OBJECTIVE Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet's disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay. RESULTS We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen. CONCLUSIONS These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.

中文翻译：

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强直性脊柱炎中炎性肠道微生物群的元基因组分析。

目的据报道，肠道功能异常与强直性脊柱炎（AS）有关，强直性脊柱炎是一种常见的慢性炎性疾病，主要影响sa关节和脊柱。通过对未经治疗的AS患者的粪便进行深度测序，我们的研究旨在深入了解AS肠道菌群。方法我们采用宏基因组shot弹枪测序分析了85例未经治疗的AS患者和62名健康对照者的粪便基因组，并收集了23例AS患者的治疗后粪便进行比较。对包括AS，类风湿性关节炎和Behcet病在内的不同队列进行了比较分析，以发现一些与炎症性关节炎相关的常见特征。微生物肽的分子模拟也通过ELISpot测定法证明。结果我们确定了富含AS的物种，包括拟杆菌，副细菌，双歧杆菌，发酵的酸性氨基球菌和普雷沃氏菌。途径分析显示AS肠道菌群中氧化磷酸化，脂多糖生物合成和糖胺聚糖降解增加。随机森林模型选择的AS肠道微生物签名显示出较高的识别精度。还发现了一些与自身免疫有关的常见特征，例如脆弱的拟杆菌（Bacteroides fragilis）和III型分泌系统（T3SS）。最后，体外实验表明，由富含AS的物种的细菌肽模拟II型胶原蛋白触发的产生IFN-γ的细胞数量增加。结论这些发现共同表明，未经诊断的AS患者具有诊断潜力的肠道菌群受到干扰，并且某些富含AS的物种可能是通过分子模拟来引发自身免疫的。另外，不同的炎性关节炎具有一些共同的微生物特征。