Nile tilapia is recognized as a suitable candidate for intensive farming and sustainability of the aquaculture industry. However, one issue limiting Nile tilapia expansion in arid and semi-arid areas is the scarcity of freshwater resources. In this study, the supplementation of synbiotics was investigated to enhance the growth performance, growth-related genes, intestinal health, and immunity of Nile tilapia reared in inland brackish groundwater. Four diets were prepared where the basal diets were mixed with the dietary mixture of probiotics and prebiotics (Synbiotic Lactic Dry®, a blend of Saccharomyces cerevisiae, Lactobacillus acidophilus, Streptococcus faecium, and Bacillus subtilis, mannan oligosaccharides and β-1.3/1.6-D-glucan) at 0, 0.5, 1, and 2 g/kg. After eight weeks, the final weight and weight gain are linearly increasing with increasing the supplementation level of synbiotic. Markedly fish fed 0.5, 1, and 2 g/kg of synbiotic had higher final weight, weight gain, and feed intake and lower feed conversion ratio (FCR) than fish fed synbiotic free diet. The specific growth rate (SGR) was significantly higher in fish fed 1 and 2 g/kg than in fish fed 0 and 0.5 g/kg. The intestine of fish fed on synbiotic shows an increase in intestinal villi density. Further, the intestine of fish fed on synbiotic showed an increase in the length and branching intestinal villi (anterior, middle, and posterior) in a dose-dependent manner. The lysozyme and phagocytic activities were significantly different from the control, while synbiotic supplementation did not affect the phagocytic index. Interestingly, the results showed marked upregulation of ghrelin, IGF-1, and GH genes in fish fed synbiotics at 0.5, 1, and 2 g/kg. In addition, fish fed 2 g/kg had the highest expression of ghrelin, IGF-1, and GH genes. In conclusion, growing Nile tilapia in inland brackish groundwater can be achieved without negative impacts on the growth performance and health status. Supplementing synbiotics (1–2 g/kg) in Nile tilapia feeds enhanced the growth and feed performances, intestinal histomorphological features, growth-related genes, and immune response.
