Faculty of Natural Sciences, School of Life Sciences, Keele University, Keele, United Kingdom.
Arthritis Research UK Primary Care Centre, Research Institute for Primary Care and Health Sciences, Keele University, Keele, United Kingdom.
Front Cell Infect Microbiol. 2020 Jan 22;9:440. doi: 10.3389/fcimb.2019.00440. eCollection 2019.
Rheumatoid Arthritis (RA) has been increasingly associated with perturbations to the microbial communities that reside in and on the body (the microbiome), in both human and animal studies. To date, such studies have mainly focused on the microbial communities that inhabit the gut and oral cavity. Mounting evidence suggests that microbial DNA can be detected in the blood circulation using a range of molecular methods. This DNA may represent an untapped pool of biomarkers that have the potential to report on changes to the microbiome of distant sites (e.g., example, the gut and oral cavity). To this end, through amplification and sequencing of the bacterial 16S rRNA variable region four, we evaluated the presence and identity of microbial DNA in blood samples obtained from RA patients (both prior to and 3 months following the instigation of treatment) in comparison to a small number of healthy control subjects and samples obtained from patients with ankylosing spondylitis (AS) and psoriatic arthritis (PA). Bacterial-derived DNA was identified in the majority of our patient samples. Taxonomic classification revealed that the microbiome community in RA was distinct from AS, PA, and the healthy state. Through analysis of paired patient samples obtained prior to and 3 months following treatment (V0 vs. V3), we found the microbiome to be modulated by treatment, and in many cases, this shift reduced the distance between these samples and the healthy control samples, suggesting a partial normalization following treatment in some patients. This effect was especially evident in seronegative arthritis patients. Herein, we provide further evidence for the existence of a blood microbiome in health and identify specific taxa modulated in disease and following treatment. These blood-derived signatures may have significant utility as disease biomarkers and suggest this area warrants further investigation.
类风湿关节炎（RA）与体内和体表微生物群落（微生物组）的改变有关，这在人类和动物研究中都有体现。迄今为止，此类研究主要集中在栖息于肠道和口腔的微生物群落上。越来越多的证据表明，可以使用一系列分子方法在血液循环中检测到微生物 DNA。这些 DNA 可能代表着一个尚未开发的生物标志物库，有可能反映远处部位（例如肠道和口腔）微生物组的变化。为此，我们通过扩增和测序细菌 16S rRNA 可变区 4，评估了从 RA 患者（在开始治疗之前和 3 个月后）获得的血液样本中微生物 DNA 的存在和身份，将其与少量健康对照样本和来自强直性脊柱炎（AS）和银屑病关节炎（PA）患者的样本进行了比较。我们在大多数患者样本中都发现了细菌来源的 DNA。分类学分析表明，RA 患者的微生物组与 AS、PA 和健康状态不同。通过分析治疗前和治疗后 3 个月（V0 与 V3）获得的配对患者样本，我们发现微生物组受治疗调节，在许多情况下，这种变化使这些样本与健康对照组样本之间的距离缩小，表明部分患者在治疗后出现部分正常化。这种影响在血清阴性关节炎患者中尤为明显。本研究进一步证明了健康人群血液微生物组的存在，并确定了疾病和治疗后调节的特定分类群。这些源自血液的特征可能具有作为疾病生物标志物的重要用途，并表明该领域值得进一步研究。
