A human gut fatty acid amide hydrolase.

Undernutrition in Bangladeshi children is associated with disruption of postnatal gut microbiota assembly; compared with standard therapy, a microbiota-directed complementary food (MDCF) substantially improved their ponderal and linear growth. Here, we characterize a fatty acid amide hydrolase (FAAH) from a growth-associated intestinal strain of cultured from these children. This enzyme, expressed and purified from hydrolyzes a variety of -acylamides, including oleoylethanolamide (OEA), neurotransmitters, and quorum sensing -acyl homoserine lactones; it also synthesizes a range of -acylamides, notably -acyl amino acids. Treating germ-free mice with -oleoylarginine and -oleolyhistidine, major products of FAAH OEA metabolism, markedly affected expression of intestinal immune function pathways. Administering MDCF to Bangladeshi children considerably reduced fecal OEA, a satiety factor whose levels were negatively correlated with abundance and expression of their FAAH. This enzyme, structurally and catalytically distinct from mammalian FAAH, is positioned to regulate levels of a variety of bioactive molecules.