Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis
Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis
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强直性脊柱炎促炎肠道微生物群的宏基因组分析
DOI：
10.1016/j.jaut.2019.102360
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发表时间：
2020-02-01
影响因子：
12.8
通讯作者：
Zhang, Xuan
中科院分区：
文献类型：
--
作者：
Zhou, Chen;Zhao, Hui;Zhang, Xuan
目的：强直性脊柱炎（AS）是一种常见的慢性炎症性疾病，主要累及骶髂关节和脊柱。方法：采用基因组鸟枪测序技术对85例未经治疗的AS患者和62例健康对照者的粪便宏基因组进行分析，并收集23例AS患者治疗后的粪便进行比较。在不同的队列包括AS，类风湿性关节炎和白塞氏病进行比较分析，以揭示一些共同的签名相关的炎性关节炎。结果：我们鉴定了富含AS的菌种，包括Bacteroides coprophilus，Parabacteroides distasonis，Eubacterium siraeum，Acidaminococcus fermentans和Prevotella copri。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。随机森林模型筛选出的AS肠道微生物特征具有较高的识别准确率。此外，还发现了一些与自身免疫相关的常见特征，如脆弱拟杆菌和III型分泌系统（T3 SS）。最后，体外实验证明，富含AS的细菌肽模拟II型胶原蛋白，可诱导产生IFN-γ的细胞数量增加。这些发现共同表明，在具有诊断潜力的未经治疗的AS患者中，肠道微生物群受到干扰，某些富含AS的物种可能通过分子模拟触发自身免疫。此外，不同的炎性关节炎有一些共同的微生物特征。
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-gamma 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.