Valine-Curcumin Improves Growth, Intestinal Immunity, and Microbiota in Largemouth Bass (Micropterus salmoides)

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 with 15, 30, 60, and 120 mg/kg of Val-Cur. Each group had three replicates (25 fish per replicate). After 8 weeks, compared with both the CK and Cur groups, 30–60 mg/kg Val-Cur displayed significantly increased growth rates, specific growth rates, and protein conversion efficiency, and significantly decreased the feed conversion ratio. Quadratic regression analysis indicated that the optimal supplementation level was approximately 51.62 mg/kg Val-Cur. The Cur and Val-Cur between 30 and 60 mg/kg groups also displayed significantly improved serum biochemical indicators (↑HDL-C, ALB, LZM, CAT and SOD, and ↓MDA). These groups also promoted the expression of intestinal anti-inflammatory factors (TGF-β1andIL-10) and physical barrier genes (Claudin1,OccludinandClaudin4). In terms of regulating the intestinal microbiota, both Cur and Val-Cur significantly reduced the bacterial diversity (↓Sobs, Chao1 and PD indices) and increased the evenness of bacterial distribution (↑Simpson, Shannon and Pielou indices). In addition, the abundance of some potential pathogens (e.g.,Plesiomonas,Plesiomonas shigelloides, andPseudomonas fluorescens) significantly decreased, while the abundance of beneficial bacteria (e.g.,Faecalibaculum,Faecalibaculum rodentiumandLactobacillus murinus) significantly increased. Pearson’s correlation analysis showed that the increase in the abundance of beneficial bacteria was positively correlated with improvement in growth performance, serum biochemical and antioxidant capacity indicators. In summary, Val-Cur exerted superior biological effects at lower dietary inclusion levels than Cur. This study laid a theoretical foundation for elucidating the mechanism of Val-Cur in improving fish immunity and promoting the application of water-soluble curcumin in aquaculture.