Abstract

Simple SummaryCurcumin holds great potential as a natural immunostimulant in animal nutrition, yet its practical application is severely constrained by low water solubility and poor bioavailability. We previously synthesized a highly water-soluble valine-curcumin conjugate (Val-Cur). This study now presents the first comprehensive in vivo evaluation of Val-Cur in largemouth bass, systematically revealing its enhanced efficacy and underlying physiological mechanisms. We found that dietary Val-Cur at doses as low as 15–30 mg/kg outperforms native curcumin (60 mg/kg) across multiple key metrics: it more effectively promotes growth, improves serum lipid profiles, and strengthens systemic antioxidant and anti-inflammatory responses. These benefits are achieved through a coordinated mechanism that includes reinforcing intestinal barrier integrity, modulating apoptosis-related gene expression, and beneficially reshaping the gut microbiota—specifically by inhibiting potential pathogens while enriching beneficial, short-chain fatty acid-producing bacteria. The poor water solubility of curcumin is a major bottleneck in animal nutrition. Our findings demonstrate that an amino acid conjugation strategy effectively reduces the effective dose while surpassing native curcumin in efficacy, representing an important step for functional feed development.Curcumin (Cur), a polyphenol with excellent antioxidant and anti-inflammatory properties, is widely used in aquaculture. However, its low water solubility limits bioavailability. This study first investigated the effects of a highly water-soluble and bioavailable valine-curcumin (Val-Cur) on growth performance, antioxidant capacity, inflammatory factor expression and gut microbiota in juvenile largemouth bass. A total of 450 healthy largemouth bass (initial weight 12.00 ± 0.45 g per fish) were randomly divided into six groups: the basal diet group (CK), the group supplemented with 60 mg/kg of curcumin (Cur), and groups that were fed