TY - JOUR
T1 - A human gut Faecalibacterium prausnitzii fatty acid amide hydrolase
AU - Cheng, Jiye
AU - Venkatesh, Siddarth
AU - Ke, Ke
AU - Barratt, Michael J.
AU - Gordon, Jeffrey
N1 - Publisher Copyright:
© 2024 the authors,
PY - 2024/10/25
Y1 - 2024/10/25
N2 - 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 Faecalibacterium prausnitzii cultured from these children. This enzyme, expressed and purified from Escherichia coli, hydrolyzes a variety of N-acylamides, including oleoylethanolamide (OEA), neurotransmitters, and quorum sensing N-acyl homoserine lactones; it also 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 considerably reduced fecal OEA, a satiety factor whose levels were negatively correlated with 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.
AB - 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 Faecalibacterium prausnitzii cultured from these children. This enzyme, expressed and purified from Escherichia coli, hydrolyzes a variety of N-acylamides, including oleoylethanolamide (OEA), neurotransmitters, and quorum sensing N-acyl homoserine lactones; it also 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 considerably reduced fecal OEA, a satiety factor whose levels were negatively correlated with 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.
UR - http://www.scopus.com/inward/record.url?scp=85207360421&partnerID=8YFLogxK
U2 - 10.1126/science.ado6828
DO - 10.1126/science.ado6828
M3 - Article
C2 - 39446943
AN - SCOPUS:85207360421
SN - 2096-5672
VL - 386
JO - Journal of Bio-X Research
JF - Journal of Bio-X Research
IS - 6720
M1 - eado6828
ER -