LAUSR

Significance Inflammatory bowel diseases (IBD) are on the rise. Many studies have highlighted an inverse correlation between infection with parasitic helminths and the incidence of immune-mediated inflammatory diseases, such as IBD. The mechanisms by which parasitic helminths suppress inflammation and prevent the onset of inflammatory diseases is not well understood. This study describes a discovery and validation pipeline of antiinflammatory biologics from the recombinant secretome of gut-dwelling hookworms as novel and safe drug leads. Numerous proteins from distinct families protected mice against inducible colitis, and lead proteins suppressed production of inflammatory cytokines from IBD patient gut biopsy T cells ex vivo, highlighting a gold mine of new biologics inspired by coevolution of humans and their macrobiome.