{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:42:34Z","timestamp":1790959354003,"version":"4.1.0"},"reference-count":94,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammopharmacol"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Previous observational studies have indicated a complex association between gut microbiota (GM) and neuropathic pain (NP). Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian randomization (MR) approach to investigate the causal relationship between GM and neuropathic pain including post-herpetic neuralgia (PHN), painful diabetic peripheral neuropathy (PDPN), and trigeminal neuralgia (TN), as well as to explore the potential mediation effects of immune cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed a two-step, two-sample Mendelian randomization study with an inverse variance-weighted (IVW) approach to investigate the causal role of GM on three major kinds of NP and the mediation effect of immune cells between the association of GM and NP. In addition, we determine the strongest causal associations using Bayesian weighted Mendelian randomization (BWMR) analysis. Furthermore, we will investigate the mediating role of immune cells through a two-step Mendelian randomization design.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We identified 53 taxonomies and pathways of gut microbiota that had significant causal associations with NP. In addition, we also discovered 120 immune cells that exhibited significant causal associations with NP. According to the BWMR and two-step Mendelian randomization analysis, we identified the following results CD4 on CM CD4\u2009+\u2009(maturation stages of T cell) mediated 6.7% of the risk reduction for PHN through the pathway of fucose degradation (FUCCAT.PWY). CD28\u2009+\u2009DN (CD4-CD8-) AC (Treg) mediated 12.5% of the risk reduction for PHN through the influence on <jats:italic>Roseburia inulinivorans<\/jats:italic>. CD45 on lymphocyte (Myeloid cell) mediated 11.9% of the risk increase for TN through the superpathway of acetyl-CoA biosynthesis (PWY.5173). HLA DR\u2009+\u2009CD8br %T cell (TBNK) mediated 3.2% of the risk reduction for TN through the superpathway of GDP-mannose-derived O-antigen building blocks biosynthesis (PWY.7323). IgD-CD38-AC (B cell) mediated 7.5% of the risk reduction for DPN through the pathway of thiazole biosynthesis I in E. coli (PWY.6892).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>These findings provided evidence supporting the causal effect of GM with NP, with immune cells playing a mediating role. These findings may inform prevention strategies and interventions directed toward NP. Future studies should explore other plausible biological mechanisms.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10787-024-01514-y","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T20:41:46Z","timestamp":1719952906000},"page":"3357-3373","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Genetically predicted immune cells mediate the association between gut microbiota and neuropathy pain"],"prefix":"10.1007","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0957-8662","authenticated-orcid":false,"given":"Zhixuan","family":"Lan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5590-0011","authenticated-orcid":false,"given":"Yi","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6957-2136","authenticated-orcid":false,"given":"Kan","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3307-9144","authenticated-orcid":false,"given":"Ruilin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2926-630X","authenticated-orcid":false,"given":"Zongbin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"1514_CR1","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1038\/nature09534","volume":"467","author":"GR Abecasis","year":"2010","unstructured":"Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA (2010) A map of human genome variation from population-scale sequencing. 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