Excess calorie intake early in life increases susceptibility to colitis in adulthood.

Nature Metabolism
Ziad Al NabhaniGérard Eberl

Abstract

Epidemiological data reveal an association between obesity and inflammatory bowel disease (IBD). Furthermore, animal models demonstrate that maternal high-fat diet (HFD) and maternal obesity increase susceptibility to IBD in offspring. Here we report that excess calorie intake by neonatal mice, as a consequence of maternal HFD, forced feeding of neonates or low litter competition, leads to an increase during weaning in intestinal permeability, expression of pro-inflammatory cytokines and hydrogen sulfide production by the microbiota. These intestinal changes engage in mutual positive feedback that imprints increased susceptibility to colitis in adults. The pathological imprinting is prevented by the neutralization of IFN-γ and TNF-α or the production of hydrogen sulfide, or by normalization of intestinal permeability during weaning. We propose that excess calorie intake by neonates leads to multiple causally linked perturbations in the intestine that imprint the individual with long-term susceptibility to IBD.

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Citations

Jan 29, 2020·Mucosal Immunology·Ziad Al Nabhani, Gérard Eberl
Oct 3, 2020·Nature Reviews. Gastroenterology & Hepatology·Charlie W Lees
Dec 9, 2020·Journal of Proteome Research·Martin BeaumontSylvie Combes
Apr 29, 2021·Critical Reviews in Food Science and Nutrition·Jielong GuoJicheng Zhan

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Methods Mentioned

BETA
transgenic
enzyme-linked immunosorbent assays
PCR

Software Mentioned

R package lme4
ANODE
R package lsmeans
GraphPad Prism
R package car
R package survival

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