergen Sensitization, and Food Allergy: A Complementary Epidemiologic and Experimental Study

The epidemiologic aspect of the study aimed to describe the association between exposure to house dust endotoxin and sensitization to food allergens, while the experimental component compared the measurement of cytokines secreted from peripheral blood mononuclear cells (PBMCs) after stimulation with endotoxin in allergic and nonallergic children.

6963 participants, ages 1 to 84 years, from the 2005–2006 NHANES were included in the epidemiologic study. Twenty-one children (ages 1–19 years) from pediatric clinics at the Mount Sinai Health System with food allergy to either egg, milk or peanut, and healthy controls were included in the experimental study.

Dust endotoxin measurement in the household was obtained from the bedroom, with the amount of endotoxin units per sieved dust weight calculated. Serum-specific IgE levels of egg white, cow’s milk, and peanut were measured, with food allergen sensitization defined as a serum-specific IgE level ≥ 0.35 kUA/L. Clinical symptoms of food allergy were not reported in NHANES participants. Food allergen sensitization and log-10–transformed endotoxin level were compared using logistic regression models. The measurement of cytokines produced from PBMCs after endotoxin stimulation were obtained for children recruited from Mount Sinai with food allergy to either egg, milk or peanut (five patients per allergen) and 6 healthy controls, without clinical history of food allergy.

The geometric mean household endotoxin level was 15.5 EU/mg, with the highest mean seen in children compared with adults among NHANES subjects. The endotoxin levels were found to be higher in those with a positive wheezing history in the past year. Of the study population, 13.5% were found to be sensitized to one or more foods, and this sensitization was more common in 1–5 year-old children. Milk sensitized participants had higher geometric mean endotoxin levels compared with those without milk sensitization (22.4 EU/mg vs 14.8 EU/mg), as did egg sensitized participants compared with those without egg sensitization (19.1 EU/mg vs 15.2 EU/mg). No significant difference in endotoxin levels when comparing peanut sensitized vs non-sensitized patients was seen. The experimental study found lower levels of secreted interferon γ from PBMCs stimulated by endotoxin in egg and milk sensitized patients compared with controls, but no significant difference in peanut sensitized patients.

The odds of milk and egg sensitization are increased with exposure to higher house dust endotoxin levels. There is a decrease in Th1–specific cytokine response, specifically interferon γ secretion, in subject sensitized to egg and milk.

There have been mixed reports regarding the relationship between endotoxin exposure and risk of development of food allergy. This study highlights the need for further study of the role of endotoxin exposure and food allergy development. Additionally, the decreased secretion of the Th1 cytokine, interferon γ, in food sensitized patients underlines the skewing of the immune response toward a Th2 response in milk and egg sensitized patients. Due to the small sample size, further studies are needed to investigate the effects of age of exposure and specific food allergy, as this was not seen in peanut allergy patients. This may result in improved understanding of the role of the environment on the development of food allergy with the goal of prevention.