TY - JOUR T1 - Excess calorie intake early in life increases susceptibility to colitis in the adult JF - bioRxiv DO - 10.1101/681759 SP - 681759 AU - Ziad Al Nabhani AU - Sophie Dulauroy AU - Emelyne Lécuyer AU - Bernadette Polomack AU - Marion Berard AU - Gérard Eberl Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/26/681759.abstract N2 - Epidemiological data report an association between obesity and inflammatory bowel disease (IBD) 1–3. Furthermore, animal models demonstrate that maternal high fat diet (HFD) and maternal obesity increase susceptibility to IBD in the offsprings 4–8. However, the mechanisms that translate maternal obesity and HFD into increased susceptibility to IBD later in life remain unknown. Here we report that excess calorie intake by neonatal mice, as a consequence of maternal HFD, forced feeding of neonates or low litter competition, lead to an increase, during weaning, in intestinal permeability, expression of pro-inflammatory cytokines and hydrogen sulfide production by the microbiota. In this context, intestinal permeability, cytokine expression and hydrogen sulfide engaged in a mutual positive feedback that imprinted increased susceptibility to colitis in the adult. This pathological imprinting was prevented by the neutralization of IFNγ and TNFα, of the production of hydrogen sulphide, or by normalization of intestinal permeability during weaning. Thus, excessive calorie intake by neonates leads to multiple causally-linked perturbations in the intestine that imprint the individual with long term susceptibility to IBD. ER -