Background <p>Angiostrongyliasis, a food-borne parasitic disease caused by <i>Angiostrongylus cantonensis</i>, is characterized by eosinophilic meningitis or meningoencephalitis, leading to serious central nervous system damage. Current diagnostic methods lack specificity or sensitivity, and the pathogenesis is complex and incompletely understood. This study aimed to comprehensively characterize the dynamic alterations in the gut microbiota and host metabolism in both suitable (rats) and non-suitable (mice) hosts following <i>A. cantonensis</i> infection and to identify potential metabolic biomarkers for early diagnosis.</p> Methods <p>Female BALB/c mice and Sprague Dawley rats (<i>n</i> = 10/group) were infected with 30 or 100 third-stage larvae, respectively. Serum, urine, feces, and brain samples were collected longitudinally. Gut microbiota was analyzed via <i>16S</i> rRNA gene sequencing and metagenomics. Host metabolism was profiled using untargeted and targeted metabolomics via ultraperformance liquid chromatography-quadrupoles/time of flight-mass spectrometry. Statistical analyses included Wilcoxon rank sum test, linear discriminant effect size analysis, Spearman correlation analysis, orthogonal partial least squares-discriminatory analysis, and receiver operating characteristic curve analysis.</p> Results <p>Infection induced significant, host-specific gut microbiota dysbiosis. In infected hosts, Firmicutes decreased (<i>P</i> &lt; 0.05) while Bacteroidetes increased (<i>P</i> &lt; 0.05). A main difference in gut flora structure between infected hosts was observed in Prevotellaceae, which increased significantly in mice (<i>P</i> &lt; 0.05) but decreased in rats (<i>P</i> &lt; 0.05). Metagenomics revealed enhanced carbohydrate metabolism and fatty acid biosynthesis in gut microbes of infected mice, whereas up-regulated amino acid and vitamin metabolism were also observed in infected rats. Infection caused pronounced disruptions in host lipid and bile acid (BA) metabolism, changes in various BA types were closely related to alterations in specific bacterial genera (<i>P</i> &lt; 0.05). Several metabolites, including phosphatidylcholine (16:0/18:1), 2-phenyl acetic acid, 2-octenoylglycine, lysophosphatidylcholine (18:2), O-glucuronide, and 2-carboxylic acid, were identified as potential early diagnostic biomarkers in the mouse model.</p> Conclusions <p><i>A. cantonensis</i> infection causes profound host-specific dysregulation of the gut microbiome and metabolome, with severe disturbances in Firmicutes, Bacteroidetes, lipid and BA metabolism being central features. These alterations highlight the critical role of the host-gut microbiota-metabolite axis in pathogenesis and offer novel insights for developing diagnostic and therapeutic strategies.</p> Graphical abstract <p></p>