Two-week administration of engineered Escherichia coli establishes persistent resistance to diet induced obesity even without antibiotic pretreatment

• Published in: Applied microbiology and biotechnology Vol. 103; no. 16; pp. 6711 - 6723
• Main Authors: Dosoky, Noura, Chen, Zhongyi, Guo, Yan, McMillan, Clara, Flynn, C. Robb, Davies, Sean S.
• Format: Journal Article
• Language: English
• Published: 15-06-2019
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-019-09958-x

Adverse alterations in the composition of the gut microbiota have been implicated in the development of obesity and a variety of chronic diseases. Re-engineering the gut microbiota to produce beneficial metabolites is a potential strategy for treating these chronic diseases.
N
-acyl-phosphatidylethanolamines (NAPEs) are a family of bioactive lipids with known anti-obesity properties, Previous studies showed that administration of
Escherichia coli
Nissle 1917 (EcN) engineered with
Arabidopsis thaliana
NAPE synthase to produce NAPEs imparted resistance to obesity induced by a high fat diet that persisted after ending their administration. In prior studies, mice were pre-treated with ampicillin prior to administering engineered EcN for 8 weeks in drinking water. If use of antibiotics and long-term administration are required for beneficial effects, implementation of this strategy in humans might be problematic. Studies were therefore undertaken to determine if less onerous protocols could still impart persistent resistance and sustained NAPE biosynthesis. Administration of engineered EcN for only two weeks without pre-treatment with antibiotics sufficed to establish persistent resistance. Sustained NAPE biosynthesis by EcN was required as antibiotic treatment after administration of the engineered
EcN
markedly attenuated its effects. Finally, heterologous expression of human Phospholipase A/acyl-transferase-2 (PLAAT2) in EcN provided similar resistance to obesity as heterologous expression of
A. thaliana
NAPE synthase, confirming that NAPEs are the bioactive mediator of this resistance.