Abstract: Infections with Giardia are 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 to Giardia muris infection. 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 to G. muris infection. Furthermore, G. muris colonization led to a significantly reduced evenness in the gut microbial communities of BALB/c mice. Our data indicate that differential susceptibility to Giardia infections may be related to RORγt+ Treg controlling Th17 activity and that changes in the microbiota composition upon Giardia infection partially depend on the host background.