Abstract: 【Objective】 To explore the relationship between the disease resistance mechanism of the superior breed Zhuangluo No. 1 tilapia resistant to Streptococcus agalactiae and the bacterial community, as well as its genetic effect in hybrid offspring, which could provide theoretical basis for the selection and breeding of tilapia with both rapid growth and disease resistance traits through hybrid breeding. 【Method】 Self-pollination and crossbreeding were carried out using GIFT and Zhuangluo No. 1 tilapia as parents to obtain the GIFT inbred F₁, Zhuangluo No. 1 inbred F₁, GIFT×Zhuangluo No. 1 hybrid F₁, and Zhuangluo No. 1×GIFT hybrid F₁. The gill and tail fin tissues of 4 groups of tilapia were collected. The V3-V4 regions of 16S rRNA were sequenced. The bacterial community structures of different samples were analyzed, and biomarkers with significant differences among different sameple bacterial communities were screened by linear discriminant analysis effect size（LEfSe）. 【Result】 Alpha diversity analysis revealed that Shannon index, Shannon even index, and Simpson index of the bacterial community in gill and tail fin of Zhuangluo No. 1 inbred F₁ were greatly lower than GIFT inbred F₁. Accordingly, bacterial community diversity of Zhuangluo No. 1×GIFT hybrid F₁ and GIFT×Zhuangluo No. 1 hybrid F₁ were also lower than GIFT inbred F₁. Beta diversity analysis indicated that relative abundance of main bacterial community composition of Zhuangluo No. 1×GIFT hybrid F₁ and GIFT×Zhuangluo No. 1 hybrid F₁ was close to that of Zhuangluo No. 1 inbred F₁, suggesting heritable bacterial community in Zhuangluo No. 1. The relative abundance of the aerobic and facultative anaerobic bacteria Enhydrobacter in the gill and tail fin of Zhuangluo No. 1 inbred F₁, Zhuangluo No. 1×GIFT hybrid F₁ and GIFT×Zhuangluo No. 1 hybrid F₁ were greatly higher than GIFT inbred F₁, including a remarkable biomarker acidophile 2013Ark19i was identified in the of Zhuangluo No. 1. inbred gill bacterial community. 【Conclusion】 The gill bacterial community of Zhuangluo No.1 tilapia contains a relatively high abundance of aerobic and acidophilic bacteria, indicating that the gill mucus creates an acidic environment that is not conducive to the growth of Streptococcus agalactiae. However, aerobic bacteria can inhibit the growth of Streptococcus agalactiae through competitive oxygen consumption. It is speculated that the disease resistance mechanism of Zhuangluo No.1 tilapia is closely related to its bacterial community, and the structure of its bacterial community is hereditary, enabling the hybrid offspring to have disease resistance close to that of Zhuangluo No. 1 tilapia.