New study suggests S. aureus and skin dysbioses cause eczema

Atopic dermatitis, also known as eczema, is a skin inflammation and rash that has an enigmatic cause.  There are many genetic and environmental risk factors involved, but to date the exact triggers and mechanisms that cause this autoimmune response are unknown.  Importantly, a growing percentage of infants and toddlers are developing this disease, which itself is a known risk factor for other autoimmune diseases like asthma and allergies.  Discovering the cause of atopic dermatitis is an important endeavor, because it may lead to a cure for a number of other diseases.

Staphylococcus aureus has long been associated with atopic dermatitis.  It appears to occur at relatively high abundances in the areas of skin that are affected.  Then again, S. aureus is a one of the most common skin microbiome bacteria (it is ubiquitous around the world), and it has yet to be definitively connected to the disease.  In addition, mouse models for many skin diseases, including this one, do not exist or are insufficient, so controllably studying the atopic dermatitis is difficult.  Recently though, a team of scientists from Japan and the NIH developed a mouse model for atopic dermatitis, and made a new discovery that showed S. aureus can indeed drive skin inflammation.  They published their results in Cell immunity.

The scientists were studying how a specific genetic mutation in mice affected bones and hair follicles when they serendipitously realized that it was causing eczema in the mice after around three weeks.  When they investigated the skin microbiomes of these mice, as well as normal mice, they realized that right around the time that the eczema was appearing in the mice, these mice’s skin microbiomes drastically shifted.  First, a bacterium called Corynebacterium mastitidis emerged, followed by S. aureus a few weeks later, which was coincident with the presentation of the worst symptoms.  Of note, species of Corynebacteria are associated with eczema in humans, much like S. aureus.

Next, the researchers then performed a series of experiments by providing mice with antibiotics in an effort to combat the dysbiosis.  When newborn mice with the genetic modification were treated with antibiotics they never developed eczema at all.  Moreover, genetically modified mice that were in the midst of the rash that were treated with antibiotics had their eczema subside soon after.  In addition, genetically modified mice that were taken off of antibiotics had eczema emerge shortly thereafter.  Strikingly, in all of the above situations changes in the skin microbiome corresponded with the disease state: a lack of S. aureus and high diversity were associated with healthy skin, and the emergence of S. aureus and a lack of diversity were associated with the disease.  Finally, when S. aureus was inoculated onto the skin of genetically modified mice, they developed eczema rapidly.

The researchers performed a number of other experiments to try and tease out the mechanism by which S. aureus causes atopic dermatitis.  Their results show that it appears a combination of genetic and environmental factors that affect the skin may be important in defining an individual’s risk for the disease.  Regardless, it appears that S. aureus is a major culprit in causing eczema, so future therapies that eradicate the bacteria, or at least decrease its abundance should be considered.

High salt diet mediates the skin immune response

Salt in our diet has been linked with all sorts of nasty side effects such as hypertension and autoimmune disease.  Researchers from Germany, though, wondered how Na+ in our diet may be affecting the skin microbiome, especially during infection.   Our skin is an important physiological barrier between our body and our microbiome, and because it is partially covered in organisms whenever we get a cut we are at risk for infection.  Fortunately our skin is actually loaded with immune cells that help destroy any of these organisms that may cause harm, and they mitigate the risk for infection.  The German researchers recently discovered that Na+ in our skin may actually be critical for our body to properly fight these infections.  The results were published in Cell Metabolism.

The scientists first infected the skin of both humans and mice with a eukaryotic organism called Leishmania major, which is a common skin pathogen primarily found in Northern Africa and the Middle East.  When they observed the infections using MRI they discovered that the local Na+ concentration around the infection increased in concentration.  They then showed that after treatment of the infection with antibiotics the local Na+ decreased.  

The scientists speculated that the Na+ was perhaps helping to fight the infections, so they designed an experiment to test this hypothesis.  They fed two groups of mice a high salt diet or a no salt diet.  Then they infected the mice with L. major.  They showed that after infection the mice that had not eaten salt struggled to clear the infection, while those that had eaten the high salt diet cleared the infection quickly.  The researchers performed a series of experiments on these mice to learn the actual mechanisms by which salt mediated the immune response, and learned that the Na+ activates and promotes certain immune cells in the skin.

This study shows an unexpected benefit to salt in the diet.  Interestingly, the salt content of our skin increases with age.  While this process has been linked to hypertension, perhaps it also helps fight bed sore infections and other types of skin infections that primarily afflict the elderly.