Dietary strategies for allergy prevention in children

There is still no treatment that can fully cure children with asthma and allergic diseases. Treatments are concentrated on tackling the symptoms. The symptoms can thus be relieved but the treatments usually have to be taken by patients for very long periods of time or even their whole lives. The best long-term therapy is still the avoidance of the causative allergen, e.g. certain foods.

As yet no effective strategies for preventing allergies have been found by researchers. There is hence a need to develop new approaches.

The prevention of allergies by means of diet in early childhood is one such approach that deserves consideration. Until recently prevention simply involved advising people to avoid certain foods, especially in infancy and early childhood. However, the latest recommendations no longer point in this direction. This is because it has not been proved that leaving out certain foods or introducing them at a later stage can actually prevent allergies. On the contrary, new proposals concentrate on the fact that early contact with allergens can induce immune tolerance. For instance, a time window might be opened in early childhood for preventing the development of allergies.

In our study on farmers’ children (PASTURE/EFRAIM) we have already shown that varied baby food in the first year of life reduces the risk of atopic dermatitis. We also demonstrated the same effect for asthma, food allergy and allergic sensitisation. Independently of these findings, we were also able to show the protective effect of supplementary baby food, mainly dairy products (e.g. yoghurt), introduced in the first year of life (as described in the Newsletter of October 2012).

Our findings from the farmers’ children study support the hypothesis that early contact with different allergens in the child’s intestinal tract is necessary for immune tolerance to develop. The nature of the diet, the gut flora and the immune response are closely interconnected. One possible explanation for the protective effect might be the early colonisation of the gut with microbes and their metabolic products. It has already been shown that what are known as short-chain fatty acids, metabolic products of certain intestinal bacteria, have an anti-inflammatory effect. These short chain fatty acids are generated by the fermentation of carbohydrates in the intestinal tract but they are also contained in food. One of these fatty acids, butyrate, is found in the triglycerides of cow’s milk. Therefore the natural butyrate content is high in dairy products.

We observed the preventive effect of short-chain fatty acids for the first time in the mouse model of allergic respiratory inflammation (similar to asthma).We gave the short-chain fatty acids orally to the mice throughout the duration of the experiment. In a healthy lung there are normally only a few macrophages passing through the lung. As soon as an allergy is triggered, the cell count in the lung rises sharply, which is mainly due to the migration of eosinophilic cells. We flushed out the lungs of mice in our allergy model and counted the cells they contained. We were able to demonstrate that the administration of short-chain fatty acids can markedly reduce the number of cells contained in the bronchoalveolar lavage (BAL, washing out the lung).

Messengers typical of an allergy also decrease markedly due to the administration of short-chain fatty acids, which further confirms the protective effect of these fatty acids in allergy.

These promising results in the mouse model have prompted us to tackle further projects along these lines. There are plans to administer short-chain fatty acids in combination with a butyrate boosting substrate as well as butyrate-producing probiotics.

In the study on farmers’ children we plan to investigate the level of short-chain fatty acids in stool samples from the first year of life. The link between fatty acid content and diet is to be investigated.

The results outlined above point to possible avenues for developing effective dietary strategies for the prevention of allergic diseases.

How flexible are neutrophils to opposing signaling?

Paola Martinez Murillo a postdoctoral researcher in Pierre-Yves Mantel’s group from CK-CARE obtained a Spark grant from the SNSF to investigate the effect of opposite signals on neutrophil biology in atopic dermatitis.

Spark is a Swiss National Science Foundation (SNSF) funding scheme aiming to support projects that show unconventional thinking and introduce a unique approach. The Spark is highly competitive and supports projects based on promising ideas of high originality. CK-CARE was recognized as an eligible institution in June 2023 by the SNSF, opening new funding opportunities for the CK-CARE researchers.

This project aims to understand how two opposing signals: eczema dysregulated immune environment (Th2 response) and bacterial colonization (Th1 response) impact neutrophils function.

Neutrophils are tiny but powerful immune cells in our blood that fight off bacteria and viruses. They live for only 2-3 days and can quickly respond to infections. Neutrophils can adapt to different situations thanks to their genetic instructions (RNA). Our body’s reversible changes in reading DNA, called epigenomic modifications, are crucial for a functional immune response.

Eczema, a chronic skin condition, happens when various factors like genetics, skin damage, and immune reactions go haywire. People with eczema have neutrophils that do not work as well in fighting bacteria, making them more prone to infections.

This study addresses a knowledge gap in neutrophil adaptation to an allergic milieu, by evaluating neutrophil adaptation to anti-bacterial response in a type 2 immune response dominated context such as atopic dermatitis using transcriptional and epigenomic profiling along with comprehensive analysis of neutrophil functionality (netosis, phagocytosis, ROS-production, bactericidal activity, chemotaxis). Building upon in-vitro stimulation insights, then we will aim for a comprehensive analysis of neutrophil functionality in atopic dermatitis patients treated or not with Dupilumab.

Environmental exposure and sensitization patterns in a Swiss alpine pediatric cohort

The level of environmental exposure throughout life may contribute to the prevalence of allergic sensitization and allergic disease. The alpine climate has been considered a healthy climate with little allergen exposure and pollution. We conducted a cross-sectional study to investigate local environmental exposure and concomitant prevalence of allergic sensitization among local school children born and raised in an alpine environment.

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Spatial transcriptomics combined with single-cell RNA-sequencing unravels the complex inflammatory cell network in atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 3%–5% of adults and 20% of children worldwide. The pathophysiology of AD involves various factors including host genetics, altered skin barrier function, and immunological abnormalities. 

Atopic dermatitis: Correlation of distinct risk factors with age of onset in adulthood compared to childhood

Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls.
An analysis of the CK-CARE-ProRaD cohort revealed adult-onset AD in nearly a quarter of patients. We identified active smoking to be associated with adult-onset AD versus controls. Food allergy, maternal food allergy, palmar hyper linearity, and academic background increased the odds of childhood-onset AD versus controls.

Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis, but reduced odds to feature multiple (3-4) atopic comorbidities. Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in “high-atopic”-clusters.

The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors.

Certification by the Swiss Biobanking Platform – VITA-Label

Building up a proper Governance through accountable mechanisms is key to foster trustworthiness and the pre-requisite for the appropriate use of biological resources. Our CK-CARE Biobank has recently been awarded by Swiss Biobanking Platform (SBP) with the VITA Label, which demonstrates compliance with the applicable legal and ethical framework. This labelling approach is part of our long-term strategy to strengthen biobanking practices and provide high-quality samples to the research community.

CK-CARE Team Meeting October 10th- 11th, 2022

This year’s CK-CARE team event in Davos focused on strengthening cross-center communication and collaboration. Our team members got to know each other and the canton of Grisons better by producing several Grisons specialties as “cross-center team building” in preparation for the scientific work. This as a goal to promote teamwork! Although there was no knowledge about the production of Graubünden delicacies, let alone anyone with appropriate skills, each team excelled in its own way. Driven by trust, respect and genuine motivation to solve the tasks set, the team members met the challenge of working together with fun and creativity as an important preparation for the following day’s research activities. It was a successful meeting – we look forward to many more.