Table 1.

Metabolites contributed by gut microbiota and their respective functions.

Metabolites	Functions	References
Short-chain fatty acids (SCFAs):	Regulate host metabolic pathways via G-protein-coupled receptor GPR41 or GPR43 -mediated signaling:	Blottière et al., 2003; Backhed et al., 2004; Xiong et al., 2004; Samuel et al., 2008; Tolhurst et al., 2012; De Vadder et al., 2014
E.g., Acetate, butyrate, propionate, hexanoate, valerate	energy homeostasis; synthesis of glucagon-like peptide 1 (GLP-1); increase leptin production. Improve glucose tolerance and insulin sensitivity. Potent histone deacetylase (HDAC) inhibitor - regulation of intestinal cell proliferation. Intestinal gluconeogenesis, lipogenesis, suppression of fasting-induced adipose factor Fiaf (lipoprotein lipase inhibitor) in intestinal epithelium. Immunomodulatory effect, activate dendritic cells, gut immunity.
Indole derivatives:	IPA as powerful antioxidant, inhibitor of amyloid-beta fibril formation, and exhibits neuroprotective and cytoprotective effects against a variety of oxidotoxins.	Bendheim et al., 2002; Deguchi et al., 2002; Wikoff et al., 2009; Venkatesh et al., 2014
E.g., Indole, indoxyl sulfate, indole-3-propionic acid (IPA)	IPA regulates intestinal barrier function via the xenobiotic sensor, pregnane X receptor (PXR), in which it reduces intestinal inflammation (downregulates enterocyte pro-inflammatory cytokines TNF-α), and regulate intestinal permeability and mucosal integrity (upregulates junctional protein-coding mRNAs). Indoxyl sulfate as uremic toxin that accumulates in the blood of patients with impaired excretion system.
Bile acid metabolites: E.g., Deoxycholic acid (DCA), lithocholic acid (LCA)	Activate host nuclear receptors and cell signaling pathways: regulation of bile acid, cholesterol, glucose, lipid, and energy metabolism. Exhibit antimicrobial effects.	Inagaki et al., 2006; Hylemon et al., 2009
Choline metabolites:	Modulate lipid metabolism and glucose homeostasis.	Dumas et al., 2006; Wang Z. et al., 2011
E.g., Choline, trimethylamine N-oxide (TMAO) and betaine	Contribute to non-alcoholic fatty liver disease and cardiovascular disease.
Phenolic derivatives:	Antimicrobial effects: repress pathogenic microbes, influence gut microbiota composition, maintenance of intestinal health.	Larrosa et al., 2006, 2010; Lee H.C. et al., 2006; Selma et al., 2009
E.g., 4-OH phenylacetic acid, equol, urolithins, enterolactone, enterodiol, 8-prenylnaringenin, 2-(3,4-dihydroxyphenyl)acetic acid, 3-(4-hydroxyphenyl)propionic acid, 5-(3,4-dihydroxyphenyl)valeric acid	Protective effect against oxidative stress. Estrogen-modulating effect. Platelet aggregation inhibition effect. Urolithin exhibits anti-inflammatory and cancer chemopreventive effects.
Vitamins:	Energy production, red blood cell formation, as enzymatic cofactor for diverse biochemical reactions.	LeBlanc et al., 2011; Nicholson et al., 2012; Forster et al., 2017; Lerner et al., 2017b
E.g., Thiamine (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), pantothenic acid (B5), biotin (B7), folate (B11–B9), cobalamin (B12), and menaquinone (K2)	DNA replication, repair and methylation, regulating cell proliferation. Production of nucleotides, vitamins and amino acids. Enhance immune functioning.
Polyamines:	Sustain high proliferation rate of Intestinal epithelial cells.	Guo et al., 2003, 2005; Perez-Cano et al., 2010; Johnson et al., 2015; Rooks and Garrett, 2016
E.g., putrescine, spermidine, and spermine	Dysregulated polyamine metabolism possibly enhances cancer development. Enhance intestinal barrier integrity and function via stimulating synthesis of intercellular junction proteins [occludin, zonula occludens-1 (ZO-1), E-cadherin]. Enhance maturation of intestinal and systemic adaptive immune system. Spermine inhibits pro-inflammatory M1 macrophage activation.