Gut-BBB Axis: Tributyrin/Butyrate HDAC Inhibition Epigenetically Restores Claud…

Proposed by etl-backfill

CLDN5 market 53% proposed
Compare across mechanisms →
Composite
71%
Novelty
72%
Feasibility
82%
Impact
—
Mechanistic
65%
Druggability
78%
Safety
72%
Confidence
74%

Mechanistic description

Gut dysbiosis-driven butyrate deficit causes HDAC-mediated silencing of CLDN5 in brain endothelial cells; tributyrin prodrug restores CLDN5 expression via H3K27ac enrichment at the CLDN5 promoter, re-sealing the BBB in a virtuous cycle linking gut microbiome to neurovascular integrity.

Evidence for (5)

  • Social stress induces neurovascular pathology promoting depression.

    PMID:29184215 2017 Nat Neurosci

  • Development, maintenance and disruption of the blood-brain barrier.

    PMID:24309662 2013 Nat Med

  • The blood-brain barrier in aging and neurodegeneration.

    PMID:35361905 2022 Mol Psychiatry

  • Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer.

    PMID:38941455 2024 Sci Adv

  • Blood-brain barrier breakdown in the aging human hippocampus.

    PMID:25611508 2015 Neuron

Evidence against (2)

Evidence matrix

5 supporting 0 contradicting
100% supporting

Supporting

  • Social stress induces neurovascular pathology promoting depression. PMID:29184215 · 2017 · Nat Neurosci
  • Development, maintenance and disruption of the blood-brain barrier. PMID:24309662 · 2013 · Nat Med
  • The blood-brain barrier in aging and neurodegeneration. PMID:35361905 · 2022 · Mol Psychiatry
  • Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer. PMID:38941455 · 2024 · Sci Adv
  • Blood-brain barrier breakdown in the aging human hippocampus. PMID:25611508 · 2015 · Neuron

Contradicting

No contradicting evidence recorded.

Cite this hypothesis

Cite this hypothesis
Citation

etl-backfill (2026). Gut-BBB Axis: Tributyrin/Butyrate HDAC Inhibition Epigenetically Restores Claud…. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/h-583535bb

BibTeX 
@misc{scidex_hypothesis_h583535b,
  title        = {Gut-BBB Axis: Tributyrin/Butyrate HDAC Inhibition Epigenetically Restores Claud…},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/h-583535bb},
  note         = {SciDEX artifact hypothesis:h-583535bb}
}

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