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

BACKGROUND: 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 gastrointestina...

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Autores principales: Clos-Garcia, Marc, Andrés-Marin, Naiara, Fernández-Eulate, Gorka, Abecia, Leticia, Lavín, José L., van Liempd, Sebastiaan, Cabrera, Diana, Royo, Félix, Valero, Alejandro, Errazquin, Nerea, Vega, María Cristina Gómez, Govillard, Leila, Tackett, Michael R., Tejada, Genesis, Gónzalez, Esperanza, Anguita, Juan, Bujanda, Luis, Orcasitas, Ana María Callejo, Aransay, Ana M., Maíz, Olga, López de Munain, Adolfo, Falcón-Pérez, Juan Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710987/
https://www.ncbi.nlm.nih.gov/pubmed/31327695
http://dx.doi.org/10.1016/j.ebiom.2019.07.031
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author Clos-Garcia, Marc
Andrés-Marin, Naiara
Fernández-Eulate, Gorka
Abecia, Leticia
Lavín, José L.
van Liempd, Sebastiaan
Cabrera, Diana
Royo, Félix
Valero, Alejandro
Errazquin, Nerea
Vega, María Cristina Gómez
Govillard, Leila
Tackett, Michael R.
Tejada, Genesis
Gónzalez, Esperanza
Anguita, Juan
Bujanda, Luis
Orcasitas, Ana María Callejo
Aransay, Ana M.
Maíz, Olga
López de Munain, Adolfo
Falcón-Pérez, Juan Manuel
author_facet Clos-Garcia, Marc
Andrés-Marin, Naiara
Fernández-Eulate, Gorka
Abecia, Leticia
Lavín, José L.
van Liempd, Sebastiaan
Cabrera, Diana
Royo, Félix
Valero, Alejandro
Errazquin, Nerea
Vega, María Cristina Gómez
Govillard, Leila
Tackett, Michael R.
Tejada, Genesis
Gónzalez, Esperanza
Anguita, Juan
Bujanda, Luis
Orcasitas, Ana María Callejo
Aransay, Ana M.
Maíz, Olga
López de Munain, Adolfo
Falcón-Pérez, Juan Manuel
author_sort Clos-Garcia, Marc
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-67109872019-08-29 Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia Clos-Garcia, Marc Andrés-Marin, Naiara Fernández-Eulate, Gorka Abecia, Leticia Lavín, José L. van Liempd, Sebastiaan Cabrera, Diana Royo, Félix Valero, Alejandro Errazquin, Nerea Vega, María Cristina Gómez Govillard, Leila Tackett, Michael R. Tejada, Genesis Gónzalez, Esperanza Anguita, Juan Bujanda, Luis Orcasitas, Ana María Callejo Aransay, Ana M. Maíz, Olga López de Munain, Adolfo Falcón-Pérez, Juan Manuel EBioMedicine Research paper BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Elsevier 2019-07-18 /pmc/articles/PMC6710987/ /pubmed/31327695 http://dx.doi.org/10.1016/j.ebiom.2019.07.031 Text en © 2019 The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Clos-Garcia, Marc
Andrés-Marin, Naiara
Fernández-Eulate, Gorka
Abecia, Leticia
Lavín, José L.
van Liempd, Sebastiaan
Cabrera, Diana
Royo, Félix
Valero, Alejandro
Errazquin, Nerea
Vega, María Cristina Gómez
Govillard, Leila
Tackett, Michael R.
Tejada, Genesis
Gónzalez, Esperanza
Anguita, Juan
Bujanda, Luis
Orcasitas, Ana María Callejo
Aransay, Ana M.
Maíz, Olga
López de Munain, Adolfo
Falcón-Pérez, Juan Manuel
Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia
title Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia
title_full Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia
title_fullStr Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia
title_full_unstemmed Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia
title_short Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia
title_sort gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710987/
https://www.ncbi.nlm.nih.gov/pubmed/31327695
http://dx.doi.org/10.1016/j.ebiom.2019.07.031
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