Diet composition drives tissue-specific intensity of murine enteric infections.

Diet composition plays a large role in regulating gut health and enteric infection. In particular, synthetic "Western-style" diets may predispose to disease, while whole-grain diets containing high levels of crude fiber are thought to promote gut health. Here, we show that, in contrast to this paradigm, mice fed with unrefined chow are significantly more susceptible to infection with Trichuris muris, a caecum-dwelling nematode, than mice fed with refined, semi-synthetic diets (SSDs). Moreover, mice fed with SSD supplemented with inulin, a fermentable fiber, developed chronic T. muris burdens, whereas mice fed with SSD efficiently cleared the infection. Diet composition significantly impacted infection-induced changes in the host gut microbiome. Mice infected with the bacterium Citrobacter rodentium were also more susceptible to pathogen colonization when fed with either chow or inulin-enriched SSD. However, transcriptomic analysis of tissues from mice fed with either SSD or inulin-enriched SSD revealed that, in contrast to T. muris, increased C. rodentium infection appeared to be independent of the host immune response. Accordingly, exogenous treatment with interleukin (IL)-25 reduced T. muris burdens in inulin-fed mice, whereas IL-22 treatment was unable to restore resistance to C. rodentium colonization. Diet-mediated effects on pathogen burden were more pronounced for large intestine-dwelling pathogens, as effects on small the intestinal helminth (Heligmosomoides polygyrus) were less evident, and protozoan (Giardia muris) infection burdens were equivalent in mice fed with chow, inulin-enriched SSD, or SSD, despite higher cyst excretion in chow-fed mice. Collectively, our results point to a tissue- and pathogen-restricted effect of dietary fiber levels on enteric infection intensity.IMPORTANCEEnteric infections induce dysbiosis and inflammation and are a major public health burden. As the gut environment is strongly shaped by diet, the role of different dietary components in promoting resistance to infection is of interest. While diets rich in fiber or whole grain are normally associated with improved gut health, we show here that these components predispose the host to higher levels of pathogen infection. Thus, our results have significance for interpreting how different dietary interventions may impact on gastrointestinal infections. Moreover, our results may shed light on our understanding of how gut flora and mucosal immune function is influenced by the food that we eat.

Anti-protozoal activity of extracts from chicory (Cichorium intybus) against Cryptosporidium parvum in cell culture.

Cryptosporidium spp. are responsible for severe public health problems and livestock production losses. Treatment options are limited to only one drug available for human and bovine cryptosporidiosis, respectively, and both drugs exhibit only partial efficacy. Sesquiterpene lactones (SL) are plant bioactive compounds that function as a defence mechanism against herbivores. SL have demonstrated anti-parasitic properties against a range of parasitic taxa but knowledge about their anti-Cryptosporidium efficacy is limited. The effect of SL-rich leaf and root extracts from chicory (Cichorium intybus cv. Spadona) was investigated using human colon adenocarcinoma (HCT-8) cells infected with Cryptosporidium parvum. C. parvum oocysts were inoculated onto the cell monolayer and i) incubated for 4 hours with extracts (leaf and root extracts 300, 150, 75, 37.5, 18.75 and 9.375 µg/mL) in triplicates followed by incubation in bioactive free media (sporozoite invasion assays) or ii) incubated for 4 hours in bioactive free media followed by 48-hours incubation with extracts (growth inhibition assays). Extract toxicity on HCT-8 cells was assessed via water-soluble tetrazolium (WST)-1 assay prior to quantifying parasitic growth via immunofluorescence. Both extracts demonstrated dose-dependent inhibition in the growth inhibition assays (p = < 0.0001 for both extracts) but not in the invasion assays. Anti-parasitic activity did not appear to be solely related to SL content, with the extract with lower SL content (leaf) exhibiting higher inhibition at 300 µg/ml. However, given the limited treatment options available for Cryptosporidium spp., our study encourages further investigation into the use of chicory extracts to identify novel active compound(s) inhibiting these protozoa.