Effects of diet, paarsite infection, and antibiotic treatment on the mouse intestinal transcriptome

Diets rich in whole grains and fermentable fibers may promote gut health, whilst processed foods can lead to inflammation and increased susceptibility to pathogens. Here, we show that mice infected with the roundworm Heligmosomoides polygyrus exhibited increased resistance to infection when fed fiber-deprived semi-synthetic diets (SSD), relative to mice fed fibre-rich isoenergetic chow. SSD-fed mice had augmented transcription of type-2 immune-related genes during infection, and worm fitness (fecundity) was reduced. Enhanced anti-helminth immunity in SSD-fed mice was associated with suppression of gene pathways related to xenobiotic metabolism and aryl-hydrocarbon receptor (AhR) activation in the gut mucosa. However, inclusion of synthetic AhR agonists in SSD did not recapitulate the effect of chow. Moreover, whilst diet composition regulated host gut microbiota (GM) changes in response to H. polygyrus, infection resistance in SSD-fed mice was independent of the GM as antibiotic depletion of the GM failed to attenuate diet-mediated effects on parasite fecundity. Thus, in contrast to well-known health-promoting effects of whole-grain diets, synthetic diet components directly enhance resistance to helminth infection in the small intestine. These findings emphasize the role of the physicochemical structure of diet in regulating host defense at mucosal surfaces.