Researchers Explore Deeper Connection Between AD, Food Allergy

As understanding of the underlying link between atopic dermatitis (AD) and food allergies continues to evolve, researchers of a new paper have explored the skin-gut axis and the coexistence of the 2 conditions.¹

An increasing amount of evidence has suggested that the link between AD and food allergy goes deeper than just sensitization | © Image credit: fusssergei - stock.adobe.com

The connection between AD and food allergies is well established, with 30% of children with moderate and severe AD also developing food allergies.² Data have suggested causation is one-sided, with AD playing a role in the development of food allergies and not vice versa.³ The bank of literature has historically suggested that food antigen exposure through the disrupted skin barrier in AD causes food antigen-specific IgE production and food sensitization. However, an increasing amount of evidence has suggested that the link between the 2 conditions goes deeper than just sensitization.

With an emerging hypothesis that inflammation of the skin prompts intestinal remodeling through various mechanisms, researchers of the new review, published in Mucosal Immunology, explored the role of inflammatory signals, microbiome alterations, metabolites, and the nervous system.¹

“The mechanisms by which inflamed skin communicates to the intestine to modulate the immune environment is an area of ongoing research, but likely involves the systemic circulation of inflammatory mediators,” explained the researchers, adding “Elevated serum IgE is a long-recognized biomarker of AD. Circulating IgE can bind FcεRI on mast cells, basophils, and other myeloid cells, and the low-affinity receptor, FcεRII, on a wide array of hematopoietic cells. Elevated circulating IgE may help to shape the intestinal immune environment by promoting mast cell maturation and survival through engagement of FcεRI.”

Mouse models have suggested that IgE promotes expansion of certain small intestine mast cell populations, including connective tissue mast cells.

Other known inflammatory mediators in AD being investigated for their potential correlation with food allergies include IL-33, IL-31, IL-22, lactate dehydrogenase, and CCL17. CCL17, for example, has been found in increased levels in blood and umbilical cord serum of children who eventually developed AD and food allergies. Mouse models have shown that the absence of CCL17 protects against colitis, suggesting that the inflammatory mediator may drive intestinal inflammation. However, the researchers noted, there remains unknowns about how CCL17 impacts susceptibility to food allergy.

Within the microbiome, a lack of fecal microbial diversity and altered microbial composition have both been observed in the 2 conditions, although investigations into which specific microbial species drive the correlation between AD and food allergy continue. Certain observed associations have suggested that lack of microbial diversity can account for AD and food allergy being more common in infancy and early childhood. For example, behaviors that restrict microbial diversity early in life, such as exposure to antibiotics and being fed with formula, are associated with an increased risk of atopic diseases. Allergy models in mice have shown that germ-free mice or specific pathogen-free mice that receive antibiotics develop more severe allergic phenotypes.

However, the researchers noted, clinical trials testing probiotics, prebiotics, or symbiotics to treat or prevent allergies have come up short.

More recently, interest has increased in the relationship between metabolites and immune regulation. Previous research in AD has shown shifts in various metabolomic pathways areas including the skin, urine, short chain fatty acids, long chain fatty acids, and tryptophan. However, the researchers explained, the cause for these shifts has remained convoluted.

“Some metabolites can even directly interact with microbiota, promoting the growth of some populations while inhibiting the expansion of others. Further complicating matters, the metabolome is heavily influenced by diet and genetics,” described the researchers. “Unfortunately, most human cohort investigations do not incorporate microbiome analysis or dietary surveys to parse out the cause of observed metabolite shifts. Regardless of the cause, metabolome alterations in AD patients may lay the foundation for dysregulated intestinal immune responses, perturbed oral tolerance, and predisposition to FA.”

Research is also increasingly implicating the nervous system in immune responses, particularly at barrier sites, suggesting that AD-associated skin inflammation has implications for neuroimmune networks at other barrier sites, including the intestine. Impairments in the intestine barrier are thought to predispose children to food allergies and with more severe symptoms resulting from increased interaction of the intestinal immune system and food antigens in the lamina propria.

References

1. Davis KL, Claudio-Etienne E, Frischmeyer-Geurrerio PA. Atopic dermatitis and food allergy: more than sensitization. Mucosal Immunol. Published online June 19, 2024. doi:10.1016/j.mucimm.2024.06.005

2. Mehta Y, Fulmali DG. Relationship between atopic dermatitis and food allergy in children. Cureus. 2022;14(12):e33160. 10.7759/cureus.33160

3. Papapostolou N, Xepapadaki P, Gregoriou S, Makris M. Atopic dermatitis and food allergy: a complex interplay what we know and what we would like to learn. J Clin Med. 2022;11(14):4232. doi:10.3390/jcm11144232