| Summary: | Plant-derived bioactive compounds with promising nutritional and therapeutic attributes (phytogenics) are among the top priorities in the aquaculture sector. Therefore, the impact of thymol (Thy) and/or thymoquinone (ThQ) on the growth, immune response antioxidant capacity, and <i>Aeromonas sobria</i> (<i>A. sobria</i>) resistance of Nile tilapia was investigated. Four fish groups were fed a control diet and three basal diets supplemented with 200 mg/kg diet of Thy or ThQ and a blend of both Thy and ThQ at a level of 200 mg/kg diet each. At the end of the feeding trial (12 weeks), the tilapias were challenged intraperitoneally with virulent <i>A. sobria</i> (2.5 × 10<sup>8</sup> CFU/mL) harboring aerolysin (<i>aero</i>) and hemolysin (<i>hly</i>) genes. The results revealed that tilapias fed diets fortified with a combination of Thy and ThQ displayed significantly enhanced growth rate and feed conversion ratio. Notably, the expression of the genes encoding digestive enzymes (pepsinogen, chymotrypsinogen, α-amylase and lipase) and muscle and intestinal antioxidant enzymes (glutathione peroxidase, catalase and superoxide dismutase) was significantly upregulated in Thy/ThQ-fed fish. An excessive inflammatory response was subsided more prominently in the group administrated Thy/ThQ as supported by the downregulation of <i>il-β</i>, <i>il-6</i> and <i>il-8</i> genes and in contrast, the upregulation of the anti-inflammatory <i>il-10</i> gene. Remarkably, dietary inclusion of Thy/ThQ augmented the expression of autophagy-related genes, whilst it downregulated that of <i>mtor</i> gene improving the autophagy process. Furthermore, Thy/ThQ protective effect against <i>A. sobria</i> was evidenced via downregulating the expression of its <i>aero</i> and <i>hly</i> virulence genes with higher fish survival rates. Overall, the current study encouraged the inclusion of Thy/ThQ in fish diets to boost their growth rates, promote digestive and antioxidant genes expression, improve their immune responses and provide defense against <i>A. sorbia</i> infections with great economic benefits.
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