Gut Microbiota Metabolically Mediate Parasite Infection in Zebrafish

Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbialcommunities across vertebrates, although how gut microbiota may facilitate or hinder parasiteinfection remain poorly defined. In this work we utilized a zebrafish model to investigate therelationship between gut microbiota, gut metabolites, and IHP infection. We found that extremedisparity in zebrafish parasite infection burden is linked to the composition of the gutmicrobiome, and that changes in the gut microbiome are associated with variation in a class ofendogenously-produced signaling compounds, N-acylethanolamines, that are known to be involved inparasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbeswhose relative abundance explains the association between gut metabolites and infection outcomes.Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, whichis putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity againstPseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findingsunderscore the importance of the gut microbiome as a mediating agent in parasitic infection andhighlights specific gut metabolites as tools for the advancement of novel therapeutic interventionsagainst IHP infection.