Composite
53%
Novelty
60%
Feasibility
40%
Impact
70%
Mechanistic
70%
Druggability
50%
Safety
50%
Confidence
60%

Mechanistic description

Dysbiotic bacteria compromise intestinal barrier integrity through zonulin pathway activation, allowing bacterial antigens and α-synuclein oligomers to enter systemic circulation and seed CNS pathology. Targeted tight junction stabilizers could prevent this peripheral-to-central disease propagation.

Evidence for (5)

  • Macrophage-derived CTSS drives the age-dependent disruption of the blood-CSF barrier.

    PMID:40015275 2025 Neuron
  • Claudin-1 interacts with EPHA2 to promote cancer stemness and chemoresistance in colorectal cancer.

    PMID:37924938 2023 Cancer Lett
  • A monoclonal antibody targeting nonjunctional claudin-1 inhibits fibrosis in patient-derived models by modulating cell plasticity.

    PMID:36542691 2022 Sci Transl Med
  • Streptococcus pneumoniae extracellular vesicles aggravate alveolar epithelial barrier disruption via autophagic degradation of OCLN (occludin).

    PMID:38497494 2024 Autophagy
  • Benvitimod Inhibits IL-4- and IL-13-Induced Tight Junction Impairment by Activating AHR/ARNT Pathway and Inhibiting STAT6 Phosphorylation in Human Keratinocytes.

    PMID:37734479 2024 J Invest Dermatol

Evidence against (2)

  • The microbiome-gut-brain axis in Parkinson disease remains difficult to translate from mechanistic models to causal human intervention evidence.

    PMID:35750883 2022 Nat Rev Neurol
  • Microbiome-based Parkinson therapies are still experimental with unresolved strain selection, endpoint, and clinical efficacy questions.

    PMID:39568727 2024 Front Nutr