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单细菌可恢复微生态失调以保护类风湿关节炎大鼠模型中的骨骼免受破坏。

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

机构信息

State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macao University of Science and Technology, Macao, China.

BGI-Shenzhen, Shenzhen, 518083, China.

出版信息

Microbiome. 2019 Jul 17;7(1):107. doi: 10.1186/s40168-019-0719-1.

DOI:10.1186/s40168-019-0719-1
PMID:31315667
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6637628/
Abstract

BACKGROUND

Early 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.

RESULTS

By 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.

CONCLUSION

A 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.

摘要

背景

早期治疗是优化药物治疗效果的关键,而目前阻止关节炎前阶段骨破坏进展的起始治疗仍不尽如人意。类风湿关节炎(RA)患者的微生物失调在有效治疗后得到显著逆转。将异常的肠道微生物组调节为健康状态是预防骨损伤的一种潜在治疗方法。

结果

通过使用宏基因组鸟枪法测序和宏基因组关联研究,我们评估了干酪乳杆菌(L. casei)对佐剂诱导关节炎(AIA)大鼠关节炎诱导以及相关肠道微生物组和免疫紊乱的影响。用 L. casei 治疗 AIA 大鼠可抑制关节肿胀,降低关节炎评分,并预防骨破坏。随着关节炎症状的缓解,L. casei 干预后关节炎大鼠的微生物组失调得到了显著改善。相对丰度降低的 AIA 乳杆菌菌株,包括人乳杆菌、雷特氏乳杆菌和阴道乳杆菌,在 L. casei 干预后恢复正常,嗜酸乳杆菌的丰度上调。此外,L. casei 下调了与 L. casei 治疗相关微生物密切相关的促炎细胞因子的表达。从功能上讲,维持氧化应激的氧化还原平衡参与了 L. casei 治疗的 AIA 大鼠的改善。

结论

单一细菌干酪乳杆菌(ATCC334)通过恢复肠道微生物组失调,显著抑制 AIA 的诱导,并保护 AIA 大鼠的骨骼免受破坏,表明使用益生菌可能是治疗 RA 的一种有前途的策略,尤其是在疾病的早期阶段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/0e7494e49433/40168_2019_719_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/6ac687aff158/40168_2019_719_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/ebb700fcf15d/40168_2019_719_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/9d5165ac7572/40168_2019_719_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/c94b7872d02d/40168_2019_719_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/0e7494e49433/40168_2019_719_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/6ac687aff158/40168_2019_719_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/ebb700fcf15d/40168_2019_719_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/9d5165ac7572/40168_2019_719_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/c94b7872d02d/40168_2019_719_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a1/6637628/0e7494e49433/40168_2019_719_Fig5_HTML.jpg

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