Fermentable dietary fiber promotes helminth infection and exacerbates host inflammatory responses. Inulin promotes Trichuris muris infection and inflammation

Fermentable dietary fibers promote the growth of beneficial bacteria, can enhance mucosal barrier integrity and reduce chronic inflammation. However, effects on intestinal type-2 immune function remain unclear. Here we used the murine whipworm Trichuris muris to investigate the effect of the fermentable fiber inulin on host responses to infection regimes that promote distinct Th1 and Th2 responses in C57BL/6 mice. In uninfected mice, dietary inulin stimulated the growth of beneficial bacteria, such as Bifidobacterium (Actinobacteria) and Akkermansia (Verrucomicrobia). Despite this, inulin prevented worm expulsion in normally resistant mice, instead resulting in chronic infection, whilst mice fed an equivalent amount of non-fermentable fiber (cellulose) expelled worms normally. Lack of expulsion in mice fed inulin was accompanied by a significantly Th1-skewed immune profile characterized by increased T-bet+-T cells and IFNγ production in mesenteric lymph nodes, increased expression of IDO1 in the caecum, and a complete absence of mast cell and IgE production. Furthermore, the combination of dietary inulin and high dose T. muris infection caused marked dysbiosis with expansion of the Firmicutes and Proteobacteria phyla, near elimination of Bacteroidetes, and marked reductions in caecal short-chain fatty acids. Neutralization of IFNγ during infection abrogated IDO1 expression, and was sufficient to restore IgE production and worm expulsion in inulin-fed mice. Our results indicate that whilst inulin promoted gut health in otherwise-healthy mice, during T. muris infection it exacerbated inflammatory responses and dysbiosis. Thus, the positive effects of fermentable fiber on gut inflammation appear to be context-dependent, revealing a novel interaction between diet and infection.