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Dietary Fatty Acids Control the Species of N-Acyl-Phosphatidylethanolamines Synthesized by Therapeutically Modified Bacteria in the Intestinal Tract
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2017-10-17 00:00:00 , DOI: 10.1021/acsinfecdis.7b00127
Noura S. Dosoky 1 , Lilu Guo 1 , Zhongyi Chen 1 , Andrew V. Feigley 1 , Sean S. Davies 1
Affiliation  

Engineering the gut microbiota to produce specific beneficial metabolites represents an important new potential strategy for treating chronic diseases. Our previous studies with bacteria engineered to produce N-acyl-phosphatidylethanolamines (NAPEs), the immediate precursors of the lipid satiety factors N-acyl-ethanolamides (NAEs), found that colonization of these bacteria inhibited development of obesity in C57BL/6J mice fed a high fat diet. Individual NAE species differ in their bioactivities. Intriguingly, colonization by our engineered bacteria resulted in increased hepatic N-stearoyl-ethanolamide (C18:0NAE) levels despite the apparent inability of these bacteria to biosynthesize its precursor N-stearoyl-phosphatidylethanolamine (C18:0NAPE) in vitro. We therefore sought to identify the factors that allowed C18:0NAPE biosynthesis by the engineered bacteria after colonization of the intestinal tract. We found that the species of NAPE biosynthesized by engineered bacteria depends on the species of dietary fatty acids available in the intestine, suggesting a simple method to fine-tune the therapeutic effects of modified microbiota.

中文翻译:

膳食脂肪酸控制肠道中经治疗性修饰细菌合成的N-酰基-磷脂酰乙醇胺的种类

工程肠道菌群以产生特定的有益代谢产物代表了一种治疗慢性疾病的重要的新潜在策略。我们先前对经过工程改造以生产N-酰基磷脂酰乙醇胺(NAPE)(脂类饱腹因子N-酰基乙醇酰胺(NAE)的直接前体)的细菌的研究发现,这些细菌的定殖抑制了喂养C57BL / 6J小鼠的肥胖症的发展高脂饮食。各个NAE物种的生物活性不同。有趣的是,尽管这些细菌显然无法生物合成其前体N,但我们工程菌的定殖导致肝脏N-硬脂酰乙醇酰胺(C18:0NAE)含量增加。-硬脂酰磷脂酰乙醇胺(C18:0NAPE)体外。因此,我们寻求确定在肠道定居后允许工程菌生物合成C18:0NAPE的因素。我们发现,由工程菌生物合成的NAPE的种类取决于肠道中可用的膳食脂肪酸的种类,这表明微调修饰微生物群的治疗效果的简单方法。
更新日期:2017-10-17
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