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. 2021 Sep 14;23(1):240.
doi: 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

Mingzhu Wang #  1 , Zhengyang Zhu #  2 , Xiaoying Lin #  1 , Haichang Li  1 , Chengping Wen  1 , Jie Bao  3 , Zhixing He  4
Affiliations

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

Mingzhu Wang et al. Arthritis Res Ther. .

Abstract

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.

Keywords: Fecal microbiota transplantation; Gut microbiota; MRL/lpr mice; Prednisone; Systemic lupus erythematosus.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Effects of prednisone on liver total superoxide dismutase (a), CuZn superoxide dismutase (b), malonaldehyde (c), IL-6 (d) and TNF-α (e), serum fasting blood-glucose (f) and cholesterol (g), and tibial bone mineral density (h) in the treatment of MRL/lpr mice. CT, the C57BL/6 mice treated with sterile water; MT, the MRL/lpr mice treated with sterile water. “**” represents p < 0.01; “*” represents p < 0.05; “ns” represents no significant difference
Fig. 2
Fig. 2
Alterations in gut microbiota caused by prednisone in MRL/lpr mice. Alpha diversity indexes [Shannon (a); Simpson (b)], PCoA score plots (c), and identified major phylum (d) in MRL/lpr mice. LEfSe and PICRUST analysis identified the significantly altered genus and KEGG pathways caused by low (e, h), middle (f, i), and high doses (g, j) of prednisone in the treatment of MRL/lpr mice
Fig. 3
Fig. 3
Significantly different genera among MT, Pred, and FMT groups. MT, the MRL/lpr mice treated with sterile water; Pred, the MRL/lpr mice treated with prednisone; FMT, the MRL/lpr mice treated with fecal microbiota transplantation. “**” represents p < 0.01; “*” represents p < 0.05; “ns” represents no significant difference
Fig. 4
Fig. 4
The differences in the lupus activity of MRL/lpr mice among MT, Pred, and FMT groups. a Serum anti-dsDNA autoantibody levels. b Serum ANA autoantibody levels. b Serum urea nitrogen (BUN) levels. d Spleen index. e Percentage of plasma cells in the spleen. f Percentage of GC B cells in the spleen. g The percentage of double negative (DN) T cells in the spleen. MT, the MRL/lpr mice treated with sterile water; Pred, the MRL/lpr mice treated with prednisone; FMT, the MRL/lpr mice treated with fecal microbiota transplantation. “**” represents p < 0.01; “*” represents p < 0.05; “ns” represents no significant difference
Fig. 5
Fig. 5
The differences in the side effects of prednisone among MT, Pred, and FMT groups. a Liver total superoxide dismutase (T-SOD) activity. b Liver CuZn superoxide dismutase (CuZn-SOD) activity. c Liver malonaldehyde (MDA) concentration. d Liver IL-6 concentration. e Liver TNF-α concentration. f Serum cholesterol (CHOL) concentration. g Tibial bone mineral density (BMD). MT, the MRL/lpr mice treated with sterile water; Pred, the MRL/lpr mice treated with prednisone; FMT, the MRL/lpr mice treated with fecal microbiota transplantation. “**” represents p < 0.01; “*” represents p < 0.05; “ns” represents no significant difference
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