The butyrate-m6A-BDNF axis: a hypothesis of gut-brain signal transduction in PSD

Absztrakt

A reduction in brain-derived neurotrophic factor (BDNF) protein levels has been reported in post-stroke depression (PSD). However, whether transcript abundance and translation efficiency change in parallel or become uncoupled in PSD remains to be determined. In addition to classical transcriptional regulation by histone deacetylase (HDAC) inhibitors, pathological processes may affect BDNF translation independently of transcription, but the relevant epitranscriptomic pathways remain unresolved. Drawing on reports that butyrate can influence m 6 A-related processes in peripheral tissues and that YTHDF1-dependent translation operates in adult hippocampus and cellular systems, this article proposes the “butyrate–m 6 A–BDNF” axis as a testable hypothesis. The hypothesis predicts that post-stroke changes in butyrate availability could alter central m 6 A regulation and thereby affect translation of a biologically motivated candidate transcript such as BDNF. The framework separates established mechanisms, cross-model evidence, and predictions that require direct measurement. The validation plan includes future exposure-resolved, genetic, and cell-type-specific studies; no validation experiments are presented here.