Microbial SCFAs as epigenetic mediators: fine-tuning the gut-brain axis in neurodegenerative disorders.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and preclinical concepts without new clinical data.
PubMed 41798063 · doi:10.1016/j.crmicr.2026.100574
What was done
This narrative review synthesized literature examining the production, metabolic fate, and epigenetic mechanisms of gut-derived short-chain fatty acids (SCFAs) within the gut-brain axis, focusing on neurodegenerative diseases like Alzheimer's disease and Parkinson's disease.
What was found
The abstract reports no numerical data. It describes that SCFAs exert neuroprotective effects (reducing neuroinflammation, supporting neurogenesis, enhancing synaptic plasticity, and maintaining blood-brain barrier integrity) predominantly through epigenetic actions. Specifically, butyrate acts as a histone deacetylase inhibitor, while SCFAs also influence DNA methylation via DNA methyltransferases and TET enzymes and participate in histone lactylation.
Why it matters
It outlines how microbiome-derived metabolites can modify the central nervous system's epigenetic landscape, framing potential targets for dietary, probiotic, or epigenetic therapies for neurodegenerative disorders.
Limits
The review provides no primary experimental data, clinical outcomes, or quantitative metrics in the abstract. Findings rely primarily on mechanistic and preclinical models, with human translational and therapeutic efficacy yet to be established.
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