Diet composition drives tissue-specific intensity of murine enteric infections

Abstract

Diet composition plays a large role in regulating gut health and enteric infection. In particular, synthetic “Westernstyle” diets may predispose to disease, while wholegrain 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 caecumdwelling nematode, than mice fed with refined, semisynthetic 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 infectioninduced 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 inulinenriched SSD. However, transcriptomic analysis of tissues from mice fed with either SSD or inulinenriched 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 inulinfed mice, whereas IL22 treatment was unable to restore resistance to C. rodentium colonization. Dietmediated effects on pathogen burden were more pronounced for large intestinedwelling 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, inulinenriched SSD, or SSD, despite higher cyst excretion in chowfed mice. Collectively, our results point to a tissue and pathogenrestricted effect of dietary fiber levels on enteric infection intensity. IMPORTANCE Enteric 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.