Researchers want to engineer intestinal microbiome to prevent childhood eczema
Researchers are to study what happens in the intestines of very young infants when they develop childhood eczema. Their goal is to find bacteria that can stop the disease from developing in the first place.
The number of children with childhood eczema – also called atopic dermatitis – has drastically increased in the Western world over the past 50 years. Today, approximately 30 per cent of all children develop the disease, and half of these children develop the first symptoms before they turn one year old.
There is currently no way of curing childhood eczema, and no exhaustive understanding of how hereditary and environmental factors might trigger this chronic skin condition.
Nevertheless, recent research suggests that bacterial development in the intestine during with the transition from a liquid to a solid diet may play an important role.
Associate Professor Clarissa Schwab from the Department of Biological and Chemical Engineering at Aarhus University is working on the project. She researches into the intestinal microbiome, and has spent the last couple of years developing biological technologies, which she uses in experiments to manipulate the composition of microorganisms in our digestive tract.
"The neonatal intestinal microbiome appears to play a crucial role in the development of atopic diseases, and there are many indications that the solution to treat childhood eczema can be found by taking a closer look at the composition of microorganisms," she says.
Indigestion may be an explanation
Since 2018, Clarissa Schwab has collaborated with a Swiss university hospital on a comprehensive birth cohort study (Childhood, Allergy, Nitrion and Environment - CARE) that includes more than 200 infants.
The study followed the infant participants during their first years of life with aim to examine the relationship between diet, microbiota and the development of allergic diseases.
Parents were asked to write a diet diary and collect stool samples from the children when they were 90, 180 and 360 days old. These helped the researchers study the development of the intestinal microbiome over time and then compare the results of healthy infants with those from infants who developed childhood eczema.
"What we saw was very interesting," Clarissa Schwab says.
She continues:
"We registered major changes in the composition of microorganisms in the intestines, particularly in connection with the transition from liquid to solid food. These changes enable children to break down a greater variety of food, which is entirely normal."
However, some of the children in the study appeared to be better at digesting a regular solid diet than others. They had a higher incidence of certain intestinal bacteria that are crucial for converting fibre and complex carbohydrates from food into short-chain fatty acids.
This caught the researchers’ attention.
One of the short chain fatty acids that Clarissa Schwab’s research group is now focusing on is butyric acid.
Butyric acid under the microscope
Butyric acid aids well-functioning intestinal mucosa, counteracts inflammation and keeps pathogenic bacteria at bay. It also has a beneficial effect on the immune system. In the CARE cohort study, researchers discovered that infants with a low or delayed potential for producing butyric acid had an increased risk of developing childhood eczema.
On the other hand, researchers also found a surprisingly strong correlation between a high incidence of these metabolites in stool samples and healthy skin. This means they can now add childhood eczema to the long list of diseases related to the human intestinal microbiome.
"There were no occurrences of childhood eczema in the children with high levels of butyric acid," Clarissa says.
“This calls on us to continue working with our findings to see if it’s possible to engineer infant intestinal microbiomes so they don’t develop childhood eczema,” says Clarissa Schwab.
Biotherapeutic bacteria to prevent disease
In a new project funded by the Leo Foundation, the researchers from Aarhus University together with their colleauges from University of Copenhagen and a university hospital in Schwitzerland will carry out a number of studies to learn more about the connection between the diet and microbiome of infants and the development of childhood eczema in early childhood.
"We don’t know whether butyric acid is important for immune regulation of skin cells, or whether it’s the intestinal cells that cause the immune system to overreact by creating an allergic response in the skin. All in all, we’d like to gain a clearer understanding of the disease at a microbiological level, so that we can ultimately design a new form of treatment for the affected children. That's what we're striving for," says Clarissa Schwab.
The composition of the intestinal microbiome is extremely complex, which is why a number of animal studies (in vivo) and some very accurate artificial models (in vitro) of the gastrointestinal system are required to study the function and interaction of the bacteria.
In recent years, Aarhus University has set up a number of experimental facilities that make it possible for researchers to begin manipulating intestinal microbiomes with unique approaches.
"We’ll have some really good opportunities to suggest new biological therapies once we know exactly how to influence the intestinal microbiome to reduce the risk of childhood eczema," says Clarissa Schwab.
What the researchers did
The researchers from Aarhus University received stool samples from the infants in the study three times during their first year of life.
The researchers analysed these samples using cultivation and marker gene sequencing to identify alterations in microbiota composition during the first year of life, and to compare the composition in healthy infants with children with atopic dermatitis.
They also measured the levels of different short chain fatty acids (the substances produced by intestinal bacteria when breaking down food) in the samples by using high-pressure liquid chromatography.
Their studies showed that especially intestinal bacteria that produce butyric acid (butyrate) influence the development of atopic dermatitis in early childhood.
Over the next three years, the researchers will continue to work with butyric acid and try to design microbiome engineering strategies that can reduce the risk of developing childhood eczema.
Contact
Clarissa Schwab, the department of Biological and Chemical Engineering, Aarhus University
Background information
The research is based on studies from the Swiss birth cohort (Childhood, Allergy, Nutitrion and Environment - CARE) and previous publications:
https://ami-journals.onlinelibrary.wiley.com/doi/full/10.1111/1751-7915.14165
https://onlinelibrary.wiley.com/doi/full/10.1111/all.15440
In the new project, researchers will carry out a number of intervention studies to learn more about the connection between infants' diet, microbiome and the development of childhood eczema in early childhood.
The project title is Dysregulated immune homeostasis through altered glycans in inflammatory skin diseases, and it has received funding from the Leo Foundation.
The researchers declare that there are no conflicts of interest in connection with this research.