Table 1.

Functions of the metabolites and neurotransmitters produced by the gut microbiota

Microbial metabolites/ neurotransmitters	Gut microbiota (Genus)	Functions	Neurological diseases
SCFAs	Faecalibacterium, Clostridium, Eubacterium, Roseburia, Anaerostipes, Bifidobacterium, Akkermansia	• Act as an energy source for colonocytes and regulate the intestinal barrier • Exert anti-inflammatory effects on the intestinal mucosal and CNS • Regulate GLP production which further influences neuronal inflammation • Regulate the integrity of the BBB	• Promote microglia activation and Aβ plaque deposition in AD • Accelerate α-syn aggregation and promote motor dysfunction in PD • Inhibit neuroinflammation and alleviate neurological damage in PD via improvement of motor impairment and dopaminergic neuron degeneration • Ameliorate EAE via induction of Treg, reduced lymphocyte infiltration, and demyelination
Tryptophan metabolites	Lactobacillus, Escherichia, Clostridium, Bacteroides, Bacillus, Burkholderia, Streptomyces, Pseudomonas	• Regulate microglial activation and the production of TGFα and VEGF-B • Impact neuronal proliferation, differentiation, and neurogenesis	• Indole decreases motor activity and enhances anxiety-like behavior • Kynurenine disrupts neurotransmission, leading to depression and altered brain function • Indole and IAA help in pathogen colonization in the gut, which negatively alters the function of the gut–brain axis in autism
GABA	Lactobacillus, Bifidobacterium, Streptococcus	• Down-regulate pro-inflammatory cytokine production and up-regulate immunoregulatory molecules • Modulate the inhibitory-excitatory balance necessary for brain function • Regulate the secretion of neuropeptides by intrinsic and extrinsic intestinal nerve fibers	• Ameliorate EAE via inhibition of inflammation, directly acting on APCs and adaptive immune cells in response to myelin proteins • Reduce stress-related disorders, such as anxiety and depression via changing cerebral GABAergic activity
Dopamine	Bacillus, Staphylococcus, Proteus, Serratia, Escherichia	• Modulate the function of effector immune cells and the production of cytokines by activated T cells • Reduce the suppressive activity and migratory activity of Treg • Regulate nitric oxide synthesis and migration of microglia	• Downregulate the production of IFN-γ and IL-17A by PBMCs in patients with relapsing–remitting MS
Norepinephrine	Escherichia, Bacillus, Saccharomyces, Proteus, Serratia	• Suppress inflammatory gene transcription and enhance BDNF production by microglia and astrocytes, which can further promote neuronal survival • Modulate excitatory neuronal responses and inter-neuronal responses	• Reduce Parkinson’s disease progression by inhibiting microglial activation and suppressing pro-inflammatory cytokine production
Serotonin	Candida, Streptococcus, Escherichia, Enterococcus, Pseudomonas, Streptococcus	• Suppress MHC class II expression and the antigen-presenting capacity of macrophages • Decrease the production of pro-inflammatory cytokines, such as IL-6 and TNF-α by macrophages and lymphocytes	• Attenuate MS or EAE by suppressing T cell proliferation, stimulating IL-10 production, inhibiting the release of IL-17A and IFN-γ, and inducing macrophage polarization into M2 macrophages