TABLE 9.
Effects of microbial metabolites on depressive behavior in rodent and human studies.
| Microbial metabolite | Family | Metabolic pathway | Metabolising bacteria | Effects on helplessness (rodent studies) | Effects on mood (human studies) | Potential mechanisms |
|---|---|---|---|---|---|---|
| Propionate | SCFA | Fermentation of fibres / carbohydrate metabolism | Roseburia, Ruminococcus, Salmonella, Blautia, Phascolarctobacterium, Dialister, Coprococcus, Megasphaera | Improves depressed mood | Depleted in MDD patients | Epigenetics (HDACi and DNA methylation modulator); receptors (GPR43, GPR41) |
| Acetate | Blautia, Marvinbryantia | - | ||||
| Butyrate | Eubacterium, Roseburia, Anaerostipes, Coprococcus, Feacalibacterium | Improves depressed mood; augments the effect of antidepressant drugs | ||||
| GABA | NT | Lactobacillus, Bifidobacterium | Antidepressant effect | Depleted in MDD patients | ||
| Serotonin | Escherichia coli, Streptococcus, Enterococcus, Akkermansia, Alistipes, Roseburia | Antidepressant effect | Depleted in MDD patients | |||
| Dopamine | Escherichia coli, Bacillus cereus, Bacillus mycoides, Bacillus subtilis, Proteus vulgaris, Serratia marcescens and Staphylococcus aureus | Antidepressant effect | Depleted in MDD patients | |||
| Acetylcholine | Lactobacillus | - | Increased in MDD patients | |||
| Oxindole | Indoles | Tryptophan metabolism | Escherichia coli, Vibrio cholerae and many others | Neurodepressant; | - | Epigenetics (HDACi); modulation of tryptophan availability; receptor AhR |
| Isatin | Anxiogenic and pro-depressive; | - | ||||
| Deoxycholic acid | Bile acids | Primary bile acid conjugation | Lactobacillus, Enterococcus, Bacteroides, Clostridium | permealization of the BBB | permealization of intestinal barrier (Caco-2 monolayer) | receptors (FXR and TGR5, PXR and VDR) |
| Glycocholic acid | increased in serum of depression model | - | receptors (FXR and TGR5, PXR and VDR) | |||
| TUDCA | neuroprotective against microglia | - | receptors (FXR and TGR5, PXR and VDR) | |||
| Taurocholic acid | FXR overexpression in the rat hippocampus is sufficient to induce depressive-like behavior, while FXR knockdown is both protective and reversing again depressive-like behavior; increased abundance of bile acids in urine, plasma and faecesof depression models | - | receptors (FXR and TGR5, PXR and VDR) | |||
| Betaine | Choline derivatives | Choline metabolism | Bacteroidetes | Reverses depressive-like behavior | Reduced in urine of MDD patients; ameliorates symptoms of depression | Affects abundance of choline available for DNA methylation and acetylcholine synthesis |
| TMA | - | Reduced in urine of MDD patients | ||||
| TMAO | - | Reduced in urine but elevated in plasma of MDD patients | ||||
| Lactate | - | Carbohydrate metabolism | L. lactis, L. gasseri, and L. reuteri, Bifidobacteria and Proteobacteria, Eubacterium, Anaerostipes, Veillonella | protective and reversing effects against depression | Increased in urine of MDD patients | Epigenetics (HDACi and DNA methylation modulator); receptor GPR81 |
| Folate (B9) | Vitamin | GTP metabolism | Lactobacillus (L. acidophilus, L. casei, L. paracasei, L. plantarum, L. reuteri, and L. salivarius) and Bifidobacterium | antidepressant effect | enhances action of antidepressant drugs (but lack of conclusive evidence) | Epigenetics (DNA methylation modulator); serotonergic, noradrenergic, opioid and NMDA receptors; BH4 and SAM synthesis |
AhR: Aryl Hydrocarbon Receptor; BBB: Blood Brain Barrier; BH4: Tetrahydrobiopterin; FXR: Farnesoid X Receptor; GPR41: G-protein coupled receptor 41; GPR43: G-protein coupled receptor 43; GPR81: G-protein coupled receptor 81; GTP: Guanosine triphosphate; HDACi: Histone deacetylase inhibitor; MDD: Major Depressive Disorder; NT: Neurotransmitter; PXR: Pregnane X receptor; SAM: S-adenosylmethionine; SCFA: Short-Chain Fatty Acids; TGR5: Takeda G-protein receptor 5; TMA: Trimethylamine; TMAO: Trimethylamine N-oxide; TUDCA: Tauroursodeoxycholic acids; VDR: Vitamin D Receptor