Stratum-specific serum metabolic reprogramming in Saanen goats with graded Brucella serological reactivity under natural exposure.

Goat brucellosis, caused by Brucella melitensis, is a globally important zoonosis, yet host metabolic responses across serological reactivity levels under natural field conditions remain poorly understood. In this exploratory cross-sectional study, 150 Saanen goats were stratified by two-step serology into seronegative (Group A), weakly seropositive (Group B; serum agglutination test (SAT) titer 1:50), and strongly seropositive (Group C; SAT titer ≥1:100) groups; eight animals per group (n = 24 total) underwent broad-targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) serum metabolomics, yielding 699 annotated metabolites across 39 categories. Metabolic separation intensified with serological reactivity and was most pronounced between Groups A and C. Amino acid metabolism pathways were consistently enriched across all pairwise comparisons, while pyruvate metabolism, the pentose phosphate pathway, and purine/pyrimidine metabolism showed stage-associated enrichment only in comparisons involving Group C. D-erythrose 4-phosphate was the sole metabolite significantly altered in all three pairwise comparisons, with monotonically increasing abundance (area under the curve (AUC): A vs. B = 0.766; A vs. C = 1.000; B vs. C = 0.891). Trimethylamine N-oxide exhibited a biphasic pattern, while symmetric dimethylarginine declined monotonically. Collectively, these results reveal a progressive, stratum-dependent reorganization of the serum metabolome in goat brucellosis and highlight D-erythrose 4-phosphate and several co-altered metabolites as priorities for validation in future studies.