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甲氨蝶呤促进关节炎引起的牙槽骨丢失的恢复,并改变口腔-肠道微生物组的组成。

Methotrexate promotes recovery of arthritis-induced alveolar bone loss and modifies the composition of the oral-gut microbiota.

机构信息

Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

Department of Dentistry, Pontifical Catholic University, Belo Horizonte, MG, Brazil.

出版信息

Anaerobe. 2022 Jun;75:102577. doi: 10.1016/j.anaerobe.2022.102577. Epub 2022 Apr 28.

DOI:10.1016/j.anaerobe.2022.102577
PMID:35490916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10782845/
Abstract

OBJECTIVES

The impact of rheumatoid arthritis (RA) on the shaping of the oral and gut microbiome raises the question of whether and how RA treatment modifies microbial communities. We examined changes in the oral and gut microbiota in a mouse model of antigen-induced arthritis (AIA) treated or not with methotrexate (MTX).

METHODS

Maxillae and stools were evaluated by the MiSeq platform of the V4 region of the 16S rRNA gene. Alveolar bone parameters were analysed by micro-computed tomography. Moreover, arthritis-induced changes in hyperalgesia and oedema were assessed, along with the impact on periodontal bone health.

RESULTS

Microbial communities in MTX-treated AIA mice revealed distinct clusters compared to the control and AIA groups. Overall, MTX impacted the richness and variability of microorganisms in the oral-gut axis microbiome at the phylum level. Regarding the oral microbiome, while in the control group the most dominant phylum was Firmicutes, in the AIA group there was a shift towards the predominance of Campilobacteriota and Bacteroidetes associated with the disease. MTX treatment led to greater dominance of the health-associated phylum Proteobacteria. In the gut microbiome, AIA induction resulted in increased abundance of the Verrucomicrobiota phylum, and MTX treatment restored its levels compared to control. Importantly, the MTX-treated AIA animals had significantly less periodontal bone loss, as well as decreased hyperalgesia and joint oedema compared to the AIA animals.

CONCLUSION

Data suggest the benefit of MTX treatment in protecting alveolar bone, in addition to providing new insights on the drug-microbiome interaction in the course of RA.

摘要

目的

类风湿关节炎(RA)对口腔和肠道微生物组的影响提出了一个问题,即 RA 治疗是否以及如何改变微生物群落。我们研究了在抗原诱导关节炎(AIA)的小鼠模型中,用甲氨蝶呤(MTX)治疗或未治疗的情况下,口腔和肠道微生物群的变化。

方法

通过 MiSeq 平台对 V4 区的 16S rRNA 基因进行上颌骨和粪便评估。通过微计算机断层扫描分析牙槽骨参数。此外,还评估了关节炎引起的痛觉过敏和水肿变化,以及对牙周骨健康的影响。

结果

与对照组和 AIA 组相比,MTX 治疗的 AIA 小鼠的微生物群落显示出明显的聚类。总体而言,MTX 影响了口腔-肠道轴微生物组在门水平上的丰富度和变异性。关于口腔微生物组,在对照组中最主要的门是厚壁菌门,而在 AIA 组中,与疾病相关的 Campilobacteriota 和拟杆菌门的优势发生了转变。MTX 治疗导致与健康相关的 Proteobacteria 门的优势更大。在肠道微生物组中,AIA 诱导导致 Verrucomicrobiota 门的丰度增加,而 MTX 治疗使其水平恢复到对照组。重要的是,与 AIA 动物相比,MTX 治疗的 AIA 动物的牙周骨丢失明显减少,痛觉过敏和关节水肿也减少。

结论

数据表明 MTX 治疗除了为 RA 病程中的药物-微生物组相互作用提供新的见解外,还能保护牙槽骨。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/10782845/8779e28dbf4c/nihms-1951698-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/10782845/b8f9a3a71876/nihms-1951698-f0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/10782845/8779e28dbf4c/nihms-1951698-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/10782845/b8f9a3a71876/nihms-1951698-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/10782845/e1adb4f5245e/nihms-1951698-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/10782845/581ba23183f4/nihms-1951698-f0003.jpg
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