Human Gut Microbiota Metabolites

ATP (Adenosine 5'-triphosphate) is a central component of energy storage and metabolism in vivo. ATP provides the metabolic energy to drive metabolic pumps and serves as a coenzyme in cells. ATP is an important endogenous signaling molecule in immunity and inflammation. ATP can activate the NLRP3 inflammasome and induce IL-1β and chemokines secretion. ATP has anti-bacterial infection effects and can protect mice against bacterial infection in mice.

Palmitic acid is a long-chain saturated fatty acid commonly found in both animals and plants. PA can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells. Palmitic acid is used to establish a cell steatosis model.

Lactic acid (DL-Lactic acid) is a hydroxycarboxylic acid receptor 1 (HCAR1) activator and an epigenetic modulator inducing lysine residues lactylation. Lactic acid is a glycolysis end-product, bridging the gap between glycolysis and oxidative phosphorylation. Lactic acid is an oncometabolite and has immune protective role of lactate in anti-tumor immunity. Lactic acid also has antimicrobial activity, which can be used as a food preservative.

Quercetin, a natural flavonoid, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC₅₀ of 2.4 μM, 3.0 μM and 5.4 μM for PI3K γ, PI3K δ and PI3K β, respectively.

Nicotinamide is a form of vitamin B3 or niacin. Nicotinamide Hydrochloride inhibits SIRT2 activity (IC₅₀: 2 μM). Nicotinamide also inhibits SIRT1. Nicotinamide increases cellular NAD₊, ATP, ROS levels. Nicotinamide inhibits tumor growth and improves survival. Nicotinamide also has anti-HBV activity.

Uric acid is an orally active oxygen free radical scavenger that helps maintain stable blood pressure and combat oxidative stress. Uric acid can scavenge ROS, such as singlet oxygen and peroxynitrite, and inhibit lipid peroxidation. Uric acid can be used as a modeling agent in research on hyperuricemia-induced hypertension models.

Hexadecanedioic acid (Thapsic acid) is an orally active metabolite produced by B. uniformis. Hexadecanedioic acid inhibits IRE1α-XBP1s-mediated flipogenesis and ferroptosis. Hexadecanedioic acid downregulates XBP1 and Hrd1 expression, activates the Nrf2/SLC7A11/GPX4 pathway. Hexadecanedioic acid can be used for the research of metabolic-associated fatty liver disease.

Dihydrogenistein is a reductive metabolite of Calycosin (HY-N0519), is an active metabolic intermediate.

D-Galactose is a natural aldohexose and C-4 epimer of glucose.

AICAR (Acadesine) is an adenosine analog and a AMPK activator. AICAR is also an autophagy, YAP and mitophagy inhibitor. AICAR regulates the glucose and lipid metabolism, and inhibits proinflammatory cytokines and iNOS production. AICAR inhibits autophagy through a mechanism independent of AMPK activity.

Arachidonic acid (Immunocytophyt) is a polyunsaturated omega-6 fatty acid and a major constituent of biomembranes. Arachidonic acid also acts as the substrate for various lipid mediators, such as prostaglandins (PGs). Arachidonic acid improves cognitive response and cardiovascular function.

L-Glutathione reduced (GSH; γ-L-Glutamyl-L-cysteinyl-glycine) is an endogenous antioxidant and is capable of scavenging oxygen-derived free radicals.

DHEA (Prasterone) is one of the most abundant steroid hormones. DHEA (Prasterone) mediates its action via multiple signaling pathways involving specific membrane receptors and via transformation into androgen and estrogen derivatives (e.g., androgens, estrogens, 7α and 7β DHEA, and 7α and 7β epiandrosterone derivatives) acting through their specific receptors.

Fosribnicotinamide (β-nicotinamide mononucleotide) is a product of the nicotinamide phosphoribosyltransferase (NAMPT) reaction and a key NAD⁺ intermediate. The pharmacological activities of Fosribnicotinamide include its role in cellular biochemical functions, cardioprotection, diabetes, Alzheimer's disease, and complications associated with obesity.

Docosahexaenoic Acid (DHA) is an omega-3 fatty acid abundantly present brain and retina. It can be obtained directly from fish oil and maternal milk.

NAD+ is a coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage.

Wortmannin (SL-2052; KY-12420) is a potent, selective and irreversible PI3K inhibitor with an IC₅₀ of 3 nM. Wortmannin also blocks autophagy formation, and potently inhibits Polo-like kinase 1 (PlK1) and Plk3 with IC₅₀s of 5.8 and 48 nM, respectively.

Spermidine maintains cell membrane stability, increases antioxidant enzymes activities, improving photosystem II (PSII), and relevant gene expression. Spermidine significantly decreases the H₂O₂ and O₂^.- contents.

Luteolin (Luteoline), a flavanoid compound, is a potent Nrf2 inhibitor. Luteolin has anti-inflammatory, anti-cancer properties, including the induction of apoptosis and cell cycle arrest, and the inhibition of metastasis and angiogenesis, in several cancer cell lines, including human non-small lung cancer cells.

L-Kynurenine is a metabolite of the amino acid L-tryptophan. L-Kynurenine is an aryl hydrocarbon receptor agonist.