Toxoplasma gondii alters gut microbiota and systemic metabolism in cats: A multi-omics approach.

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite with a complex life cycle that culminates in cats-its only definitive host. While its immunological impact is well studied, how T. gondii shapes the feline gut microbiota and systemic metabolism remains largely unexplored. To investigate host-parasite-microbiome interactions, we performed a multi-omics study combining metagenomic sequencing and untargeted serum metabolomics in cats before and after T. gondii infection. Fecal samples were used to construct a comprehensive microbial gene catalog and assess functional shifts, while serum samples were analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) to capture systemic metabolic changes. Infection with T. gondii, particularly during its sexual replication phase, significantly disrupted gut microbial diversity, composition, and function. Functional annotation revealed downregulation of microbial genes involved in vitamin, cofactor, and energy metabolism, alongside upregulation of carbohydrate metabolism pathways. Concurrently, metabolomic profiling showed marked alterations in lipid profiles, amino acid pathways, and folate-mediated one-carbon metabolism. Integrated analysis uncovered strong correlations between specific microbial taxa-such as Bifidobacterium adolescentis and Ligilactobacillus animalis-and host metabolites, underscoring a tight link between microbial function and host metabolic responses to infection. To our knowledge, this is the first study to comprehensively map the microbiome and metabolic landscape of T. gondii infection in the feline host. Our findings reveal profound parasite-induced shifts in microbial function and systemic metabolism, offering new insights into the molecular interplay between host, parasite, and microbiota. These insights may inform future strategies for therapeutic modulation of host responses in toxoplasmosis.