{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:14:30Z","timestamp":1779916470024,"version":"3.53.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study sought to explore the potential causal relationships among immune cell traits, Guillain-Barre syndrome (GBS) and metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Employing a two-sample Mendelian randomization (MR) approach, the study investigated the causal associations between 731 immune cell traits, 1400 metabolite levels and GBS leveraging summary-level data from a genome-wide association study (GWAS). To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study revealed a causal relationship between CD3 on activated &amp;amp; secreting Tregs and GBS. Higher CD3 on activated and secreting Regulatory Tregs increased the risk of GBS (primary MR analysis odds ratio (OR) 1.31\/SD increase, 95% confidence interval (CI) 1.08\u20131.58, <jats:italic>p<\/jats:italic> = 0.005). There was no reverse causality for GBS on CD3 on activated &amp;amp; secreting Tregs (<jats:italic>p<\/jats:italic> = 0.36). Plasma metabolite N-Acetyl-L-Alanine (ALA) was significantly positively correlated with GBS by using the IVW method (OR = 2.04, 95% CI, 1.26\u20133.30; <jats:italic>p<\/jats:italic> = 0.00038). CD3 on activated &amp;amp; secreting Tregs was found to be positively associated with ALA risk (IVW method, OR, 1.04; [95% CI, 1.01\u20131.07], <jats:italic>p<\/jats:italic> = 0.0078). Mediation MR analysis indicated the mediated proportion of CD3 on activated &amp;amp; secreting Tregs mediated by ALA was 10% (95%CI 2.63%, 17.4%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, our study identified a causal relationship between the level of CD3 on activated &amp;amp; secreting Tregs and GBS by genetic means, with a considerable proportion of the effect mediated by ALA. In clinical practice, thus providing guidance for future clinical research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2024.1398653","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T13:27:59Z","timestamp":1726838879000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetically predicted N-Acetyl-L-Alanine mediates the association between CD3 on activated and secreting Tregs and Guillain-Barre syndrome"],"prefix":"10.3389","volume":"18","author":[{"given":"Qi","family":"Lyu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianlian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.molcel.2020.05.034","article-title":"Targeting metabolism to improve the tumor microenvironment for cancer immunotherapy.","volume":"78","author":"Bader","year":"2020","journal-title":"Mol. 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