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,...

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Main Authors: Ruud P. H. Raijmakers, Megan E. Roerink, Anne F. M. Jansen, Stephan P. Keijmel, Ranko Gacesa, Yang Li, Leo A. B. Joosten, Jos W. M. van der Meer, Mihai G. Netea, Chantal P. Bleeker-Rovers, Cheng-Jian Xu
Format: Article
Language:English
Published: BMC 2020-11-01
Series:Journal of Translational Medicine
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Online Access:http://link.springer.com/article/10.1186/s12967-020-02585-5
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author Ruud P. H. Raijmakers
Megan E. Roerink
Anne F. M. Jansen
Stephan P. Keijmel
Ranko Gacesa
Yang Li
Leo A. B. Joosten
Jos W. M. van der Meer
Mihai G. Netea
Chantal P. Bleeker-Rovers
Cheng-Jian Xu
author_facet Ruud P. H. Raijmakers
Megan E. Roerink
Anne F. M. Jansen
Stephan P. Keijmel
Ranko Gacesa
Yang Li
Leo A. B. Joosten
Jos W. M. van der Meer
Mihai G. Netea
Chantal P. Bleeker-Rovers
Cheng-Jian Xu
author_sort Ruud P. H. Raijmakers
collection DOAJ
description 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.
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spelling doaj.art-272ed69de73146399ef0ba3f4f57919e2022-12-21T22:57:25ZengBMCJournal of Translational Medicine1479-58762020-11-0118111310.1186/s12967-020-02585-5Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndromeRuud P. H. Raijmakers0Megan E. Roerink1Anne F. M. Jansen2Stephan P. Keijmel3Ranko Gacesa4Yang Li5Leo A. B. Joosten6Jos W. M. van der Meer7Mihai G. Netea8Chantal P. Bleeker-Rovers9Cheng-Jian Xu10Division of Infectious Diseases 463, Department of Internal Medicine, Radboud Expertise Center for Q Fever, Radboud University Medical CenterDepartment of Internal Medicine, Radboud University Medical CenterDivision of Infectious Diseases 463, Department of Internal Medicine, Radboud Expertise Center for Q Fever, Radboud University Medical CenterDivision of Infectious Diseases 463, Department of Internal Medicine, Radboud Expertise Center for Q Fever, Radboud University Medical CenterDepartment of Genetics, University Medical Center GroningenDepartment of Internal Medicine, Radboud University Medical CenterDivision of Infectious Diseases 463, Department of Internal Medicine, Radboud Expertise Center for Q Fever, Radboud University Medical CenterDivision of Infectious Diseases 463, Department of Internal Medicine, Radboud Expertise Center for Q Fever, Radboud University Medical CenterDivision of Infectious Diseases 463, Department of Internal Medicine, Radboud Expertise Center for Q Fever, Radboud University Medical CenterDivision of Infectious Diseases 463, Department of Internal Medicine, Radboud Expertise Center for Q Fever, Radboud University Medical CenterDepartment of Internal Medicine, Radboud University Medical CenterAbstract 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.http://link.springer.com/article/10.1186/s12967-020-02585-5QFSCFSFatigueQ feverOmicsInflammation
spellingShingle Ruud P. H. Raijmakers
Megan E. Roerink
Anne F. M. Jansen
Stephan P. Keijmel
Ranko Gacesa
Yang Li
Leo A. B. Joosten
Jos W. M. van der Meer
Mihai G. Netea
Chantal P. Bleeker-Rovers
Cheng-Jian Xu
Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndrome
Journal of Translational Medicine
QFS
CFS
Fatigue
Q fever
Omics
Inflammation
title Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndrome
title_full Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndrome
title_fullStr Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndrome
title_full_unstemmed Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndrome
title_short Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndrome
title_sort multi omics examination of q fever fatigue syndrome identifies similarities with chronic fatigue syndrome
topic QFS
CFS
Fatigue
Q fever
Omics
Inflammation
url http://link.springer.com/article/10.1186/s12967-020-02585-5
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