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More specific and sensitive diagnostic markers for latent syphilis and neurosyphilis should be found. Here the metabolic profiles of 88 cerebrospinal fluid samples from syphilis patients and controls were analyzed by LC\/MS-based untargeted metabolomics. In total, 272 metabolites based on 3937 features obtained in ESI\u2212 mode and 252 metabolites based on 3799 features in ESI+ mode were identified. The experimental process was evaluated by principal component analysis, partial least squares discriminant analysis, and hierarchical cluster analysis. A clear separation between latent syphilis and neurosyphilis was found. Levels of lipid and linoleic acid metabolites, such as 9-oxo-octadecadienoic acid and 9,10,13-trihydroxyoctadecenoic acid, 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\u2013kynurenine 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. 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. Our results may promote the development of biomarkers for diagnosis of latent syphilis from neurosyphilis, and for that of asymptomatic neurosyphilis from symptomatic neurosyphilis in the future.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/d3mo00026e","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T08:41:38Z","timestamp":1681893698000},"page":"484-491","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of potential biomarkers for diagnosis of syphilis from the cerebrospinal fluid based on untargeted metabolomic analysis"],"prefix":"10.1093","volume":"19","author":[{"given":"Liguo","family":"Liu","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College a , Beijing 100730, China \u00a0 huahero@ipbcams.ac.cn \u00a0 zdsys@vip.sina.com \u00a0 lunwenhui@163.com \u00a0 +86-01067877731 \u00a0 +86 010 67877732 \u00a0 +86 010 67837323"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Ditan Hospital, Capital Medical University b , Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Infections Disease Center, Beijing Ditan Hospital, Capital Medical University d , Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of infectious diseases, Yantai Qishan Hospital e , Yantai, Shandong, 264001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of dermatology and venereology, Beijing Ditan Hospital, Capital Medical University c , Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaheng","family":"Deng","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College a , Beijing 100730, China \u00a0 huahero@ipbcams.ac.cn \u00a0 zdsys@vip.sina.com \u00a0 lunwenhui@163.com \u00a0 +86-01067877731 \u00a0 +86 010 67877732 \u00a0 +86 010 67837323"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6000-0326","authenticated-orcid":false,"given":"Jianhua","family":"Zheng","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College a , Beijing 100730, China \u00a0 huahero@ipbcams.ac.cn \u00a0 zdsys@vip.sina.com \u00a0 lunwenhui@163.com \u00a0 +86-01067877731 \u00a0 +86 010 67877732 \u00a0 +86 010 67837323"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Jin","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College a , Beijing 100730, China \u00a0 huahero@ipbcams.ac.cn \u00a0 zdsys@vip.sina.com \u00a0 lunwenhui@163.com \u00a0 +86-01067877731 \u00a0 +86 010 67877732 \u00a0 +86 010 67837323"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Lun","sequence":"additional","affiliation":[{"name":"Department of dermatology and venereology, Beijing Ditan Hospital, Capital Medical University c , Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"2026010813052073500_cit1","author":"Ha"},{"key":"2026010813052073500_cit2","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1056\/NEJMc1914502","volume":"381","author":"Wormser","year":"2019","journal-title":"N. 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