143 research outputs found

    Gut microbiota links to serum ferritin and cognition

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    ABSTRACTIron is required for the replication and growth of almost all bacterial species and in the production of myelin and neurotransmitters. Increasing clinical studies evidence that the gut microbiota plays a critical role in iron metabolism and cognition. However, the understanding of the complex iron-microbiome-cognition crosstalk remains elusive. In a recent study in the Aging Imageomics cohort (n = 1,030), we identified a positive association of serum ferritin (SF) with executive function (EF) as inferred from the semantic verbal fluency (SVF,) the total digit span (TDS) and the phonemic verbal fluency tests (PVF). Here, we explored the potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively. Different bacterial species belonging to the Proteobacteria phylum (Klebsiella pneumoniae, Klebsiella michiganensis, Unclassified Escherichia) were negatively associated both with SF and executive function. At the functional level, an enrichment of microbial pathways involved in phenylalanine, arginine, and proline metabolism was identified. Consistently, phenylacetylglutamine, a metabolite derived from microbial catabolism of phenylalanine, was negatively associated with SF, EF, and semantic memory. Other metabolites such as ureidobutyric acid and 19,20-DiHDPA, a DHA-derived oxylipin, were also consistently and negatively associated with SF, EF, and semantic memory, while plasma eicosapentaenoic acid was positively associated. The associations of SF with cognition could be mediated by the gut microbiome through microbial-derived metabolites

    Association of depression phenotypes and antidepressant treatment with mortality due to cancer and other causes: a community-based cohort study

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    ObjectiveThis study aimed to assess the association of somatic depressive symptoms (SDS), cognitive/emotional depressive symptoms (C-EDS), and antidepressant treatment on mortality due to cancer and other causes in a community cohort.MethodsA community-based sample recruited in 1995, 2000, and 2005 aged between 35 and 75 years was examined in two waves and followed for a median of 6.7 years. SDS and C-EDS phenotypes were assessed using the Patient Health Questionnaire-9. Medication used by participants was collected. Deaths and their causes were registered during follow-up. Cox proportional hazard models stratified by sex were performed to determine the association between depressive phenotypes and mortality.ResultsThe cohort consisted of 5,646 individuals (53.9% women) with a mean age of 64 years (SD = 11.89). During the follow-up, 392 deaths were recorded, of which 27.8% were due to cancer. C-EDS phenotype was associated with an increased risk of cancer mortality in both men (HR = 2.23; 95% CI = 1.11-4.44) and women (HR = 3.69; 95% CI = 1.69-8.09), and SDS was significantly associated with non-cancer mortality in men (HR = 2.16; 95 CI % = 1.46-3.18). Selective serotonin reuptake inhibitors (SSRIs) were significantly associated with both cancer (HR = 2.78; 95% CI = 1.10-6.98) and non-cancer mortality (HR = 2.94; 95% CI = 1.76-4.90) only in the male population.ConclusionC-EDS phenotype was related to an increased risk of cancer mortality at 6 years. In addition, the use of SSRIs in the male population was associated with cancer and all-cause mortality

    Association of depression phenotypes and antidepressant treatment with mortality due to cancer and other causes: a community-based cohort study

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    Fàrmac antidepressiu; Càncer; Síndrome depressiuFármaco antidepresivo; Cáncer; Síndrome depresivoAntidepressant drug; Cancer; Depressive syndromeObjective: This study aimed to assess the association of somatic depressive symptoms (SDS), cognitive/emotional depressive symptoms (C-EDS), and antidepressant treatment on mortality due to cancer and other causes in a community cohort.Methods: A community-based sample recruited in 1995, 2000, and 2005 aged between 35 and 75 years was examined in two waves and followed for a median of 6.7 years. SDS and C-EDS phenotypes were assessed using the Patient Health Questionnaire-9. Medication used by participants was collected. Deaths and their causes were registered during follow-up. Cox proportional hazard models stratified by sex were performed to determine the association between depressive phenotypes and mortality.Results: The cohort consisted of 5,646 individuals (53.9% women) with a mean age of 64 years (SD = 11.89). During the follow-up, 392 deaths were recorded, of which 27.8% were due to cancer. C-EDS phenotype was associated with an increased risk of cancer mortality in both men (HR = 2.23; 95% CI = 1.11–4.44) and women (HR = 3.69; 95% CI = 1.69–8.09), and SDS was significantly associated with non-cancer mortality in men (HR = 2.16; 95 CI % = 1.46–3.18). Selective serotonin reuptake inhibitors (SSRIs) were significantly associated with both cancer (HR = 2.78; 95% CI = 1.10–6.98) and non-cancer mortality (HR = 2.94; 95% CI = 1.76–4.90) only in the male population.Conclusion: C-EDS phenotype was related to an increased risk of cancer mortality at 6 years. In addition, the use of SSRIs in the male population was associated with cancer and all-cause mortality.Objectiu: aquest estudi pretenia avaluar l'associació de símptomes depressius somàtics (SDS), símptomes depressius cognitius/emocionals (C-EDS) i tractament antidepressiu sobre la mortalitat per càncer i altres causes en una cohort comunitària. Mètodes: una mostra basada en la comunitat reclutada el 1995, 2000 i 2005 d'entre 35 i 75 anys es va examinar en dues onades i es va seguir durant una mitjana de 6,7 anys. Els fenotips SDS i C-EDS es van avaluar mitjançant el Patient Health Questionnaire-9. Es van recollir els medicaments utilitzats pels participants. Durant el seguiment es van registrar les morts i les seves causes. Es van realitzar models de risc proporcional de Cox estratificats per sexe per determinar l'associació entre fenotips depressius i mortalitat. Resultats: La cohort estava formada per 5.646 individus (53,9% dones) amb una edat mitjana de 64 anys (DE = 11,89). Durant el seguiment es van registrar 392 defuncions, de les quals el 27,8% van ser per càncer. El fenotip C-EDS es va associar amb un augment del risc de mortalitat per càncer tant en homes (HR = 2,23; IC 95% = 1,11-4,44) com en dones (HR = 3,69; IC 95% = 1,69-8,09), i el SDS es va associar significativament. amb mortalitat no per càncer en homes (HR = 2,16; IC 95 % = 1,46–3,18). Els inhibidors selectius de la recaptació de serotonina (ISRS) es van associar significativament tant amb el càncer (HR = 2,78; IC 95% = 1,10-6,98) com amb la mortalitat no per càncer (HR = 2,94; IC 95% = 1,76-4,90) només a la població masculina. Conclusió: el fenotip C-EDS es va relacionar amb un augment del risc de mortalitat per càncer als 6 anys. A més, l'ús d'ISRS a la població masculina es va associar amb càncer i mortalitat per totes les causes.This study was supported by the research grant STL006/17/00234 from the Strategic Plan for Health Research and Innovation (PERIS) 2016–2020 of the Department of Health, Government of Catalonia. The funding sources played no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, nor in the preparation, review, or approval of the manuscript

    Adipose tissue coregulates cognitive function

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    Obesity is associated with cognitive decline. Recent observations in mice propose an adipose tissue (AT)-brain axis. We identified 188 genes from RNA sequencing of AT in three cohorts that were associated with performance in different cognitive domains. These genes were mostly involved in synaptic function, phosphatidylinositol metabolism, the complement cascade, anti-inflammatory signaling, and vitamin metabolism. These findings were translated into the plasma metabolome. The circulating blood expression levels of most of these genes were also associated with several cognitive domains in a cohort of 816 participants. Targeted misexpression of candidate gene ortholog in the Drosophila fat body significantly altered flies memory and learning. Among them, down-regulation of the neurotransmitter release cycle-associated gene SLC18A2 improved cognitive abilities in Drosophila and in mice. Up-regulation of RIMS1 in Drosophila fat body enhanced cognitive abilities. Current results show previously unidentified connections between AT transcriptome and brain function in humans, providing unprecedented diagnostic/therapeutic targets in AT

    The presence of Blastocystis in gut microbiota is associated with cognitive traits and decreased executive function [Dataset]

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    1. metadata_BLASTOCYSTIS Contains relevant clinical and cognitive information about the subjects: age, BMI, sex, years of ecudation and measures of executive function (total digit Span, trail making test part B, stroop interference). 2. Metabolomics_Plasma_HPLC_MS_positive_mode Contains the plasma metabolomic raw data (intensities) measured by HPLC-ESI-MS/MS in positive mode for each subjects according to the mass and retention time (mass@retention time). 3. Metabolomics_Plasma_HPLC_MS_negative_mode Contains the plasma metabolomic raw data (intensities) measured by HPLC-ESI-MS/MS in negative mode for each subjects according to the mass and retention time (mass@retention time). 4. Metabolomics_Plasma_NMR Contains the integrations of the plasma metabolites measures by 1H-NMR for each subject. 5. Metabolomics_Feces_HPLC_MS_positive_mode Contains the fecal metabolomic raw data (intensities) measured by HPLC-ESI-MS/MS in positive mode for each subjects according to the mass and retention time (mass@retention time). 6. Metabolomics_Feces_HPLC_MS_negative_mode Contains the fecal metabolomic raw data (intensities) measured by HPLC-ESI-MS/MS in negative mode for each subjects according to the mass and retention time (mass@retention time). 7. Metabolomics_Feces_NMR Contains the integrations of the fecal metabolites measures by 1H-NMR for each subject.Peer reviewe

    Control of Therapeutic Levels of Anticoagulation and Associated Factors: A Prospective Cohort Study

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    Teràpia anticoagulant; Vitamin K; Estudis de cohortsTerapia anticoagulante; Vitamin K; Estudios de cohortesAnticoagulant therapy; Vitamin K; Cohort StudiesMaintaining therapeutic levels of anticoagulation is essential to avoid health complications in people who take vitamin K antagonists. This study aimed to analyze the influence of people’s characteristics and the presence of changes in their lives in the control of therapeutic levels of anticoagulation. A longitudinal multicenter study with a 1-year follow-up of a cohort of 199 people receiving anticoagulant therapy was performed. The effect of biological, clinical, social, lifestyle, and changes in life on the international normalized ratio (INR) was analyzed. During the follow-up, 46.7% of participants presented good INR control. At baseline, a diagnosis of atrial fibrillation (P = .00), the lack of comorbidities (P = .03), absence of depression (P = .04), and not following a pharmacological treatment with hypoglycemia drugs (P = .01) were associated with good INR control. During the follow-up, the variable of making changes to the usual diet was associated with poor INR control (P = .05). In the binary multiple regression model, factors associated with poor control were taking hypoglycemia drugs (P = .02) and the presence of depression (P = .04), and only the diagnosis of atrial fibrillation was associated with good control (P = .03). People with a diagnosis of atrial fibrillation had good INR control. Having comorbidities, suffering depression, taking hypoglycemia drugs, and making changes to the diet have a negative effect on INR control

    Microbiota alterations in proline metabolism impact depression

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    The microbiota-gut-brain axis has emerged as a novel target in depression, a disorder with low treatment efficacy. However, the field is dominated by underpowered studies focusing on major depression not ad- dressing microbiome functionality, compositional nature, or confounding factors. We applied a multi-omics approach combining pre-clinical models with three human cohorts including patients with mild depression. Microbial functions and metabolites converging onto glutamate/GABA metabolism, particularly proline, were linked to depression. High proline consumption was the dietary factor with the strongest impact on depression. Whole-brain dynamics revealed rich club network disruptions associated with depression and circulating proline. Proline supplementation in mice exacerbated depression along with microbial translocation. Human microbiota transplantation induced an emotionally impaired phenotype in mice and alterations in GABA-, proline-, and extracellular matrix-related prefrontal cortex genes. RNAi-mediated knockdown of pro-line and GABA transporters in Drosophila and mono-association with L. plantarum, a high GABA producer, conferred protection against depression-like states. Targeting the microbiome and dietary proline may open new windows for efficient depression treatment

    Gender analysis of the frequency and course of depressive disorders and relationship with personality traits in general population: a prospective cohort study

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    DepressiĂł; Epidemiologia; PersonalitatDepresiĂłn; EpidemiologĂ­a; PersonalidadDepression; Epidemiology; PersonalityBackground: We aimed to determine the prevalence and course of subthreshold depressive symptomatology (sDS) and probable major depressive episode (MDE) and to examine their association with personality traits among men and women. Methods: A community-based sample aged 35 years or older was examined in two waves (median follow-up of 6.9 years). The Patient Health Questionnaire-9 (PHQ-9) was used to assess sDS and MDE. The 10-item version of the Big Five Inventory was used to assess personality traits. Prevalence was assessed at baseline (n=5,557) and incidence and persistence-recurrence rates were computed at follow up (n=3,102). Logistic regression models were adjusted to explore the association of personality traits with prevalence and course of depressive disorders. Results: The prevalence of sDS and MDE was 14.04% (95% CI = 17.04-19.08) and 8.54 (95% CI=7.82-9.31), the incidence was 14.30 per 1,000 person-years (95% CI=12.49-16.31) and 4.34 per 1,000 person-years (95% CI=3.46-5.36), and the persistence-recurrence was 35.04 per 1,000 person-years (95% CI=29.00-41.96) and 28.8 per 1,000 person-years (95% CI=20.49-38.14). The gender gap was higher for MDE. Personality traits were differentially associated with the prevalence and course of depressive disorders between men and women. Limitations: Because this study used questionnaires to assess depressive disorders and personality traits, information bias could not be ruled out. Conclusions: The gender gap was higher for the prevalence and course of the probable MDE. There were more personality traits related with the course of the sDS and they had a major role in the course of the probable MDE in women.This study was supported by research grant STL006/17/00234 from the Strategic Plan for Health Research and Innovation (PERIS) 2016-2020 of the Department of Health. Government of Catalunya

    Presence of blastocystis in gut microbiota is associated with cognitive traits and decreased executive function

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    Growing evidence implicates the gut microbiome in cognition. Blastocystis is a common gut single-cell eukaryote parasite frequently detected in humans but its potential involvement in human pathophysiology has been poorly characterized. Here we describe how the presence of Blastocystis in the gut microbiome was associated with deficits in executive function and altered gut bacterial composition in a discovery (n = 114) and replication cohorts (n = 942). We also found that Blastocystis was linked to bacterial functions related to aromatic amino acids metabolism and folate-mediated pyrimidine and one-carbon metabolism. Blastocystis-associated shifts in bacterial functionality translated into the circulating metabolome. Finally, we evaluated the effects of microbiota transplantation. Donor's Blastocystis subtypes led to altered recipient's mice cognitive function and prefrontal cortex gene expression. In summary, Blastocystis warrant further consideration as a novel actor in the gut microbiome-brain axis.This study was partially funded by the Catalan Government (AGAUR, #SGR2017-0734, ICREA Academia Award 2021) to J.M.F.-R., Instituto de Salud Carlos III (Madrid, Spain) through the projects PI15/01934, PI18/01022 and PI21/01361 to JMF-R, the project PI20/01090 (Co-funded by European Regional Development Fund “A way to make Europe”) to JM-P, and the project PI20/0155 to MP-O; the grants SAF2015-65878-R from Ministry of Economy and Competitiveness, Prometeo/2018/A/133 from Generalitat Valenciana, Spain and also by Fondo Europeo de Desarrollo Regional (FEDER) funds (“A way to build Europe”), European Commission (FP7), the Catalan Government (AGAUR, #SGR2017-669, ICREA Academia Award 2020 and Ministerio de Ciencia e Innovación PID2020- 120029GB-I00/MICIN/AEI/10.13039/501100011033, and RD21/0009/0019, European Commission-DG Research” (PainFact, H2020-SC1-2019-2-RTD-848099, QSPain Relief, H2020-SC1-2019-2-RTD-848068 to R.M.), the Spanish Instituto de Salud Carlos III (RTA, #RD16/0017/0020) and the European Regional Development Fund (project No. 01.2.2-LMT-K-718-02-0014) under grant agreement with the Research Council of Lithuania (LMTLT). We also acknowledge funding from the Spanish Ministry of Science, Innovation and Universities (RTI2018-099200-B-I00), and the Generalitat of Catalonia (Agency for Management of University and Research Grants (2017SGR696) and Department of Health (SLT002/16/00250)) to RP; María Arnoriaga-Rodríguez is funded by Instituto de Salud Carlos III, Río Hortega (CM19/00190). JM-P is funded by Instituto de Salud Carlos III through the Miguel Servet Program project CP18/00009 (Co-funded by the European Social Fund “Investing in your future”). MJ is a “Serra-Hunter” fellow

    Microbiota alterations in proline metabolism impact depression

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    Aminoàcids; Depressió; MicrobiotaAminoácidos; Depresión; MicrobiotaAmino acids; Depression; MicrobiotaThe microbiota-gut-brain axis has emerged as a novel target in depression, a disorder with low treatment efficacy. However, the field is dominated by underpowered studies focusing on major depression not addressing microbiome functionality, compositional nature, or confounding factors. We applied a multi-omics approach combining pre-clinical models with three human cohorts including patients with mild depression. Microbial functions and metabolites converging onto glutamate/GABA metabolism, particularly proline, were linked to depression. High proline consumption was the dietary factor with the strongest impact on depression. Whole-brain dynamics revealed rich club network disruptions associated with depression and circulating proline. Proline supplementation in mice exacerbated depression along with microbial translocation. Human microbiota transplantation induced an emotionally impaired phenotype in mice and alterations in GABA-, proline-, and extracellular matrix-related prefrontal cortex genes. RNAi-mediated knockdown of proline and GABA transporters in Drosophila and mono-association with L. plantarum, a high GABA producer, conferred protection against depression-like states. Targeting the microbiome and dietary proline may open new windows for efficient depression treatment.This work was partially supported by Instituto de Salud Carlos III (Madrid, Spain) through the research grants PI15/01934, PI18/01022, and PI21/01361 to J.M.F.-R. and PI20/01090 (co-funded by the European Regional Development Fund. “A way to make Europe”) to J.M.-P.; the Catalan Government (AGAUR, #SGR2017-0734, ICREA Academia Award 2021) to J.M.F.-R.; the Spanish Ministry of Science, Innovation and Universities (PID2019-105969GB-I00); Generalitat Valenciana (Prometeo/2018/133), Spain; and Fondo Europeo de Desarrollo Regional (FEDER) funds to A.M. This work was also supported by the European Commission (FP7, NeuroPain #2013-602891); the Catalan Government (AGAUR, #SGR2017-669, ICREA Academia Award 2020) to R.M.; the Spanish Instituto de Salud Carlos III (RTA, #RD16/0017/0020) to R.M.; Ministry of Science and Innovation and State Research Agency (#PID2020- 120029GB-I00/MICIN/AEI/10.13039/501100011033) to R.M.; the European Regional Development Fund (project no. 01.2.2-LMT-K-718-02-0014) under grant agreement with the Research Council of Lithuania (LMTLT); and the Project ThinkGut (EFA345/19), 65% co-financed by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra program (POCTEFA, 2014–2020). We also acknowledge funding from the Spanish Ministry of Science, Innovation and Universities (RTI2018-099200-B-I00) and the Generalitat of Catalonia (Agency for Management of University and Research Grants [2017SGR696] and Department of Health [SLT002/16/00250]) to R.P. M.A.-R. is funded by Instituto de Salud Carlos III, Río Hortega (CM19/00190). J.M.-P. is funded by a Miguel Servet contract (CP18/00009) from the Instituto de Salud Carlos III. J.S. is funded by a predoctoral PERIS contract (SLT002/16/00250) from the Catalan Government. M.J. is a professor under “Serra Hunter” program (Generalitat de Catalunya)
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