New research on the microbiome, the family of all microbes that live on the body, has uncovered clues about why we experience allergic reactions and may pave the way for new early-life strategies for the prevention of allergic diseases.

The research, run jointly by scientists from Monash University and Switzerland’s University of Lausanne, examined allergic reactions to dust mite in the skin and lungs of both adult and newborn mice within the lab.

While allergic responses were triggered in the lungs of mice of both age groups, researchers found that only adult mice with a mature microbiome had a reaction on their skin.

The paper1, which was published in The Journal of Allergy and Clinical Immunology, thus suggests that the microbiome has a key but complicated role to play in how our immune system responds to and protects us from allergens.

Lead author of the paper, Professor Benjamin Marsland, said it was “striking” that scientists still did not understand why some children developed allergies such as atopic dermatitis, a condition which makes the skin red and itchy, and asthma.

“The skin is not just an important barrier but a site at which key immunological decisions need to be made. Should I respond to this allergen, or ignore it? Understanding the rules that govern this process might be key to developing preventative approaches, and we’ve been striving to uncover these rules,” he said.

Sensitisation and reaction

In order to uncover more about the link between the skin’s microbiome and allergic reactions, Professor Marsland together with collaborators in Norway and Sweden originally looked at whether atopic dermatitis in a child’s first year of life could be reduced by applying skin emollients during infancy.

While this first paper2, published earlier this year in The Lancet, showed a negative result, the Monash team was not disheartened and moved onto more generalised research, examining the mechanisms behind atopic dermatitis.

In this later research, both newborn and adult mice were sensitised to one of the most common household allergens, house dust mite. Allergic reactions were then tested on both the skin and in the lungs.

“Sensitisation is essentially the priming and activation of cells, such that the next time they see the allergen, e.g. house dust mite, they will fight against it by producing inflammatory factors,” Professor Marsland told Lab Down Under.

While this type of response helps our bodies fight against pathogens such as viruses and bacteria, some people had the same unwanted response against allergens which resulted in an allergic disease, he said.

The researchers then examined the skin and microbiome of the sensitised mice, including RNA sequencing and genetic analysis, to determine the precise types of skin cells found in the adult and newborn mice.

An education about allergens

What was discovered was that the adult mice had an inflammatory response in both the skin and the lungs. This skin response was missing from the newborn mice however.

This showed that the microbiome had been able to “educate” the cells of older mice over time. In essence, this led to the production of local messenger molecules called chemokines that recruit what are known as antigen presenting cells (APCs). These APCs flag pathogens or allergens to the immune system, creating an inflammatory response.

While the skin microbiome could thus create an overreaction leading to an allergic response, these signals were not always bad and were often a necessary part of the immune system’s function in defeating pathogens, Professor Marsland said.

“Generally, these types of signals are important for maintaining healthy tissue, and it is only when you have an exaggerated response, for example when there is an infection, that these signals lead to local inflammation,” he told Lab Down Under.

“We need to be careful about concluding the microbiome is harmful as that could be misinterpreted. However, the microbiome does lead to the maturation of immune cells and as a consequence, those immune cells are ready to respond to various exposures such as an infection with a pathogen, or in the experimental model we used, to respond to allergens on the skin.”

The study also suggested that the microbiome had further benefits, increasing the integrity of the skin barrier function which actually prevents allergens from penetrating the skin.

With further research, this may lead to treatments such as “skin microbial transfers” which could help better protect newborn babies from allergens in the environment, Professor Marsland said.

The search for ‘simple’ solutions

While the Monash research was conducted on mice, Professor Marsland said the findings highlighted the impact that the skin microbiome in humans had on both barrier function and immune function in the skin.

“It essentially validates the idea that we should be investigating further which microbes on the skin of humans can influence skin barrier integrity and the immune system. Based on that, we might be able to design effective intervention strategies, e.g. one based around ‘skin probiotics’.”

The paper also suggested that what happened on the skin had important implications for the types of allergic responses that occurred within the lungs.

How the different organs communicated, both immunologically and microbiologically, is an important area of research that Professor Marsland said his team was currently investigating.

“The skin remains one of the most accessible body sites for intervention studies, so I hope that there will be many clinical studies in the future, where we’ll start looking at how skin microbes could be at the heart of good health.”

Finding “simple” solutions such as these to prevent diseases such as allergies including atopic dermatitis and asthma was appealing, Professor Marsland said, and could lead to better preventative measures in the future.

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1 Ubags N, Trompette A, Pernot J, Nibbering B, Wong N, Pattaroni C, Rapin A, Nicod L, Harris N, Marsland B. Microbiome-induced antigen-presenting cell recruitment coordinates skin and lung allergic inflammation. The Journal of Allergy and Clinical Immunology, July 2020.

2 Skjerven H, Rehbinder E, Vettukattil R, LeBlanc M, Granum B, Haugen G, Hedlin G, Landrø L, Marsland B, Rudi K, Sjøborg K, Söderhäll C, Staff A, Carlsen K, Asarnoj A, Bains K, Carlsen O, Endre K, Granlund P, Hermansen J, Gudmundsdóttir H, Hilde K, Håland G, Kreyberg I, Olsen I, Mägi C, Nordhagen L, Saudners C, Skrindo I, Tedner S, Værnesbranden M, Wiik J, Jonassen C, Nordlund B, Carlsen K. Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial. The Lancet. 2020 March 21;395(10228):951-961.

Featured image: Child with Eczema. Picture by NIAID. Used under the Creative Commons Attribution 2.0 Generic (CC BY 2.0) licence.

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