<i>Akkermansia muciniphila</i> enhances chicken resistance to infectious bronchitis virus by boosting GABA synthesis and suppressing the NF‐κB inflammatory pathway

Abstract Infectious bronchitis virus (IBV) is a major viral pathogen causing substantial economic losses in the global poultry industry. However, the limited efficacy of commercial vaccines and the absence of approved antiviral drugs underscore the urgent need for novel strategies to combat IBV, particularly in the context of antibiotic‐free poultry production. Emerging evidence suggests that gut microbiota plays a crucial role in shaping host immunity and antiviral resilience. In this study, we demonstrated that gut microbiota composition is a key determinant of IBV resistance in chickens, as revealed through a fecal microbiota transplantation (FMT) model. Utilizing multi‐omics approaches, we conducted a comprehensive characterization of microbiomic, viromic, and metabolic differences among adult chickens, young chickens, and FMT‐treated young chickens for the first time, establishing a mechanistic link between gut microbiota and IBV resistance. Building on these insights, longitudinal microbiome profiling in a newly developed persistent IBV infection model identified Akkermansia muciniphila as the key bacterium conferring IBV resistance, with its administration improving survival rates from 30–35% to 90–95%. Additionally, two novel candidate probiotics, Cloacibacillus porcorum and Neglecta timonensis , exhibited moderate yet measurable protective effects. Mechanistic investigations revealed that Akkermansia muciniphila enhances γ‐aminobutyric acid (GABA) production, which suppresses NF‐κB‐driven inflammatory responses, reduces pro‐inflammatory cytokine levels, alleviates nephritis, and upregulates antiviral interferon expression, thereby fortifying host defenses against IBV infection. These findings provide a scientific foundation for deploying live biotherapeutic products as an intervention strategy against IBV and highlight the broader potential of gut microbiota modulation in mitigating infectious diseases and optimizing poultry health management.