title: Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity.
abstract: Metabolic disorders, including obesity, diabetes, and cardiovascular disease, are widespread in Westernized nations. Gut microbiota composition is a contributing factor to the susceptibility of an individual to the development of these disorders; therefore, altering a person's microbiota may ameliorate disease. One potential microbiome-altering strategy is the incorporation of modified bacteria that express therapeutic factors into the gut microbiota. For example, N-acylphosphatidylethanolamines (NAPEs) are precursors to the N-acylethanolamide (NAE) family of lipids, which are synthesized in the small intestine in response to feeding and reduce food intake and obesity. Here, we demonstrated that administration of engineered NAPE-expressing E. coli Nissle 1917 bacteria in drinking water for 8 weeks reduced the levels of obesity in mice fed a high-fat diet. Mice that received modified bacteria had dramatically lower food intake, adiposity, insulin resistance, and hepatosteatosis compared with mice receiving standard water or control bacteria. The protective effects conferred by NAPE-expressing bacteria persisted for at least 4 weeks after their removal from the drinking water. Moreover, administration of NAPE-expressing bacteria to TallyHo mice, a polygenic mouse model of obesity, inhibited weight gain. Our results demonstrate that incorporation of appropriately modified bacteria into the gut microbiota has potential as an effective strategy to inhibit the development of metabolic disorders.
authors: Zhongyi
authors: Z
authors: Chen
authors: Lilu
authors: L
authors: Guo
authors: Yongqin
authors: Y
authors: Zhang
authors: Rosemary L
authors: RL
authors: Walzem
authors: Julie S
authors: JS
authors: Pendergast
authors: Richard L
authors: RL
authors: Printz
authors: Lindsey C
authors: LC
authors: Morris
authors: Elena
authors: E
authors: Matafonova
authors: Xavier
authors: X
authors: Stien
authors: Li
authors: L
authors: Kang
authors: Denis
authors: D
authors: Coulon
authors: Owen P
authors: OP
authors: McGuinness
authors: Kevin D
authors: KD
authors: Niswender
authors: Sean S
authors: SS
authors: Davies
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004064:Digestive System / Q000382:microbiology*; D004195:Disease Models, Animal; D004435:Eating; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D009765:Obesity / Q000382:microbiology* / Q000473:pathology / Q000628:therapy*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain
chemical_list: D029681:Arabidopsis Proteins; D004268:DNA-Binding Proteins; C000592803:MHF2 protein, Arabidopsis; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; D000217:Acyltransferases; C042139:phosphatidylethanolamine N-acyltransferase