Frei Lab

Up to 30% of children currently suffer from at least one allergic disease, making allergies a major burden for affected children, their families, and society. Atopic dermatitis (AD) is often the first atopic disease to develop in early childhood, and children with AD are at increased risk of subsequently developing other allergic diseases, such as asthma and food allergies.
AD is a complex inflammatory disease involving skin barrier dysfunction, immune dysregulation, and microbial dysbiosis. Environmental factors have been shown to strongly influence the risk of allergy development. For example, cesarean section and antibiotic use during pregnancy or early life have been identified as risk factors for AD. In contrast, growing up on a farm, having older siblings, or consuming a diverse diet during the first year of life have been associated with a reduced risk of allergic disease development. These factors share a common feature in that they influence the maturation of the gut and skin microbiome.
Indeed, we found that children with a highly diverse diet, including dairy products and vegetables during the first year of life, showed an increased levels of short-chain fatty acid (SCFA) and increased abundance of SCFA-producing bacteria, such as Ruminococcus bromii. SCFAs are known to promote immune tolerance toward allergens and to improve epithelial barrier integrity. Furthermore, we observed that children with high SCFA levels during the first year of life suffered significantly less frequently from allergic diseases later in life.

Children Allergy, Nutrition, and Environment (CARE) Study

The CARE study is an ongoing Swiss birth cohort study aiming to identify early-life environmental factors associated with protection against the development of AD and other allergic diseases later in life. Newborns are recruited at the University Hospital Bern and the Cantonal Hospital St. Gallen. We collect detailed longitudinal information on diet during the first year of life using questionnaires, assess the development of AD and other allergic diseases during clinical visits, and collect biological samples such as blood and feces to evaluate immune status and the gut microbiome.


 

Farming Environment: The PASTURE Study

Growing up on a farm has been identified as one of the strongest environmental factors associated with a significantly reduced risk of developing allergic diseases. The PASTURE study is a longitudinal birth cohort conducted across five European countries, including 530 children from farming families and 603 children from non-farming families. The children were followed until the age of 16 years.
Within the framework of the PASTURE study, we identified highly relevant farm-related environmental exposures together with the underlying immune mechanisms associated with a reduced risk of allergy development. Exposures linked to a significantly lower risk of allergic diseases in early life include contact with a greater abundance and diversity of microbes present in environmental farm dust, exposure to farm animals and pets, and a more diverse diet during the first year of life.

Our Key Findings from the PASTURE and CARE Studies

  • Using latent class analysis, we identified distinct phenotypes of atopic dermatitis (AD) and asthma based on disease onset and progression throughout childhood. The prevalence of asthma and food allergy by 6 years of age was markedly increased among children with early-onset AD phenotypes. 
  • Increased dietary diversity during the first year of life, including the consumption of dairy products, vegetables, and fruits, was associated with a reduced risk of developing asthma, AD, and food allergy later in life. 
  • Consumption of unprocessed cow’s milk protects infants against common respiratory infections. 
  • Increased short-chain fatty acid (SCFA) levels during the first year of life were associated with a reduced risk of developing allergic diseases later in life. Moreover, administration of SCFAs in mice reduced symptoms in a model of allergic airway inflammation and promoted regulatory T-cell differentiation. 
  • A higher abundance of the primary degrader Ruminococcus bromii was associated with elevated fecal butyrate levels during the first year of life and a lower prevalence of AD in infancy. 
  • Early maturation of the gut microbiota, including colonization with butyrate-producing bacteria during the first year of life, was associated with a lower risk of asthma development later in childhood. 
  • Initial butyrate producers during infant gut microbiota development are endospore-forming bacteria. 
  • Breastfeeding and the major fermentation metabolite lactate influence the occurrence of Peptostreptococcaceae in infant feces. 
  • Electrical impedance spectroscopy (EIS) detects skin barrier dysfunction in childhood AD. 
  • A Mediterranean and diverse maternal diet during pregnancy was associated with a reduced risk of AD development in children.