ABSTRACT
Several hypotheses link altered microbial exposure in affluent societies to increased prevalence of allergies, but none have been experimentally tested in humans. Here we capitalize on the opportunity to study a cohort of infants (CORAL) raised during COVID-19 associated social distancing measures to test the interactions between bacterial exposure and fecal microbiome composition with atopic outcomes. We show that fecal Clostridia levels were significantly lower in CORAL infants and correlated with a microbial exposure index. Microbiota composition was the most significant component of regression models predicting risk of atopic dermatitis (AUC 0.86) or food allergen sensitization (AUC 0.98) and mediated the effects of multiple environment factors on disease risk. Although diet had a larger effect on microbiota composition than environmental factors linked to dispersal, most effects were mediated through the microbiota. This study provides critical information to refine existing hypothesis on the importance of the gut microbiota to immune development.