Pediatric IgE-mediated allergy is a global health problem. Food allergies are a particular concern, as there are no curative treatment and patients risk severe reactions and life-long suffering. Recent trials with oral immunotherapy (OIT) to achieve unresponsiveness/tolerance in severely peanut individuals have however given positive results, particularly in young children. Tolerance to food antigens is not just a result of ignorance, but an active and complex process with a series of events, comprising the gut environment (including microbiota, dietary factors & metabolites), several immune cell types and mechanisms. 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 study is unique in an international perspective, with its in-depth analyses of immune- and microbiota characteristics and function in young children participating in a randomized controlled clinical trial with OIT against peanut at Sachs Children’s Hospital, Stockholm (Small Children OIT peanut, acronym SmaChO). In this particular project we aim to perform exploratory ATAC sequencing on whole PBMC; at base-line, after 1 and 3 years, as well as after a final four-week period of no peanut consumption (endpoint) of the study. We compare children developing sustained unresponsiveness/tolerance with those who remain peanut allergic to identify mechanistic checkpoints in tolerance development. In parallel other studies are performed on gene expression and protein levels. 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.