Abstract

There have been attempts to reveal the possible associations between systemic lupus erythematosus (SLE) and gut microbiota. Using MRL/lpr mice, this study was performed to reveal whether early and short-term interventions in gut microbiota affect lupus. MRL/lpr mice were treated with antibiotics or fecal microbiota transplantation (FMT) before onset. Then, prednisone was used to treat the lupus mice with initially different gut microbiota compositions. The compositions of gut microbiota were assessed by the V3-V4 region of 16S rRNA gene sequence. Early and short-term antibiotics exposure aggravated lupus severity by depleting beneficial gut microbiota for lupus, such as Lactobacillus and Bifidobacterium, and enriching harmful gut microbiota for lupus, such as Klebsiella and Proteus. FMT alleviated lupus severity by renovating the antibiotic-induced dysbiosis of gut microbiota in the following 1 week after antibiotics exposure. Besides, short-term antibiotics exposure before onset imposed no significant effects on lupus progression, but the following one week of FMT suppressed lupus progression. Moreover, the short-term antibiotics or FMT before onset inhibited the therapeutic efficiency of prednisone on lupus from 9 to 13 weeks old of MRL/lpr mice. These data demonstrate that the gut microbiota before onset is important for lupus severity, progression and treatment.

Highlights

  • Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by lymphocyte over activation and autoantibody production (Wen et al, 2016)

  • This study demonstrated that the early and short-term interventions in the gut microbiota could affect lupus-like conditions caused by genetic mutations

  • The depletion of microbiota through antibiotics exposures resulted in increased lupus severity in MRL/lpr mice

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Summary

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by lymphocyte over activation and autoantibody production (Wen et al, 2016). The pathogenesis of SLE is influenced by a combination of genetic and environmental factors. Gut Microbiota Affects Lupus-Like Conditions who will develop the disease (Jeong et al, 2018). The gut microbiota, plays major roles in antibody production, shaping the human B cell repertoire and maintaining the homeostasis of different populations of helper T cells and the Th17: Treg balance, is one such environmental factor correlated with SLE disease manifestations (Lopez et al, 2016). The disturbance of the gut microbiota, called dysbiosis, has been demonstrated in SLE patients and lupus mice models (Hevia et al, 2014; Zhang et al, 2014; Luo et al, 2018). Whether dysbiosis is merely a consequence of lupus progressions or is itself pathogenic remains unknown

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