Nurture, not nature: Impaired skin barrier in infants born to Rural Households

Abstract

To the Editor,The recently introduced epithelial barrier hypothesis posits that the totality of environmental exposures, or the exposome, is responsible for the growing prevalence of an extensive list of disorders, including atopic conditions. 1 Environmental insults damage the epithelial barriers, including that of the skin, thereby setting off a cascade of detrimental events. The theory, coupled with the known genetic underpinnings of atopic dermatitis, asthma, food allergies, and other conditions, provides for a comprehensive picture of geneenvironment interactions that result in disease.The integrity of the skin barrier is important for maintaining health, and its impairment has been associated with a number of medical conditions. Early-life impairment of the skin barrier, as measured by transepidermal water loss (TEWL), has been associated with atopic dermatitis, 2 aeroallergen sensitization, 3 and food allergen sensitization. 4 Intriguingly, these associations are often independent of loss-of-function filaggrin mutations. Filaggrin plays an important role in epidermal integrity, and loss-of-function filaggrin mutations are a risk factor for the development of atopic dermatitis, food allergies, allergic rhinitis, and asthma. 5 However, the lack of overlap between infant TEWL values and subsequent atopic conditions compared with filaggrin mutations and atopic conditions is perplexing. We hypothesized that TEWL values in infancy may reflect environmental exposures and not genetic predisposition. This report explores the hypothesis using data from the Comprehending Atopic Risk Elements (CARE) cohort, an observational prospective birth cohort whose study design has been previously described.The CARE study is a multicenter, prospective observational longitudinal study, and the CARE birth cohort was recruited between June 2020 and April 2022 from a representative sample of births in the Israeli Health Services,