{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T21:22:32Z","timestamp":1775942552905,"version":"3.50.1"},"reference-count":59,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Urolithiasis is a common and recurrent condition with significant health burdens; however, the causal relationships between dietary factors, plasma metabolites, and the urolithiasis risk remain poorly understood. To address this, we aimed to identify the causal associations between food habits and the risk of urolithiasis, and quantify the mediating role of plasma metabolites, employing two\u2010sample Mendelian randomization (MR) and experimental approaches. This MR analysis was based on summary statistics for calculus of kidney and ureter from published genome\u2010wide association studies (GWAS), including 10,556 cases and 400,681 controls of European ancestry. Furthermore, we used a two\u2010step MR to quantify the proportion of the effect of 1400 plasma metabolites\u2010mediated food habits on urolithiasis. Our MR analysis identified eight food intake factors and 15 food liking factors associated with urolithiasis. Metabolomic\u2010wide MR analysis identified 50 plasma metabolites associated with urolithiasis. Seven pairs of stone\u2010associated food factors and their metabolites were identified. Consistent with the MR results, widely targeted metabolomics analysis revealed that Mannose (fold change, FC\u2009=\u20090.54,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001) and Threonate (FC\u2009=\u20090.64,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0269) levels were significantly decreased in calcium oxalate (CaOx) kidney stone rat models compared with the control group. Integration of GWAS and eQTL data revealed 21 metabolite\u2010related genes using a summary\u2010data\u2010based MR (SMR) test. Analysis of GSE73680 revealed that LAMA2 (logFC\u2009=\u2009\u22121.31,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.003) and CSNK1G3 (logFC\u2009=\u2009\u22120.76,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.042) were downregulated in the CaOx group. Both genes (LAMA2: OR\u2009=\u20090.74, 95% CI\u2009=\u20090.56\u20130.98,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04; CSNK1G3: OR\u2009=\u20090.74, 95% CI\u2009=\u20090.58\u20130.94,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01) were associated with a reduced risk of CaOx stones. RNA\u2010Seq and RT\u2010qPCR assays validated that the expression of LAMA2 and CSNK1G3 was decreased in oxalate\u2010induced HK\u20102 and NRK\u201052E cells. Our study identified a causal relationship between food habits and the risk of urolithiasis with the effect mediated by plasma metabolites.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.70800","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T04:11:02Z","timestamp":1755663062000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dietary Influence on Urolithiasis Risk Mediated by Plasma Metabolites: A Mendelian Randomization and Experimental Study Linking Genes, Metabolites, and Clinical Outcomes"],"prefix":"10.1002","volume":"13","author":[{"given":"Dawei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghui","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology Suzhou Wu Zhong People's Hospital  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9407-4670","authenticated-orcid":false,"given":"Shuxin","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Fujian Medical University  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Affiliated Suqian First People's Hospital of Nanjing Medical University  Suqian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangxiu","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Urology, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010physiol\u2010052521\u2010121822"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102896\u20102"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345\u2010020\u201003466\u20108"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345\u2010020\u201003561\u2010w"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxaa079"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/ede.0000000000000559"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00240\u2010023\u201001467\u2010x"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201002014\u20108"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2020.104450"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010022\u201001270\u20101"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10101516"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.09.035"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345\u2010018\u20102562\u20106"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12030779"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.11661112"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.114.089987"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfaa360"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0690"},{"issue":"3","key":"e_1_2_13_20_1","first-page":"333","article-title":"Urolithiasis: 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