MULTILAYER MOLECULAR DISRUPTION IN ANOREXIA NERVOSA: CONVERGING SIGNALS FROM EPIGENOME TO MICROBIOME

Anorexia nervosa (AN) represents one of the most lethal psychiatric disorders, with characteristic adolescent onset suggesting fundamental alterations in brain maturation processes. We applied an integrated multiomics framework - DNA methylation, miRNA expression, and oral microbiome composition - to characterize molecular perturbations across regulatory levels in 38 adolescent patients with AN compared to 40 healthy controls.
Genome-wide methylation profiling revealed epigenetic modifications in genes governing synaptic transmission, particularly those encoding ion channels essential for neuronal excitability and transcriptional regulators controlling chromatin accessibility. Parallel expression analysis identified 74 dysregulated microRNAs, with network-based approaches revealing their involvement in pathways regulating neuronal firing properties and neurotrophic signaling cascades. Oral microbiome profiling uncovered marked compositional variability, with 42% of AN participants displaying severe dysbiosis characterized by pathogenic bacterial dominance, indicating potential biological stratification within the disorder.
These cross-platform observations demonstrate coordinated disruption spanning epigenetic, post-transcriptional, and microbial dimensions, all converging on mechanisms critical for adolescent neural circuit refinement. The specific targeting of membrane excitability systems and growth factor networks suggests broader destabilization of developmental timing machinery. Identified microRNA signatures may serve as accessible biomarkers or therapeutic entry points, while microbiome heterogeneity supports the existence of molecularly distinct patient subgroups. This integrative approach provides a systems-level framework for understanding AN pathophysiology and generates mechanistic hypotheses linking disrupted neurodevelopment to disorder vulnerability, with implications for precision intervention strategies.