This study aimed to assess the effects of diets containing a blend of plant protein sources (cottonseed meal, sunflower meal, and jojoba meal) fermented with yeast (Saccharomyces cerevisiae) at three different levels (25 %, 50 %, and 75 %) instead of fishmeal (FM) on the growth performance, anti-nutritional factors content, and blood profile response of Nile tilapia (Oreochromis niloticus). Four experimental diet (33.6 % crude protein) and (18.61 MJ kg−1 gross energy) were formulated. The study included four diets: a control diet, FCSJM-25 %, FCSJM-50 %, FCSJM-75 % which replaced fishmeal based on protein content. Fries (3.53± 0.07 g) were randomly allocated into twelve glass aquaria (180 L capacity) in triplicate per each treatment (25 fish/ aquarium) for 90 days. After the 90-day feeding trial, the results showed that fish fed the control diet, FCSJM-25 %, and FCSJM-50 % had the highest final body weight, weight gain, specific growth rate, and average daily gain, whereas fish fed FCSJM-75 % had the lowest values for these parameters. The best feed conversion ratio (FCR) was observed in fish fed FCSJM-25 % or FCSJM-50 % (P < 0.05). The highest apparent protein digestibility was found in fish fed the control diet or FCSJM-25 %. Diets with FCSJM-25 % had the highest white blood cells (WBCs) values (P < 0.05). Control diet, FCSJM-25 %, and FCSJM-50 % resulted in the highest levels of complement component (C3), C4, growth hormone, and IgM (P < 0.05). However, control diet had the highest triglyceride and HDL levels, while fish fed FCSJM-25 % had the highest levels of LDL (P < 0.05). Fish fed a diet with FCSJM-50 % recorded the highest cholesterol content. The control or FCSJM-25 % diets showed the highest values of creatinine, phosphorus, and calcium (P < 0.05). There were no significant differences in ALT, AST, and uric acid among the treatments. The study concluded that FM can be replaced with either FCSJM-25 % and FCSJM-50 % without affecting growth performance and feed utilization.
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