A human gut Faecalibacterium prausnitzii fatty acid amide hydrolase

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