585 - Nasal microbiota differences in young infants are associated with early childhood irritability

Poster Number: 585
Publication Number: 585.308

Rebecca A. Ebbott, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Rachel Bass, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Sebastian Otero, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Sheila Krogh-Jespersen, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Lawrence Gray, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Xiaotian Zheng, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Chido O. Chikuturudzi, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Emma McGarrity, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Yudong Zhang, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Stefan J. Green, Rush University Medical Center, Chicago, IL, United States; Laurie Wakschlag, Northwestern University, Chicago, IL, United States; Patrick Seed, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Leena B. Mithal, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States

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, and 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.

Objective: We sought to investigate associations between the nasal microbiota of infants < 60 days of age and early childhood irritability.

Design/Methods: 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 (Table 1). 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, 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, Fig 1). Of the 18 taxa that were compared, Haemophilus, Streptococcus, Staphylococcus, and Gardnerella were significantly less abundant in the high dysregulation group (q < 0.005, Fig 2). Parasutterella was more abundant in a subset of the high dysregulation group.Conclusion(s): 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.
Table 1: Characteristics of patient cohort
Figure 1: Alpha-diversity Shannon index lower in infants with high dysregulationAlpha-diversity (Shannon index) comparison of infant nasal bacterial composition between groups with and without high dysregulation. Plot [A] without removal of potential media background and plot [B] after corrections for potential contaminant taxa and samples with low sequence yield.