Interactive effects of dietary tryptophan and inulin on gut microbiota–mediated tryptophan metabolism and intestinal health

Abstract Tryptophan (Trp) is catabolized by gut microorganisms, resulting in a wide range of metabolites implicated in both beneficial and adverse host effects. Inulin, a fermentable fiber, has the potential to reshape the gut microbial environment. However, whether inulin interacts with dietary Trp levels to direct microbial Trp metabolism toward beneficial rather than potential harmful metabolites remains unclear. In this study, combined Trp and inulin supplementation was associated with a distinct microbial Trp metabolic profile characterized by increased indole-3-propionic acid and reduced indole levels. This shift was accompanied by concurrent changes in short-chain fatty acids and positive associations with markers related to intestinal barrier integrity. Inulin intake was also linked to an increased abundance of Faecalibaculum rodentium , a taxon associated with Trp metabolism. In addition, the altered metabolic profile was associated with activation of the aryl hydrocarbon receptor and pregnane X receptor, together with higher interleukin-22 levels. These findings suggest that inulin may help redirect microbial Trp metabolism toward beneficial derivatives under increased Trp availability, supporting a potential prebiotic–amino acid synergy in maintaining gut epithelial homeostasis.