Interplay of Metabolome and Gut Microbiome in Individuals With Major Depressive Disorder vs Control Individuals

• DOI: 10.1001/jamapsychiatry.2023.0685
• Publication Date: 2023-04-19T15:06:37Z
• Authors: Najaf Amin; Jun Liu; Bruno Bonnechere; Siamak Mahmoudian...; Matthias Arnold; Richa Batra; Yu-Jie Chiou; Marco Fernandes; M. Arfan Ikram; Robert Kraaij; Jan Krumsiek; Danielle Newby; Kwangsik Nho; Djawad Radjabzadeh; Andrew J. Saykin; Liu Shi; William Sproviero; Laura Winchester; Yang Yang; Alejo J. Nevado-H...; Gabi Kastenmüller; Rima Kaddurah-Daouk; Cornelia M. van D...
• Keywords: Mendelian Randomization; Metabolome; Depression

Importance Metabolomics reflect the net effect of genetic and environmental influences thus provide a comprehensive approach to evaluating pathogenesis complex diseases, such as depression. Objective To identify metabolic signatures major depressive disorder (MDD), elucidate direction associations using mendelian randomization, evaluate interplay human gut microbiome metabolome in development MDD. Design, Setting Participants This cohort study used data from participants UK Biobank (n = 500 000; aged 37 73 years; recruited 2006 2010) whose blood was profiled for metabolomics. Replication sought PREDICT BBMRI-NL studies. Publicly available summary statistics 2019 genome-wide association depression were randomization (individuals with MDD 59 851; control individuals 113 154). Summary metabolites obtained OpenGWAS MRbase 118 000). depression, performed Dutch cohorts. Data analyzed March December 2021. Main Outcomes Measures lifetime recurrent MDD, 249 nuclear magnetic resonance spectroscopy Nightingale platform. Results The included 6811 compared 51 446 4370 62 508 individuals. Individuals younger (median [IQR] age, 56 [49-62] years vs 58 [51-64] years) more often female (4447 [65%] 2364 [35%]) than Metabolic consisted 124 spanning energy lipid metabolism pathways. Novel findings 49 metabolites, including those involved tricarboxylic acid cycle (ie, citrate pyruvate). Citrate significantly decreased (β [SE], −0.07 [0.02]; FDR 4 × 10 −04 ) pyruvate increased 0.04 0.02) Changes observed these particularly lipoproteins, consistent differential composition microbiota belonging order Clostridiales phyla Proteobacteria / Pseudomonadota Bacteroidetes Bacteroidota . Mendelian suggested that fatty acids intermediate very large density lipoproteins changed disease process but high-density did not. Conclusions Relevance showed disturbed may play role