This study evaluated the growth performance, immune response, hepatopancreatic health, and disease resistance in Litopenaeus vannamei fed diets supplemented with fermented pomegranate peel polyphenols (FPPP) for 45 days. Five diets were formulated to contain various levels of FPPP: FP0 (no FPPP), FPPP inclusion at 0.015% (FP1), 0.030% (FP2), 0.060% (FP3), and 0.120% (FP4). The results indicated there were no significant variations in weight gain rate (WGR), specific growth rate (SGR), and feed conversion rate (FCR) of shrimp in all treatment groups (p > 0.05), but the survival (SR) of shrimp was significantly higher in all groups with the addition of FPPP (p < 0.05). Compared with FP0 group, the contents of total protein (TP) and globulin (GLB) in serum biochemical indexes of FP3 and FP4 groups were significantly increased, and the content of blood urea nitrogen (BUN) was significantly decreased (p < 0.05). Compared with FP0 group, the activities of superoxide dismutase (SOD), catalase (CAT), alkaline phosphatase (AKP), acid phosphatase (ACP), and lysozyme (LZM) in the hepatopancreas and serum of FP3 and FP4 groups were significantly increased (p < 0.05). Similarly, the activities of glutathione peroxidase (GSH‐Px), total antioxidant capacity (T‐AOC), and phenoloxidase (PO) in the hepatopancreas and serum of FP2 group were significantly higher than those of FP0 group (p < 0.05). In addition, the content of malondialdehyde (MDA) in the hepatopancreas and serum of shrimp in FPPP‐added groups was decreased (p < 0.05). Compared with FP0 group, the expression levels of SOD, CAT, glutathione S‐transferase (GST), LZM, prophenoloxidase (ProPO), penaeidin‐3 (Pen3), Crustin, immune deficiency (Imd), Toll, and Relish genes were significantly upregulated in the hepatopancreas of shrimp in FP3 and FP4 groups (p < 0.05). Additionally, increasing the addition level of FPPP resulted in a more compact hepatosomal arrangement of the shrimp’s hepatopancreas, a more visible star‐shaped lumen structure, and a significantly higher number of B cells. Finally, the cumulative SR of shrimp in FPPP groups was significantly higher than that in FP0 group after 7 days of infection with Vibrio alginolyticus (p < 0.05). In summary, dietary supplementation of FPPP can improve SR, immunity, and hepatopancreatic health and resistance to Vibrio alginolyticus of L. vannamei.
