The mammalian intestinal microbiome plays key roles in antagonizing systemic viral infections, but few studies have asked if this is true in poultry as well. So, a team of researchers examined how the microbiome impacts disease progression in chickens infected with nephropathogenic infectious bronchitis (IBV). Nephropathogenic IBV is a coronavirus that causes high mortality in chickens, and new control methods for the disease are desperately needed. To that end, the research team depleted the intestinal microbiota in specific pathogen free (SPF) chickens using broad-spectrum oral antibiotics (ABX). Microbiota depletion led to increased pathogenicity and viral burden upon infection with nephropathogenic IBV. The ABX-treated chickens also had severely reduced macrophage activation and impaired production of type I interferon (IFN), a core effector cytokine for host antiviral immunity. However, Lactobacillus isolated from SPF chickens restored the macrophage activation and type I IFN response in ABX-treated chickens, which ultimately limited IBV infection. Further, exopolysaccharide (EPS) metabolites of Lactobacillus spp. on their own could induce IFN-β. Overall, these results describe the IBV resistance mechanism employed by the microbiota in SPF chickens, and, although more research is needed, these results could lead to new prevention and control mechanisms for nephropathogenic IBV in poultry.