The Janus face of Bifidobacterium in the development of atopic eczema: A role for compositional maturation.

Background: Atopic eczema often develops in the first year of life, when the composition of the gut microbiota is most plastic as illustrated by the decrease in bifidobacteria after weaning. This may provide the opportunity for microbial stimuli and their environmental determinants to alter the disease course.

Objectives: To determine the role of the genus Bifidobacterium for atopic eczema in early childhood.

Methods: We analysed the bacterial composition in fecal samples of 618 children of the PASTURE ("Protection against Allergy-Study in Rural Environments") birth cohort using 16S rRNA amplicon sequencing of fecal samples collected at 2 and 12 months of age. Atopic eczema was defined as a parent-reported doctor's diagnosis until 2 years, and patterns of rash symptoms were classified by latent class analysis. We applied mediation models to assess direct and microbiota-mediated effects of environmental determinants on atopic eczema.

Results: The Bifidobacterium composition observed at 2 months was inversely related to atopic eczema (OR = 0.68 [0.53-0.87], p = .002) and persistent rash. This association was not seen at 12 months, when the composition of Bifidobacterium amplicon sequence variants (ASVs) was altered. The effect of beneficial ASVs at 2 months (OR = 0.72 [0.57-0.91]) was lost at 12 months (OR = 0.97 [0.76-1.24]), when distinct bifidobacteria tended to be positively related to late-onset rash.

Conclusions: The subgenus composition of Bifidobacterium undergoes substantial changes in the first year of life. The protective effect of Bifidobacterium depends on the ASV composition at the respective age of the infant, highlighting the importance of timing in prevention strategies targeting infant-microbe interactions.