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1.
EBioMedicine ; 46: 499-511, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31327695

ABSTRACT

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.


Subject(s)
Fibromyalgia/etiology , Fibromyalgia/metabolism , Gastrointestinal Microbiome , Glutamates/metabolism , Metabolome , Metabolomics , Adult , Aged , Biomarkers , Chromatography, High Pressure Liquid , Computational Biology/methods , Cytokines/metabolism , Female , Humans , Male , Metabolomics/methods , Metagenome , Metagenomics/methods , Middle Aged , RNA, Ribosomal, 16S/genetics , ROC Curve , Tandem Mass Spectrometry
2.
J Stroke Cerebrovasc Dis ; 27(5): e86-e87, 2018 May.
Article in English | MEDLINE | ID: mdl-29331613

ABSTRACT

Carotid artery web is considered an exceptional cause of recurrent ischemic strokes in the affected arterial territory. The underlying pathology proposed for this entity is an atypical fibromuscular dysplasia. We present the case of a 43-year-old woman with no cardiovascular risk factors who had experienced 2 cryptogenic ischemic strokes in the same arterial territory within an 11-month period. Although all diagnostic tests initially yielded normal results, detailed analysis of the computed tomography angiography images revealed a carotid web; catheter angiography subsequently confirmed the diagnosis. Carotid surgery was performed, since which time the patient has remained completely asymptomatic. The histological finding of intimal hyperplasia is consistent with previously reported cases of carotid artery web. Carotid artery web is an infrequent cause of stroke, and this diagnosis requires a high level of suspicion plus a detailed analysis of vascular imaging studies.


Subject(s)
Brain Ischemia/etiology , Carotid Artery Diseases/complications , Carotid Artery, Internal/pathology , Fibromuscular Dysplasia/complications , Stroke/etiology , Adult , Aspirin/therapeutic use , Atorvastatin/therapeutic use , Biopsy , Brain Ischemia/diagnostic imaging , Cardiovascular Agents/therapeutic use , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/drug therapy , Carotid Artery Diseases/pathology , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/drug effects , Computed Tomography Angiography , Female , Fibromuscular Dysplasia/diagnostic imaging , Fibromuscular Dysplasia/drug therapy , Fibromuscular Dysplasia/pathology , Humans , Hyperplasia , Neointima , Recurrence , Risk Factors , Stroke/diagnostic imaging
4.
J Stroke Cerebrovasc Dis ; 26(8): 1670-1677, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28412318

ABSTRACT

OBJECTIVE: The aims of this study are, first, to calculate the risk of brain ischemia recurrence and embolic source diagnosis in the follow-up of patients with ESUS (embolic stroke of undetermined source) and, second, to identify the predictors of these events including cardiologic, laboratory, and clinical factors. METHODS: A retrospective observational cohort study of stroke patients admitted to the stroke unit in a single tertiary hospital from 2012 to 2014 was performed. Patients fulfilling ESUS criteria were identified and followed by medical history review until March 2016. Statistical analysis comprised Kaplan-Meier analysis and Cox proportional hazards multivariate analysis including clinical characteristics, cardiologic data, and blood test results. RESULTS: One hundred and thirteen patients, 8.3% of the overall stroke patients, filled ESUS criteria and they were younger, had less vascular risk factors, and suffered milder strokes than the remainder of stroke patients. Median follow-up of ESUS was 25.6 months. Risk of brain ischemia recurrence was 8.4, 10.8, and 15% at 12, 24, and 36 months, respectively, and was associated to age (HR 1.07, P = .027) and to a higher total cholesterol (TC)/high-density lipoprotein (HDL)-cholesterol (HR = 1.38, P = .002) and low-density lipoprotein (LDL)-cholesterol/HDL-cholesterol ratios (HR = 1.48, P = .001). The risk of major embolic source diagnosis was 6.7, 7.8, 13.6% at 12, 24, and 36 months, and was associated to female sex (HR = 6.05, P = .021). CONCLUSIONS: Brain ischemia recurrence increases with age and increased values of nontraditional lipid variables, TCHDLr and LDLHDLr, in ESUS patients, and women are more frequently diagnosed with a major embolic source in the follow-up.


Subject(s)
Brain Ischemia/etiology , Dyslipidemias/complications , Intracranial Embolism/etiology , Lipids/blood , Stroke/etiology , Aged , Aged, 80 and over , Biomarkers/blood , Brain Ischemia/blood , Brain Ischemia/diagnostic imaging , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dyslipidemias/blood , Dyslipidemias/diagnosis , Female , Humans , Intracranial Embolism/blood , Intracranial Embolism/diagnostic imaging , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , Recurrence , Retrospective Studies , Risk Factors , Sex Factors , Stroke/blood , Stroke/diagnostic imaging , Tertiary Care Centers , Time Factors
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