Gut Microbiota Metabolites in Major Depressive Disorder-Deep Insights into Their Pathophysiological Role and Potential Translational Applications.
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ABSTRACT:
SUBMITTER: Ortega MA
PROVIDER: S-EPMC8778125 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Vortioxetine hydrobromide is a common clinical medication for major depressive disorder (MDD). However, it remains unclear whether vortioxetine hydrobromide acts by affecting the structure and composition of gut microbiota. Here, we analyzed fecal samples from 28 healthy controls (HCs) and 26 patients with MDD before treatment with vortioxetine hydrobromide, at 4 weeks after treatment, and at 8 weeks after treatment. High-throughput pyrosequencing showed that, according to the Chao1 and Shannon indices, fecal bacterial α-diversity was higher in the patients with MDD than in the HCs (p < 0.05), but no significant differences were observed after vortioxetine hydrobromide treatment (p > 0.05). PCoA results revealed that the gut microbiota composition was significantly different between the MDD groups and HCs. Proteobacteria and Actinobacteria were strongly increased, whereas Firmicutes were significantly reduced in the MDD group compared with the HCs. After treatment with vortioxetine hydrobromide, Firmicutes were significantly increased, and the proportion of Bacteroidetes decreased. Most notably, Lachnospira, Roseburia, and Faecalibacterium were negatively correlated with the severity of depressive symptoms. Taken together, our data indicate changes in the fecal microbiota composition in MDD patients compared with HCs, and vortioxetine hydrobromide may treat MDD through regulation of the gut microflora.
| S-EPMC8138160 | biostudies-literature
Project description:BackgroundGrowing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer's disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ).MethodsA two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively.ResultsWe found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79-0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92-1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD. Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00-1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83-0.98; P = 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00-1.15; P = 0.047). Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02-1.12; P = 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition.ConclusionsThese data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.
| S-EPMC7532639 | biostudies-literature
Project description:ObjectiveThe etiology of major depressive disorder (MDD) is multi-factorial and has been associated with a perturbed gut microbiota. Thus, it is therefore of great importance to determine any variations in gut microbiota in patients with MDD.MethodsA systematic literature search was conducted including original research articles based on gut microbiota studies performed in patients with MDD. Demographic and clinical characteristics, applied methodology and observed gut microbiota composition were compared between included studies.ResultsSeventeen studies were included with a total of 738 patients with MDD and 782 healthy controls using different DNA purification methods, sequencing platforms and data analysis models. Four studies found a reduced α-diversity in patients with MDD, while gut microbiota compositions clustered separately according to β-diversity between patients and controls in twelve studies. Additionally, there was an increase in relative abundance of Eggerthella, Atopobium, and Bifidobacterium and a decreased relative abundance of Faecalibacterium in patients with MDD compared with healthy controls.ConclusionGut microbiota differs significantly when comparing patients with MDD and healthy controls, though inconsistently across studies. The heterogeneity in gut microbiota compositions between the studies may be explained by variations in study design.
| S-EPMC8323045 | biostudies-literature
Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.
2011-10-04 | E-GEOD-19738 | biostudies-arrayexpress
Project description:Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.
| S-EPMC8692500 | biostudies-literature
Project description:Major depressive disorder (MDD) is among the most prevalent mental disorders worldwide. Factors causing the pathogenesis of MDD include gut microbiota (GM), which interacts with the host through the gut-brain axis. In previous studies of GM in MDD patients, 16S rRNA sequencing was used, which provided information about composition but not about function. In our study, we analyzed whole metagenome sequencing data to assess changes in both the composition and functional profile of GM. We looked at the GM of 36 MDD patients, compared with that of 38 healthy volunteers. Comparative taxonomic analysis showed decreased abundances of Faecalibacterium prausnitzii, Roseburia hominis, and Roseburia intestinalis, and elevated abundances of Escherichia coli and Ruthenibacterium lactatiformans in the GM of MDD patients. We observed decreased levels of bacterial genes encoding key enzymes involved in the production of arginine, asparagine, glutamate, glutamine, melatonin, acetic, butyric and conjugated linoleic acids, and spermidine in MDD patients. These genes produced signature pairs with Faecalibacterium prausntizii and correlated with decreased levels of this species in the GM of MDD patients. These results show the potential impact of the identified biomarker bacteria and their metabolites on the pathogenesis of MDD, and should be confirmed in future metabolomic studies.
| S-EPMC9496097 | biostudies-literature
Project description:The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.
| S-EPMC9126816 | biostudies-literature
Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD.
2011-10-05 | GSE19738 | GEO
Project description:Major depressive disorder (MDD) exhibits numerous clinical, epidemiological, and molecular features that are consistent with partially inherited and partially acquired epigenetic misregulation. We performed microarray based DNA modification study of MDD, utilizing affected and unaffected samples from white blood cells from monozygotic twins discordant for MDD, post-mortem prefrontal cortex tissues, and sperm samples. We performed DNA methylome analysis on white blood cells from monozygotic twins discordant for depression (n=200), pre-frontal cortex (n=71), and germline samples (n=33) from affected individuals and controls (total n=304). DNA samples were enriched for unmodified fraction of the genome using DNA-modification sensitive restriction enzyme digestion followed by adaptor-mediated PCR. The enriched fractions were labelled with a fluorescent dye (Cy5) and hybridized onto the array with a common reference pool (Cy3) generated from individuals unrelated to this study.
2012-04-27 | E-GEOD-37579 | biostudies-arrayexpress
Project description:Gut microbiota and childhood maltreatment are closely related to depressive symptoms. This study aimed to analyze the characteristics of gut microbiota in major depressive disorder (MDD) patients with childhood maltreatment experience and explore the correlation between gut microbiota, childhood maltreatment, and depressive symptoms. A total of 37 healthy controls (HCs) and 53 patients with MDD were enrolled, including 18 MDD patients without childhood maltreatment experience and 35 MDD patients with childhood maltreatment experience. The Hamilton's Depression Scale (HAMD-24) and Childhood Trauma Questionnaire-Short Form (CTQ-SF) were used to evaluate their depressive symptoms and childhood maltreatment experience, respectively. The composition of gut microbiota was evaluated using 16S rRNA sequencing. Spearman's correlation analysis was used to evaluate the correlation between different gut microbiota, depressive symptoms and childhood maltreatment. The mediation analysis was used to evaluate the mediating effect of gut microbiota. In the α-diversity analysis, we found that the Simpson index and Pielou's Evenness index differed significantly between MDD patients without childhood maltreatment experience and HCs. In the β-diversity analysis, principal coordinate analysis (PCoA) showed significant differences between MDD patients without childhood maltreatment experience, MDD patients with childhood maltreatment experience and HCs. Twenty-seven different bacteria were identified through Linear discriminant analysis effect size (LEfSe) analysis at different levels of classification. The analysis of the correlation showed that Blautia, Bifidobacterium, Bacteroides, Roseburia, and Phascolarctobacterium were significantly correlated with HAMD and CTQ-SF scores. The mediation analysis showed that childhood maltreatment had a significant direct effect on the patients' depressive symptoms, and Blautia, Bifidobacterium, Roseburia had a significant mediating effect. The findings of this study suggested that MDD patients with childhood maltreatment experience had different gut microbiota, which might have a mediating effect on the influence of childhood maltreatment on depressive symptoms.
| S-EPMC9238290 | biostudies-literature