The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
The Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science. 2024 Oct 25;386(6720):eado6828. doi: 10.1126/science.ado6828.
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 cultured from these children. This enzyme, expressed and purified from hydrolyzes a variety of -acylamides, including oleoylethanolamide (OEA), neurotransmitters, and quorum sensing -acyl homoserine lactones; it also synthesizes a range of -acylamides, notably -acyl amino acids. Treating germ-free mice with -oleoylarginine and -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 FAAH. This enzyme, structurally and catalytically distinct from mammalian FAAH, is positioned to regulate levels of a variety of bioactive molecules.
孟加拉国儿童的营养不良与肠道微生物组后装配的破坏有关；与标准疗法相比，微生物组导向的补充食品（MDCF）显著改善了他们的体重和线性生长。在这里，我们从这些儿童培养的生长相关肠道菌株中鉴定出一种脂肪酸酰胺水解酶（FAAH）。这种酶在大肠埃希氏菌中表达和纯化，可水解多种 -酰基酰胺，包括油酰乙醇酰胺（OEA）、神经递质和群体感应 -酰基高丝氨酸内酯；它还合成多种 -酰基酰胺，特别是 -酰基氨基酸。用 -油酰精氨酸和 -油酰组氨酸处理无菌小鼠，这是 FAAH OEA 代谢的主要产物，显著影响了肠道免疫功能途径的表达。给孟加拉国儿童服用 MDCF 大大降低了粪便 OEA 的水平，OEA 是一种饱腹感因子，其水平与他们的 FAAH 的丰度和表达呈负相关。这种酶在结构和催化上与哺乳动物 FAAH 不同，有望调节多种生物活性分子的水平。
