A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis

Hudan Pan,Jian Wang,Huanming Yang,Huijue Jia,Ruijin Guo,Hua Zhou,Yanfang Zheng,Bin Tong,Ying Xie,Xun Xu,Yanmei Ju,Liang Xiao,Jun Zhu ,Zhongqiu Liu,Qi Wang,Runze Li,Linlin Lu,Fĕi Li ,Ting Li,Elaine Lai‐Han Leung ,Liang Liu

doi:10.1186/s40168-019-0719-1

Abstract

BackgroundEarly treatment is key for optimizing the therapeutic success of drugs, and the current initiating treatment that blocks the progression of bone destruction during the pre-arthritic stages remains unsatisfactory. The microbial disorder in rheumatoid arthritis (RA) patients is significantly reversed with effective treatment. Modulating aberrant gut microbiomes into a healthy state is a potential therapeutic approach for preventing bone damage.ResultsBy using metagenomic shotgun sequencing and a metagenome-wide association study, we assessed the effect of Lactobacillus casei (L. casei) on the induction of arthritis as well as on the associated gut microbiota and immune disorders in adjuvant-induced arthritis (AIA) rats. Treatment of AIA rats with L. casei inhibited joint swelling, lowered arthritis scores, and prevented bone destruction. Along with the relief of arthritis symptoms, dysbiosis in the microbiome of arthritic rats was significantly reduced after L. casei intervention. The relative abundance of AIA-decreased Lactobacillus strains, including Lactobacillus hominis, Lactobacillus reuteri, and Lactobacillus vaginalis, were restored to normal and Lactobacillus acidophilus was upregulated by the administration of L. casei to the AIA rats. Moreover, L. casei downregulated the expression of pro-inflammatory cytokines, which are closely linked to the effect of the L. casei treatment-associated microbes. Functionally, the maintenance of the redox balance of oxidative stress was involved in the improvement in the L. casei-treated AIA rats.ConclusionA single bacterium, L. casei (ATCC334), was able to significantly suppress the induction of AIA and protect bones from destruction in AIA rats by restoring the microbiome dysbiosis in the gut, indicating that using probiotics may be a promising strategy for treating RA, especially in the early stage of the disease.

Highlights

Rheumatoid arthritis (RA) is a common systemic autoimmune disease associated with bone destruction [1]
After a 30-day intervention, the rats treated with L. casei or MTX showed less aggravated symptoms, as assessed by the arthritis scores and hind paw volumes (Fig. 1a, b), and rats treated with a combined therapy of L. casei and MTX revealed an even better improvement than those with MTX or L. casei monotherapy (Additional file 3: Figure S3)
L. casei exerted its anti-arthritic effect without migrating to the places beside the gut as L. casei is facultative anaerobic bacteria and no bacteremia was detected in the L. casei-treated animals

Summary

Introduction

Rheumatoid arthritis (RA) is a common systemic autoimmune disease associated with bone destruction [1]. We recently reported on the first catalog of the gut microbiota of Sprague-Dawley (SD) rats established by shotgun metagenomic sequencing [9] Profiling of this catalog showed that the gut microbiome of rats compared to mice is slightly more similar to that of humans [9], and at the functional level, 97% of the pathways are shared suggesting that rat at the functional level to a certain extent may serve as a model for humans. The causation of changes and the dynamic changes in the gut microbiome throughout the progression of arthritis are unclear, and whether a single bacterium used as a probiotic is able to prevent or ameliorate the early stage of disease remains to be proven. Modulating aberrant gut microbiomes into a healthy state is a potential therapeutic approach for preventing bone damage

Methods

Results

Discussion

Conclusion