Fig. 3.

Crosstalk between gut microbiome, metabolites, and host within the gut, the microbiome inhabits the most superficial mucin layer with abundance estimated to reach 10¹⁴. At this level, there is an intense crosstalk between microbial populations, diet, metabolic processes with production of several molecules, enterohepatic circulation of primary and secondary bile acids, and membrane-associated and nuclear receptors especially in colonocytes and endocrine L cells. Among the others, Microbial/Pathogen-associated molecular patterns (PAMPs), lipopolysaccharides (LPS) from the microbiota are detected by pattern recognition receptors, including toll-like receptors (TLRs). Akkermansia muciniphila provides a protective effect on intestinal barrier and reduces the inflammation by producing Amuc_1100 on the outer membrane which interacts with TLR2. Other microbes secrete endocannabinoids from digestion of dietary components such as SCFAs or from metabolization of endogenous. Several receptors on the luminal plasmamembrane or nuclear receptors can sense the effects of such molecules. Abbreviations: AGEs, advanced glycation end products; AhR, aryl hydrocarbon receptor; CB1, CB2, cannabinoid receptor type 1 and type 2; BSCFAs, branched short chain fatty acids; CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; FXR, farnesoid X receptor; GPBAR1, G-protein-coupled bile acid receptor-1; GPR119, GPR43, GPR41, G-protein coupled receptor 119, 43 and 41; LCA, lithocholic acid; MYD88, myeloid differentiation primary response 88; PPARα/γ, peroxisome proliferator-activated receptors alpha and gamma; SCFAs, short chain fatty acid; TRPV1, transient receptor potential cation channel subfamily V member 1; UDCA, ursodeoxycholic acid