Cell-Type-Specific WTAP and ALKBH5-Mediated m6A Methylation Orchestrates Mental Disorders via Gut-Brain Axis Metabolite Signaling: Multi-Omics Evidence and Pyroptosis-Associated Loop Mechanism - PubMe
3 hours ago
- #mental-disorders
- #m6A-methylation
- #gut-brain-axis
- Mental disorders affect one billion people and contribute 5% of global DALYs.
- N6-methyladenosine (m6A) modification, gut microbiota, cerebrospinal fluid (CSF) metabolites, and pyroptosis are implicated in disease pathogenesis.
- Two-sample Mendelian randomization (MR) and single-cell eQTL data were used to explore causal links.
- Distinct causal associations of m6A modifiers (WTAP/ALKBH5) with mental disorders were identified.
- Gut microbiota and CSF metabolites mediate 5.06%-45.28% of these effects, forming pathways like WTAP → GCA-900066755 → theophylline → ADHD.
- Single-cell eQTL mapping linked WTAP's ADHD risk with XCL1-NK cells (OR = 1.445).
- Pyroptosis showed a tentative statistical association (3.99% explanatory power).
- The study hypothesizes an m6A-microbiota-metabolite axis potentially associated with mental disorders, with pyroptosis as a related peripheral factor.
- Experimental validation is required to confirm the biological mechanisms.