Raijmakers Ruud P H, Roerink Megan E, Jansen Anne F M, Keijmel Stephan P, Gacesa Ranko, Li Yang, Joosten Leo A B, van der Meer Jos W M, Netea Mihai G, Bleeker-Rovers Chantal P, Xu Cheng-Jian
Division of Infectious Diseases 463, Department of Internal Medicine, Radboud Expertise Center for Q Fever, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
J Transl Med. 2020 Nov 26;18(1):448. doi: 10.1186/s12967-020-02585-5.
Q fever fatigue syndrome (QFS) is characterised by a state of prolonged fatigue that is seen in 20% of acute Q fever infections and has major health-related consequences. The molecular mechanisms underlying QFS are largely unclear. In order to better understand its pathogenesis, we applied a multi-omics approach to study the patterns of the gut microbiome, blood metabolome, and inflammatory proteome of QFS patients, and compared these with those of chronic fatigue syndrome (CFS) patients and healthy controls (HC).
The study population consisted of 31 QFS patients, 50 CFS patients, and 72 HC. All subjects were matched for age, gender, and general geographical region (South-East part of the Netherlands). The gut microbiome composition was assessed by Metagenomic sequencing using the Illumina HiSeq platform. A total of 92 circulating inflammatory markers were measured using Proximity Extension Essay and 1607 metabolic features were assessed with a high-throughput non-targeted metabolomics approach.
Inflammatory markers, including 4E-BP1 (P = 9.60 and 1.41) and MMP-1 (P = 7.09 and 3.51), are significantly more expressed in both QFS and CFS patients compared to HC. Blood metabolite profiles show significant differences when comparing QFS (319 metabolites) and CFS (441 metabolites) patients to HC, and are significantly enriched in pathways like sphingolipid (P = 0.0256 and 0.0033) metabolism. When comparing QFS to CFS patients, almost no significant differences in metabolome were found. Comparison of microbiome taxonomy of QFS and CFS patients with that of HC, shows both in- and decreases in abundancies in Bacteroidetes (with emphasis on Bacteroides and Alistiples spp.), and Firmicutes and Actinobacteria (with emphasis on Ruminococcus and Bifidobacterium spp.). When we compare QFS patients to CFS patients, there is a striking resemblance and hardly any significant differences in microbiome taxonomy are found.
We show that QFS and CFS patients are similar across three different omics layers and 4E-BP1 and MMP-1 have the potential to distinguish QFS and CFS patients from HC.
Q热疲劳综合征（QFS）的特征是长期疲劳状态，在20%的急性Q热感染中可见，且对健康有重大影响。QFS背后的分子机制在很大程度上尚不清楚。为了更好地理解其发病机制，我们采用多组学方法研究QFS患者的肠道微生物组、血液代谢组和炎症蛋白质组模式，并将其与慢性疲劳综合征（CFS）患者和健康对照（HC）进行比较。
研究人群包括31名QFS患者、50名CFS患者和72名HC。所有受试者在年龄、性别和一般地理区域（荷兰东南部）方面进行了匹配。使用Illumina HiSeq平台通过宏基因组测序评估肠道微生物组组成。使用邻近延伸分析测量了总共92种循环炎症标志物，并采用高通量非靶向代谢组学方法评估了1607种代谢特征。
与HC相比，包括4E-BP1（P = 9.60和1.41）和MMP-1（P = 7.09和3.51）在内的炎症标志物在QFS和CFS患者中均有显著更高的表达。将QFS（319种代谢物）和CFS（441种代谢物）患者与HC进行比较时，血液代谢物谱显示出显著差异，并且在鞘脂代谢等途径中显著富集（P = 0.0256和0.0033）。将QFS患者与CFS患者进行比较时，在代谢组中几乎未发现显著差异。将QFS和CFS患者的微生物组分类与HC的进行比较，发现拟杆菌门（重点是拟杆菌属和阿里斯普利斯菌属）、厚壁菌门和放线菌门（重点是瘤胃球菌属和双歧杆菌属）的丰度均有增减。当我们将QFS患者与CFS患者进行比较时，发现微生物组分类有惊人的相似之处，几乎没有显著差异。
我们表明，QFS和CFS患者在三个不同的组学层面上相似，4E-BP1和MMP-1有潜力将QFS和CFS患者与HC区分开来。
