Atopic march has long been recognized as the progression from atopic dermatitis (AD) to food allergy (FA) and asthma during infancy and childhood. However, effective blocking is hampered by the lack of specific biomarkers.
In this study, we aimed to investigate the pathological progression of atopic march trajectories from the skin to the gut.
We built an atopic march mouse model by mechanical skin injury and percutaneous sensitization to peanut allergen. Anaphylaxis from the skin to the small intestine was then investigated by ELISA, RNA-Seq, quantitative real-time PCR, histopathology analysis and flow cytometry. The findings from the mice results were also verified by the serum samples of allergic pediatric patients.
After modeling, inflammation in the skin and small intestine manifested as a mixed type of T2 and T17. Further analysis identified elevated succinate in the circulation and expanded tuft cells with upregulated IL-25 in the small intestine, resulting in increased intestinal Type-2 innate lymphoid cells and an enhanced Type 2 inflammatory response. In addition, free mitochondrial DNA (mtDNA) released after tissue damage was also involved in inflammation march from injured skin to small intestine through STING pathway. Analysis of clinical samples verified that serum concentrations of succinate and mtDNA were higher in AD allergic children than non-AD allergic children.
Our study demonstrates succinate and mtDNA play key roles in skin-to-gut crosstalk during atopic march from AD to FA and can be considered as biomarkers for risk assessment or targets for atopic march prevention strategies.

Copyright © 2022. Published by Elsevier Inc.