Commensal bacteria are found to have important roles in human health, as bacterial metabolites are likely to be key components of host interactions by which they affect mammalianphysiology.N-acyl amidesynthase genes are found enriched in gastrointestinalbacteria and the lipids, that they encode, interact with GPCRs, which regulate gastrointestinal tract physiology, where cell-based models have demonstrated, that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, and the clearest overlap in structure and function between bacterial and human GPCR-active ligands, is found for the endocannabinoid receptor GPR119.
The experiment have isolated both the palmitoyl and oleoyl analogs of N-acyl serinol, and found the latter only differs from 2-OG: C21H40O4 by the presence of an amide instead of an ester, and from OEA: C20H39NO2 by the presence of an additional ethanol substituent, where the N-oleoyl serinol (C21H41NO3; 18:1,n-9), is a similarly potent GPR119 agonist compared to the endogenous ligand OEA (EC50 12 µM vs. 7 µM), but elicits almost a 2-fold greater maximum activation, do suggest that chemical mimicry of eukaryoticsignalling molecules may be common among commensal bacteria, that communicate through interactions between these two fundamental systems—which form the gut microbiota-endocannabinoidomeaxis.
^Shah U (July 2009). "GPR119 agonists: a promising new approach for the treatment of type 2 diabetes and related metabolic disorders". Current Opinion in Drug Discovery & Development. 12 (4): 519–532. PMID19562648.
^Semple G, Fioravanti B, Pereira G, Calderon I, Uy J, Choi K, et al. (September 2008). "Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119". Journal of Medicinal Chemistry. 51 (17): 5172–5175. doi:10.1021/jm8006867. PMID18698756.