An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice

ISME J. 2013 Apr;7(4):880-4. doi: 10.1038/ismej.2012.153. Epub 2012 Dec 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat
  • Endotoxins / metabolism
  • Enterobacter / classification
  • Enterobacter / isolation & purification*
  • Enterobacter / metabolism
  • Germ-Free Life
  • Humans
  • Inflammation / microbiology
  • Insulin Resistance
  • Lipopolysaccharides / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Obesity, Morbid / microbiology*

Substances

  • Endotoxins
  • Lipopolysaccharides