Phylogenetic analysis of 218 protein sequences that bear sequence similarity to F. prausnitzii FAAH

Here we characterize a fatty acid amide hydrolase (FAAH) from Faecalibacterium prausnitzii (Fp), an organism whose abundance increases in the gut microbiota of undernourished Bangladeshi children treated with a microbiota-directed complementary food (MDCF) that improves their ponderal and linear growth. Assays of purified Fp FAAH revealed bidirectional activity, with hydrolysis of multiple N-acylamides (including quorum-sensing N-acyl homoserine lactones) and synthesis of N-acyl amino acids. Fp FAAH is structurally unrelated to its human counterpart, and insensitive to inhibitors of the mammalian enzyme. Oleoylarginine/oleoylhistidine, the major N-acyl amino acid products of oleoylethanolamide metabolism by Fp FAAH, were characterized for their effects on intestinal gene expression in gnotobiotic mice. Analyses of fecal samples from MDCF-treated children disclosed significant negative correlations between levels of an Fp strain encoding this FAAH, Fp FAAH gene expression, and levels of oleoylethanolamide/oleoylarginine. These results suggest Fp FAAH regulates intestinal levels of N-acylated amine signaling molecules, with potential therapeutic implications.