Potential Biomarkers for Neurobrucellosis Diagnosis and Treatment Based on Cerebrospinal Fluid Metabolomics Analysis

BACKGROUND: Zhenzhu Tongluo pills (ZZTL) have been utilized for the treatment of neurobrucellosis (NB) in the Inner Mongolia region of China. However, the specific mechanism underlying the neuroprotective effects of ZZTL in NB remains insufficiently explored. Therefore, this study aimed to analyze the metabolite profiles across different groups to identify potential biomarkers for the diagnosis and treatment of NB. METHODS: LC-MS analysis was used to screen differential metabolites in cerebrospinal fluid (CSF) samples from control subjects, NB patients, and NB patients undergoing ZZTL therapy. RESULTS: We identified 225 common metabolites across two comparison groups (NB vs. control group and NB + ZZTL vs. NB group). Among these metabolites, 138 were downregulated, and 87 were upregulated in the NB group compared to the control group, while the levels of these metabolites were reversed by ZZTL therapy. Creatinine exhibited the highest VIP score in both comparison groups, with elevated levels observed in CSF samples from NB patients compared to controls; however, its levels were reduced following ZZTL therapy. Additionally, hypoxanthine and uric acids levels were also increased in CSF samples from NB patients, indicating dysregulation of purine metabolism in NB; however, these changes were reversed by ZZTL. Furthermore, pantothenic acid (vitamin B5) and niacinamide (vitamin B3) levels were decreased in CSF samples from NB patients, suggesting a potential link between NB and vitamin B3 and B5 deficiency; however, these changes were reversed by ZZTL. CONCLUSION: Collectively, CSF metabolomics may effectively differentiate NB patients from control subjects, providing valuable insights for NB diagnosis and treatment.