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疾病活动度和 HLA-B27 状态与脊柱关节炎患者的肠道微生物失调有关。

Both Disease Activity and HLA-B27 Status Are Associated With Gut Microbiome Dysbiosis in Spondyloarthritis Patients.

机构信息

Université Paris-Saclay and MetaGenoPolis, INRAE, Jouy-en-Josas, France.

AgroParisTech, Université Paris-Saclay and the Micalis Institute, INRAE, Jouy-en-Josas, France, and Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France.

出版信息

Arthritis Rheumatol. 2023 Jan;75(1):41-52. doi: 10.1002/art.42289. Epub 2022 Nov 19.

Abstract

OBJECTIVE

Gut microbiome dysbiosis has previously been reported in spondyloarthritis (SpA) patients and could be critically involved in the pathogenesis of this disorder. The objectives of this study were to further characterize the microbiota structure in SpA patients and to investigate the relationship between dysbiosis and disease activity in light of the putative influence of the genetic background.

METHODS

Shotgun sequencing was performed on fecal DNA isolated from stool samples from 2 groups of adult volunteers: SpA patients (n = 102) and healthy controls (n = 63). A subset of the healthy controls comprised the age-matched siblings of patients whose HLA-B27 status was known. Changes in gut microbiota composition were assessed based on species diversity, enterotypes, and taxonomic and functional differences.

RESULTS

Dysbiosis was confirmed in SpA patients as compared to healthy controls. The restriction of microbiota diversity was detected in patients with the most active disease, and the abundance of several bacterial species was correlated with Bath Ankylosing Spondylitis Disease Activity Index score. Among healthy controls, significant differences in microbiota composition were also detected between the HLA-B27-positive and the HLA-B27-negative siblings of SpA patients. We highlighted a decreased abundance of several species of bacteria in SpA patients, especially those bacteria belonging to the Clostridiales order. Among the few species of bacteria showing increased abundance, Ruminococcus gnavus was one of the top differentiating species.

CONCLUSION

These findings reveal that genetic background and level of disease activity are likely to influence the composition of the gut microbiota of patients with SpA. It may be appropriate for further research on chronic arthritis to focus on these key parameters.

摘要

目的

先前有研究报道,脊柱关节炎(SpA)患者存在肠道微生物组失调,这可能在该疾病的发病机制中起关键作用。本研究的目的是进一步描述 SpA 患者的微生物组结构,并根据遗传背景的潜在影响,研究肠道微生物失调与疾病活动度之间的关系。

方法

对来自 2 组成年志愿者粪便样本中的粪便 DNA 进行了 shotgun 测序:SpA 患者(n=102)和健康对照者(n=63)。健康对照组的一部分是患者 HLA-B27 状态已知的年龄匹配的兄弟姐妹。根据物种多样性、肠型以及分类和功能差异,评估肠道微生物群落组成的变化。

结果

与健康对照者相比,SpA 患者存在微生物失调。在疾病活动度最高的患者中检测到微生物多样性受限,并且几种细菌的丰度与 Bath 强直性脊柱炎疾病活动指数评分相关。在健康对照者中,还检测到 SpA 患者的 HLA-B27 阳性和 HLA-B27 阴性兄弟姐妹之间的微生物群落组成存在显著差异。我们发现 SpA 患者中几种细菌的丰度降低,尤其是属于梭状芽胞杆菌目(Clostridiales)的细菌。在少数丰度增加的细菌中,瘤胃球菌(Ruminococcus gnavus)是一种重要的差异物种。

结论

这些发现表明遗传背景和疾病活动度可能影响 SpA 患者的肠道微生物群落组成。进一步研究慢性关节炎时,可能需要关注这些关键参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9281/10099252/895c4d3ec544/ART-75-41-g005.jpg

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