Identification of taurine as a resistance-associated metabolite against Aeromonas salmonicida and its protective, immune-regulatory, and microbiota-shaping effects in turbot (Scophthalmus maximus)

Infectious diseases represent a major challenge for aquaculture, leading to substantial economic losses and compromising fish welfare. Consequently, identifying viable and environmentally sustainable solutions is a key priority for the sector. This study aimed to identify metabolic markers associated with resistance to Aeromonas salmonicida subsp. salmonicida in turbot ( Scophthalmus maximus ), with the ultimate goal of incorporating resistance-associated metabolites into functional diet formulations. A comparative metabolomic analysis was performed on two full-sibling families with differing susceptibility to the pathogen, revealing a subset of metabolites with differential abundance in the head kidney or liver. Preliminary screening in zebrafish ( Danio rerio ) larvae identified 5-L-glutamyl-taurine as a promising protective compound. Due to its high cost, its precursors taurine and L-glutamic acid were tested and also provided protection in zebrafish larvae infected with A. hydrophila . Dietary supplementation with 1.5 % taurine significantly increased survival in turbot challenged with A. salmonicida , yielding a 34 % higher survival rate compared to controls, despite increased bacterial loads observed at 24 h post-infection (hpi). Taurine supplementation also modulated the intestinal microbiota, reducing alpha diversity through expansion of Vibrionaceae and Marinobacteraceae . RNA-Seq analysis of head kidney and intestinal tissues suggested that taurine's protective effect may involve attenuation of the early inflammatory response, potentially minimizing tissue damage. Overall, these findings support taurine as a promising dietary supplement to enhance resistance to bacterial infections in aquaculture species. • Untargeted metabolomics identified 5-L-glutamyl-taurine as a resistance marker in turbot. • 5-L-glutamyl-taurine and its precursors, L-glutamic acid and taurine protected zebrafish larvae from A. hydrophila . • A taurine-enriched diet enhanced turbot survival despite higher A. salmonicida loads. • Taurine modulated turbot gut microbiota, reducing alpha diversity and expanding Vibrionaceae and Marinobacteraceae . • RNA-Seq suggested taurine's protective effect could involve dampening inflammation and promoting immune tolerance.