ArticleJournal of molecular neuroscience : MN2026
Genetically Proxied Associations Among 473 Gut Microbial Taxa, 1,400 Circulating Metabolites, and Mental and Behavioral Disorders: A Mendelian Randomization Study.
Article in Journal of molecular neuroscience : MN, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Mental and behavioural disorders substantially impair everyday functioning, yet the biological mechanisms through which the gut microbiome may contribute to psychiatric vulnerability remain insufficiently characterized. We jointly analysed genome-wide association study data for 473 gut microbial taxa, approximately 1,400 circulating metabolites, and seven mental and behavioural disorders, including schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, chronic depression, bulimia nervosa, and hypersomnia. Mendelian randomization was used to estimate genetically proxied associations among these traits, and two-step MR was used to evaluate candidate statistical mediation by circulating metabolites. We identified FDR-supported associations for eight microbial taxa across four disorders: UBA8904, Dorea, and Ruminococcus A sp000432335 with ADHD; Pseudomonas aeruginosa, Bifidobacterium kashiwanohense, and CAG-273 sp003534295 with chronic depression; Syntrophorhabdia with bulimia nervosa; and Aneurinibacillales with hypersomnia. Twelve circulating metabolites were statistically consistent with partial mediation of candidate microbiota-disorder associations. Glycocholate glucuronide (1) accounted for an estimated 5.95% of the Syntrophorhabdia-bulimia nervosa association, whereas 5-dodecenoate (12:1n7) was consistent with mediation of 8.28% of the inverse association between CAG-273 sp003534295 and chronic depression. Target enrichment prioritized lipid metabolism and neuroactive ligand-receptor interaction pathways for further study. The inverse association between genetically predicted 5-dodecenoate and depression was reproduced in an independent depression GWAS. These findings nominate candidate microbiota-metabolite pathways for mechanistic investigation; however, residual horizontal pleiotropy and linkage-disequilibrium-related confounding cannot be excluded, and the results should not be interpreted as definitive causal evidence.
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