Immune modulation by hookworm excretory/secretory proteins improves insulin sensitivity in a mouse model of type 2 diabetes

We treated mice fed on normal or diabetes-promoting diets with excretory/secretory products (ES) from the gas-trointestinal helminth Nippostrongylus brasiliensis. We demonstrated that treatment with crude ES products from adult worms (AES) or infective third-stage larvae (L3ES) from N. brasiliensis improved glucose tolerance and attenuated body weight gain in mice fed on a high glycemic index diet. N. brasiliensis ES administration to mice was associated with a type 2 immune re-sponse measured by increased eosinophils and IL-5 in peripheral tissues but not IL-4, and with a decrease in the level of IL-6 in adipose tissue and corresponding increase in IL-6 levels in the liver. Moreover, treatment with AES or L3ES was associated with significant changes in the com-munity composition of the gut microbiota at the phylum and order levels. These data highlight a role for N. brasiliensis ES in modulating the immune response associated with T2D, and sug-gest that N. brasiliensis ES contain molecules with therapeutic potential for treating metabolic syndrome and T2D.