The microbiota-gut-immunity axis in teleost fish: dual regulatory mechanisms of viral infections and prospects for microbiome-based antiviral strategies.

Bacteria and viruses engage in complex synergistic and antagonistic interactions with profound implications for host health, particularly through functional modulation by intestinal and other mucosal (e.g., skin, gill) microbiota. In teleost models, intestinal microbiota demonstrates dual regulatory capacities-either potentiating or suppressing viral infections. However, the mechanistic underpinnings of these interactions remain inadequately explored in aquatic species. This review systematically delineates the dual regulatory pathways (facilitative vs. inhibitory) through which the gut microbiota modulates viral infections in fish. Based on these mechanisms, we propose a novel microbiota-gut-immunity axis framework-defined as the bidirectional communication network linking gut microbial communities, intestinal barrier function, and host systemic immunity-for the development of integrated antiviral interventions. Furthermore, we critically evaluate emerging strategies-including probiotics, prebiotics, postbiotics, synbiotics, fecal microbiota transplantation (FMT), microalgae, seaweed, and phytoactive compounds-to develop preventive and therapeutic countermeasures. Based on mechanistic insights, probiotics and prebiotics emerge as the most promising candidates for large-scale application, as they directly reshape gut microbial composition and enhance host immunity along the microbiota-gut-immunity axis. In contrast, FMT and herbal medicines, while acting on multiple nodes of the axis, currently face safety and standardization challenges, positioning them as adjunctive therapies. Importantly, these mechanistic insights reveal evolutionarily conserved immune pathways with significant translational potential for human virology.