Japanese encephalitis virus infection modulates gut microbiota of immunocompetent mice

Japanese encephalitis virus (JEV), a neurotropic pathogen, causes severe encephalitis in humans and animals. It invades the central nervous system, and triggers neuroinflammation leading to neuronal damage. However, the impact of JEV on the gut microbiome of adult immunocompetent hosts remains unclear. Here, we characterized JEV-induced gut microbiota alterations in C57BL/6 J mice using 16S rRNA sequencing of the V3-V4 region and cytokine/chemokine profiling. Alpha diversity analysis showed a higher Shannon index and lower Simpson index in JEV-infected group. Relative abundance of bacterial groups revealed increased Deferribacteres and Spirochaetes and decreased Actinobacteria and Firmicutes at phylum level. LEfSe analysis demonstrated enhanced relative abundance of Lachnospiraceae_NK4A136_group, norank_f_Lachnospiraceae and Lachnoclostridium, whereas that of Turicibacter, Coriobacteriaceae_UCG-002 and Romboutsia decreased at genus level. At 14dpi, IL-6, IL-10, TNF-α, CCL2, IFN-γ, and IFN-β were upregulated in the brain, while only IFN-γ was elevated in colon tissue, accompanied by mild pathological damage in colonic epithelium. These findings demonstrate that JEV infection remodels gut microbiota composition and disrupts colonic homeostasis in immunocompetent adult mice, suggesting that gut microbial alterations may be mediated by brain-derived IFN-γ-producing lymphocytes via the brain-gut axis.