摘要

OBJECTIVES:Diverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome.
METHODS:The stools from a case-control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray.
RESULTS:Previous reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients.
CONCLUSION:These findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.

译文

目的: 包括临床、遗传和微生物组研究在内的多种证据支持肠道微生物组在常见免疫介导的关节病强直性脊柱炎 (AS) 中的主要作用。我们着手 (1) 进一步定义驱动疾病的关键微生物特征，以及 (2) 检查肿瘤坏死因子抑制剂 (TNFi) 治疗对微生物组的影响。
方法: 对 250 例中国汉族受试者的病例对照队列的粪便进行鸟枪法宏基因组测序。所有受试者使用 Illumina CoreExome SNP 微阵列进行基因分型。
结果: 先前关于 AS 肠道生物失调的报道被再次证实，并且几个值得注意的细菌种类和功能类别差异丰富。TNFi 疗法与恢复在未经治疗的 AS 病例中观察到的扰动微生物组与健康对照的微生物组相关，包括一些以前与 AS 和其他相关疾病相关的重要细菌物种。在 AS 患者的粪便中观察到与 HLA-B27-presented 抗原表位同源的细菌肽的富集，这表明要么 HLA-B27 未能清除这些抗原表位，要么它们参与驱动 HLA-B27-associated 的免疫反应。TNFi 疗法在很大程度上恢复了未经治疗的 AS 病例中观察到的扰动微生物组，使其恢复为健康对照，包括一些以前与 AS 和其他相关疾病相关的重要细菌物种。与未治疗的患者相比，强直性脊柱炎患者的 TNFi 治疗也与潜在的关节源性细菌肽的减少相关。
结论: 这些发现强调了肠道微生物在驱动 AS 发病机制中的关键作用，并强调了潜在的治疗和/或预防靶点。