Dietary tryptophan rescues growth impairment during giardiasis independently of parasite burden

Giardiasis is an intestinal disease caused by the parasite Giardia duodenalis. Intestinal barrier dysfunction during Giardia infection has been linked to childhood growth stunting, particularly in communities with prevalent malnutrition and repeated exposure to Giardia. In pediatric cohort studies, growth stunting has been strongly associated with asymptomatic Giardia detection in fecal samples. Several studies have described potential mechanisms by which Giardia disrupts the epithelial barrier, but less is known about factors that may support epithelial homeostasis in response to infection. Microbiota-derived tryptophan metabolites that activate aryl hydrocarbon receptor (AHR) signaling are a key pathway involved in epithelial barrier homeostasis. We tested whether dietary tryptophan availability influenced host growth outcomes and aryl hydrocarbon receptor activity during giardiasis. We used established murine Giardia malnutrition models and compared host growth, a correlate of barrier dysfunction, with a tryptophan-supplemented diet group. Giardia-infected mice fed a low-protein diet failed to gain weight whereas infected mice fed an isocaloric regular protein diet gained weight similar to diet-matched controls. Tryptophan supplementation of the low-protein diet rescued this diet-dependent and infection-induced weight defect in C57BL/6J and BALB/c mice. This growth rescue was associated with increased intestinal Cyp1a1 expression, a canonical AHR target, but without a reduction in infection burden. Glycine supplementation, used as a non-essential amino acid control that is not expected to generate AHR ligands, did not produce the same effect, suggesting that the growth rescue observed with tryptophan supplementation was not due to general amino acid supplementation. Measurements of circulating tryptophan metabolites in plasma showed limited and inconsistent differences across experimental groups, which may suggest that the growth rescue phenotype may be dependent on local intestinal or mucosal AHR-associated signaling rather than an increase in circulating metabolites. Our findings show that dietary tryptophan availability shapes host growth outcomes during giardiasis. This may also be important as it highlights that host nutrition may be a key contributor to post-infection growth impairment in young children.