Skin injury may bring on food allergies

eczema — Credit: Unsplash/CC0 Public Domain

There’s a mysterious connection between our skin and our guts, specifically when it comes to food allergies. For reasons scientists don’t fully understand, chronic skin conditions such as eczema are linked to food allergies; while the national prevalence of childhood food allergies is only around 8%, that prevalence rises to 30% in children with eczema. Researchers have discovered that in some cases, eczema can precede food allergies.

Now, a new study led by researchers at Yale School of Medicine (YSM) and published April 4 in the journal Science Immunology introduces a new hypothesis about this link: In mice, skin damage can trigger food allergies.

Working with mice with different kinds of skin injuries, including lacerations and ultraviolet light damage, the scientists found that introducing new food proteins directly into the gut via a feeding tube at the time of skin damage induced new food allergies in the animals. The food had to be new to the animals; they wouldn’t develop allergies to foods they’d previously eaten. And the introduction of the allergen—a substance that causes allergic reactions—had to happen within several hours of the skin injury. Foods introduced the next day seemed to be safe.

Before these findings, it was not clear whether events taking place so far apart from each other in the body could be linked through the immune system to trigger an allergy, the researchers said.

“It’s a mindset change that these things don’t have to happen in the same place in the body,” said Daniel Waizman, Ph.D., a former YSM doctoral student and lead author on the study, who is now a postdoctoral researcher at the University of California, San Francisco. “We need to take a closer look at how these different organ systems talk to each other.”

A skin–gut connection

Some have speculated that allergens could enter the body through damaged and inflamed skin, leading to an allergy which can result in life-threatening anaphylaxis when food containing those allergens is later eaten.

But this idea didn’t sit right with the two senior authors of the study—Anna Eisenstein, MD, Ph.D., assistant professor of dermatology, and Andrew Wang, MD, Ph.D., associate professor of internal medicine (rheumatology). Both Wang and Eisenstein had young children who were relatively new to solid food around the time they initiated the study.

“Anna and I had chatted about this concept and agreed that, generally, our kids didn’t like to smear food on inflamed and damaged skin because it hurts,” Wang said. “So the three of us wondered if there were other ways that the immune system could ‘remember’ something you ate as being dangerous, a possibility which people may have overlooked.”

The existence of food allergies is somewhat of a scientific conundrum because the gut tends to be tolerant, immunologically speaking. The immune environment in our digestive tracts evolved so we can safely eat a wide variety of foods and to allow foreign but beneficial bacteria to take up residence in our guts. If food allergies are actually due to an immune reaction in a different organ altogether, such as the skin, that could partially explain this conundrum.

The researchers tested several kinds of skin injuries, including puncture wounds and sunburns, at the same time as feeding mice ovalbumin, an egg white protein that is a common food allergen, through a feeding tube. Even though different kinds of skin damage trigger different forms of immune responses, all seemed to induce a food allergy to the egg white protein in mice that hadn’t previously been exposed to this protein.

Environmental exposure through damaged skin was not a requirement, as animals that were exposed to ovalbumin in their environments but not directly fed the protein did not develop an allergy.

The scientists identified several cytokines—molecules released by the immune system when it is active—that were essential for the development of the egg white allergy. They hypothesize that some form of immune cell is responsible for coordinating signals between the skin and gut to trigger the allergy and are currently working to pin down the identity of those go-between cells.

Although their findings may not have direct relevance for treating human food allergies, they do remind us not to ignore skin damage, the researchers said. Food allergies are not the only internal ailment tied to skin injuries; inflammatory bowel disease and rheumatoid arthritis have also been linked to eczema, and the skin condition psoriasis increases the risk of heart disease.

“As a dermatologist, to me these findings really highlight the importance of treating inflammation on the skin,” said Eisenstein. “Treating skin disease is more than just treating what you see, but also the inflammation within and the potential for other systemic diseases.”

More information:
Daniel A. Waizman et al, Skin damage signals mediate allergic sensitization to spatially unlinked antigen, Science Immunology (2025). DOI: 10.1126/sciimmunol.adn0688

Provided by
Yale University