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Obesity-associated gut bacteria harvest more energy from food
Background: Bacteria present in the gut are instrumental in harvesting energy, since they break down indigestible components of food. Rapid and dramatic weight gain is observed upon bacterial colonization of the gut in germ-free mice. Two types of bacteria make up >90% of the gut flora in mice and in humans: the Bacteroidetes and the Firmicutes. Although genetically obese mice deficient in leptin have increased weight due to higher levels of food intake, they also have a 50% reduction in Bacteroidetes compared with lean littermates. Obese vs lean humans also have lower levels of Bacteroidetes. Furthermore, when obese individuals lose weight, the Bacteroidetes to Firmicutes ratio increases in a manner proportionate to the extent of weight loss.

Turnbaugh et al investigated whether obesity-associated gut flora may contribute to the pathophysiology of obesity.

Methods: Microbial DNA prepared from the gut cecum of genetically obese mice and littermates was sequenced by two complementary methods. The relative abundance of Bacteroidetes and Firmicutes was assessed by taxonomic analysis of environmental gene tags and 16S ribosomal RNA gene fragments.

Results:
  • The ratio of Firmicutes to Bacteroidetes in the gut of obese and lean mice was 7.3 and 1.5, respectively.
  • Bomb calorimetry indicated that significantly less energy remained in the feces of obese vs lean mice (P < 0.001).
  • In germ-free lean mice colonized with gut bacteria from either obese or lean donors:
    • Initial body fat and initial weight were similar.
    • Chow consumption remained similar over 2 weeks.
    • At 2 weeks, recipients of bacteria from obese vs lean mice had a significantly greater percent increase in body fat (47% +/- 8.3% vs 27% +/- 3.6%).
    • The difference in the efficiency of energy harvest corresponded to 2% of total calories consumed.
Conclusions: The gut flora of obese mice have an increased capacity to extract energy from food relative to their lean counterparts. Furthermore, gut flora transplantation experiments indicate that the trait is transmissible.

Comment: "The alteration in efficiency of energy harvest from the diet produced by changes in gut microbial ecology does not have to be great to contribute to obesity, given that small changes in energy balance, over the course of a year, can result in significant changes in body weight," wrote the investigators. "Our results indicate that if the gut microbiome of obese humans is comparable to that of obese mice, then it may be a biomarker, a mediator and a new therapeutic target for people suffering from this increasingly worldwide disease."
 
Nature. 2006; 444: 1027-1031
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI.

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