Chikungunya virus drives gut microbiota shifts and IFN-Mediated intestinal repair: insights into microbiota-immune interplay

Chikungunya virus (CHIKV) infection causes joint damage and gastrointestinal clinical symptoms, including vomiting and diarrhea, particularly in elderly populations, reflecting the potential role of gut immunity in infection. However, the mechanisms by which CHIKV induces gastrointestinal diseases remain largely unexplored. This study investigated the characteristics of fecal and gut microbiota, gut metabolites, and gut immunity post-infection using multi-omics analysis. The role of gut microbiota was further validated through Oral antibiotic depletion (Abx). Importantly, a systematic comparison of age-dependent differences in gut microbiota composition and immune responses following CHIKV infection was conducted to elucidate the involvement of gut microbiota in CHIKV pathogenesis. CHIKV joint inoculation induces gastrointestinal infection and histological damage, drives fluctuations in gut microbiota, markedly increasing the abundance of Bacteroides fragilis and Prevotella sp. and upregulates conjugates of taurine and bile acids. CHIKV infection further exacerbates systemic inflammatory burden and activates intestinal interferon (IFN) signaling cascades, which supports gut repair and mucosal regeneration, but low antiviral responses to CHIKV infection compared with that of adult animals. Our results suggest that the gastrointestinal tract, along with its microbes and metabolites, modulates CHIKV infection in an age-dependent manner, providing critical insights for diagnosis, treatment, and novel therapeutic development.