ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1616985
This article is part of the Research TopicNew Progress on the Role of Gut Microbiota in the Incidence and Prevention of Liver DiseasesView all 22 articles
Influence of the Gut Microbiota on the Pharmacokinetics of Tacrolimus in Liver Transplant Recipients: Insights from Microbiome Analysis
Provisionally accepted
- 1First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi Province, China
- 2Microbiological Laboratory of Ophthalmology, Shanxi Eye Hospital, Taiyuan, Shanxi Province, China
- 3Department of Hepatobiliary Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
- 4Shanxi Provincial Key Laboratory for Digestive Diseases and Organ Transplantation, First Hospital of Shanxi Medical University, Taiyuan, China, Taiyuan, Shanxi Province, China
- 5Department of Biliopancreatic surgery, First Hospital of Shanxi Medical University, Taiyuan, China
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Tacrolimus is crucial for immunosuppression after liver transplantation, but its pharmacokinetics vary markedly among individuals. Emerging evidence suggests that the gut microbiota may influence its metabolism, athough the underlying mechanisms remain unclear. This study analyzed the fecal microbiota from 38 postliver transplant patients and 31 healthy controls via 16S rDNA amplicon and shotgun metagenomic sequencing. Patients were stratified into three groups on the basis of oral tacrolimus dosage and blood concentration: LDLBC (low dose, low blood concentration), LDHBC (low dose, high blood concentration), and SDLBC (standard dose, low blood concentration). Posttransplant patients presented significantly reduced gut microbial diversity. Specific bacterial taxa, including Enterococcus raffinosus, Intestinibacter bartlettii, and Bacteroides fragilis, were enriched in patients with lower tacrolimus blood concentrations. In contrast, Phascolarctobacterium faecium and Streptococcus salivarius were associated with increased drug levels. Functional analysis revealed differences between patient subgroups in ATP-binding cassette (ABC) transporters and drug efflux pumps, suggesting a potential microbial influence on tacrolimus absorption and metabolism. Additionally, antibiotic resistance genes were more abundant in patients with lower tacrolimus blood concentrations, particularly in the Escherichia coli-enriched groups. These findings underscore the influence of the gut microbiota on tacrolimus pharmacokinetics and support the potential of microbial composition as a biomarker for optimizing immunosuppressive therapy.
Keywords: gut microbiome, Tacrolimus, pharmacokinetics, Liver Transplantation, ATP-Binding Cassette Transporters, immunosuppressive therapy
Received: 24 Apr 2025; Accepted: 27 Aug 2025.
Copyright: © 2025 Wang, Bai, Liu, Wang, Lai and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhiyong Lai, Department of Biliopancreatic surgery, First Hospital of Shanxi Medical University, Taiyuan, China
Jun Xu, Department of Hepatobiliary Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
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