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P090 Exposure to high fat diet early in life impacts colitis severity in adult mice

Z. Al Nabhani*1, S. Dulauroy1, E. Lécuyer1, G. Eberl1

1Insitut Pasteur, Immunology, Paris, France

Background

Epidemiological data report an association between obesity and inflammatory bowel disease (IBD). Likewise, animal models demonstrate that maternal high-fat diet (HFD) and maternal obesity increase susceptibility to IBD in the offsprings. However, underlying cellular and molecular mechanisms remain enigmatic. We aim to determine how exposure to HFD early in life impact the intestinal immunity and increase the susceptibility to develop IBD at adult age.

Methods

The impact of HFD on immune system response was assessed during suckling, weaning or adulthood period. Dextran sodium sulphate (DSS)-induced colitis was employed as experimental model of IBD. The differential response to DSS in mice fed HFD treated or not with cocktail of antibiotics until 2, 4, 6, or 12 weeks was compared with mice fed normal chow.

Results

Exposure to HFD early in life lead to an increase, during weaning, in intestinal permeability, expression of pro-inflammatory cytokines and hydrogen sulphide production by the microbiota. In this context, intestinal permeability, cytokine expression and hydrogen sulphide engaged in a mutual positive feedback that imprinted increased susceptibility to colitis in the adult. This pathological imprinting was prevented by the neutralisation of TNF-α and IFN-γ, or the production of hydrogen sulphide, or by normalisation of intestinal permeability or by antibiotics treatment during weaning.

Conclusion

As the human population is increasingly hygienic and exposed to HFD, normalisation of diet and complementation with key bacteria may become effective strategies to prevent, early in life, the development of IBD later in life.