Table 1 Functions of the metabolites and neurotransmitters produced by the gut microbiota

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