It is possible to reduce FM and FO down to 10 and 3% in diets for European sea bass juveniles without affecting fish growth. A reduction of FM down to 5 or 0% significantly reduces growth. FM replacements by alternative meals modify European sea bass posterior gut cytokine microenvironment. FM replacements by alternative meals modulate of the mucosa microbial species populations. FO replacement by VO increases lipid deposition in the anterior intestinal lamina propria. Supplementation of 0%FM/0%FO diets with LC-PUFA contributed to maintain gut homeostasis in relation to GALT response and microbiota profiles.