Table 1.

Typical gut microbiota metabolites and their roles in health and diseases.

Groups	Typical metabolites	Typical targets	Specific functions	Typical diseases associated	Ref.
Short-chain fatty acids	Acetate, propionate, butyrate, hexanoate, isovalerate, isobutyrate, 2-methylpropionate, valerate	Directly act on GPR41, GPR43, GPR109A, GPR81, GPR91, HDAC1 and HDAC3	Regulation of gut microbiota composition, gut barrier integrity, appetite, energy homeostasis, gut hormone production, circadian clocks; inhibit proinflammatory cytokines; stimulate water and sodium absorption; modulate systemic immune response	Diabetes, obesity, pancreatitis, nonalcoholic fatty liver disease, hypertension, atherosclerosis, chronic kidney disease, ulcerative colitis, radiation proctitis, Crohn’s disease, colorectal cancer, autism spectrum disorder, sclerosis, Parkinson’s disease, asthma, diarrhea	[15-21]
Bile acids	Cholate, hyocholate, deoxycholate, taurohyocholate, ursodeoxycholate, taurocholate, tauro- α-muricholate, glycocholate, hyodeoxycholate, tauro- β-muricholate, lithocholate, taurodeoxylcholate	Directly act on FXR, VDR, PXR/SXR, constitutive androstane receptor (CAR), TGR5, sphingosine 1-phosphate receptor 2 (S1PR2), formyl-peptide receptor (FPR), muscarinic acetylcholine receptor (mAChR)	Facilitate lipid and vitamin absorption; regulation of gut microbiota composition, gut hormones, intestinal immunity, intestinal electrolyte and fluid balance, gut motility, lipid homeostasis, glucose homeostasis, amino acid homeostasis, circadian clocks; influence neurotransmission and physiology	Primary biliary cholangitis, primary sclerosing cholangitis, obesity, nonalcoholic fatty liver disease, non-alcoholic steatohepatitis, atherosclerosis, ulcerative colitis, cancer, hepatic encephalopathy, multiple sclerosis, Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke and amyotrophic lateral sclerosis	[8,22-25]
Gases	H2S, H2, CO2, CH4, NO	NO targets soluble guanylate cyclase, H2S cause conformational changes of target proteins by sulfhydration	CH4 slows gut motility; H2S regulates gut inflammation, motility, epithelial secretion and susceptibility to infections; NO mediates gastric mucosal protection and regulate mucosal blood flow	Parkinson’s disease, colitis, ulcer	[26-31]
Tryptophan and indole derivatives	Indole-3-lactic acid, indole acetic acid, indole-3-acetamide, indole pyruvic acid, indoxyl sulfuric acid, indole, serotonin	Directly targeting on AhR and PXR	Influence the gut microbial spore formation, drug resistance, biofilm formation, and virulence; regulate intestinal barrier functions, gut hormone secretion, gut motility, systemic immune response	Ulcerative colitis, Crohn’s disease, obesity, stroke, mucosal candidiasis, autism spectrum disorder, Alzheimer’s disease, Parkinson's disease, migraine, schizophrenia, irritable bowel syndrome	[32-36]
Choline metabolites	TMA, methylamine, dimethylglycine, dimethylamine,	Direct target unknown, but can activate NF-кB, protein kinase C (PKC), NLRP3 inflammasome	Inhibits bile acid synthesis; promote inflammation, thrombosis; affects myocardial hypertrophy and fibrosis; exacerbates mitochondrial dysfunction	Nonalcoholic fatty liver disease, obesity, atherosclerosis, diabetes, heart failure, hypertension	[37-39]
Vitamins	Vitamin B2, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin B9, Vitamin B12, vitamin K	Vitamin receptors	Involved in cellular metabolism; modulate immune function and cell proliferation; supply vitamins for hosts	Vitamin associated diseases such as schizophrenia, autism, and dementia	[40,41]
Neurotransmitters	Dopamine, catecholamines, 5-HT, and GABA	Adrenergic receptors, 5-HT receptors, GABA receptors	Regulate gut motility, memory and stress responses, immune function of nervous system	Parkinson's disease, autism	[27,42,43]
Lipids	Conjugated fatty acids, cholesterol, phosphatidylcholines, triglycerides, LPS	LPS targets directly on TLR4	LPS triggers systemic inflammation; conjugated fatty acids regulate hyperinsulinemia, immune system, lipoprotein profiles; cholesterol acts as material bases for bile acid synthesis.	Diabetes, obesity, nonalcoholic fatty liver disease, hyperinsulinemia, hypercholesterolemia, chronic hepatitis C.	[7,44,45]
Others	Ethanol; triphosadenine; lantibiotic such as ruminococcin A and cytolysin; microcin such as microcin B17; organic acids such as benzoate and hippurate; polyamines such as cadaverine, and spermidine	Triphosadenine activate P2X and P2Y receptors	Enhance or damage gut barrier; regulate intestinal or systemic immune response; act as antibiotics to modulate gut microbiota composition; supply the nutrients; be toxic to host cells	Fatty liver disease, C. difficile and H. pylori infections, irritable bowel syndrome, ulcerative colitis	[7,46-48]