TY - JOUR

T1 - Diet composition drives tissue-specific intensity of murine enteric infections

AU - Israelson, Helene

AU - Vedsted-Jakobsen, Amalie

AU - Zhu, Ling

AU - Gagnaire, Aurelie

AU - von Münchow, Alexandra

AU - Polakovicova, Nina

AU - Valente, Angela H.

AU - Raza, Ali

AU - Andersen-Civil, Audrey I.S.

AU - Olsen, John E.

AU - Myhill, Laura J.

AU - Geldhof, Peter

AU - Williams, Andrew R.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Citrobacter

KW - diet

KW - Giardia

KW - helminths

KW - immune response

U2 - 10.1128/mbio.02603-23

DO - 10.1128/mbio.02603-23

M3 - Journal article

C2 - 38179939

AN - SCOPUS:85185196177

VL - 15

JO - mBio

JF - mBio

SN - 2161-2129

IS - 2

M1 - e0260323

ER -