CIC bioGUNE
Published July 23, 2019 | Version v1
Journal article Open

Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia

Creators

  • 1. Exosomes Laboratory, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain; Department of Gastroenterology, Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), CIBERehd (Centro de investigación en red de enfermedades hepáticas y digestiva) San Sebastian, Spain
  • 2. Department of Neurology, Donostia University Hospital, San Sebastian, Spain
  • 3. Department of Neurology, Donostia University Hospital, San Sebastian, Spain; Neuroscience Area, Biodonostia Health Research Institute, San Sebastian, Spain
  • 4. Macrophage and Tick Vaccine Laboratory, CIC bioGUNE, Bizkaia Technology Park, Derio, Spain
  • 5. Bioinformatics Unit, CIC bioGUNE, Bizkaia Technology Park, Derio, Spain
  • 6. Metabolomics Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain
  • 7. Exosomes Laboratory, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain
  • 8. Department of Rheumatology, Donostia University Hospital, San Sebastian, Spain
  • 9. Department of Rheumatology, Gipuzcoa Policlinic, San Sebastian, Spain
  • 10. Department of Anesthesiology and Pain Unit, Hospital Galdakao-Usansolo, Bizkaia, Spain
  • 11. Deusto University, San Sebastian, Spain
  • 12. Abcam, Cambridge, MA, United States
  • 13. Macrophage and Tick Vaccine Laboratory, CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
  • 14. Department of Gastroenterology, Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), CIBERehd (Centro de investigación en red de enfermedades hepáticas y digestiva) San Sebastian, Spain
  • 15. Genome Analysis Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain
  • 16. Department of Neurology, Donostia University Hospital, San Sebastian, Spain; Neuroscience Area, Biodonostia Health Research Institute, San Sebastian, Spain; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Spain; Department of Neurosciences, University of Basque Country UPV/EHU, San Sebastian, Spain
  • 17. Exosomes Laboratory, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain; Metabolomics Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

Description

Fibromyalgia is a complex, relatively unknown disease characterised by chronic, widespread musculoskeletal pain. The gut-brain axis connects the gut microbiome with the brain through the enteric nervous system (ENS); its disruption has been associated with psychiatric and gastrointestinal disorders. To gain an insight into the pathogenesis of fibromyalgia and identify diagnostic biomarkers, we combined different omics techniques to analyse microbiome and serum composition.

We collected faeces and blood samples to study the microbiome, the serum metabolome and circulating cytokines and miRNAs from a cohort of 105 fibromyalgia patients and 54 age- and environment-matched healthy individuals. We sequenced the V3 and V4 regions of the 16S rDNA gene from faeces samples. UPLC-MS metabolomics and custom multiplex cytokine and miRNA analysis (FirePlex™ technology) were used to examine sera samples. Finally, we combined the different data types to search for potential biomarkers.

We found that the diversity of bacteria is reduced in fibromyalgia patients. The abundance of the Bifidobacterium and Eubacterium genera (bacteria participating in the metabolism of neurotransmitters in the host) in these patients was significantly reduced. The serum metabolome analysis revealed altered levels of glutamate and serine, suggesting changes in neurotransmitter metabolism. The combined serum metabolomics and gut microbiome datasets showed a certain degree of correlation, reflecting the effect of the microbiome on metabolic activity. We also examined the microbiome and serum metabolites, cytokines and miRNAs as potential sources of molecular biomarkers of fibromyalgia.

Our results show that the microbiome analysis provides more significant biomarkers than the other techniques employed in the work. Gut microbiome analysis combined with serum metabolomics can shed new light onto the pathogenesis of fibromyalgia. We provide a list of bacteria whose abundance changes in this disease and propose several molecules as potential biomarkers that can be used to evaluate the current diagnostic criteria.

Files

Clos-Garcia - 2019 - Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia.pdf

Files (3.5 MB)