title: An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice.
abstract: Lipopolysaccharide endotoxin is the only known bacterial product which, when subcutaneously infused into mice in its purified form, can induce obesity and insulin resistance via an inflammation-mediated pathway. Here we show that one endotoxin-producing bacterium isolated from a morbidly obese human's gut induced obesity and insulin resistance in germfree mice. The endotoxin-producing Enterobacter decreased in relative abundance from 35% of the volunteer's gut bacteria to non-detectable, during which time the volunteer lost 51.4 kg of 174.8 kg initial weight and recovered from hyperglycemia and hypertension after 23 weeks on a diet of whole grains, traditional Chinese medicinal foods and prebiotics. A decreased abundance of endotoxin biosynthetic genes in the gut of the volunteer was correlated with a decreased circulating endotoxin load and alleviated inflammation. Mono-association of germfree C57BL/6J mice with strain Enterobacter cloacae B29 isolated from the volunteer's gut induced fully developed obesity and insulin resistance on a high-fat diet but not on normal chow diet, whereas the germfree control mice on a high-fat diet did not exhibit the same disease phenotypes. The Enterobacter-induced obese mice showed increased serum endotoxin load and aggravated inflammatory conditions. The obesity-inducing capacity of this human-derived endotoxin producer in gnotobiotic mice suggests that it may causatively contribute to the development of obesity in its human host.
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Na
authors.initials: N
authors.lastname: Fei
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004731:Endotoxins / Q000378:metabolism; D004754:Enterobacter / Q000145:classification / Q000302:isolation & purification* / Q000378:metabolism; D005856:Germ-Free Life; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D007333:Insulin Resistance; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009767:Obesity, Morbid / Q000382:microbiology*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides