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.

中文翻译：

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Shotgun宏基因组学揭示了强直性脊柱炎患者潜在交叉反应细菌表位的富集，以及TNFi治疗对微生物组组成的影响

目标 包括临床、遗传和微生物组研究在内的各种证据支持肠道微生物组在常见的免疫介导的关节病、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 名汉族受试者的病例对照队列的粪便进行了鸟枪法宏基因组测序。使用 Illumina CoreExome SNP 微阵列对所有受试者进行基因分型。结果 先前关于 AS 肠道菌群失调的报告得到再次证实，并且几种值得注意的细菌种类和功能类别差异丰富。TNFi 治疗与在未治疗的 AS 病例中观察到的扰乱微生物组恢复到健康对照组相关，包括以前与 AS 和其他相关疾病相关的几种重要细菌物种。在 AS 患者的粪便中观察到与 HLA-B27 呈递表位同源的细菌肽的富集，这表明 HLA-B27 未能清除这些或它们参与驱动 HLA-B27 相关的免疫反应。TNFi 疗法在很大程度上将未治疗的 AS 病例中观察到的紊乱微生物组恢复到健康对照组，包括以前与 AS 和其他相关疾病相关的几种重要细菌物种。与未接受治疗的患者相比，AS 患者的 TNFi 治疗也与潜在的致关节炎细菌肽的减少有关。