Atopic Dermatitis

If you have AD, chances are it started when you were a baby. According to the National Eczema Association, about 9.6 million American children and 16.5 million adults suffer from AD. The condition has been studied extensively, and genomic mapping has found that many people with eczema and/or AD have a mutation that changes the barrier function of filaggrin, a protein found in the epidermal layer of skin. The mutation reduces the skin’s ability to retain water and raises its pH level. This means that the skin can’t fully perform its duties of keeping outside agents—like toxins and bacteria—from penetrating the body. [1]

AD involves two major biological pathways in the body: barrier dysfunction (from the filaggrin mutation) and an overactive immune (allergic) response. It’s well-known that people who have AD tend to develop other allergic conditions like allergic rhinitis (hay fever) or asthma. Because these three conditions share many of the same inflammatory and immune system processes, they form the “atopic triad.” Even if you don’t suffer from the other two conditions, take a few minutes to read our articles on Allergies and Allergic Rhinitis, which will give you a broader understanding of allergic conditions.

As in allergic rhinitis and asthma, the immune responses in AD begin with sensitization to an allergen and the production of IgE antibodies. That sets in motion various immune cells, which can be either pro-inflammatory or anti-inflammatory. Ideally, the body is able to quickly tone down the pro-inflammatory processes and restore a balance. T helper cells are an important part of this balancing act. Th1 cells lower the inflammatory response while Th2 cells result in the production of pro-inflammatory cytokines. In allergic conditions like AD, the Th2 side is dominant, resulting in chronic inflammation.

Although AD is a very visible illness because it changes the skin’s appearance, there’s more to it than meets the eye. In fact, the important mechanisms that produce the itching and discomfort happen in the microscopic world of bacteria where both good and bad actors perform a complex drama.

The main character, Staphylococcus aureus, mostly sows mayhem. Although S. aureus is a normal inhabitant of most people’s skin, the wide diversity of other microorganisms usually keeps it from getting out of line. In AD, though, S. aureus gains too much prominence, and the quantity of beneficial bacteria on the skin’s surface decreases. This relative vacuum allows S. aureus to send out a half-dozen different types of molecules through the skin and into the body. Like microscopic henchmen, these molecules set out to wreak havoc by producing inflammation in a variety of ways. [2]

The result? Itching, swelling, redness, discomfort, and pain. Stated another way, dysbiosis of the skin microbiome disrupts the normal balance in the skin, which produces the signs and symptoms of AD.

Ah! But the plot thickens! It’s not just the microbiome on the skin that causes the inflammation of AD. Other invisible actors on a distant stage—the intestinal tract—play an important role as well. The microorganisms that live in the gut interact with the nervous system and immune system. Through the biological molecules they produce, they send messages to the lungs, brain, and skin. The cross-talk among the gut, immune system, and skin creates what’s called the gut-skin axis.

If you have AD, you’ve probably noticed that it can flare up when it’s least welcome—when you’re under stress from work, school, family, or relationships. It seems the more stressed you feel, the itchier you get. As mentioned above, the gut microbiome produces neurotransmitters, and those important molecules find their way to the brain where they influence mood and thinking. A variety of feedback loops occur between the gut and the brain, and these are known as the gut-brain axis. Since the gut microbiome communicates with both the brain and the skin, these three are constantly intertwined.

The gut microbiome helps regulate cytokine levels in the blood, and cytokines influence brain function, anxiety, and stress responses. [3] It works in the other direction, too, in a feedback loop.

When you feel stressed, your body produces higher levels of cortisol, the stress hormone. Cortisol can produce imbalances in the gut microbiome that can change the permeability of the intestinal lining so that it doesn’t perform its barrier function as well. As a result, the epithelium of the digestive tract allows more products into the bloodstream than it should. Some of these
molecules find their way to the skin, where they can produce inflammation and impair the skin’s barrier function. [3]

Managing your stress can help not just your moods and mental function but also your gut and skin.

About 30% of people who have AD also have food allergies, and recent research suggest that this combination may represent a distinct type of AD. [4] Although the idea that food allergies cause eczema is prevalent and may happen sometimes, with the AD + Food Allergies type, the reverse is true. Dermatitis appears to cause food allergies. When the impaired skin barrier allows antigens to cross into the body through the skin, the body recognizes the foreign invader and creates antibodies. Later when that food is consumed, the immune system reacts, producing inflammation.

Eight potentially problematic foods account for 90% of food allergies in children. [5] They are:

• Cow’s milk
• Eggs
• Tree nuts
• Peanuts
• Shellfish
• Wheat
• Soy
• Fish

Eating these foods when you’re allergic can produce a range of symptoms. Severe food allergies are emergencies that require the use of epi-pens to prevent anaphylaxis. Less severe reactions include tingling sensations in the mouth or throat, breathing difficulties, digestive problems, and skin eruptions. If you know you react to certain foods, you should avoid them, but cutting them out of your diet won’t cure your AD. In fact, you may find that when your AD settles down, you can handle the foods that bother you during an AD flare. Knowing what you can eat and when can be confusing because reactions aren’t always consistent.

Not too long ago, conventional wisdom and pediatric advice agreed that babies shouldn’t be exposed to potential allergy-causing foods. There’s been an about-face on that advice because of recent research. Introducing babies as young as six months old to tiny amounts of eggs, peanuts, wheat, and nuts can prevent them from developing allergies to these foods in childhood.

These findings show that the foods themselves are not the problem. Focusing on the immune system and how to restore the balance between pro-inflammatory and anti-inflammatory processes is more likely to produce lasting relief from the symptoms of AD.

Although you may never have thought about it, the intestinal lining is actually a type of “skin” and performs similar functions. The contents of the digestive tract are “not of the body.” This foreign material must not be allowed to contact the cells, tissues, and bloodstream until it has been properly broken down. That gatekeeper duty belongs to the intestinal lining, called the epithelium, and its “tight junctions”—cells that fit together so tightly that only fully metabolized molecules can pass through.

The same genetic mutation that impairs the barrier function of the skin also impairs the tight junctions of the intestinal tract, allowing larger molecules to enter the bloodstream. [1] The immune system recognizes them as foreign invaders, which sets an inflammatory process in motion. This is another cause of food allergies for people with AD.

Besides genetic mutation, other things can cause increased intestinal permeability—also called “leaky gut.” As stated above, elevated levels of cortisol, the stress hormone, can affect the microbiome and weaken the barrier function of the intestinal lining whether you have AD or not. In fact, anything that alters the balance or diversity of microorganisms in the digestive tract can produce leaky gut and food allergies in people with and without AD.

If you have AD, you’ll want to pay special attention to the health of your digestive tract. Addressing dysbiosis and improving gut health can be a major step in reducing the inflammatory processes that produce your symptoms.

Atopic dermatitis is an inflammatory disorder. Is it possible to correct the overactive immune system response that causes that inflammation? That would be the key to finding relief for dry, itchy, unattractive skin.

First, let’s find the immune system. Do you know where it’s located? Most people would probably say it’s in the blood—where the white blood cells are.

Surprisingly, 70% of the body’s immune cells are found in the gastrointestinal lining and gut-associated lymphoid tissue (GALT). So to address immune system challenges, we must look to the gut.

As we’ve seen, tight junctions and the microbiome play central roles in AD and inflammation. Over the last two decades, research has highlighted the benefits of glutamine and probiotic supplements for both digestive and skin conditions.

L-glutamine is a conditionally essential amino acid that helps keeps the intestinal lining healthy. When taken as a supplement, it has been shown to preserve tight junctions, decrease intestinal permeability, and improve the barrier function of the gut. [6] In vitro research suggests that in people with an AD mutation, glutamine supplementation can correct the T helper cell imbalance and reduce the inflammatory response. [7] Pre-term infants who were given glutamine supplements were less likely to develop AD during their first year of life and at age six. [8]

Since an imbalance of the microbiome is associated with inflammation and AD flares, it makes sense to focus on establishing a healthy, diverse microbiome in the intestinal tract. Research shows that probiotic supplements containing various strains of bacteria can balance the ratio of Th1 and Th2 cells toward less inflammatory responses. [3] Another study showed that Lactobacillus paracasei supplements reduced skin sensitivity and improved barrier function in people with skin problems other than AD. [9]

Because probiotic supplements and l-glutamine support a healthy digestive tract, they can positively impact the immune system and reduce the inflammatory processes of atopic dermatitis.

1 Zaniboni MC, Samorano LP, Orfali RL, Aoki V. Skin barrier in atopic dermatitis: beyond filaggrin. An Bras Dermatol. 2016;91(4):472-478. doi:10.1590/abd1806-4841.20164412

2 Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and Atopic Dermatitis: A Complex and Evolving Relationship. Trends Microbiol. 2018;26(6):484-497. doi:10.1016/j.tim.2017.11.008

3 Lee SY, Lee E, Park YM, Hong SJ. Microbiome in the Gut-Skin Axis in Atopic Dermatitis. Allergy Asthma Immunol Res. 2018;10(4):354-362. doi:10.4168/aair.2018.10.4.354

4 Tham EH, Leung DY. Mechanisms by which Atopic Dermatitis predisposes to Food Allergy and the atopic march. Allergy Asthma Immunol Res. 2019;11(1):4-15. doi:10.4168/aair.2019.11.1.4

5 Bergmann MM, Caubet JC, Boguniewicz M, Eigenmann PA. Evaluation of food allergy in patients with atopic dermatitis. J Allergy Clin Immunol Pract. 2013;1(1):22-28.

6 Rao R, Samak G. Role of Glutamine in Protection of Intestinal Epithelial Tight Junctions. J Epithel Biol Pharmacol. 2012;5(Suppl 1-M7):47-54. doi:10.2174/1875044301205010047

7 Ma CA, Stinson JR, Zhang Y, et al. Germline hypomorphic CARD11 mutations in severe atopic disease [published correction appears in Nat Genet. 2017 Oct 27;49(11):1661]. Nat Genet. 2017;49(8):1192-1201. doi:10.1038/ng.3898

8 van Zwol A, Moll HA, Fetter WP, van Elburg RM. Glutamine-enriched enteral nutrition in very low birthweight infants and allergic and infectious diseases at 6 years of age. Paediatr Perinat Epidemiol. 2011;25(1):60-66. doi:10.1111/j.1365-3016.2010.01173.x

9 Gueniche A, Philippe D, Bastien P, et al. Randomised double-blind placebo-controlled study of the effect of Lactobacillus paracasei NCC 2461 on skin reactivity. Benef Microbes. 2014;5(2):137-145. doi:10.3920/BM2013.0001