The human immune system shows substantial interindividual immune variation that relates to genetic differences as well as environmental exposures. Our closest environment - our microbiota - has received considerable attention during the last decade(s). We know that the gut environment is instrumental for immune maturation in mice, but there is still a large knowledge gap regarding gut environment-immune crosstalk in humans, in particular regarding mechanisms. The general purpose of our work is to study how the gut environment is involved in immune modulation, in physiological and pathological conditions but also whether this impacts allergy and tolerance, and by what mechanisms this microbe-mediated immune instruction takes place. We study this in clinical material involving children ad young adults as well as in different in vitro models, where human (immune) cells are exposed to different microbial factors. Large hypothesis-generating studies suggest a connection between the microbiome/metabolome and allergy, although the mechanisms are still largely unknown, in particular in humans. We follow allergy and tolerance development in real time to gain mechanistic insights, to fully understand the series of events resulting in either tolerance or persistent allergy, and how they are connected. Our clinical studies are unique in an international perspective, with its in-depth analyses of immune- and microbiota characteristics and function in longitudinal samples from children from different allergy-related cohorts. In this particular project we aim to perform exploratory ATAC sequencing and/or RNA seq on whole PBMC. We will also be able to link changes in the immune compartment to alterations in the microbiome and metabolic profile as blood and fecal samples are collected at the same time points.