Metatranscriptomic Profiling Reveals Species-Level Microbial Shifts and Metabolic Remodeling in Feline Oral Inflammatory Disease

Progressive oral mucosal inflammatory diseases are common among mammals. Cats are a valuable natural model for these conditions because they frequently develop oral diseases with varying severity, yet causative microbes remain unidentified in part because longitudinal studies are challenging and sampling is difficult. The lack of individual pathobionts suggests community-scale taxonomic and functional remodeling of the microbiome may be a contributor to oral disease. This study evaluated the microbiome composition and function of 33 cats across three cohorts with different levels of inflammation: healthy, aggressive periodontitis, and feline gingivostomatitis. Ultradeep metatranscriptomic sequencing was used to assign microbial taxonomy and examine functional changes via differential gene expression analysis to reveal genera that maintained stable relative abundance across all three disease states, including Porphyromonas and Treponema, while others had more subtle shifts in species activity, including multiple members of Moraxella and Mycoplasmopsis. Disease status was marked by co-occurring changes in low activity species accompanied by microbiome-level changes in protein, arginine, and nitrogen metabolism. Cats with aggressive periodontitis and gingivostomatitis displayed microbiome shifts in species that correlated to disease state. Microbial differential expression analysis revealed induction of stress-related genes and metabolic genes involved in amino acid metabolism, polyamine production, and nitric oxide production. Together, species identification and functional profiling suggest oral inflammation was correlated to shifts in the activity of multiple species that were involved with NO and polyamines. These coordinated metabolic signatures represent potential diagnostic targets for feline oral inflammatory disease.