The Impact of Early Life Obesity on Susceptibility to IBD in the Adult.

Inflammatory Bowel Disease (IBD) is caused by the accumulation of genetic, microbial and lifestyle factors that increase the susceptibility to the disease beyond a red line. The number and complexity of such factors makes prediction of pathogenesis and therapy particularly difficult. Nevertheless, clinical and experimental observations demonstrate a strong association of early life events with susceptibility to IBD later in life. In particular, a loss in microbiota, for example after prolonged antibiotic therapy, leads to higher incidence in pediatric IBD. We have observed, using a mouse model, that the vigorous reaction of the immune system to the expanding microbiota during weaning protects from high susceptibility to IBD later in life. We further found that early life diet provided to the mother and pups is an important element that determines the composition of the microbiota and the reactivity of the immune system. In particular, high fat diet (HFD) given early imprints high susceptibility to IBD in adulthood, through mechanisms that we explore in this project. As the human population is increasingly hygienic and exposed to HFD, normalization of diet and complementation with key bacteria may become effective strategies to prevent, early in life, the development of IBD later in life.