Dietary deficiencies of unsaturated fatty acids and starch cause atopic dermatitis-like pruritus in hairless mice

Hairless mice fed with a special diet (named HR-AD) show atopic dermatitis (AD)-like pruritic skin inflammation that is almost completely resolved with the supplementation of an unsaturated fatty acid (UFA), the linoleic acid (LA). This suggests that the dietary deficiency of LA is the key cause of this dermatitis. However, because there is no appropriate control diet for HR-AD, the involvement of other dietary ingredients cannot be ruled out. Furthermore, it has not yet been tested whether only UFA deficiency can cause such AD-like pruritus. In this study, using semi-purified custom diets, we attempted to reproduce this syndrome. Four-week-old hairless mice were maintained on a widely used standard diet American Institute of Nutrition-76A (AIN-76A), its modifications, or HR-AD. Several modifications of fat and carbohydrate components revealed that dietary deficiency of both UFAs and cornstarch was required to induce severe skin barrier dysfunction as typically occurred in HR-AD-fed mice. An UFA- and cornstarch-deficient diet caused severe AD-like pruritus comparable to HR-AD, despite weak Th2 immune responses and absence of immunoglobulin E production. On the other hand, a diet lacking UFAs but containing cornstarch significantly alleviated the development of pruritic dermatitis. Furthermore, the supplementation of wheat starch similarly improved skin barrier function. In conclusion, this study showed that a lack of certain starches might also be the cause of diet-induced AD. Our findings could help to reproduce the diet-induced AD itch model and also provide evidence that certain starches can have protective and ameliorative effects on AD-like pruritus.