The role of skin dysbiosis in the progression of pediatric atopic dermatitis to asthma

Summary: Abstract Body: We aimed to investigate the role of skin dysbiosis and barrier protein expression in the progression of pediatric atopic dermatitis (AD) to asthma. Approximately one-third to one-half of patients with AD characterized by skin dysbiosis and barrier dysfunction, develop asthma. However, the exact mechanisms of AD progression to asthma remain unclear. We utilized a subset of participants with skin metagenomics shotgun sequencing (MSS) data at Visit 1 and an asthma diagnosis at Visit 5 (n = 89) in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort. Skin tape samples from non-lesional (NL) skin at Visit 1 were used to analyze the microbial MSS data and expression of barrier proteins including FLG, DSG-1, AHR, and OVOL1. Asthma was diagnosed at Visit 5 via symptoms and spirometry results. We then analyzed microbial alpha and beta diversities, differential species abundance, and barrier protein expression between the asthma and no asthma groups. Alpha (Shannon Index) and beta diversity did not significantly differ between the two groups. The asthma group had 9 bacterial species less abundant than the no asthma group including Streptococcus infantis, Rothia mucilaginosa, and Streptococcus mitis. The asthma group had 2 additional core taxa, including Staphylococcus epidermidis, compared to the no asthma group. There were no differences in the proportion of participants with detectable FLG, DSG-1, AHR, and OVOL1 expression between the two groups. Overall, patients with AD who went on to develop asthma showed a shift in the NL skin microbiome with an increased presence of inflammatory bacteria and a decreased abundance of barrier-protective and anti-inflammatory bacteria compared to those who did not progress to asthma. These findings suggest that the skin microbiome may play a key role in the progression of pediatric AD to asthma. Alexa DeRegnaucourt¹, Arya Dahal¹, Wan Chi Chang¹, Seth Jenkins¹, Daniel Spagna¹, Latha Satish^{1, 2}, Jocelyn Biagini^{1, 2}, Gurjit Khurana Hershey^{1, 2} 1. Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States. 2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States. Innate Immunity, Microbiology, and Microbiome