Can the genetic background modulate the effects of feed additives? Answers from gut microbiome and transcriptome interactions in farmed gilthead sea bream (Sparus aurata) fed with a mix of phytogenics, organic acids or probiotics

This study evaluated how genetic background modulates responses to dietary additives in gilthead sea bream (Sparus aurata). Reference (REF) and growth-selected (GS) fish were fed control diets supplemented with phytogenics (PHY), organic acids (OA), or a Bacillus-based probiotic (PROB) over 12 weeks. GS fish exhibited significantly superior growth performance, lower feed conversion ratios (1.19 in GS-PROB vs 1.64 in REF-PROB), and reduced individual microbiota variability compared to REF fish. PROB supplementation improved feed efficiency (0.84) and intestinal barrier function in GS fish, coinciding with mucosal establishment of Bacillus (>2.5%) and higher abundance of Kocuria. In contrast, REF fish showed reduced performance when fed PROB. PHY supplementation selectively up-regulated transcriptomic markers of epithelial integrity, sphingolipid, and cholesterol/bile salt metabolism in GS fish without altering gut microbiota composition. OA supplementation decreased potential pathogens (Streptococcus, Staphylococcus) in REF fish while increasing submucosal granulocyte infiltration and altering neutrophil degranulation pathways. Overall, the efficacy of functional feed additives strongly depends on the host genome and its gut microbiota interactions.