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New Study Sheds Light on Gut Microbiome’s Role in MDD Development
Energy metabolism is disturbed in individuals with major depressive disorder (MDD), and the relationship of the gut microbiome and blood metabolome affects lipid metabolism in those individuals, a new cohort study found. Furthermore, the research published in JAMA Psychiatry identified novel metabolic signatures associated with MDD, shedding light on the gut microbiome's role in the disorder's development.
"Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression," lead author Najaf Amin, PhD, Nuffield Department of Population Health, University of Oxford, United Kingdom, and co-authors wrote. "To our knowledge, this is the largest and most comprehensive study investigating the association of NMR-confirmed metabolites with major depression."
Researchers used data from participants in the UK Biobank cohort, which included 500,000 individuals aged 37 to 73 years, recruited from 2006 to 2010, whose blood was profiled for metabolomics. The study aimed to identify the metabolic signatures of MDD, elucidate the direction of associations using Mendelian randomization, and evaluate the interplay of the human gut microbiome and metabolome in the development of MDD.
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The study included 6811 individuals with lifetime MDD compared with 51,446 control individuals and 4370 individuals with recurrent MDD compared with 62,508 control individuals. Study outcomes were defined as lifetime and recurrent MDD, with 249 metabolites profiled with nuclear magnetic resonance spectroscopy using the Nightingale platform. The metabolic signatures of MDD consisted of 124 metabolites spanning the energy and lipid metabolism pathways, including 49 novel metabolites, such as citrate and pyruvate, involved in the tricarboxylic acid cycle.
Citrate was found to be significantly decreased (β [SE], −0.07 [0.02]; FDR = 4 × 10−04), and pyruvate was significantly increased (β [SE], 0.04 [0.02]; FDR = 0.02) in individuals with MDD. Changes observed in these metabolites, particularly lipoproteins, were consistent with the differential composition of gut microbiota belonging to the order Clostridiales and the phyla Proteobacteria/Pseudomonadota and Bacteroidetes/Bacteroidota.
Mendelian randomization suggested that fatty acids and intermediate and very large density lipoproteins changed in association with the disease process. Conversely, high-density lipoproteins and the metabolites in the tricarboxylic acid cycle did not.
Study findings have important implications for developing new treatments for MDD, authors suggest. By identifying the specific metabolic pathways disrupted in individuals with the disorder, researchers may be able to develop more targeted and effective therapies addressing the underlying biological mechanisms of the condition.
However, future experimental studies and trials are needed to resolve whether metabolic profiles in patients improve after intervention with respect to their gut microbiomes," researchers concluded.
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