The presence of healthy gut microbiota in the gastrointestinal tract of fish is important for the optimal function of gut, which plays a significant role in the host growth and health. The aim of the present study was to investigate the effect of dietary stress worry free (SWF®) on growth, feed utilization and disease resistance of hybrid sturgeon (Acipenser baerii x Acipenser schrenckii). Sturgeon were fed for three weeks with SWF® supplemented or basal diet. The weight gain and FCR of sturgeon fed on the diet supplemented with SWF® were significantly improved (P<0.05). SWF® supplemented diet provoked an increase in the resistance of sturgeon against A. veronii Hm091 (P=0.09). In terms of gut microbiota, the number of total bacteria, Fusobacteria, Firmicutes, and Proteobacteria were increased significantly in the SWF® group (P<0.05), whereas significant reduction of Actinobacteria was observed in the gut of the SWF® group compared with the control group (P<0.01). Moreover, at the end of the experiment the gut microbiota of sturgeon, were colonized to germ-free (GF) zebrafish for three days. Results indicated that, the expression of growth promoter genes mTOR, MyoD and Myogenin was significantly higher in GF zebrafish colonized with gut microbiota of SWF® group of sturgeon. Furthermore, TGF-β was increased significantly in GF zebrafish colonized with gut microbiota from SWF® group (P<0.01), whereas the expression of TNF-α was significantly decreased (P<0.05). The expression of non-specific immune related genes DEFBL-1, C3a and Lysozyme was significantly increased in GF zebrafish colonized with gut microbiota of sturgeon fed on SWF® (P<0.05). Group of GF zebrafish colonized with gut microbiota of sturgeon fed on SWF® had significantly higher survival rate against A. veronii Hm091 (P<0.05). Our study suggests that, the gut microbiota induced by SWF® played a great role in growth and disease resistance of sturgeon using GF zebrafish model.