Saccharomycetes and Malassezia fungi associate with early-life gut maturation and allergic disease risk in childhood.

Abstract

While early-life gut bacterial microbiota maturation has been well studied and linked to childhood disease, the development of the gut mycobiome remains poorly understood. Few studies have defined fungal succession in infancy, and even fewer have integrated fungal and bacterial maturation, allowing interkingdom analysis within the same individuals. In this study, we analyzed a subset of the CHILD Study Cohort (n = 1409 participants) and generated both ITS2 amplicon and shotgun metagenomic sequencing data from infant stool samples (n = 2256 samples). We hypothesized that the infant mycobiome follows predictable developmental trajectories that influence childhood health outcomes. We found that fungi are reliable biomarkers for gut maturation, with the notable emergence of Saccharomyces and Malassezia as some of the strongest indicators across both fungi and bacteria. Fungal composition was strongly associated with infant age (R = 0.79, p < 0.001) and with the later development of both atopic dermatitis (adj. p = 0.029) and food allergy (adj. p = 0.013). Further, differences in fungal development coincided with changes in key gut immune-modulating metabolites such as butyrate and glycerol, indicating the functional importance of infant gut mycobiome maturation in early-life immune development. Together, these results highlight the early life mycobiome as a potential therapeutic target to mitigate allergic disease development.