*Purpose: FK506 is one of the most common immunosuppressant drugs in organ transplantation, which have been demonstrated to cause glucose metabolism disorder and alterd the gut microbiota. Meanwhile glucose metabolism was reported influenced by gut microbiota and its metabolites, especially short chain fatty acids (SCFAs). In this article, we indicated the relationship of gut microbiota altered by FK506 and glucose metabolism in mice and also found the improvement in FK506 related glucose metabolism disorder by one of the SCFAs—butyrate.

*Methods: Mice models were established using C57BL6 mice. FK506 was used to induce glucose disorder model in mice. FK506 group(FK506 group)(n=4) were given 10mg/kg of FK506 by gavage each day; Butyrate treated group(But T group)(n=4) were given butyrate in drinking water by 150mM based on the established model; control group(Con group)(n=6) were given 10ml/kg water by gavage. Blood glucose was detected by fasting glucose and oral glucose tolerance test. Comparison of gut microbiota was analyzed by pyro sequencing the 16S rRNA genes. LEfSe(linear discriminant analysis) and PCA(Principal component analysis) were utilized to visualize significant differences in taxa between groups. PICRUSt(Phylogenetic Investigation of Communities by Reconstruction of unobserved States) analysis was performed to predict the functional capacity of the gut microbiota.

*Results: Glucose disorder model was established at 6^th week(Figure 1A1B). We found FK506 group showed significant difference to Con group in phylogenetic classification(Figure1C). The differences in the overall community compositions between FK506 and Con group had shown by LEfSe and PCA(Figure 1C1D). PICRUSt analysis was performed based on the 16S rRNA OTUs table enriched 13 pathways included in 7 metabolic functions’ change(Figure1E).

*Conclusions: According to these findings, the FK506 related glucose metabolism disorder could be efficaciously improved by butyrate orally in mice. Butyrate or the SCFAs could be a newly potential therapeutic target of the post transplantation diabetes mellitus.

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