Microbial SCFAs as epigenetic mediators: fine-tuning the gut-brain axis in neurodegenerative disorders
Highlights ● SCFAs function as gut-derived epigenetic regulators, bridging dietary fiber metabolism to brain-wide chromatin remodeling in neurodegenerative diseases. ● Butyrate acts as a potent HDAC inhibitor, enhancing histone acetylation to suppress neuroinflammation and promote synaptic plasticity in AD and PD models. ● SCFAs modulate DNA methylation dynamics via TET-DNMT balance, correcting aberrant gene expression linked to Aβ and α-synuclein pathologies. ● Emerging evidence positions histone lactylation as a novel SCFA-sensitive mechanism linking microglial metabolism to neuroinflammatory loops in neurodegeneration.