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. Overall design: Female C57BL/6 mice aged 6 weeks on arrival were used for all experiments and purchased from Envigo (The Netherlands). Mice were housed in cages of six with individual ventilation, wood chips, nesting material and ad libitum water and diet in each cage. At arrival, mice were fed either a standard grain-based diet,standard chow; a semisynthetic open-source diet (13 kJ% fat (#E15051); ssniff Spezialdiäten GmbH, Germany), SSD; or the an SSD diet containing 200 mg/kg indole-3-carbinol (#E0241). Mice were fed their respective diets for two weeks before infection with approximatively 200 L3 stage larvae of Hp. Infections were obtained by dispensing 0.2 mL/mouse of a water-larvae suspension by oral gavage. Mice were euthanized by cervical dislocation at 7-, 14-, or 28-days post infection (DPI). Mice treated with antibiotics were treated 14 days prior to and throughout infection. The treatment was administered through drinking water ad libitum. The drinking water contained 1 mg/mL Ampicillin sodium salt (Sigma-Aldrich #A9518), 1 mg/mL Neomycin trisulfate salt hydrate (Sigma #N1876), and 0.5 mg/mL Gentamycin (Sigma #G1272).