Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndrome

Abstract

Background: 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). Methods: 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. Results: Inflammatory markers, including 4E-BP1 (P = 9.60-16 and 1.41-7) and MMP-1 (P = 7.09-9 and 3.51-9), 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.Conclusions: 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.

Belgian bulk tank milk surveillance program reveals the impact of a continuous vaccination protocol for small ruminants against Coxiella burnetii

“…QFS is characterized by a state of prolonged fatigue and has major health‐related consequences, including long‐term psychosocial impairment (Reukers et al., 2019). Recent results highlighted the striking resemblance of the gut microbiome from QFS patients with chronic fatigue syndrome patients due to other causes (Raijmakers et al., 2020). Due to the lack of acute pathognomonic symptoms, human cases are likely to be underestimated.…”

Astragali Radix–Codonopsis Radix–Jujubae Fructus water extracts ameliorate exercise‐induced fatigue in mice via modulating gut microbiota and its metabolites

“…It was reported that the relative abundance of Actinobacteria in the gut was significantly lower in Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients than the healthy controls 44 . In addition, a decrease in Actinobacteria when comparing Q fever fatigue syndrome (QFS) patients to healthy controls (HCs) was also observed 45 . In this study, the abundance of Actinobacteria was decreased after exhaustive swimming, which could be reversed after ACJ treatment.…”

“…44 In addition, a decrease in Actinobacteria when comparing Q fever fatigue syndrome (QFS) patients to healthy controls (HCs) was also observed. 45 In this study, the abundance of Actinobacteria was decreased after exhaustive swimming, which could be reversed after ACJ treatment.…”

Incidence of chronic Q fever and chronic fatigue syndrome: A 6 year follow‐up of a large Q fever outbreak

“…(2015) showed in their work that cognitive‐behavioural variables may also play a role in that there is a negative association between physical activity and CFS after Q fever infection. The bacterial strain additionally appears to play a decisive role (Sukocheva et al., 2010; Raijmakers et al., 2020). In summary, CFS is a highly complex clinical picture with a heterogeneous pattern of influencing factors.…”