{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T18:54:43Z","timestamp":1780599283986,"version":"3.54.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"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>Background<\/jats:title><jats:p>Previous evidence suggests a link between gut microbiota and chronic pain, but the causal relationship is not yet fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We categorized gut microbiota based on phylum, class, order, family, and genus levels and gathered pain-related information from the UKB and FinnGen GWAS project. Then, we conducted MR analysis to explore the potential causal relationship between gut microbiota and chronic pain at 12 specific locations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We have discovered a direct connection between genetic susceptibility in the gut microbiota (gut metabolites) and pain experienced at 12 specific locations. Notably, Serotonin (5-HT) and Glycine were found to be associated with a higher risk of pain in the extremities. On the other hand, certain microbial families and orders were found to have a protective effect against migraines. Specifically, the family Bifidobacteriaceae (IVW, FDR <jats:italic>p<\/jats:italic>\u2009=\u20090.013) was associated with a lower risk of migraines. Furthermore, the genus Oxalobacter (IVW, FDR <jats:italic>p<\/jats:italic>\u2009=\u20090.044) was found to be linked to an increased risk of low back pain. Importantly, these associations remained significant even after applying the Benjamini-Hochberg correction test. Our analysis did not find any heterogeneity in the data (<jats:italic>p<\/jats:italic>\u2009&amp;gt;\u20090.05), as confirmed by the Cochrane\u2019s <jats:italic>Q<\/jats:italic>-test. Additionally, both the MR-Egger and MR-PRESSO tests indicated no significant evidence of horizontal pleiotropy (<jats:italic>p<\/jats:italic>\u2009&amp;gt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our MR analysis demonstrated a causal relationship between the gut microbiota and pain, highlighting its potential significance in advancing our understanding of the underlying mechanisms and clinical implications of microbiota-mediated pain.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2024.1369996","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T04:28:00Z","timestamp":1713328080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Multiple reports on the causal relationship between various chronic pain and gut microbiota: a two-sample Mendelian randomization study"],"prefix":"10.3389","volume":"18","author":[{"given":"Yuxin","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyang","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozhi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihua","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1111\/apt.13858","article-title":"Chronic opioid use is associated with altered gut microbiota and predicts readmissions in patients with cirrhosis","volume":"45","author":"Acharya","year":"2017","journal-title":"Aliment. 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