Two-week Administration of Engineered Escherichia Coli Establishes Persistent Resistance to Diet-induced Obesity Even Without Antibiotic Pre-treatment

Overview

Journal Appl Microbiol Biotechnol

Specialties Biomedical Engineering
Biotechnology
Microbiology

Date 2019 Jun 17

PMID 31203417

Citations 6

Authors

Noura S Dosoky

Zhongyi Chen

Yan Guo

Clara McMillan

C Robb Flynn

Sean S Davies

Affiliations

Soon will be listed here.

Abstract

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 2 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/acyltransferase-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.

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References

Baur D, Gladstone B, Burkert F, Carrara E, Foschi F, Dobele S . Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis. 2017; 17(9):990-1001. DOI: 10.1016/S1473-3099(17)30325-0. View

Zhang Y, Li S, Gan R, Zhou T, Xu D, Li H . Impacts of gut bacteria on human health and diseases. Int J Mol Sci. 2015; 16(4):7493-519. PMC: 4425030. DOI: 10.3390/ijms16047493. View

Rodriguez de Fonseca F, Navarro M, Gomez R, Escuredo L, Nava F, Fu J . An anorexic lipid mediator regulated by feeding. Nature. 2001; 414(6860):209-12. DOI: 10.1038/35102582. View

Shen T, Albenberg L, Bittinger K, Chehoud C, Chen Y, Judge C . Engineering the gut microbiota to treat hyperammonemia. J Clin Invest. 2015; 125(7):2841-50. PMC: 4563680. DOI: 10.1172/JCI79214. View

Rinne P, Guillamat-Prats R, Rami M, Bindila L, Ring L, Lyytikainen L . Palmitoylethanolamide Promotes a Proresolving Macrophage Phenotype and Attenuates Atherosclerotic Plaque Formation. Arterioscler Thromb Vasc Biol. 2018; 38(11):2562-2575. DOI: 10.1161/ATVBAHA.118.311185. View

Diep T, Madsen A, Holst B, Kristiansen M, Wellner N, Hansen S . Dietary fat decreases intestinal levels of the anorectic lipids through a fat sensor. FASEB J. 2010; 25(2):765-74. DOI: 10.1096/fj.10-166595. View

Chen Z, Guo L, Zhang Y, Walzem R, Pendergast J, Printz R . Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity. J Clin Invest. 2014; 124(8):3391-406. PMC: 4109548. DOI: 10.1172/JCI72517. View

Shiwa M, Yoneda M, Okubo H, Ohno H, Kobuke K, Monzen Y . Distinct Time Course of the Decrease in Hepatic AMP-Activated Protein Kinase and Akt Phosphorylation in Mice Fed a High Fat Diet. PLoS One. 2015; 10(8):e0135554. PMC: 4534138. DOI: 10.1371/journal.pone.0135554. View

Carding S, Verbeke K, Vipond D, Corfe B, Owen L . Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 2015; 26:26191. PMC: 4315779. DOI: 10.3402/mehd.v26.26191. View

10.

Ni J, Shen T, Chen E, Bittinger K, Bailey A, Roggiani M . A role for bacterial urease in gut dysbiosis and Crohn's disease. Sci Transl Med. 2017; 9(416). PMC: 5808452. DOI: 10.1126/scitranslmed.aah6888. View

11.

Guo L, Amarnath V, Davies S . A liquid chromatography-tandem mass spectrometry method for measurement of N-modified phosphatidylethanolamines. Anal Biochem. 2010; 405(2):236-45. PMC: 2922460. DOI: 10.1016/j.ab.2010.06.027. View

12.

Igarashi M, DiPatrizio N, Narayanaswami V, Piomelli D . Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents. Biochim Biophys Acta. 2015; 1851(9):1218-26. PMC: 4516666. DOI: 10.1016/j.bbalip.2015.05.006. View

13.

Lauffer L, Iakoubov R, Brubaker P . GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes. 2009; 58(5):1058-66. PMC: 2671052. DOI: 10.2337/db08-1237. View

14.

Gillum M, Zhang D, Zhang X, Erion D, Jamison R, Choi C . N-acylphosphatidylethanolamine, a gut- derived circulating factor induced by fat ingestion, inhibits food intake. Cell. 2008; 135(5):813-24. PMC: 2643061. DOI: 10.1016/j.cell.2008.10.043. View

15.

Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodriguez de Fonseca F . Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature. 2003; 425(6953):90-3. DOI: 10.1038/nature01921. View

16.

Chen Z, Zhang Y, Guo L, Dosoky N, de Ferra L, Peters S . Leptogenic effects of NAPE require activity of NAPE-hydrolyzing phospholipase D. J Lipid Res. 2017; 58(8):1624-1635. PMC: 5538284. DOI: 10.1194/jlr.M076513. View

17.

Lasaro M, Liu Z, Bishar R, Kelly K, Chattopadhyay S, Paul S . Escherichia coli isolate for studying colonization of the mouse intestine and its application to two-component signaling knockouts. J Bacteriol. 2014; 196(9):1723-32. PMC: 3993324. DOI: 10.1128/JB.01296-13. View

18.

Bulat E, Garrett T . Putative N-acylphosphatidylethanolamine synthase from Arabidopsis thaliana is a lysoglycerophospholipid acyltransferase. J Biol Chem. 2011; 286(39):33819-31. PMC: 3190788. DOI: 10.1074/jbc.M111.269779. View

19.

Mardian E, Bradley R, Duncan R . The HRASLS (PLA/AT) subfamily of enzymes. J Biomed Sci. 2015; 22:99. PMC: 4624172. DOI: 10.1186/s12929-015-0210-7. View

20.

Wellner N, Diep T, Janfelt C, Hansen H . N-acylation of phosphatidylethanolamine and its biological functions in mammals. Biochim Biophys Acta. 2012; 1831(3):652-62. DOI: 10.1016/j.bbalip.2012.08.019. View