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Interplay of metabolome and gut microbiome in individuals with major depressive disorder vs control individuals
Metabolomics offers a thorough method for assessing the pathophysiology of complex disorders like depression since it reflects the whole impact of genetic and environmental factors. Amin et al. (2023) conducted this study to analyze the interaction between the human gut microbiota and metabolome in the development of major depressive disorder (MDD), determine the metabolic fingerprints of MDD, and clarify the direction of correlations in both lifetime and recurrent MDD. Data on participants in the UK Biobank cohort (n = 500 000; ages 37 – 73; 2006 to 2010) whose blood was analyzed for metabolomics provided the data for this cohort research. Mendelian randomization was performed using summary statistics from a 2019 genome-wide association study of depression (MDD n = 59851 vs. controls n = 113154). OpenGWAS MRbase (n = 118 000) was used to capture metabolite summary statistics. Metabolic markers of the gut microbiome were collected from a 2019 study conducted in Dutch cohorts to assess how the metabolome and the gut microbiota interact in the pathophysiology of depression. The Nightingale platform was used to characterize 249 metabolites of interest. Data analysis revealed that 6811 people with lifetime MDD were included in the research, compared to 51446 controls, and 4370 people with recurring MDD were included, compared to 62 508 controls. In comparison to controls, those with lifelong MDD were younger (median age = 56 vs. 58 years) and more likely to be female (4447 [65%] vs. 2364 [35%]). 124 metabolites from lipid and energy metabolism pathways made up the metabolic fingerprints of MDD. A total of 49 metabolites, including those involved in the tricarboxylic acid cycle (such as citrate and pyruvate), were discovered to be novel. In those with MDD, pyruvate was substantially elevated, while citrate was considerably reduced. The differences in gut microbiota composition between those belonging to the phyla Proteobacteria/Pseudomonadota and Bacteroidetes/Bacteroidota and the order Clostridiales were consistent with changes seen in these metabolites, notably in lipoproteins. Mendelian randomization showed that high-density lipoproteins and tricarboxylic acid cycle metabolites did not alter in relation to the illness process but that fatty acids and intermediate and very large-density lipoproteins did. Through the study’s findings, the authors concluded that people with MDD had abnormal energy metabolism and that blood metabolome and gut microbiota interactions may affect how people with MDD process lipids. [NPID: Metabolome, gut microbiome, major depressive disorder, recurrent depression, diet, energy metabolism, lipids, lipoproteins, UK biobank]
Year: 2023
