Abstract
Purpose: The infection rate of syphilis continues to rise, and the difficulty in detecting and treating neurosyphilis promptly needs to be resolved. The metabolic profiles of cerebrospinal fluid (CSF) of different patients were analyzed to understand the pathogenesis of syphilis better. Method: The metabolic profiles of 88 CSF samples from patients were analyzed by UPLC-Q Exactive-MS. The experimental process was evaluated by PCA, PLS-DA, and HCA. T-test statistics were used to compare levels of metabolites to determine significant differences between groups. Pathway analysis was based on the KEGG database.Result: In total, 272 metabolites based on 3937 features obtained in ESI- mode and 252 metabolites based on 3799 features in ESI+ mode were identified. A clear separation between latent syphilis and neurosyphilis was found. Levels of lipid and linoleic acid metabolites, such as 9-OxoODE and 9,10,13-TriHOME, were increased in syphilis patients. In patients with neurosyphilis, significant changes in levels of 5-hydroxy-L-tryptophan (5-HTP) and acetyl-N-formyl-5-methoxykynurenamine (AFMK) in the tryptophan-kynurenine pathway were also detected. Only one metabolite, theophylline, differed significantly between symptomatic and asymptomatic neurosyphilis patients. Additionally, KEGG analysis revealed significant enrichment of tryptophan metabolism pathways, indicating a high correlation between tryptophan metabolism and syphilis symptoms. Conclusions: Levels of linoleic acid metabolites, 5-HTP, AFMK and theophylline were significantly altered in different patients. The role of these differential metabolites in the development of syphilis is worthy of further exploration, probably improving the treatment and diagnosis of neurosyphilis and occult syphilis in the future.
Metabolites of the Kynurenine Pathway of Tryptophan Metabolism in the Cerebrospinal Fluid of Malawian Children with Malaria