{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:34:46Z","timestamp":1787067286478,"version":"build-2736575974"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Basic Research Program of Yunnan Science and Technology Department","award":["202301AY070001-112"],"award-info":[{"award-number":["202301AY070001-112"]}]},{"name":"Yunnan Provincial Health Commission Medical Leading Talent Training Program","award":["L-2018012"],"award-info":[{"award-number":["L-2018012"]}]},{"name":"Construction Unit of Yunnan Provincial Clinical Pharmacy Center"},{"name":"Kunming City Health Science and Technology Talents Training Program","award":["2023-SW (Leading Talents)-04"],"award-info":[{"award-number":["2023-SW (Leading Talents)-04"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Liver transplantation (LT) is an effective treatment for patients with end-stage liver disease. In recent years, more and more evidence has supported the association between gut microbiota dysbiosis and the pathogenesis and progression of liver diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study included 36 patients who received tacrolimus treatment after liver transplantation. Patients were stratified into subgroups according to three key variables: tacrolimus treatment duration, whole-blood tacrolimus concentration, and tacrolimus concentration-to-dose (C\/D) ratio. Fecal samples and whole-blood specimens were collected from all participants. The Illumina HiSeq X platform was used to detect the gut metagenome, analyzing the composition and characteristics of the gut microbiota. Liquid chromatography-tandem mass spectrometry (LC-MS\/MS) technology was employed to detect metabolites of the gut microbiota, revealing their metabolic profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      As the duration of tacrolimus use increased, the diversity of the gut microbiota also increased, and the abundance of\n                      <jats:italic>Escherichia coli_D<\/jats:italic>\n                      and\n                      <jats:italic>Bacteroides stercoris<\/jats:italic>\n                      rose. Additionally, the abundance of\n                      <jats:italic>Brunovirus<\/jats:italic>\n                      and\n                      <jats:italic>Uetakevirus<\/jats:italic>\n                      tended to decrease. The abundance of gene functions related to chemical carcinogenesis and bacterial invasion of epithelial cells significantly decreased. In the gut microbiota metabolites, 16 substances like Astragaloside A and Acetyl-L-carnitine significantly increased, while 108 substances like Capsaicin and TLK significantly decreased. Within a certain range, as the concentration of tacrolimus in whole blood increased, the diversity of the gut microbiota increased. The abundance of\n                      <jats:italic>Phocaeicola<\/jats:italic>\n                      and\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      increased, and the abundance of\n                      <jats:italic>Peduovirus<\/jats:italic>\n                      among viruses also rose. However, excessively high concentrations may lead to a decrease in the diversity of the gut microbiota and a decrease in the abundance of\n                      <jats:italic>Phocaeicola<\/jats:italic>\n                      . With respect to the C\/D ratio, increased ratios were linked to significantly higher levels of 57 fecal metabolites (e.g., PC 34:2, 5-Methyl-2\u2019-deoxycytidine), whereas 13 metabolites (e.g., FAHFA 2:0\/16:0) showed substantial declines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tacrolimus treatment is associated with distinct alterations in gut microbiota and metabolites among LT recipients. These findings provide a preliminary framework for future investigations aimed at optimizing immunosuppressive regimens, although their clinical translational potential requires validation in larger-scale, prospective cohort studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0343817","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T18:36:11Z","timestamp":1772130971000},"page":"e0343817","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of tacrolimus treatment on the gut microbiota and metabolites in liver transplant 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Want","year":"2006","journal-title":"Anal Chem"},{"key":"pone.0343817.ref028","doi-asserted-by":"crossref","first-page":"1559521","DOI":"10.3389\/fmicb.2025.1559521","article-title":"Understanding dysbiosis and resilience in the human gut microbiome: biomarkers, interventions, and challenges","volume":"16","author":"A Safarchi","year":"2025","journal-title":"Front Microbiol"},{"issue":"1","key":"pone.0343817.ref029","doi-asserted-by":"crossref","first-page":"10109","DOI":"10.1038\/s41598-024-59148-7","article-title":"Genome plasticity shapes the ecology and evolution of Phocaeicola dorei and Phocaeicola vulgatus","volume":"14","author":"E Da Silva Morais","year":"2024","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0343817.ref030","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3390\/pathogens11040457","article-title":"Fecal DNA virome is associated with the development of colorectal neoplasia in a murine model of colorectal cancer","volume":"11","author":"Y 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liver transplantation","volume":"24","author":"J-W Jiang","year":"2018","journal-title":"World J Gastroenterol"},{"issue":"5","key":"pone.0343817.ref040","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0233646","article-title":"Gut microbial diversity, inflammation, and oxidative stress are associated with tacrolimus dosing requirements early after heart transplantation","volume":"15","author":"DL Jennings","year":"2020","journal-title":"PLoS One"},{"issue":"2","key":"pone.0343817.ref041","first-page":"122","article-title":"Lactobacillus casei regulates differentiation of Th17\/Treg cells to reduce intestinal inflammation in mice","volume":"81","author":"K Wang","year":"2017","journal-title":"Can J Vet Res"},{"issue":"1","key":"pone.0343817.ref042","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1097\/TP.0000000000001492","article-title":"Immunosuppressive treatment alters secretion of ileal antimicrobial peptides and gut microbiota, and favors subsequent 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Chandok","year":"2012","journal-title":"Liver Transpl"},{"issue":"4","key":"pone.0343817.ref046","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.ccell.2018.03.015","article-title":"The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy","volume":"33","author":"V Gopalakrishnan","year":"2018","journal-title":"Cancer Cell"},{"issue":"10","key":"pone.0343817.ref047","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.4254\/wjh.v7.i10.1355","article-title":"Review on immunosuppression in liver transplantation","volume":"7","author":"M Moini","year":"2015","journal-title":"World J Hepatol"},{"key":"pone.0343817.ref048","doi-asserted-by":"crossref","DOI":"10.1177\/1758835919848184","article-title":"Diagnostic and therapeutic potential of the gut microbiota in patients with early hepatocellular carcinoma","volume":"11","author":"FR Ponziani","year":"2019","journal-title":"Ther Adv Med 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