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. 2025 Feb;20(3):237-246.
doi: 10.1080/17460913.2024.2444761. Epub 2024 Dec 22.

Changes in the gut microbiota and derived fecal metabolites may play a role in tacrolimus-induced diabetes in mice

Minyan Qian  1   2 , Zhenwei Jiang  1   2 , Caomei Xu  1   2 , Liying Wang  1 , Nan Hu  1
Affiliations

Changes in the gut microbiota and derived fecal metabolites may play a role in tacrolimus-induced diabetes in mice

Minyan Qian et al. Future Microbiol. 2025 Feb.

Abstract

Aims: A notable scarcity of research has focused on examining alterations in gut microbiota and its metabolites within tacrolimus (TAC)-induced diabetes models.

Methods: Tacrolimus-induced changes in glucose and lipid metabolism indices were analyzed through different routes of administration. The potential role of gut microbiota and its metabolites in TAC-induced diabetes was investigated using 16S rRNA sequencing and non-targeted metabolomics.

Results: After intraperitoneal(ip) and oral(po) administration of TAC, the α-diversity index of gut microbiota was significantly increased. The gut microbiota of the three groups of mice was significantly separated, and there were significant changes in composition and functional genes. Fecal metabolites changed significantly after TAC administration by different routes, and 53 metabolites (38 down-regulated and 15 up-regulated) were identified (CON vs. TACip). Similarly, 29 metabolites (8 down-regulated and 21 up-regulated) were identified (CON vs. TACpo). KEGG pathway analysis identified 4 and 13 significantly altered metabolic pathways, respectively. Correlation analysis suggested that microbiota and metabolites were involved in the pathogenesis of TAC-induced diabetes.

Conclusion: This study investigated the alterations in gut microbiota and fecal metabolites in TAC-induced diabetic mice and evaluated the correlation between these changes. These findings provide valuable insights into potential biomarkers in the development of TAC-induced diabetes.

Keywords: Tacrolimus; diabetes mellitus; gut microbiota; mice; non-targeted metabolomics.

Plain language summary

The study investigated the effects of tacrolimus (TAC), an immunosuppressive drug widely used to prevent organ rejection in transplant patients, on the development of diabetes. Gut bacteria and the metabolites they produce play an important role in health and disease, including diabetes. Not much is known about how these bacteria and their metabolites play a role when TAC induces diabetes. To explore this, we studied mice given TAC by two methods, intraperitoneal injection and oral administration, and looked at the changes in their gut bacteria and feces. We found that TAC changed the species and function of gut bacteria. These changes are linked to changes in important biological processes, such as the pathways that break down fats and other chemicals. Mice treated with TAC by different routes all showed signs of diabetes, such as elevated blood glucose levels. We suggest that specific bacteria and metabolites may play a role in causing diabetes after TAC treatment.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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