Table 2.
Association of CNS diseases and gut microbial metabolites in humans.
| Diseases | Metabolites or their precursors | Effects of metabolites on disease | Effects of metabolites on cells and molecules | Ref |
|---|---|---|---|---|
| MS | SCFAs | Exacerbation |
Induction of IL-17+CD8 T cells; Increased C2 levels in MS patient serum |
135,136 |
| SCFAs | Suppression |
Increased Tregs but decreased Th1 cells; Increased mitochondrial oxidation |
118,122,132,134 | |
| Trp and Trp metabolites (indole, I3S, I3P, I3A) | Suppression |
Limited the pathogenic activity of microglia and astrocytes; AhR activation |
116,150 | |
| Secondary bile acids | Suppression |
Activation of GPBAR1 in astrocytes; TUDCA-mediated suppression of microglial and astrocytic inflammatory polarization |
143 | |
| PD | SCFAs | Exacerbation | Dysbiosis-mediated gut leakage | 219 |
| Suppression |
Decreased Prevotellaceae and Enterobacteriaceae; Increased blood levels of CXCL8 and IL-1β; Increased gut permeability |
160,167,174 | ||
| Secondary bile acids | Exacerbation |
Decreased lipid metabolism; Dysbiosis and elevated BA levels |
165,166 | |
| TMAO | Exacerbation | Increased α-syn aggregation and inflammation | 220 | |
| AD | SCFAs | Exacerbation |
Increased production of inflammatory cytokines; Endothelial dysfunction |
187 |
| Suppression | Increased IL-10 levels | 187 | ||
| Tryptophan | Suppression | Decreased tryptophan but increased blood Kyn/Trp ratio in AD patients | 201 | |
| Secondary Bile acid | Exacerbation |
Increased DCA but decreased primary BAs (cholic acid); Increased levels of TCA, 3-DCA and UDCA in the brain of AD patients |
202,203 | |
| ASD | SCFAs | Exacerbation |
Increased levels of butyrogenic bacteria; Increased levels of fecal SCFAs in ASD patients |
221,222 |
| Suppression | Decreased fecal levels of SCFAs in ASD patients | 211,212 |
AhR aryl hydrocarbon receptor, α-syn α-synuclein, BA bile acid, DCA deoxycholic acid, I3A GPBAR G-protein-coupled bile acid receptor, I3A indole-3-carboxaldehyde, I3P indole-3-propionic acid, I3S indoxyl 3-sulfate, TCA trichloroacetic acid, TGF transforming growth factor, TMAO trimethylamine N-oxide, Trp tryptophan, TUDCA tauroursodeoxycholic acid, UDCA ursodeoxycholic acid, VEGF vascular endothelial growth factor.