Environmental imprinting of the Human Immune System Early in Life

Purpose and aimImmune mediated diseases originate early in life, are linked with perturbed immune-microbe interactions and are increasingly prevalent.

Our hypothesis is that environmental exposures at birth, and during the first months of life exert imprinting effects on developing immune cells, which determine an individual’s trajectory towards immunological health or disease.

MethodsIn a birth cohort in Stockholm with 309 children, monitored for up to four years, we are analyzing longitudinal blood and stool samples, comparing children born at term or preterm, by vaginal or cesarean delivery and fed breastmilk or formula, whilst keeping track of many environmental factors such as the evolving gut microbiome, vaccines, and nutrients.

We assess in vivo developmental outcomes; atopy and serological responses to vaccines and compare children with different outcomes with respect to immunological features, metagenomes, and microbial metabolites.

Furthermore, we aim to perform more in-depth in vitro experiments to investigate microbial metabolites for receptor binding, and functional modulation of epithelial cells and developing immune cells and the functional consequences thereof.

ImportanceThese studies hold important potential by guiding future interventions in the form of pre/probiotics, metabolites, and nutritional supplements that hopefully can provide all children with a healthier start in life and promote immune-microbe mutualism and reduced risks of disease long term.