A human gut <i>Faecalibacterium prausnitzii</i> 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 <i>Faecalibacterium prausnitzii</i> cultured from these children. This enzyme, expressed and purified from <i>Escherichia coli,</i> hydrolyzes a variety of <i>N</i>-acylamides, including oleoylethanolamide (OEA), neurotransmitters, and quorum sensing <i>N</i>-acyl homoserine lactones; it also synthesizes a range of <i>N</i>-acylamides, notably <i>N</i>-acyl amino acids. Treating germ-free mice with <i>N</i>-oleoylarginine and <i>N</i>-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 <i>F. prausnitzii</i> FAAH. This enzyme, structurally and catalytically distinct from mammalian FAAH, is positioned to regulate levels of a variety of bioactive molecules.