Profiling Fecal Microbiome and Metabolites in a Feline Infectious Peritonitis Virus Challenge Model in Kittens: A Pilot Discovery Study.

Feline infectious peritonitis (FIP), caused by FIPV, is a highly fatal disease. The coordinated shifts in gut microbiota, metabolome, and their interactions following FIPV infection remain poorly understood. In this pilot discovery work, we established an oral FIPV DF-2 challenge model in kittens, which reproduced typical FIP phenotypes confirmed by clinical scores and pathology for exploratory multi-omics profiling. Using V3-V4 16S rRNA sequencing on Illumina PE300 and UHPLC-MS-based untargeted metabolomics, combined with LEfSe, OPLS-DA, and Pearson correlation, we preliminarily characterized fecal microbial and metabolic alterations associated with FIP onset in this exploratory animal model. FIP-affected kittens exhibited reduced abundances of Ligilactobacillus, Bifidobacterium, and Limosilactobacillus, alongside elevated Roseburia, Helicobacter, and Campylobacter. Differential metabolites were enriched in six core pathways, which preliminarily suggest potential links to oxidative stress, energy metabolism impairment, immune suppression, and systemic inflammatory response during FIP progression. Correlation analyses linked beneficial genera to upregulated 4-hydroxynonenal and xanthosine, while opportunistic taxa (Helicobacter, Campylobacter, Enterobacterales) correlated with caffeine, 1-methyluric acid, and retinoic acid derivatives. These preliminary findings suggest unique fecal microbial-metabolic signatures in FIP, providing hypothesis-generating mechanistic insights and potential therapeutic targets. However, given the exploratory nature of this pilot study, these results require validation in larger, independently controlled cohorts.