From dysbiosis to disease: the role of gut microbial communities in Toxoplasma gondii pathogenesis, zoonotic transmission, diagnostic innovation, and therapeutic outcomes.

Toxoplasma gondii, an obligate intracellular protozoan infecting approximately one-third of the global human population, causes substantial morbidity in immunocompromised individuals, congenital complications, neuropsychiatric sequelae, and considerable economic losses in livestock production. Gut microbial communities critically modulate T. gondii infection susceptibility, disease progression, and clinical outcomes, positioning the microbiome as a central axis in toxoplasmosis pathogenesis. This review examines the bidirectional relationship between gut microbiota and T. gondii, wherein dysbiosis functions simultaneously as a consequence and driver of disease severity. Protective commensal taxa reinforce intestinal barrier integrity, produce short-chain fatty acids, and stimulate anti-parasitic immunity through IFN-γ, IL-12, and tryptophan-aryl hydrocarbon receptor signaling, while pathobionts exacerbate immunopathology via TLR4 and inflammasome activation. Conversely, acute infection drives rapid microbial community collapse with persistent Proteobacteria expansion, butyrate-producing taxa depletion, neuroinflammation, and cognitive impairment in chronic infection. Across the One Health spectrum, host-specific microbiome signatures in felids, livestock, wildlife, and environmental reservoirs modulate zoonotic transmission dynamics and population-level susceptibility. Diagnostically, emerging microbiome-based approaches including metagenomics and multi-omics platforms offer promising biomarker discovery opportunities, though validated clinical signatures remain absent. Microbiome-targeted therapeutic strategies including probiotics, prebiotics, fecal microbiota transplantation, and postbiotics show preclinical promise, although human clinical trial validation is critically lacking. Critical research gaps and interdisciplinary One Health priorities are identified to advance microbiome-informed surveillance, diagnosis, and treatment of toxoplasmosis.