Genetically Engineered Escherichia coli Nissle 1917 Secreting GLP‐1 Analog Exhibits Potential Antiobesity Effect in High‐Fat Diet‐Induced Obesity Mice

Abstract

Objective: This study aimed to investigate the potential antiobesity effect of genetically modified Escherichia coli Nissle 1917 (EcN-GM) in mice fed a high-fat diet (HFD). Methods: The mice were randomly divided into six groups: a normal diet group (ND), a HFD group, a HFD + EcN group, and three HFD + EcN-GM groups. The effects of EcN-GM on body weight, food intake, fat pad and organ weight, and an oral glucose tolerance test were measured, in addition to hepatic biochemistry and histological analysis. The mRNA expression of neuropeptides related to food intake regulation in the hypothalamus was also detected. Results:The results showed that EcN-GM decreased body weight, body weight gain, food intake, fat pad weight, and hepatic weight of HFD mice. There were beneficial effects of EcN-GM on blood glucose, hepatic biochemistry, and hepatic histological alterations. A dramatic switch of food intake-regulating gene expression in the hypothalamus was also observed in mice. Conclusions: This work has revealed that a modified live bacterial therapeutic, EcN-GM, has potential beneficial effects on obesity. This effect may be related to the regulating of the neuropeptide expression of energy intake and expenditure in the hypothalamus. This study demonstrates a successful example of engineered EcN-GM as a novel approach for weight management.Obesity (2020) 28, 315-322.

Engineered probiotics

“…GLP-1 secreted by this strain can reprogram intestinal cells into insulin-producing cells, thereby reducing hyperglycemia in mice. Similar studies have shown an engineered EcN-GM that induces GLP-1 expression, which may have a beneficial effect on obesity, hyperglycemia and liver steatosis [ 23 ]. Precigen ActoBio has genetically modified Lactococcus lactis to obtain a engineered bacteria named AG019.…”

Native and Engineered Probiotics: Promising Agents against Related Systemic and Intestinal Diseases

“…Functions/Benefits Reference express autotransporter 43 adhesins antigen use optogenetics to activate secretion against colitis/precise spatiotemporal colonization [198] express IL-10 phone visual diagnosis and optogenetics based secretion against colitis/mobile health service [199] express GLP-1 analog GLP-1 analog diminishes food intake against obesity [200] express N-acylphosphatidylethanolamines N-acylphosphatidylethanolamines induce satiety against obesity [201] express antimicrobial peptides antimicrobial peptides target and kill Enterococcus against vancomycin-resistant Enterococcus [202] develop a synthetic genetic system sense and kill Pseudomonas aeruginosa against Pseudomonas aeruginosa [203] express N-acylphosphatidylethanolamines reduce body weight, liver inflammation, fibrosis and atherosclerotic necrosis against cardiovascular metabolic disease [204] express PQQ and other metabolizing enzymes relieve oxidative stress against heavy metal toxicity/iron deficiency/fructoseinduced dyslipidemia/hyperglycemia/hepatic steatosis [205][206][207] express l-arg biosynthetic enzyme exhausts ammonia for L-arginine biosynthesis against hyperammonemia [208] express phenylalanine ammonia lyase and L-amino acid deaminase consume phenylalanine within the gastrointestinal tract against PKU [209] Express adjuvant therapeutic factors express 5-ALA 5-ALA contributes to photodynamic therapy against cancer [210] express CAT increase the production of O2 contributing to radiotherapy against cancer [211] produce…”

“…In particular, to combat obesity and prevent related chronic diseases, EcN has been modified to secrete dipeptidyl peptidase 4-degradation-resistant GLP-1 [ 200 ] or N -acyl-phosphatidylethanolamines. Both possess anti-obesity properties [ 201 ], which have numerous benefits for obese mice.…”

ProbioticEscherichia coliNISSLE 1917 for inflammatory bowel disease applications

“…9 EcN, a Gram-negative bacillus with excellent colonization characteristics in the intestine, exhibits many probiotic properties such as antagonistic function against many pathogens and enhancement of the immunological function of the host, 10 serving as the most widely applied probiotics for the prevention and treatment of IBD. Though EcN has also been explored to alleviate other diseases such as cancer, 11 obesity, 12 asthma, 13 diabetes, 14 HIV, 15 etc., 16 this review will focus on the mechanisms and the recent advances in the application of functionalized EcN in the remission of IBD.…”