Type l diabetes in childhood and adolescence, environmental exposures and gut microbiota

Sammanfattning: Environmental factors leading to disturbances in the gut microbiota might play an important role as triggers for, and/or contributing factors in, the development of type 1 diabetes (T1D). The overall aim of the research underlying this thesis was to study the influence of environmental factor exposure on the risk of T1D in childhood and adolescence, and gut microbiota composition in early childhood.In this project, national registers provided information about T1D onset and exposure to animals, antibiotics, caesarean section and severe stress, defined as death of a first degree relative. In the first study (1,999 T1D events), no evidence supported an association between early exposure to dog or farm animals and T1D in childhood. In the second study (1,297 T1D events), dispensed prescriptions of antibiotics in the first year of life was found to be associated with T1D during childhood. Sibling analysis did not indicate confounding from familial factors. Furthermore, the effect estimate for the association between antibiotics and T1D was largest in children delivered by caesarean section. In the third study (10,789 T1D events), death of a close relative was associated with an increased risk for T1D within the first years following the loss, and when the loss occurred during the teenage years. The fourth study was a longitudinal study using 16S rRNA sequencing to analyse faecal samples from 83 children to study the gut microbiota development from birth to 2 years of age. Having a furry pet in the household was associated with a lower abundance of a bacterial species belonging to the genus Bifidobacterium. The overall gut microbiota composition was associated with prenatal exposure to antibiotics and caesarean section. Finally, caesarean section was associated with a lower abundance of Bacteroidetes and a higher abundance of Firmicutes.In conclusion, no evidence was found in the present study to support the association of exposure to animals to lowered risk of T1D in the general population. Although exposure to antibiotics was associated with T1D, it is likely to only make a small contribution to the overall risk of T1D. Our findings support the hypothesis that severe stress might accelerate T1D onset during certain time periods. Furthermore, our findings add to the body of research showing that exposure to animals, prenatal antibiotics and caesarean section account for some of the inter-individual variation in early childhood microbiota development.