Figure 1.

The communication between the liver and the gut is bidirectional. The liver secretes primary bile acids and antimicrobial molecules (immunoglobulin A (IgA) and angiogenin) into the biliary tract. Molecules reach the intestinal lumen and contribute to maintenance of gut eubiosis (while inhibiting intestinal bacterial overgrowth). During the enterohepatic circulation of bile, BAs act as signalling molecules by interacting with the nuclear receptor farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor (GPBAR1). This interaction contributes to modulate hepatic bile acid synthesis, glucose metabolism, lipid metabolism and dietary energy utilization. Gut products include host and/or microbial metabolites and microbial-associated molecular patterns (MAMPs). The systemic circulation also plays a role, since products are translocated to the liver via the portal vein and can influence liver functions. The systemic circulation extends the gut–liver axis since liver metabolites from dietary, endogenous or xenobiotic substances (free fatty acids, choline metabolites and ethanol metabolites) are transported to the intestine through the capillary system. This mechanism of continuous recirculation of molecules across blood capillaries can distinctively affect the intestinal barrier. Butyrate, the short chain fatty acids, is protective (i.e. improves the colonic defensive border), while acetaldehyde can activate a barrier damage. Abbreviations: BAs, bile acids; MAMPs, microbial-associated molecular patters; TMA, trimethylamine; TMAO, trimethylamine N-oxide; VLDL, very-low density lipoprotein. Adapted from Tripathi et al. [11] and Di Ciaula et al. [12].