**Background:** Coho salmon (Oncorhynchus kisutch) is a high-value aquaculture species in China, but the rising cost and limited supply of fish meal—the primary protein source in aquafeeds—necessitate alternative protein sources. Soybean meal is a promising candidate due to its availability and cost, but it contains anti-nutritional factors that can harm fish health. Microbial fermentation can reduce these anti-nutritional factors and improve nutritional quality. This study aimed to evaluate the effects of replacing fish meal with unfermented and/or fermented soybean meal (using Bacillus cereus) on growth performance, body composition, antioxidant capacity, immunity, and related gene expression in juvenile coho salmon.
**Methods:** Four iso-nitrogenous (≈41% protein) and iso-lipidic (≈15% lipid) diets were formulated: G0 (control, 28% fish meal protein), G1 (10% fish meal protein replaced with unfermented soybean meal), G2 (5% unfermented + 5% fermented soybean meal replacement), and G3 (10% fermented soybean meal replacement). Soybean meal was fermented with Bacillus cereus (10% v/m inoculum, 1:1.4 material-to-water ratio, 37°C for 60 h). A total of 360 juvenile coho salmon (initial weight 159.63 ± 9.54 g) were randomly assigned to 12 net cages (30 fish per cage, triplicate per diet) and fed for 12 weeks. Growth parameters, whole-body composition (moisture, crude protein, crude lipid, ash), serum biochemical indices (TP, GLU, T-CHO, ALB, AKP), liver antioxidant capacity (SOD, CAT, MDA, T-AOC, GSH-PX, GST, OH·-CR, O2·-CR, GSH), and mRNA expression of sod, cat, gsh-px, gst, nrf2, tnf-α, and il-6 genes were measured. Statistical analysis used one-way ANOVA with Duncan's test (p < 0.05).
**Key Results:** The G3 diet (10% fermented soybean meal) significantly improved growth performance: WGR, SGR, CF, and PER were significantly higher (p < 0.05) in G3 compared to G0, while HSI, VSI, and FCR were significantly lower (p < 0.05). Conversely, G1 and G2 showed significantly lower WGR, SGR, CF, and PER and higher HSI, VSI, and FCR (p < 0.05). No significant differences were found in survival rate or whole-body composition (moisture, crude protein, crude lipid, ash) across all groups (p > 0.05). Serum biochemical indices (TP, GLU, ALB, AKP, T-CHO) were significantly higher in G3 and significantly lower in G1 and G2 compared to G0 (p < 0.05). Liver antioxidant capacity: SOD, CAT, GSH-PX, GSH, GST, OH·-CR, O2·-CR, and T-AOC were significantly higher in G3 and significantly lower in G1 and G2 versus G0 (p < 0.05). MDA was significantly lower in G3 and significantly higher in G1 and G2 (p < 0.05). Gene expression: sod, cat, gsh-px, gst, and nrf2 were significantly upregulated in G3 and downregulated in G1 and G2 (p < 0.05). The inflammatory cytokine genes il-6 and tnf-α were significantly downregulated in G3 and significantly upregulated in G1 and G2 (p < 0.05).
**Clinical Implications:** Replacing 10% of fish meal protein with fermented soybean meal (Bacillus cereus) significantly enhances growth performance, serum health markers, and antioxidant/immunity capacity while reducing inflammatory gene expression in juvenile coho salmon. Unfermented soybean meal produced opposite effects, likely due to anti-nutritional factors. These findings provide a theoretical basis for developing cost-effective, sustainable coho salmon feeds that reduce reliance on fish meal without compromising fish health or growth. The results are specific to the 10% replacement level; higher substitution ratios may yield different outcomes and warrant further investigation.