#49 Nasal microbiota differences in young infants are associated with early childhood irritability

Abstract

Abstract Background The etiology and pathophysiology of childhood mental health are poorly understood. Early childhood irritability is a transdiagnostic marker that portends significant risk for subsequent mental health problems. Robust evidence demonstrates irritability can be quantified early in infancy. The early life microbiome is implicated in defining health trajectories including neurodevelopment. In contrast to the gut microbiome, however, a relationship between the infant nasal microbiome and early childhood irritability remains undefined. We sought to investigate associations between the nasal microbiota of infants <60 days of age and early childhood irritability. Method This case-control study included infants with archived respiratory nasal samples collected for routine clinical care at ≤60 days of age from an emergency department visit (1/2016-5/2019). Parents completed an online survey when children were 14-42 months of age that included questions about medical history, development, and irritability (Multidimensional Assessment of Preschool Disruptive Behavior, MAP-DB). The upper quartile of the MAP-DB Temper Loss Score was classified as high dysregulation. Additional clinical data were collected from the electronic health record. DNA extracted from archived viral media specimens were subjected to 16S rRNA gene (V3-V4 region) next generation sequencing (NGS). Ecological diversity and differential taxon analysis were performed. Results Seventy-two children were initially included, with 16 categorized as high dysregulation. The median age at nasal sample collection was 30 days (IQR 14-44), and age at parent survey was 28 months (IQR 19-31). Fifty-weight percent of the cohort was white, 6% Black, 6% Asian, 20% other, and 25% identified as Lantine ethnicity. The infants were 49% female sex, 77% were born by vaginal delivery, and 43% had a virus identified at time of nasal sample. After removal of extraction/PCR contaminants, taxa present only or at higher levels in media, and samples with <80 sequences, the final microbiota comparison dataset was n=33 children, 7 with high dysregulation. Alpha-diversity (Shannon index) was lower in the high dysregulation group (p=0.0031 pre-background taxa removal, p=0.1288 post-correction, Figure 1A-B). Of the 18 taxa that were compared, Haemophilus, Streptococcus, Staphylococcus, and Gardnerella were significantly less abundant in the high dysregulation group (false discovery corrected significance q<0.005, Figure 1C). Parasutterella was more abundant in a subset of the high dysregulation group. Conclusion Differences in the nasal microbiota of infants, decreased diversity and abundance of certain respiratory bacteria, are associated with early childhood irritability, a marker of mental health risk. Further study may provide mechanistic insights and potentially guide new risk assessment or treatment options.