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Background  Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs.    Methods  Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone.    Results  The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing  Ruminococcus  and  Alistipes  and retaining the abundance of  Lactobacillus . However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as  Parasutterella ,  Parabacteroides , and  Escherichia-Shigella .    Conclusions  These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13075-021-02620-w.

Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice