AbstractInfections withGiardiaare among the most common causes of food and water-borne diarrheal disease worldwide. Here, we investigated Th17, Treg and IgA responses, and alterations in gut microbiota in two mouse lines with varying susceptibility toGiardia murisinfection. Infected BALB/c mice shed significantly more cysts compared with C57BL/6 mice. Impaired control of infection in BALB/c mice was associated with lower Th17 activity and lower IgA levels compared with C57BL/6 mice. The limited metabolic activity, proliferation and cytokine production of Th17 cells in BALB/c mice was associated with higher proportions of intestinal Foxp3+RORγt+regulatory T cells and BALB/c mice developed increased RORγt+Treg:Th17 ratios in response toG. murisinfection. Furthermore,G. muriscolonization led to a significantly reduced evenness in the gut microbial communities of BALB/c mice. Our data indicate that differential susceptibility toGiardiainfections may be related to RORγt+Treg controlling Th17 activity and that changes in the microbiota composition uponGiardiainfection partially depend on the host background.