Table 2.

Microbial metabolites related to the pathogenesis of PD

Microbial metabolites		Bacterial genera	Gut-brain communication	Mechanisms in the pathogenesis of PD
NAM		63% human gut bacteria genomes [56]	Circulation [59]	NAM acts as a precursor of NAD to provide coenzymes required by the mitochondrial respiratory chain and protect mitochondria from damage [60].
BAs		Clostridium, Eubacteria [61]	Circulation [62]	TUDCA and UDCA promote mitophagy to protect mitochondrial function [63, 64].
SCFAs		Most gut anaerobes: acetate Firmicutes: butyrate Bacteroidetes: propionate [42, 65]	Circulation and vagus nerve [66]	SCFAs act as energy substrates for mitochondria and promote mitochondrial fusion [67, 68]
Tryptophan		Escherichia coli Tryptophan is primarily dependent on exogenous uptake [69]	Circulation [70]	1. KP: The neuroprotective metabolites of KP such as KYNA, picolinic acid, and NAD+, and neurotoxic products such as QA, 3-HK [71]. 2. Serotonin pathway: 5-HT in the brain is related to memory, mood, cognitive function, and severity of resting tremor in PD [72, 73]. Melatonin provides a substrate for the mitochondrial respiratory chain and reduces oxidative stress and apoptosis [74, 75].
Neurotransmitters	Histamine	Escherichia coli Morganella morganii Lactobacillus Lactococcus Streptococcus Pediococcus Enterococcus spp [76, 77]	Vagus nerve [78]	Histamine activates H2R to increase mitochondria-dependent apoptosis [79].
	GABA	Lactobacillus Bifidobacterium [80]	Vagus nerve [81]	GABA can accurately control the quantity of Ca2+ that enters the cell to protect mitochondria from damage caused by Ca2+ overload [82].

PD, Parkinson’s disease; NAM, niacinamide; NAD, nicotinamide adenine dinucleotide; BAs, bile acids; TUDCA, tauro ursodesoxy cholic acid; UDCA, ursodesoxy cholic acid; SCFA, short-chain fatty acid; KP, kynurenine pathway; QA, quinolinic acid; 3-HK, 3-hydroxykynurenine; KYNA, kynurenic acid; 5-HT, 5-hydroxytryptamine; H2R, histamine 2 receptor; GABA, γ-aminobutyric acid