Influence of probiotic treatment on allergy methylomics : Gene network analysis of epigenetic methylation patterns in CD4+ T cells from newborns treated with Lactobacillus reuteri

Abstract: The composition and diversity of the gastrointestinal microbiota and its interaction with human cells have been frequently associated with immune system functions and disease development, including autoimmunity and allergy. This is believed to be mediated in part through epigenetic modifications, mainly as DNA methylation. Several studies have collectively supported the beneficial effects of probiotics for the prevention of allergic disease. However, there have been few studies addressing the possibility for probiotic supplementation to induce epigenetic changes and its importance for allergy development. This study aims to investigate whether probiotic treatment with Lactobacillus reuteri, distributed during and after the pregnancy period, leads to epigenetic changes in the offspring and if this have any effect on the development of allergic disease. DNA methylation data received from a clinical allergy prevention study was analysed through a set of bioinformatics methods and basic network analysis. The obtained results suggests that supplementation with L. reuteri indeed induces some significant changes in DNA methylation. These changes did not exhibit any significant correlation with allergy outcome of the children. Furthermore, the methylation changes were found at positions located in genes not enriched for any allergy-related biological pathways. However, when taking the genes interactions with other genes into account an interconnected gene interaction module could be identified that showed enrichment for biological processes involved in the T cell receptor signaling pathway, central for immune response transduction. Further analyses did not fit into the time-frame of this thesis, but the obtained results gives a first informative view of the effects of L. reuteri on methylation patterns, and points out directions for the continuing project work.