Dulauroy, S. | Search bioRxiv

bioRxiv2026

ILC3s are Required for Enterocyte Homeostasis to Food Intake

Food provides nutrients that are selectively absorbed by the intestine, but, at the same time, may contain elements that challenge the intestinal barrier and induce post-prandial inflammation (PPI). How PPI is controlled in order to avoid pathological perturbation of homeostasis remains unclear. Here, we report that during fasting, enterocytes increase their absorptive potential and oxidative metabolism, a program that is largely reversed upon food intake of lipids that perturb the intestinal barrier and induce PPI. Such perturbation is countered by ILC3s, in the absence of which PPI increases, program reversal does not occur, and enterocytes engage into excessive oxidative metabolism. This enterocyte state leads to critical hypoglycemia as a consequence of decreased glucose absorption and increased insulinemia, recapitulating the pathological situation found in patients suffering from intestinal damage and sepsis. We hereby uncover a critical function for ILC3s in maintaining enterocyte homeostasis upon challenging food intake.

immunology↗

bioRxiv2019

Excess calorie intake early in life increases susceptibility to colitis in the adult

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 IFN{gamma} and TNF, 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.

immunology↗