Toxoplasma gondii disrupts intestinal microbiota and host metabolism in a rat model

Toxoplasma gondii infection disrupts the gut microbiota and host systemic metabolism, which plays a key role in the pathophysiology of toxoplasmosis. To investigate these interactions, we conducted metagenomic sequencing and untargeted serum metabolomics on 18 Sprague-Dawley rats across control, acute, and chronic stages of infection. De novo assembly of 148 Gb of high-quality reads produced a comprehensive non-redundant microbial gene catalog comprising over 5.7 million genes. Infection led to a marked reduction in microbial diversity and significant shifts in community structure. Chronic infection, in particular, was characterized by the enrichment of Lactobacillus johnsonii, Lactobacillus intestinalis, and Limosilactobacillus reuteri, alongside a marked depletion of Akkermansia muciniphila and Rothia nasimurium. These compositional changes coincided with reduced abundance of carbohydrate-active enzymes, suggesting impaired microbial metabolic capacity. Pathway analysis revealed distinct, stage- and gut-region-specific metabolic disruptions, including suppressed amino acid and energy metabolism, and enhanced glycan and carbohydrate pathways during chronic infection. Untargeted LC-MS/MS profiling uncovered 883 differentially abundant serum metabolites, enriched in pathways related to amino acid metabolism, bile acid transformation, and aromatic compound processing. Importantly, L. johnsonii and L. reuteri were positively correlated with metabolites implicated in immune modulation and oxidative stress response, whereas A. muciniphila showed negative associations. These findings demonstrate that T. gondii infection orchestrates a coordinated host-microbiota-metabolome network, advancing our understanding of disease mechanisms and pointing to novel microbial and metabolic targets for therapy.