An eight-week feeding trial was conducted to evaluate the effects of a basal control diet (CON), Bacillus subtilis at 10⁷ (BS₇) and at 10⁸ CFU/g diet (BS₈), Lactococcus lactis at 10⁷ CFU/g (LL₇) and at 10⁸ CFU/g diet (LL₈), and oxytetracycline (OTC) at 4 g/kg diet on Nile tilapia. Fish with initial body weight of 2.83 ± 0.05 g (mean ± SD) were fed two times a day. Weight gain, specific growth rate, feed efficiency, protein efficiency ratio and lysozyme activity of fish fed BS₈, LL₈ and LL₇ diets were significantly higher than those of fish fed CON diet (p < 0.05). Superoxide dismutase and myeloperoxidase activity of fish fed BS₈, LL_8, BS₇, LL₇ and OTC diets were significantly higher than those of fish fed CON diet. Intestinal villi length and muscular layer thickness of fish fed BS₈, LL₈ and LL₇ diets were significantly higher than those of fish fed CON and OTC diets. Also, heat shock protein 70 (HSP70), interleukin (IL-1β), interferon-gamma (IFN-γ) and tumour necrosis factor (TNF-α) gene expression of fish fed BS₈ and LL₈ diets were significantly higher than those of fish fed CON diet. After 13 days of challenge test, cumulative survival rate of fish fed BS₈ and LL₈ diets were significantly higher than those of fish fed CON, BS₇ and OTC diets. Based on these results, B. subtilis and L. lactis at 10⁸ (CFU/g) could replace antibiotics, and have beneficial effects on growth, immunity, histology, gene expression, and disease resistance in Nile tilapia.

Prebiotics, probiotics, and synbiotics are considered natural functional food ingredients and an alternative feeding strategy for immunomodulation and antibiotic eradication. Olive flounder (Paralichthys olivaceus) is commercially cultured in China, Japan, and Korea. Antibiotics used in flounder aquaculture produce antibiotic-resistant pathogens and residual effects on human. Prebiotics are non-digestible oligosaccharides, fermented by intestinal microbiota to produce short-chain fatty acids that bind G protein receptors. Probiotics are usually incorporated into the diet at a certain concentration to alter the intestinal microbial population through colonization or implantation. Synbiotics are combinations of prebiotics and probiotics that produce synergistically better benefits than separately. Previous studies on olive flounder have revealed that various types of immunostimulants, prebiotics, probiotics, synbiotics, and potentially immunoreactive feed additives can increase growth and feed utilization; cellular and humoral immunity; immune gene expression; blood/serum biochemistry; and infectious-disease resistance. Additive concentrations, their activity, and viability after feed storage and in the intestine, and interactions with the intestinal microbial community are major limiting factors. This review summarizes and discusses changes in growth and feed utilization, innate immunity, biochemical parameters, gene transcription, and disease protection in olive flounder after diet supplementation with various types of additives. It also indicates areas needing greater attention for future research.