Figure 2.

Dialogue between gut microbial metabolites and host metabolism. Metabolites derived from gut microbiota contribute to metabolic and endocrine homeostasis in a wide range of organs, including the liver, adipose tissue, pancreas, and brain. SCFAs are critical regulators of lipid metabolism, insulin secretion, satiety, and inflammation by activating GPRs. In addition, SCFAs reduce luminal PH to suppress TPH and redirect tryptophan degradation toward indole. Since indole and its derivatives possess superior properties to inhibit inflammation and lipogenesis compared to other tryptophan compounds like serotonin and kynurenine. As for the BAs, they affect host metabolism and liver fibrosis via an array of signaling pathways, including the hepatic and intestinal FXRs, as well as the TGR5. Aside from that, TMAO and endogenous ethanol contribute to liver inflammation.

ACC, acetyl-coenzyme A carboxylase; AhRs, aryl hydrocarbon receptors; AKT, protein kinase B; AMPK, AMP-activated protein kinase; BAs, bile acids; CYP7A1, cholesterol 7α-hydroxylase 1; DNL, de novo lipogenesis; GABA, γ-aminobutyric acid; GLP-1, glucagon-like peptide-1; GLP-1R, glucagon-like peptide-1 receptor; GPRs, G protein-coupled receptors; FAO, fatty acid oxidation; FASN, fatty acid synthase; FGF15, fibroblast growth factor 15; FGFR4, fibroblast growth factor receptor 4; FXRs, farnesoid X receptors; IGN, intestinal gluconeogenesis; IL-6, interleukin 6; IR, insulin resistance; M1, M1 macrophages; NF-κB, nuclear factor κB; PI3K, Rho-like GTPases and phosphatidylinositol 3-kinase; PYY, peptide YY; SHP, small heterodimer partner; SREBP-1c, sterol regulatory element-binding protein-1c; TGR5, takeda G protein-coupled receptor 5; TMA, trimethylamine; TMAO, trimethylamine N-oxide; TNF-α, tumor necrosis factor α; TPH, tryptophan hydroxylase; UCP2, uncoupling protein 2; 5-HT, serotonin.