Antiviral effect of lactoferrin against infectious bronchitis virus (IBV) are associated with alterations in the gastrointestinal microbiome.

Coronaviruses (CoVs) are an enveloped, polymorphic, positive-sense single-stranded RNA viruses. Currently, both humans and animals are threatened by CoVs, making them a major public health concern. Among the four genera of the family Coronaviridae, infectious bronchitis virus (IBV), which belongs to the genus Gammacoronavirus, continues to cause substantial economic losses in the poultry industry. Nephropathogenic IBV strains, including the Taiwan-I (TW-I) and Taiwan-II (TW-II) serotypes, are the most prevalent IBVs in Taiwan and China and have continued to spread and generate variants through mutation and genetic recombination. Because IBV can replicate in the epithelial cells of the trachea, lung, kidney, and intestine, this study investigated the dysbiosis of the ileal microbiota caused by IBV TW-I and TW-II serotypes. The reduced weight gain of chickens infected with IBV TW-I or TW-II was improved by lactoferrin (LF). The antiviral effects of LF included a significant reduction in viral loads in the ileum of infected chickens. Furthermore, the villus shedding, decreased villus height, increased crypt depth, and reduced number of goblet cells induced by IBV infection were markedly attenuated by LF. Alterations in the ileal microbiome were also observed following LF treatment. Regarding cytokine responses, the IBV-induced upregulation of TGF-β and IL-10 and the elevated infiltration of CD3+ T cells in the ileum were reduced by LF, whereas the mRNA expression levels of IFN-γ, IL-2, and IL-4 were upregulated by LF. Moreover, the IBV-induced downregulation of MUC2, occludin, and ZO-1 in the ileum was reversed by LF. LF shifted the ileal microbiota toward homeostasis, regulated the immune response to facilitate viral clearance, and restored the intestinal barrier damaged by IBV TW-I and TW-II infection.