Composition and Associations of the Infant Gut Fungal Microbiota with Environmental Factors and Childhood Allergic Outcomes

Although often neglected in gut microbiota studies, recent evidence suggests that imbalanced, or dysbiotic, gut mycobiota (fungal microbiota) communities in infancy coassociate with states of bacterial dysbiosis linked to inflammatory diseases such as asthma. In the present study, we (i) characterized the infant gut mycobiota at 3 months and 1 year of age in 343 infants from the CHILD Cohort Study, (ii) defined associations among gut mycobiota community composition and environmental factors for the development of inhalant allergic sensitization (atopy) at age 5 years, and (iii) built a predictive model for inhalant atopy status at age 5 years using these data. We show that in Canadian infants, fungal communities shift dramatically in composition over the first year of life. Early-life environmental factors known to affect gut bacterial communities were also associated with differences in gut fungal community alpha diversity, beta diversity, and/or the relative abundance of specific fungal taxa. Moreover, these metrics differed among healthy infants and those who developed inhalant allergic sensitization (atopy) by age 5 years. Using a rationally selected set of early-life environmental factors in combination with fungal community composition at 1 year of age, we developed a machine learning logistic regression model that predicted inhalant atopy status at 5 years of age with 81% accuracy. Together, these data suggest an important role for the infant gut mycobiota in early-life immune development and indicate that early-life behavioral or therapeutic interventions have the potential to modify infant gut fungal communities, with implications for an infant's long-term health. <b>IMPORTANCE</b> Recent evidence suggests an immunomodulatory role for commensal fungi (mycobiota) in the gut, yet little is known about the composition and dynamics of early-life gut fungal communities. In this work, we show for the first time that the composition of the gut mycobiota of Canadian infants changes dramatically over the course of the first year of life, is associated with environmental factors such as geographical location, diet, and season of birth, and can be used in conjunction with knowledge of a small number of key early-life factors to predict inhalant atopy status at age 5 years. Our study highlights the importance of considering fungal communities as indicators or inciters of immune dysfunction preceding the onset of allergic disease and can serve as a benchmark for future studies aiming to examine infant gut fungal communities across birth cohorts.