A human gut Faecalibacterium prausnitzii fatty acid amide hydrolase

• 成果类型: Article
• 署名作者: Cheng, Jiye; Venkatesh, Siddarth; Ke, Ke; Barratt, Michael J.; Gordon, Jeffrey I.
• 署名单位: Washington University (WUSTL); Washington University (WUSTL)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8942
• DOI: 10.1126/science.ado6828
• 发表日期: 2024-10-25
• 关键词: molecular characterization; homoserine lactone; anandamide; biosynthesis; degradation; activation; inhibitors; DISCOVERY; alignment; biology

摘要

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.