Various Vibrio species are known to cause severe mortality events in oyster aquaculture and are a threat to oyster farmers . In France, Vibrio aestuarianus, V. coralliilyticus , V. harveyi , and V. crassostreae have been identified as major pathogens causing disease in Pacific oysters (Crassostrea gigas ). This project focused on addressing these challenges by identifying and characterizing next-generation probiotic bacteria capable of mitigating Vibrio diseases at various oyster life stages (larvae, spat, and adult oysters) , ultimately enhancing oyster health and welfare. The methodology involved isolating bacteria from oyster tissues and microalgae cultures on a wide variety of oligotrophic media. Sequential screening of bacterial colonies for antagonistic activity against key pathogens (Vibrio aestuarianus, V. coralliilyticus , V. harveyi , V. crassostreae , V. europaeus , V. neptunius , and V. tubiashii ) was conducted using a replica plating technique. For further characterization, isolates inhibiting the growth of pathogens were tested for hemolytic activity and antibiotic susceptibility. In addition, they were identified via 16S rRNA gene sequencing, and genome analysis (after dereplication) . The sequential screening results are shown in Figure 0. A large number of colonies (9280) processed via replica plating technique, yielded 42 candidate probiotic strains exhibiting antagonistic effects against pathogenic Vibrio spp. From these 42 candidates, 16 stains exhibiting robust activity profiles and were selected for genome analysis. Ultimately, strain AESF22 emerged as a promising probiotic, demonstrating both efficacy and safety in oyster aquaculture. This research represents a significant advancement in combatting bacterial diseases in oyster aquaculture, promoting sustainable practices within the industry.