{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:33:16Z","timestamp":1775885596896,"version":"3.50.1"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"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. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Currently, there has been observed a significant alteration in the composition of the gut microbiome (GM) and serum metabolites in patients with psoriatic arthritis (PsA) compared to healthy individuals. However, previous observational studies have shown inconsistent results regarding the alteration of gut microbiota\/metabolites. In order to shed light on this matter, we utilized Mendelian randomization to determine the causal effect of GM\/metabolites on PsA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrieved summary-level data of GM taxa\/metabolites and PsA from publicly available GWAS statistics. Causal relationships between GM\/metabolites and PsA were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the robustness of our findings, we conducted sensitivity analyses, multivariable MR analysis (MVMR), and additional analysis including replication verification analysis, LDSC regression, and Steiger test analysis. Furthermore, we investigated reverse causality through a reverse MR analysis. Finally, we conducted an analysis of expression quantitative trait loci (eQTLs) involved in the metabolic pathway to explore potential molecular mechanisms of metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings reveal that eight GM taxa and twenty-three serum metabolites are causally related to PsA (<jats:italic>P<\/jats:italic>&amp;lt; 0.05). Notably, a higher relative abundance of Family<jats:italic>Rikenellaceae<\/jats:italic>(OR<jats:sub><jats:italic>IVW<\/jats:italic><\/jats:sub>: 0.622, 95% CI: 0.438\u20130.883, FDR = 0.045) and elevated serum levels of X-11538 (OR<jats:sub><jats:italic>IVW<\/jats:italic><\/jats:sub>: 0.442, 95% CI: 0.250\u20130.781, FDR = 0.046) maintain significant causal associations with a reduced risk of PsA, even after adjusting for multiple testing correction and conducting MVMR analysis. These findings suggest that Family<jats:italic>Rikenellaceae<\/jats:italic>and X-11538 may have protective effects against PsA. Our sensitivity analysis and additional analysis revealed no significant horizontal pleiotropy, reverse causality, or heterogeneity. The functional enrichment analysis revealed that the eQTLs examined were primarily associated with glycerolipid metabolism and the expression of key metabolic factors influenced by bacterial infections (<jats:italic>Vibrio cholerae<\/jats:italic>and<jats:italic>Helicobacter pylori<\/jats:italic>) as well as the mTOR signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, our study demonstrates that Family<jats:italic>Rikenellacea<\/jats:italic>e and X-11538 exhibit a strong and negative causal relationship with PsA. These particular GM taxa and metabolites have the potential to serve as innovative biomarkers, offering valuable insights into the treatment and prevention of PsA. Moreover, bacterial infections and mTOR-mediated activation of metabolic factors may play an important role in this process.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1287637","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T05:35:03Z","timestamp":1707975303000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigating causal associations among gut microbiota, metabolites, and psoriatic arthritis: a Mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Xiao","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin-yun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan-Hong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-ling","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Xiang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature09534","article-title":"A map of human genome variation from population-scale sequencing.","volume":"467","author":"Abecasis","year":"2010","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cells7100159","article-title":"Pathophysiological alterations of redox signaling and endocannabinoid system in granulocytes and plasma of psoriatic patients.","volume":"7","author":"Ambro\u017cewicz","year":"2018","journal-title":"Cells"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1002\/art.40183","article-title":"Intestinal metabolites are profoundly altered in the context of HLA-B27 expression and functionally modulate disease in a rat model of spondyloarthritis.","volume":"69","author":"Asquith","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214158","article-title":"Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.","volume":"78","author":"Aterido","year":"2019","journal-title":"Ann. 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