{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:36:04Z","timestamp":1782970564705,"version":"3.54.5"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The development of cirrhosis is closely intertwined with metabolic processes. No previous studies have reported a clear causal relationship between cirrhosis and metabolic processes. Thus, this study aimed to explore the potential associations between blood metabolites and cirrhosis using Mendelian randomization (MR) combined with targeted metabolomics analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A two-sample MR analysis was conducted using genome-wide association study data to evaluate the associations of circulating metabolites with cirrhosis. Statistical evaluations employed inverse variance-weighted models, MR-Egger regression, and sensitivity tests addressing pleiotropy and heterogeneity. In addition, blood samples were collected from 10 patients with liver cirrhosis and 10 healthy controls. Blood amino acid concentrations were measured using liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) to provide preliminary clinical evidence supporting the MR-derived candidate metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The MR analysis found that increases in 11 metabolites\/metabolic ratios were associated with elevated risks of liver cirrhosis, whereas increases in the remaining 3 metabolites were related to the prevention of the occurrence of liver cirrhosis. Among these candidates, genetically predicted higher glutamine degradant levels were associated with a lower risk of cirrhosis (OR\u202f=\u202f0.877, 95% CI: 0.784\u20130.981,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.022). Pathway analysis further suggested that arginine biosynthesis, proline metabolism, and nitrogen metabolism may be involved in metabolic alterations related to cirrhosis. The LC\u2013MS\/MS analysis showed lower glutamate and glutathione levels in patients with cirrhosis than in controls, providing preliminary support for altered glutamine-related metabolism in cirrhosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides suggestive MR evidence linking specific circulating metabolites to cirrhosis risk. In particular, glutamine-related metabolic alterations may be associated with susceptibility to cirrhosis. These findings provide exploratory insights into metabolite-related pathways that may contribute to cirrhosis development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1809188","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:23:49Z","timestamp":1782966229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring potential associations between blood metabolites and cirrhosis risk: a Mendelian randomization and LC\u2013MS\/MS analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Duoduo","family":"Lv","sequence":"first","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital of Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital of Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Han","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital of Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital of Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Tang","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital of Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital of Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1111\/apt.16831","article-title":"Review article: current and emerging therapies for the management of cirrhosis and its complications","volume":"55","author":"Tapper","year":"2022","journal-title":"Aliment Pharmacol Ther"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/s41575-023-00759-2","article-title":"Global epidemiology of cirrhosis - aetiology, trends and predictions","volume":"20","author":"Huang","year":"2023","journal-title":"Nat Rev Gastroenterol 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