Table 2.

Enlist key uremic toxins and their effect on depression

Uremic toxins	Origin	Mechanism	Impact on brain
Indoxyl sulfate	Gut microbiota and liver	Activates aryl hydrocarbon receptor, increases BBB permeability	Reduce serotonin synthesis (approximately 40%), ↑ neuroinflammation (IL-6, TNF-α, NO)[46-48]
Kynurenines	Tryptophan kynurenine pathway	Modulate glutamatergic signaling, regulate inflammation	Imbalance in KA/QA ratio linked to severe depression[44]
p-cresyl sulfate	Phenylalanine metabolism	Poorly understood	May contribute to mood dysregulation[49]
4-ethylphenyl sulfate	Gut-derived phenol	Behavioral effects in mice	Possible link to anxiety and cognition[50]
Indole-3-propionic acid	Gut microbiota	Neuroprotective in some contexts	May improve social function (Janus-faced effect)[51]

BBB: Blood-brain barrier; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α; NO: Nitric oxide; KA/QA: Kynurenic acid/quinolinic acid.